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Published by DOS Secretariat, 2020-04-25 01:24:44

DOS Times Vol 25 No 4

DOS Times Vol 25 No 4

DVolume 25, No. 4 SJanuary-February 2020 For Private Ciruculation Only
TIMES

pecial Issue

on COVID-19

Official Bulletin Magazine of

DELHI
OPHTHALMOLOGICAL
SOCIETY

Highlights

Microbiology of Corona Viruses & Laboratory Diagnosis
of COVID-19 Infection

Chest CT Manifestations in COVID–19 Disease: A Review

Ophthalmology Practice in the Era of COVID-19 Pandemic

Virus of the Century, CORONA: An Ophthalmic Perspective

Advisory on the use of Hydroxy-Chloroquine in COVID-19
in India and other Countries

DOS Office Bearers

Dr. Rakesh Mahajan Dr. Subhash C Dadeya Dr. Namrata Sharma Dr. Hardeep Singh
President Vice President Secretary Joint Secretary

Dr. Jatinder S Bhalla Dr. Vinod Kumar Dr. Manav Deep Singh
Treasurer Editor Library Officer

Executive Members

Dr. Dewang Angmo Dr. Jatinder Bali Dr. Shantanu Gupta Dr. C. P. Khandelwal

Dr. Rahul Mayor Dr. Vipul Nayar Dr. Rajendra Prasad Dr. Kirti Singh

DOS Representative to AIOS Ex-Officio Members

Prof. J.S. Titiyal Prof. M. Vanathi Dr. S.K. Khokhar Dr. Subhash C Dadeya Dr. Arun Baweja

Contents COVID-19 Special

Editorial 07 Microbiology of Corona Viruses & Laboratory Diagnosis of
COVID-19 Infection
05 Prof. (Dr.) Namrata Sharma
Secretary, DOS 12 Novel Coronavirus Disease: COVID-19: Diagnosis and Pulmonary
Aspects
Guest Editorial
14 Chest CT Manifestations in COVID–19 Disease: A Review
06 Dr. Jatinder Singh Bhalla 18 Ophthalmology Practice in the Era of COVID-19 Pandemic
25 Virus of the Century, Corona: An Ophthalmic Perspective
28 Glaucoma Management in COVID-19 Era
32 Retina Practice in Times of COVID-19
36 Advisory on the use of Hydroxy-Chloroquine in COVID-19 in India

and other Countries
40 Vaccines for COVID-19
47 Teleophthalmology and Telemedicine: Getting Practice Ready in the

Changing Scenario
52 The Impact of COVID-19 Pandemic on Young Ophthalmologists
54 Medico-legal Advisory on COVID-19 Pandemic
57 Post COVID-19 Scenario – Let’s Plan A New Beginning
61 Financial Implications for Ophthalmologists due to

COVID-19 Outbreak
65 Acute Psychological Effects in the Times of COVID-19 Pandemic
69 Artificial Intelligence in Fight Against COVID-19
72 COVID–19: Investigational Anti-Viral Treatments
75 Variable Success in Fight Against COVID-19 Amongst Different

Countries- An Epidemiological and Scientific Perspective

www.dosonline.org/dos-times DOS Times - Volume 25, Number 4, January-February 2020 01



VolVuomluem2e52N5o,.N3o, N. 4o,vJeamnubaerry--DFecbermuabreyr,22002109

Editor In Chief DOS Times Editorial Board
Namrata Sharma
Editorial Board National Board
Editor Dr. Parul Icchpujani
Prafulla Kumar Maharana Dr. Atul Kumar Dr. Ronnie George
Dr. Aniruddha Maiti Dr. Sushmita Kaushik
Assistant Editors Dr. Apporva Ayachit Dr. Gopal Pillai
Dr. Jitendra Jethani Dr. Usha Singh
Ritu Nagpal Siddhi Goel Dr. Mita Joshi Dr. Subhendu Boral
Dr. P. Dutta Majumdar Dr. Meena Chakrabarti
Dr. Noopur Gupta Dr. Raksha Rao
Dr. Brijesh Kakkar Dr. Kumudini Verma
Dr. Digvijay Singh Dr. Rashmin Gandhi
Dr. Ritika Sachdev Dr. Siddharth Kesarwani
Dr. Dewang Angmo Dr. Chaitra Jayadev
Dr. Rebika Dr. Bibhuti P. Sinha
Dr. Saurabh Sawhney Dr. Amit Porwal
Dr. Reena Sharma Dr. Prashant Bawankule
Dr. Rajat Jain Dr. Arvind Kumar Morya
Dr. Jaya Gupta
Deepali Singhal Sahil Agarwal Dr. Anita Ganger
Ritika Mukhija Rahul Kumar Bafna Dr. Umang Mathur
Dr. Neera Agarwal
Farin Shaikh Divya Agarwal Dr. Poonam Jain
Mohamed Ibrahime Asif Venkatesh Nathiya Dr. Manisha Agarwal
Dr. Hardeep Singh
Dr. Anita Sethi
Dr. Tushar Agarwal
Dr. Rohit Saxena
Dr. Swati Phuljhele
Dr. Vivek Dave
Dr. Mohita Sharma
Dr. Rajesh Sinha
Dr. Aitu Arora
Dr. P.K. Pandey
Dr. H.K. Yaduvanshi
Dr. O.P. Anand

Anusha Sachan Abhijeet Beniwal

Gunjan Saluja Akshaya Balaji
www.dosonline.org/dos-times
DOSDTOimSeTsim- Veoslu- mVoelu2m5,eN2u5m, Nbeurm3b, eNro4v,eJmanbuearr-yD-Feecebmrubaeryr 201290 03



Editorial

From the
Editor Desk

Prof. (Dr.) Namrata Sharma Dear Members,
The tragedy of the COVID-19 pandemic is having a profound effect on the lives of
(MD, DNB, MNAMS) millions of people around the world. Our worldwide medical community is facing
its biggest challenge in modern history. We are collectively in a situation in which
Hony. General Secretary we have no experience and for which we have limited preparation.
Delhi Ophthalmological Society Alongside the deep distress felt as many states in India are experiencing a peak in
cases or brace for it, there is also a growing understanding of the importance of the
Cornea, Cataract & Refractive Surgery Services collective and community.
Dr. R.P. Centre for Ophthalmic Sciences, With the cancellation or delay of all elective surgical procedures and the limiting
All India Institute of Medical Sciences (AIIMS) of outpatient visits, the backlog will be enormous when restrictions are lifted, and
New Delhi it is likely that concerns regarding dissemination of the virus will persist for some
time. More importantly, emergency/urgent procedures need to be carried out for
the benefit of the patient. To provide the ophthalmic community with the most
up-to-the-date relevant information, this issue of DOS Times is focused on varied
aspects of COVID19 and Ophthalmology.
With COVID19 came a lot of advisories and to make it easier for the members, we
have articles on Advisory regarding COVID19 with respect to Ophthalmologists
and also Medico legal advisory on COVID19 pandemic.
The articles on Glaucoma Management and Retina Practices in times of COVID
era will furnish you all with information on how to manage the patient without
compromising with the safety of the patient and the health care provider.
Tele ophthalmology as is the need of time and is continue to stay with us, so the
article will give you all the nuances of Teleophthalmology and will help you initiate
it in your practice.
For the benefit of the young ophthalmologists, we have discussed the effect of
COVID on young ophthalmologists and have also focused on the psychological
impact of this pandemic on our community.
The financial aspect will throw light on how this pandemic has affected everyone
financially and how to deal with it in the best possible way.
Whilst this crisis has brought unprecedented challenges for all of us, and we’ve been
humbled by the wave of inspiring new ideas developed in response. Innovation is
more important now than ever before, and we look forward to your constructive
feedback. Hope to get back to our “New Normal life” soon.
Stay Home, Stay Safe and Fight CORONA together.

www.dosonline.org/dos-times DOS Times - Volume 25, Number 4, January-February 2020 05

Guest Editorial

Dr Jatinder Singh Bhalla Respected seniors & dear Friends,

MS, DNB, MNAMS There are decades when nothing happens and there are weeks when decades
happen- Lenin
Hony. Treasurer
Delhi Ophthalmological Society If someone told us that we have to make a choice between disaster and calamity,
we would simply go numb. That is exactly what has happened. A pneumonia of
HOD (Ophthalmology) unknown cause ,detected in Wuhan was first reported to the WHO on 31st December
Deen Dayal Upadhyay hospital 2019. The outbreak was declared a Public Health Emergency of International
Hari Nagar, New Delhi, India Concern on30.1.20. On the basis of ”alarming levels of spread ,severity and by the
alarming levels of inaction”, the Director-General of WHO declared it as Pandemic
on March 11, 2020. Over the past 2 months, the COVID-19 pandemic has marched
relentlessly across the globe.

To respond to COVID-19, most countries have used a combination of confinement
and extenuation activities with the aim of delaying major surges of patients and
controlling the demand for hospital beds, while protecting the most susceptible
from infection, including elderly people and those with co morbidities. Most
national response strategies include varying levels of contact tracing and self-
isolation or quarantine; promotion of public health measures, including hand
washing, respiratory formalities & protocol, and social distancing; preparation of
health systems for a deluge of critical patients who require isolation, oxygen, and
mechanical ventilation; strengthening health facility ,infection prevention and
control, and postponement or cancellation of large-scale public gatherings.

We are faced with a stressful situation of unprecedented proportions. We cannot
just wish it away passively. Failing to embrace the stress creates more stress. So it
makes sense to acknowledge the stress & face it head on. We being doctors have the
advantage of not only being frontline warriors, we also have the added responsibility
of giving medical knowledge to our patients, friends, family members and lay
persons.

Having said that, it is important for the authorities to provide the frontline warriors
with the proper PPE kits and protective armory to fight this war. If we sincerely
follow the basic steps of public health and follow lockdown fastidiously, we should
be able to annihilate Corona.

We have to join hands with our PM, be positive and build hope. Our sincere efforts
will lead to coronation of India as a leader in the fight against Corona. On the
contrary, a small chink in the armour can lead us to be labelled as Corona-nation.
Whether we want the status of Coronation or Corona-nation, the choice is entirely
yours.

We all sincerely pray that things return to normal in the near future; but in the
rush to return to normal, let us decide which parts of normal are worth rushing to.
Concepts and situations have changed quite a bit post Corona. New baselines will
emerge and a new world order will bloom.

What feels like the end is often the beginning. Let us make a new beginning.

To update you all with Scientific facts & guidelines regarding COVID 19, we are
bringing out a special CORONA issue of DOS TIMES. Hope, you will find it useful.

06 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

Microbiology of Corona Viruses &
Laboratory Diagnosis of COVID-19
Infection

Manpreet Bhalla MD1, Jaideep Singh Bhalla MBBS2
1Senior Consultant Microbiologist, National Institute of TB & Respiratory Diseases (NITRD), New Delhi
2Maulana Azad Medical College, New Delhi

Coronaviruses were first discovered in Figure 1: Structure of Coronavirus Inside the envelope, there is the
the 1930’s when an acute respiratory nucleocapsid, which is formed from
infection of domesticated chickens enveloped, non-segmented positive- multiple copies of the nucleocapsid
was shown to be caused by infectious sense RNA viruses. They all contain (N) protein, which are bound to the
bronchitis virus (IBV). In the 1940’s, very large genomes for RNA viruses, positive-sense single-stranded RNA
two more animal coronaviruses, mouse with Coronavirinae having the largest genome in a continuous beads-on-a-
hepatitis virus (MHV) and transmissible identified RNA genomes, containing string type conformation.9 The lipid
gastroenteritis virus (TGEV), were approximately 30 kilobase (kb) bilayer envelope, membrane proteins,
isolated.1 genomes. In fact, the Nidovirales order and nucleocapsid protect the virus
Human coronaviruses were discovered name is derived from these nested 3’ when it is outside the host cell.10
in the 1960’s2 The earliest ones studied mRNAs as nido is Latin for “nest”.4
were from human patients with The name coronavirus is derived from Coronavirus Life Cycle
the common cold, which were later the Latin corona, meaning “crown” or Attachment and Entry
named human coronavirus 229E and “halo”, which refers to the characteristic The initial attachment of the virion to
human coronavirus OC433. Other appearance reminiscent of a crown or a the host cell is initiated by interactions
human coronaviruses have since been solar corona around the virions (virus between the S protein and its receptor.
identified, including SARS CoV in 2003, particles).5,6 The sites of receptor binding domains
HCoV NL63 in 2004, HKU1 in 2005, Coronavirus virus is made up of a (RBD) within the S1 region of a
MERS-CoV in 2012, and SARS CoV in lipid bilayer containing four main coronavirus S protein vary depending
2019. Most of these have caused serious structural proteins. These are the spike on the virus, with some having the RBD
respiratory tract infections. (S), membrane (M), envelope (E), and at the N-terminus of S1 (MHV) while
Coronaviruses (CoVs) are the largest nucleocapsid (N) proteins, all of which others (SARS-CoV) have the RBD at
group of viruses belonging to the are encoded within the 3’ end of the the C-terminus. The S-protein/receptor
Nidovirales order, which includes viral genome.7,8
Coronaviridae, Arteriviridae, and
Roniviridae families. The Coronavirinae
comprise one of two subfamilies in the
Coronaviridae family, with the other
being the Torovirinae. The Coronavirinae
are further subdivided into four
groups, the alpha, beta, gamma and
delta coronaviruses. The viruses were
initially sorted into these groups based
on serology but are now divided by
phylogenetic clustering.
All viruses in the Nidovirales order are

www.dosonline.org/dos-times DOS Times - Volume 25, Number 4, January-February 2020 07

COVID-19 Special

occurs inside the endoplasmic
reticulum. The viral structural proteins
S, E, and M move along the secretory
pathway into the Golgi intermediate
compartment. Progeny viruses are then
released from the host cell by exocytosis
through secretory vesicles.9

Structural Representation of α, β & γ CoVs Laboratory Testing for the
E: envelope protein gene; M: membrane protein gene; N: nucleocapsid protein gene; ORF: Respiratory Coronavirus Disease
open reading frame; RdRp: RNA-dependent RNA polymerase gene; S: spike protein gene. 2019 (COVID-19)
HCoV-229E, human coronavirus 229E; MHV, mouse hepatitis virus; SARS-CoV, severe Includes methods that detect the
acute respiratory syndrome coronavirus; MERS-CoV, Middle East respiratory syndrome presence of virus and those that detect
coronavirus; IBV, infectious bronchitis virus. antibodies produced in response to
infection. Detection of antibodies
(serology) can be used both for clinical
purposes and population surveillance.

Detection of virus using PCR tests
Reverse transcription polymerase chain
reaction (RT PCR)

Using real-time reverse transcription
polymerase chain reaction (rRT-PCR)13
the test can be done on respiratory
samples obtained by various methods,
including nasopharyngeal swab or
sputum sample.4 Results are generally
available within a few hours to 2 days.

interaction is the primary determinant α-coronaviruses utilize aminopeptidase The CDC’s 2019-nCoV Laboratory Test Kit
for a coronavirus to infect a host species N (APN) as their receptor, SARS-CoV Thermocycler or thermal cycler, also known
and also governs the tissue tropism of use angiotensin-converting enzyme 2 as a PCR machine
the virus.11 (ACE2) as their receptor.12

Figure 1: Illustration of the coronavirus Replication
structure and viral receptor ACE2 on the A number of the nonstructural proteins
host cell surface. coalesce to form a multi-protein
Many coronaviruses utilize peptidases replicase-transcriptase complex (RTC).
as their cellular receptor. Many The main replicase-transcriptase protein
is the RNA-dependant RNA polymerase
(RdRp). It is directly involved in the
replication and transcription of RNA
from an RNA strand.9

Release
The replicated positive-sense genomic
RNA becomes the genome of the
progeny viruses. These mRNAs are
translated by the host’s ribosomes into
the structural proteins. RNA translation

08 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

Demonstration of a nasopharyngeal swab for COVID-19 testing Disease Control & Prevention (CDC) is
distributing its 2019-Novel Coronavirus
False Negative (2019-nCoV) Real-Time RT-PCR
Specimen collected too early or too late, improper specimen, poor handling or transport of Diagnostic Panel to public health labs
specimen. through the International Reagent
If you get negative result from a patient with a high index of suspicion: Repeat collection of Resource.21 One of three genetic tests
sample from lower respiratory tract , if earlier sample was from upper respiratory tract.14 in older versions of the test kits caused
inconclusive results due to faulty
RT PCR (Real Time Polymerase Chain and formed the basis of 250,000 kits reagents, and a bottleneck of testing
Reaction). It is a 2 stage test. for distribution by the World Health at the CDC in Atlanta; this resulted in
First line screening assay: E gene assay Organisation (WHO).15 The United an average of fewer than 100 samples
Confirmatory assay: Orf gene & RdRp Kingdom had also developed a test by a day being successfully processed
gene assay 23 January 2020.16 throughout the whole of February
Right now, First line screening assay is The South Korean company 2020. Tests using two components
done(onEgeneofvirus)&ifitispositive, Kogenebiotech developed a clinical were not determined to be reliable until
it is confirmed by Confirmatory assay grade, PCR-based SARS-CoV-2 detection 28 February 2020, and it was not until
(on Orf gene & RdRp gene of virus). kit (PowerChek Coronavirus) on 28 then that state and local laboratories
Confirmatory test is highly sensitive as January 2020.17,18 It looks for the “E” were permitted to begin testing.22 The
it is able to detect just 3.8 RNA Copies/ gene shared by all Beta Coronaviruses, test was approved by the FDA under an
reaction. and the RdRp gene specific to SARS- Emergency Use Authorisation.
Additional Confirmatory assay: N gene CoV-2.19 US commercial labs began testing
assay may be done if required In China, BGI Group was one of the in early March 2020. As of 5 March
One of the early PCR tests was developed first companies to receive emergency 2020LabCorp announced nationwide
at Charite in Berlin in January 2020 use approval from China’s National availability of COVID-19 testing
using real-time reverse transcription Medical Products Administration for a based on RT-PCR.23 Quest Diagnostics
polymerase chain reaction (rRT-PCR), PCR-based SARS-CoV-2 detection kit.20 similarly made nationwide COVID-19
In the United States, the Center For testing available as of 9 March 2020.24 No
quantity limitations were announced;
specimen collection and processing
must be performed according to CDC
requirements.
In Russia, the COVID-19 test was
developed and produced by the
State Research Center of Virology
& Biotechnology VECTOR. On 11
February 2020 the test was registered by
the Federal Service for Surveillance in
Healthcare.25
On 12 March 2020, Mayo Clinic was
reported to have developed a test to
detect COVID-19 infection.26
On 13 March 2020, Roche Diagnostics
received FDA approval for a test which
could be performed within 3.5 hours,
thus allowing one machine to do
approximately 4,128 tests in a 24-hour
period.27
On 19 March 2020, the FDA issued
Emergency Use Authorisation (EUA)
to Abbott Laboratories for a test on
Abbott’s m2000 system; the FDA had
previously issued similar authorization

www.dosonline.org/dos-times DOS Times - Volume 25, Number 4, January-February 2020 09

COVID-19 Special

to Hologic LabCorp, and Thermo Fisher Table 1: VARIATION IN LEVELS OF SARS CoV2 RNA & ANTIGEN, IgM, IgG
Scientific.28 On 21 March 2020, Cepheid levels after infection
similarly received EUA from the FDA
for a test that takes about 45 minutes.29 Table 2: Clinical Significance of an IgM/IgG Serological Test Result

A test which uses a Monoclonal References 4. Anthony R. Fehr and Stanley Perlman.
Antibody which specifically binds to the 1. McIntosh K (1974). Arber W, Haas R, Coronaviruses: An Overview of Their
Nucleocapsid protein (N protein) of the Replication and Pathogenesis Methods
novel coronavirus is being developed Henle W, Hofschneider PH, Jerne NK, Mol Biol. 2015; 1282: 1–23.
in Taiwan, with the hope that it can Koldovský P, Koprowski H, Maaløe
provide results in 15 to 20 minutes just O, Rott R (eds.). “Coronaviruses: A 5. Almeida JD, Berry DM, Cunningham
like a Rapid Influenza test.30 Comparative Review”. Current Topics in CH, Hamre D, Hofstad MS, Mallucci
Microbiology and Immunology / Berlin, L, McIntosh K, Tyrrell DA Virology:
Serology Test for COVID-19 Heidelberg: Springer: 87 Coronaviruses”. Nature. 1968;220 (5168):
The serology test will look for the 2. Kahn JS, McIntosh K . “History and recent 650.
presence of antibodies,IgG & IgM which advances in coronavirus discovery”. The
are specific proteins made in response Pediatric Infectious Disease Journal. 6. Sturman LS, Holmes KV , Lauffer MA,
to infections. Antibodies can be found 2005;24 (11 Suppl) Maramorosch K (eds.). “The molecular
in the blood and in other tissues of 3. Geller C, Varbanov M, Duval RE biology of coronaviruses”. Advances in
those who are tested after infection. The Human coronaviruses: insights into Virus Research. 1983;28: 35–112
antibodies detected by this test indicate environmental resistance and its
that a person had an immune response influence on the development of new 7. Beniac DR, Andonov A, Grudeski E,
to SARS-CoV-2, whether symptoms antiseptic strategies. Viruses. 2012; Booth TF. Architecture of the SARS
developed from infection or the 4(11): 3044–68. coronavirus prefusion spike. Nature
infection was asymptomatic. Antibody structural & molecular biology.
test results are important in detecting 2006;13(8):751–752.
infections with few or no symptoms.31

It is to be used as screening test in
clusters or hot spot areas. Asymptomatic
Negatives & Positives on Serological
test are to be tested on RT PCR for
Confirmation. Being a fast test, as it’s
result may be available in minutes
compared to 2.5 - 4 hours for RT PCR;
it can be useful for rapid screening
testing.31

Other Tests
In addition to above, PCR positive
samples are to be subjected to
sequencing protocols for nCoV specific
identification in laboratories with
Sanger or Next Generation Sequencing

ELISA assays are also under
development.

Electron microscopy (For academic
purposes) reveals virus with a
characteristic crown morphology:
Coronavirus Cell culture on Vero
E6, LLC-MK2 cells and fetal rhesus
monkey kidney cells only in WHO
recommended reference laboratories.

10 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

8. Delmas B, Laude H. Assembly of PCR testing. Radiology. Published online 26. Plumbo, Ginger. “Mayo Clinic develops
coronavirus spike protein into trimers February 12, 2020. test to detect COVID-19 infection”. Mayo
and its role in epitope expression. Clinic. Retrieved 13 March 2020.
Journal of virology. 1990;64(11):5367– 15. Sheridan, Cormac (19 February
5375. 2020). “Coronavirus and the race to 27. “US regulators approve Roche’s new and
distribute reliable diagnostics”. Nature faster COVID-19 test”. ETHealthworld.
9. Fehr AR, Perlman S , Maier HJ, Bickerton Biotechnology com. Retrieved 14 March 2020
E, Britton P (eds.). “Coronaviruses:
an overview of their replication and 16. BBC News. 23 January 2020. 28. FDA Approves Abbott Laboratories
pathogenesis”. Methods in Molecular Coronavirus Test, Company To Ship
Biology. Springer. 2015;1282: 1–23. 17. KogeneBiotech”. Kogene.co.kr. Retrieved 150,000 Kits”. IBTimes.com. 19 March
16 March 2020. 2020.
10. Chang CK, Hou MH, Chang CF, Hsiao
CD, Huang TH . “The SARS coronavirus 18. Jeong, Sei-im (28 February 2020). “Korea 29. Sunnyvale company wins FDA
nucleocapsid protein-forms and approves 2 more COVID-19 detection approval for first rapid coronavirus
functions”. Antiviral Research. 2014; kits for urgent use – Korea Biomedical test with 45-minute detection time”.
103: 39–50. Review”. www.koreabiomed.com (in EastBayTimes.com. 21 March 2020.
Korean). Retrieved 12 March 2020.
11. Simmons G, Zmora P, Gierer S, Heurich 30. www.sinica.edu.tw. Sinca. Retrieved 12
A, Pöhlmann S “Proteolytic activation 19. “ABOUT US | NEWS”. www.kogene. March 2020.
of the SARS-coronavirus spike protein: co.kr.
cutting enzymes at the cutting edge of 31. ICMR Guidance on Rapid Antibody kits
antiviral research”Antiviral Research. 20. BGI Sequencer, Coronavirus Molecular for COVID 19.
2013;100 (3): 605–14. Assays Granted Emergency Use
Approval in China”. GenomeWeb. Corresponding Author:
12. Roujian et al. Genomic characterization Retrieved 9 March 2020.
& epidemiology of 2019 novel Corona Dr. Manpreet Bhalla MD
Virus: implication for virus origin & 21. “International Reagent Resource”. www. Dept. of Microbiology, National Institute of TB
Receptor binding. 2020:395(10224);565- internationalreagentresource.org. and Respiratory Diseases, Sri Aurobindo Marg,
57. New Delhi - 110030, India
22. Transcript for the CDC Telebriefing
13. Diagnosis of COVID-19 by the novel, Update on COVID-19, 28 February 2020
highly sensitive and specific COVID-
19-RdRp/Hel real-time reverse 23. “LabCorp Launches Test for Coronavirus
transcription-polymerase chain reaction Disease 2019 (COVID-19)”. Laboratory
assay. JFW Chan, CCY Yip, KKW To, Corporation of America Holdings.
THC Tang et al - Journal of Clinical …,
2020(Posted Online 4 March 2020) 24. “Covid19: COVID-19”.
www.questdiagnostics.com.
14. Xie X, Zhong Z, Zhao W, Zheng C, Wang
F, Liu J. Chest CT for typical 2019-nCoV 25. В России зарегистрирована
pneumonia: relationship to negative RT- отечественная тест-система для
определения коронавируса”. Interfax-
Russia.ru. 14 February 2020.

www.dosonline.org/dos-times DOS Times - Volume 25, Number 4, January-February 2020 11

COVID-19 Special

Novel Coronavirus Disease:
COVID-19: Diagnosis and
Pulmonary Aspects

S.K. Chhabra, MD, FCCP
Department of Pulmonary, Sleep and Critical Care Medicine,
Primus Superspeciality Hospital, New Delhi

China first intimated to WHO on 31 in India. Currently, 411/736 districts illness and having been in contact
December 2019, a case of a pneumonia have cases with inhomogeneous spread, with a confirmed or probable
of unknown cause detected in largely sparing the eastern parts of the COVID-19 case in the last 14 days
Wuhan, China. Identification and country. Clusters have appeared in prior to symptom onset
gene sequencing was done by mid- multiple states, particularly Kerala,
January and it was identified as a Maharashtra, Rajasthan, Uttar Pradesh, Probable case
novel coronavirus, a new coronavirus Delhi, Punjab, Karnataka, Telangana 1. A suspect case for whom testing for
hitherto known to infect only animals and UT of Ladakh. The risk of further
such as bats and never known to infect spread remains very high. Hence the the COVID-19 virus is inconclusive
humans. Previous coronavirus diseases, current vigil, containment efforts and or
theSevere Acute Respiratory Syndrome focus on future preparedness. 2. A suspect case for whom testing
(SARS) of 2003 andthe Middle East could not be performed for any
Respiratory Syndrome (MERS) of Case Definitions reason
2012 were also acquired from animals
and have been largely contained. The Suspect case Confirmed Case
novel coronavirus (nCOV2) disease 1. A patient with acute respiratory 1. A person with laboratory
subsequently spread globally. In the
first three months after COVID-19 illness (fever and at least one sign/ confirmation of COVID-19 infection
emerged,more than 2.5 million people symptom of respiratory disease, e.g., by RT-PCR test, irrespective of
have been infected worldwide and more cough, shortness of breath), and a clinical signs and symptoms
than 165000 people have died. history of travel to or residence in
a location reporting community Contact
The WHO started to work 24/7 to transmission of COVID-19 disease 1. A contact is a person with any one of
analyse data, provide advice, coordinate during the 14 days prior to symptom
with partners, help countries prepare, onset the following exposures during the 2
increase supplies and manage expert days before and the 14 days after the
networks. It declared a public health 2. A patient with any acute respiratory onset of symptoms of a probable or
emergency of international concern illness and having been in contact confirmed case:
on 30 January 2020 and a new name with a confirmed or probable a. Face-to-face contact with a
for the coronavirus disease was given COVID-19 case in the last 14 days
on 11 February 2020: COVID-19 It was prior to symptom onset probable or confirmed case
declared a pandemic on 11 March, 2020. within 1 meter and for more than
3. A patient with severe acute 15 minutes
Though India has also been affected, the respiratory illness (fever and b. Direct physical contact with a
incidence and prevalence have been on at least one sign/symptom of probable or confirmed case (like
the lower side compared to the world respiratory disease, e.g., cough, hand shake)
average, the major disease burden being shortness of breath; AND requiring c. Direct care for a patient with
in US and Europe. As of today, more hospitalization) and in the absence probable or confirmed COVID-19
than 17000 cases have been identified of an alternative diagnosis that fully disease without using proper
explains the clinical presentation personal protective equipment
(HCP)
4. A patient with any acute respiratory

12 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

Clinical Features 1. All symptomatic individuals who mechanical ventilationand often extra
The infection spreads mainly by have undertaken international travel corporeal membrane oxygenation
droplets that are aerosolized when in the last 14days (ECMO) and carry a mortality of 30-
an infected patient coughs, speaks or 40%.
sneezes. A close contact can catch the 2. All symptomatic contacts of Results with antiviral drugs have
virus that usually enters the nose or the laboratory confirmed cases not been encouraging. Drugs like
mouth and affects mainly the upper hydroxychloroquin (HCQS) and
and lower respiratory tract. The virus 3. All symptomatic healthcare azithromycin are reserved for severely
may survive on hard surfaces for 12-36 personnel (HCP) affected patients with limited clinical
hours. evidence so far and are likely to cause
4. All hospitalized patients with severe substantial adverse effects including
The incubation period is around 5-6 acute respiratory illness ( SARI) cardia (QTc prolongation and
days. The patient is infectious about 2 (fever AND cough and/or shortness arrhythmias) and therefore require
days before the onset of symptoms. of breath) caution and monitoring.
Plasma therapy from convalescent
The main symptoms are medium to 5. Asymptomatic direct and high risk patients is another therapy that has
high grade fever and dry cough. Other contacts of a confirmed case (should been tried and is under evaluation in
symptoms include myalgias, nausea, be tested once between day 5 and day clinical trials.
diarrhea and weakness. Dyspnoea 14 after contact)
occurs in moderate and severe disease Prevention
and indicates lower respiratory Symptomatic refers to fever/cough/ There is no vaccine available yet. Efforts
involvement. A few patients may shortness of breath. Direct and high- in this direction have started. The
complain of changed sense of taste and risk contacts are those who live in the current pillars of preventive strategy
smell but frank running nose is not same household with a confirmed case include isolation, social distancing,
common. Symptomatic recovery takes and HCP who examined a confirmed cough etiquettes, use of face masks and
upto 14 days. A patient is declared cured case frequent hand washing for 20 seconds
when two specimens are negative, with soap and water or with alcohol
spaced 24 hours apart. A Rapid Antibody Testing Strategy based hand rubs and sanitization of
was announced by the ICMRon 4 workplace and homes.
Secondary pneumonias may occur in April 2020 for areas reporting clusters
less than 5% of patients. A dreaded (containment zones) and in large Prognosis
complication that can occur in less than migration gatherings/evacuees centres. The limited data available so far
5% of severely affected patients is Adults suggests that about 80% of the cases
Respiratory Distress Syndrome (ARDS) The test measures serum IgM and IgG are mild infections and are likely to
characterized by severe hypoxemia antibodies to coronavirus (nCov 2). recover without residual effects in 2-4
and diffuse lung damage showing Serum IgM indicates current infection weeks. About 15% patients will have
widespread opacities on imaging. and increases from end of first week severe disease and about 5% patients
Severe sepsis may be associated with lasting till end of 3 weeks, Serum IgG require intensive treatment including
multiorgan dysfunction and failure. starts to increase by days 10-14 and may mechanical ventilator support. The
persist longer indicating old infection mortality is estimated to vary from 3 to 4%.
Though primarily a respiratory disease, and recovered case.
COVID 19 has been found to cause Corresponding Author:
cardiac, renal, neurological, hepatic and The diagnostic validity of antibody tests
ophthalmic manifestations. remains to be established. Therefore, it Prof. SK Chhabra MD, FCCP
not yet to be used as a diagnostic test but Ex-Director-Professor, Vallabhbhai Patel Chest
Diagnosis and Current Testing for epidemiological and surveillance Institute and Head, Department of Pulmonary,
Strategy purposes and is being done in cases Sleep and Critical Care Medicine, Primus
The revised Guidelines on Clinical of Influenza Like Illness (ILI) in the Superspeciality Hospital, New Delhi
Management of COVID –19, Ministry clusters and hotspots.
of Health and Family Welfare, GOI
released on 31-03-2020 have given Treatment
the following indications for testing
with RT-PCR, the gold standard test for There is no specific treatment for COVID
COVID 19. This is usually done on nasal 19. Management is only supportive and
or oropharyngeal swabs that must be symptomatic. This includes isolation,
collected and properly transported. antipyretics, fluid management and
nutritional support. Severe cases with
hypoxemia require oxygen therapy and
patients with extensive disease with
severe respiratory failure may require

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COVID-19 Special

Chest CT Manifestations in
COVID–19 Disease: A Review

Narainder Gupta MD1, Vaibhav Gulati MBBS2, Parveen Gulati MD3
1University of Pennsylvania Hospital & Perelman School of Medicine, Philadelphia, USA
2National Heart Institute, New Delhi, India
3Dr. Gulati Imaging Institute, New Delhi, India

Abstract: Coronavirus disease 2019 (COVID-19), a highly infectious viral disease caused by severe acute respiratory syndrome
corona virus 2 (SARS-CoV-2) was first reported in Wuhan, China but has spread globally. Chest radiograph is both insensitive
for early changes as well as non-specific. CT chest has been found to be most useful radiological investigation to supplement
the diagnosis and assess the severity, progression and follow up of these patients. This article is aimed to review the typical and
atypical CT findings in COVID-19 patients which can help in management.
Key Words: Pneumonia, COVID – 19, Wuhan, Corona, CT, Chest radiograph

In Decemeber 2019, a number of detection of viral genetic material. 8. Fibrosis
pneumonia cases with unknown There are studies which emphasize 9. Vascular Enlargement
etiology were reported in Wuhan, the importance of CT examination in 10. Air Bubble Sign
China.1 These were subsequently COVID – 19 patients with false negative 11. Nodules & Halo Sign
confirmed to be due to a novel RT-PCR results.3,4 Additionally, CT helps 12. Lymphadenopathy & Pericardial
coronavirus, confirmed to be due to in assessing the severity, monitoring
severe acute respiratory syndrome disease progression and evaluating effusion
coronavirus 2 (SARS-CoV-2) and the treatment response.
disease in shorthand was named as Ground Glass Opacity
COVID-19 from Corona Virus Disease In this article, we review and describe Ground glass opacity (GGO) is defined
– 2019. Belonging to the family the typical and atypical CT findings as hazy areas with slightly increased
Coronaviridae, the novel coronavirus in COVID-19 positive patients. As this density/Hounsfield-values in lungs with
shares the family with viruses that cause disease is still evolving, there may be no obscuration of bronchial & vascular
diseases ranging from common cold other findings that may be described in margins likely result of partial filling
to severe acute respiratory syndrome future. of air spaces or interstitial thickening
(SARS) and the middle east respiratory (Figure 1,2). The distribution may be
syndrome (MERS).2 The virus has since CT Manifestations unilateral or bilateral and is usually
then rapidly spread throughout the COVID – 19 patients on CT chest may peripheral and subpleural.6–8 GGO
world, and COVID-19 was declared a show varying spectrum depending has been found to be the earliest CT
pandemic on the 11th of March 2020 by upon the time course and disease manifestation.9,10 Post mortem studies
the World Health Organisation.1 severity. The common patterns seen suggest these changes are likely to be
The common clinical features in are5: result of pulmonary edema and hyaline
patients include lower respiratory 1. Ground Glass Opacity membrane formation. GGO with small
tract illness with low grade fever, dry 2. Consolidation areas of consolidation indicate an
cough and dyspnoea. Initially and still 3. Reticular Pattern organising pneumonia pattern of lung
at most of places, the diagnosis is based 4. Crazy Paving Pattern injury.
upon the real time reverse transcription 5. Air Bronchogram
polymerase chain reaction (RT-PCR) 6. Airway Changes Consolidation
of viral nucleic acid. Recently a rapid 7. Pleural Changes & effusion Alveolar air getting replaced with fluid,
test that gives results in five minutes cells or tissues results in consolidation
or so has been launched based on the and it is seen on CT as an increase in

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COVID-19 Special

pulmonary parenchymal density obscuring the margins of
underlying vessels and airway walls.11 The distribution is
multifocal, patchy or segmental in subpleural area or along
the broncho-vascular bundles (Figure 3-6). Consolidation is
considered as an indication of disease progression and usually
seen at 2 weeks after symptoms onset. The changes are more
extensive in patients with longer time interval between the
symptoms onset and CT scan & in patients older than 50 years
of age.7

Reticular Pattern Figure 1: (a) Axial CT scan in a 66 years old male showing multiple
Thickening of pulmonary interstitial structures like ground glass opacities with reticular & interlobular septal thickening
interlobular septae and intralobular lines on CT are seen as – crazy paving pattern in the upper segment of right lower lobe and
innumerable small linear opacities, this pattern is referred focal ground glass opacities in the superior segment of left lower lobe.
as reticular pattern (Figure 3). Several studies have reported (b) Small mediastinal lymph nodes
reticular pattern to be most common CT finding after GGO
and consolidation in patients of COVID-19.7 It has also been
reported that prevalence of reticular pattern increases as the
disease course gets longer.12

Crazy Paving Pattern Figure 2: Follow up scan of the same patient after 5 days showing
Crazy paving pattern is seen as thickened interlobular septae progression of the disease with development of bilateral pleural
and intralobular lines superimposed on GGO background effusion
giving it irregular paving stone appearance (Figure 3). This has
been reported in CT scans of 5-36% of patients and along with
GGO & consolidation signals disease entering progressive or
peak stage.13 Pathologically this is result of alveolar edema
with interstitial inflammatory changes due to acute lung
injury.

Air Bronchogram Figure 3: Axial CT images in a 65 years old woman on admission
Air bronchogram has been reported as another CT (a) shows patchy ground-glass opacities in the posterior segment of
manifestation of COVID-19 and this is defined as a pattern upper right lobe; (b) with mildly enlarged mediastinal lymph nodes
of air filled low attenuating bronchi on a background of
opaque high attenuating airless lung.11 However, autopsies in
these patients have shown gelatinous mucus in the bronchi
indicating low attenuation in the bronchi as a result of this
gelatinous material and not air.14 Dry cough seen in these
patients has also been attributed to this viscous gelatinous
mucus and damage to dilated bronchioles.

Airway Changes
Airways changes in the form of bronchiectasis and
bronchial wall thickening have been seen though not very
commonly.3,10,15 These are more common in severe disease
and critical patients. These changes are likely to be sequelae
to inflammatory damage to bronchial wall resulting in
bronchial obstruction, proliferation of fibrous tissue, fibrosis
and traction bronchiolectasis and bronchiectasis.

Pleural Changes Figure 4: Axial CT images in a 65 years old woman on admission
Pleural thickening and pleural effusion (Figure 4,6) both have shows (a) patchy ground-glass opacities in the posterior segment of
been reported, the former being relatively more prevalent upper right lobe; (b) with mildly enlarged mediastinal lymph nodes
– pleural thickening in 30% & pleural effusion in 5%.12,16

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COVID-19 Special

Pleural effusion has been shown to be associated with poor
prognosis. Sub pleural line secondary to pulmonary edema or
fibrosis has also been seen in about 20% of patients.15

Fibrosis Figure 5: Non contrast Axial CT scans (a &b) in a 35 years old male
Fibrous lesions in the form of fibrosis or fibrous stripes may showing multiple focal patchy areas of ground glass opacities along
form during healing stage as well as during active stage due the bronchial bundles in right middle and lower lobe
to replacement of cellular components with scar tissue. Pan et
al reported fibrous stripes in 17% of their patients.6 Although
Pan et.al reported that fibrosis indicates poor prognosis, Kong
and Aggarwal concluded otherwise and it can be said that
there is no direct correlation between the extent of fibrosis
and prognosis till date.17

Vascular Enlargement
Described as the dilatation of pulmonary vessels around and
within the lesion. Although not commonly reported, this was
seen in most of the cases reported by Ye Zheng et al. They
attributed this to damage and swelling of the capillary wall
caused by pro-inflammatory factors.5

Air Bubble Sign Figure 6: Axial CT images in a 29years old male with COVID -19
Also termed as cavity sign, it refers to a small air containing showing (a) ill defined focal areas of ground glass opacity marked
space in the lung which may be due to pathological dilatation with arrow in right lower lobe; and (b) subpleural region of left
of a physiological space or cross section of a bronchiolectasis/ lower lobe
bronchiectasis or due to process of consolidation resorption.5
number of other findings may be seen depending upon
Nodules & Halo Sign the time interval and severity of the disease. CT is the main
A nodule refers to a rounded or irregular opacity with well or imaging modality which may supplement the diagnosis, raise
poorly defined edges measuring less than 3 cm in diameter.11 the suspicion of disease in falsely negative tests for Covid-19
The nodules have been associated with viral pneumonia.18 and help in managing these patients. As this pandemic is still
3-13% of patients may have multifocal solid irregular evolving, many questions are still unanswered. As we get
nodules6 or nodule with Halo sign.19 Nodules with the Halo more reports of pathology/autopsy in these cases, radiologic-
sign are defined as nodules or masses surrounded by ground pathological correlation will become more clear and help in
glass opacification. This sign in the past has been associated management of this disease.
with perilesional haemorrhage in angioinvasive fungal
infection or hypervascular metastasis as well as viral and Acknowledgments
organising pneumonias, the pathophysiology of these lesions The authors are highly grateful to Dr Vincenzo-Schinina from
in COVID-19 remains uncertain. National Institute of Infectious disease, Italy for permitting us
to use the CT images of their patients.
Lymphadenopathy & Pericardial Effusion
Mediastinal lymphadenopathy has been reported in 4-8% of References
patients and has been considered to be a significant risk factor
of severe/critical COVID 19 pneumonia (Figure 3,5). Along 1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel
with pleural effusion and multiple nodules it may suggest coronavirus from patients with pneumonia in China, 2019. N
superadded bacterial infection.10,12,15 Engl J Med [Internet]. 2020 Feb 20 [cited 2020 Apr 3];382(8):727–
Pericardial effusion is rare in COVID-19, if present indicates 33.
severe inflammation.
2. Coronavirus disease 2019 [Internet]. [cited 2020 Apr 3]. Available
Summary from: https://www.who.int/emergencies/diseases/novel-
Early diagnosis and isolation of COVID-19 patients is essential coronavirus-2019
for controlling this evolving pandemic. Although ground glass
opacity and consolidation are the commonest CT findings, 3. Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for
Typical 2019-nCoV Pneumonia: Relationship to Negative RT-
PCR Testing. Radiology [Internet]. 2020 Feb 12 [cited 2020 Apr
3];200343.

4. Huang P, Liu T, Huang L, Liu H, Lei M, Xu W, et al. Use of Chest CT

16 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

in Combination with Negative RT-PCR 10. Li K, Wu J, Wu F, Guo D, Chen L, Fang Z, 16. Bernheim A, Mei X, Huang M, Yang
Assay for the 2019 Novel Coronavirus et al. The Clinical and Chest CT Features Y, Fayad ZA, Zhang N, et al. Chest CT
but High Clinical Suspicion. Radiology Associated with Severe and Critical Findings in Coronavirus Disease-19
[Internet]. 2020 Apr 12 [cited 2020 Apr COVID-19 Pneumonia. Invest Radiol. (COVID-19): Relationship to Duration of
3];295(1):22–3. 2020 Feb;1. Infection. Radiology [Internet]. 2020 Feb
20 [cited 2020 Apr 3];200463.
5. Ye Z, Zhang Y, Wang Y, Huang Z, Song 11. Hansell DM, Bankier AA, MacMahon
B. Chest CT manifestations of new H, McLoud TC, Müller NL, Remy J. 17. Kong W, Agarwal PP. Chest Imaging
coronavirus disease 2019 (COVID-19): Fleischner Society: Glossary of terms for Appearance of COVID-19 Infection.
a pictorial review. Eur Radiol [Internet]. thoracic imaging. Vol. 246, Radiology.
2020 Mar 19 [cited 2020 Apr 3];1–9. Radiological Society of North America; Radiol Cardiothorac Imaging
Available from: http://link.springer. 2008. p. 697–722. [Internet]. 2020 Jan 1 [cited 2020 Apr
com/10.1007/s00330-020-06801-0 3];2(1):e200028.
12. Shi H, Han X, Jiang N, Cao Y, Alwalid O,
6. Pan Y, Guan H, Zhou S, Wang Y, Li Q, Gu J, et al. Radiological findings from 18. Franquet T. Imaging of pulmonary
Zhu T, et al. Initial CT findings and 81 patients with COVID-19 pneumonia viral pneumonia. Vol. 260, Radiology.
temporal changes in patients with the in Wuhan, China: a descriptive study. Radiological Society of North America,
novel coronavirus pneumonia (2019- Lancet Infect Dis [Internet]. 2020 Feb Inc.; 2011. p. 18–39.
nCoV): a study of 63 patients in Wuhan, 24 [cited 2020 Apr 3];20(4):425–34.
China. Eur Radiol. 2020 Feb 13;1–4. Available from: http://www.ncbi.nlm. 19. Li X, Zeng X, Liu B, Yu Y. COVID-19
nih.gov/pubmed/32105637 Infection Presenting with CT Halo
7. Song F, Shi N, Shan F, Zhang Z, Shen Sign. Radiol Cardiothorac Imaging
J, Lu H, et al. Emerging 2019 Novel 13. Pan F, Ye T, Sun P, Gui S, Liang B, Li L, [Internet]. 2020 Jan 1 [cited 2020 Apr
Coronavirus (2019-nCoV) Pneumonia. et al. Time Course of Lung Changes 3];2(1):e200026.
Radiology [Internet]. 2020 Apr 6 [cited On Chest CT During Recovery From
2020 Apr 3];295(1):210–7. 2019 Novel Coronavirus (COVID-19) Corresponding Author:
Pneumonia. Radiology [Internet]. 2020
8. Ng M-Y, Lee EY, Yang J, Yang F, Li Feb 13 [cited 2020 Apr 3];200370. Dr. Parveen Gulati
X, Wang H, et al. Imaging Profile of Dr. Gulati Imaging Institute
the COVID-19 Infection: Radiologic 14. Xi Liu RW, Guoqiang Q WY et al. J-16, Hauz Khas Enclave, New Delhi - 110016
Findings and Literature Review. Radiol A observational autopsy report of India
Cardiothorac Imaging [Internet]. 2020 COVID-19 (Chinese). J Forensic Med.
Feb 1 [cited 2020 Apr 3];2(1):e200034. (36):19–21.

9. Chung M, Bernheim A, Mei X, Zhang 15. Wu J, Wu X, Zeng W, Guo D, Fang Z,
N, Huang M, Zeng X, et al. CT Imaging Chen L, et al. Chest CT Findings in
Features of 2019 Novel Coronavirus Patients with Corona Virus Disease
(2019-nCoV). Radiology [Internet]. 2020 2019 and its Relationship with Clinical
Apr 4 [cited 2020 Apr 3];295(1):202–7. Features. Invest Radiol. 2020 Feb;1.

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COVID-19 Special

Ophthalmology Practice in the Era
of COVID-19 Pandemic

Jatinder Singh Bhalla, Amit Mehtani, Yati Gothwal, Satender Kumar Singh, Kanika Jain
DDU Hospital, New Delhi

The outbreak of the pandemic caused Background 7 January 2020 as a novel coronavirus
by the 2019 novel coronavirus In late December a young Chinese (nCOV). The genetic sequence of
(COVID-19) is rapidly changing the ophthalmologist Li Wenliang working at least 19 strains found in infected
way the health communities are in the central hospital of the Wuhan in patients has been published so far and
working. The ophthalmology clinics Hubei province alarmed his colleagues comparisons are being made with
are one of the most crowded areas and the government via social media severe acute respiratory syndrome
of the hospital with patients of all about an outbreak of severe acute (SARS) and Middle East respiratory
age groups. Ophthalmologist pose respiratory syndrome (SARS) like syndrome (MERS), also both caused by
a direct risk due to the proximity of illness. But the local authorities in coronaviruses.2,4,5
eye health professionals to patients Wuhan upbraided him for spreading Virology: Coronaviruses are important
and during eyeexaminations. There false comments. He contracted the human and animal pathogens. Full-
are reports that the virus can cause disease from a patient of acute angle genome sequencing and phylogenic
conjunctivitisand pass transmit closure glaucoma. The symptoms of analysis indicated that the coronavirus
through tear of infected,1,2 COVID-19 which manifested in January 2020 causing COVID-19 is a betacoronavirus
has implications for ophthalmologist and he succumbed to the disease on belonging to same subgenus as the
and ophthalmic practices alike. Travel February 2020.3 SARS virus as well as several bat
restrictions, reprioritisation of health coronaviruses. There is striking
resources and economic consequences On 31 December 2019, Chinese similarity in the structure of the receptor
are impacting ophthalmologists. government notified WHO of a binding gene region of both viruses and
We have tried to evaluate the ocular pneumonia like outbreak of an they have strong affinity for the same
effects of this pandemic in the patients, unknown aetiology in Wuhan, a city receptor i.e. Angiotensin converting
preventive measures and the impact on in Hubei province. The sea food market enzyme 2 (ACE 2) for cellular invasion.4
ophthalmic practice. of Wuhan was thought to be the source The Coronavirus Study Group of the
and was closed on 1 January 2020. The International Committee on Taxonomy
causative organism was identified on

Figure 1: (A) Spike proteins on the surface of the coronavirus bind to angiotensin-converting enzyme2 (ACE-2) receptors on the surface of
the target cell; (B) the type II transmembrane serine protease (TMPRSS2) binds to and cleaves the ACE-2 receptor. In the process, the spike
protein is activated; (C) Cleaved ACE-2 and activated spike protein facilitate viral entry. TMPRSS2 expression increases cellular uptake of
the coronavirus.8-10

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COVID-19 Special

of Viruses has proposed that this virus Figure 2: Showing various modes of transmission of SARS CoV-2 virus
be designated severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2).6 one sign/symptom of respiratory probable or confirmed COVID-19
According to a study, the incubation disease, e.g., cough, shortness of breath), disease without using proper PPE,
period is 2 to 14 days of exposure. Some and a history of travel to or residence OR
cases also reported a shorter incubation in a location reporting community - Other situations as indicated by local
period of 5.2 days, hence further support transmission of COVID-19 disease risk assessments. i.e. asymptomatic
recommending two weeks quarantine.7 during the 14 days prior to symptom cases, the period of contact being
onset. OR measured as the 2 days before and
Extent of the problem: more than through the 14 days after the date on
50,000 people have died worldwide A patient with any acute respiratory which the sample was taken which
with over one million infected as illness and having been in contact with led to confirmation.
per the WHO data. China reported a confirmed or probable COVID-19 case
82875 confirmed cases and 3335 in the last 14 days prior to symptom yy Risk factors for severe illness -
deaths whereas in Italy, the death toll onset. OR Severe illness can occur in otherwise
has surpassed 14681. United States healthy individuals of any age, but it
of America has recorded the highest A patient with fever and at least one predominantly occurs in adults with
number of confirmed cases i.e. 241703. sign/symptom of respiratory disease, advanced age or underlying medical
In India as per the data available with e.g. cough, shortness of breath; and comorbidities.
the Ministry of Health and Family requiring hospitalization and the
Welfare (MOHFW) website 3219 active absence of an alternative diagnosis that yy Comorbidities associated with
cases in India with 83 deaths reported fully explains the clinical presentation. severe illness and mortality include,
till date. According the world health chronic lung disease, cardiovascular
organization, community spread has Contact: A contact is a person who disease, diabetes mellitus,
not been reported so in any part of the experienced any one of the following hypertension, chronic kidney disease
world. exposures during 2 days before and 14 and cancer. It was reported that of 355
days after the onset of symptoms of a patients who died with COVID-19
Mode of transmission: person-to- probable or confirmed case: in Italy, the mean number of pre-
person spread of SARS-CoV-2 occurs - Face-to-face contact with a probable existing comorbidities was 2.7%, and
mainly via respiratory droplets, only 3 patients had no underlying
resembling that of influenza. When or confirmed case within 1 meter and condition.13 Laboratory features
an infected individual cough, sneeze for more than 15 minutes. shown to be associated with worse
or talk, the droplets carrying the virus - Direct physical contact with a outcomes include: Lymphopenia,
are released and transmitted to another probable or confirmed case. Elevated liver enzymes, Elevated
person. Another way of transmission - Direct care for a patient with lactate dehydrogenase (LDH),
is through direct contact if made
with infected surfaces and further the
individual then touches his or her eyes,
nose, or mouth. Droplets typically do
not travel more than six feet (about
two meters) and do not linger in the
air; however, it is still speculated that
the virus remain viable in aerosols
under experimental conditions for at
least three hours.11 Given the current
uncertainty regarding transmission
mechanisms, regular had wash with
soap, alcohol-based hand sanitizers and
use of personal protective device (PPE)
to prevent airborne transmission is
recommended routinely.

Definition as per WHO
Suspect case: A patient with acute
respiratory illness (fever and at least

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COVID-19 Special

Elevated inflammatory markers on RT-PCR for tear and conjunctival - Ophthalmologists should only
(e.g., C-reactive protein [CRP], secretion stating a weak but possible provide emergency services for OPD
ferritin), Elevated D-dimer (>1 mcg/ transmission of the virus through ocular and OT. But the urgency must be
mL), Elevated prothrombin time, secretions in patients of conjunctivitis. decided by one’s judgement and the
Elevated troponin, Elevated creatine Due to the high infectivity of the social, medical, ethical and economic
phosphokinase (CPK), Acute kidney disease a systematic and detailed ocular circumstances of the patient.
injury.14 examination deemed necessary cannot
Ocular manifestations of COVID-19 be carried out and its effect on other General Measures:
Li Wenliang the young Chinese ocular tissues has not been studied or - All staff members to must wear triple
ophthalmologist had contracted the reported.
disease during examination from a layer surgical or N-95 face mask.
patient of acute angle closure glaucoma In a study by Zhang et al.21 of 72 - Social distancing to be practiced by
since then several reports suggest the confirmed COVID-19 patients, only 2
transmission via ocular surface and patients presented with conjunctivitis staff amongst themselves and as well
transmission by aerosol contact if an only of them tested positive for as with patients.
no eye protection is worn. Virus can SARS-CoV-2. Zhou et al.22 in another - Every patient/staff shall do hand
cause a mild follicular conjunctivitis study of 63 confirmed COVID-19 wash if possible or use hand
otherwise indistinguishable from patients in Wuhan, reported only one sanitizers at the hospital at entry
other viral causes.1 There are reports case of conjunctivitis with a negative point.
of conjunctivitis being the first test result. - No attendant policy to be followed
symptom.15-16 Patients presenting with (attendant only in cases with visual
conjunctivitis, fever and respiratory These reports from china and other impairment, mentally or physically
symptoms including cough and parts of the world indicate a potential challenged, and pediatric patient).24
shortness of breath, recent history of risk to the ophthalmologist. Thus, - Patient education about the current
travel internationally, particularly to certain guidelines have been laid down situation, preventive measures to
hotspot areas with known outbreaks by the various authorities across the be taken to safeguard themselves,
or with family members recently back globe for urgent eye care and triage. It early identification of symptoms and
from one of these areas, should be is important to understand what the essential actions to be taken. Enough
looked with suspicion as they could be ocular emergency conditions are (Table material should be displayed at
possible cases of COVID-19.17 2 and 3), that must be treated and at the clinic with possible modes of
the same time the spread of the disease transmission
In a recent study of 30 patients should not be overlooked. - Open door practice: All the doors of
hospitalized for COVID-19 in China, the OPD including the registration
only one had reported conjunctivitis Basic outline for eye care during the desk, waiting hall and consultation
suggesting that SARS-CoV-2 can infect pandemic of Covid 19 as proposed room should remain open.
the conjunctiva causing conjunctivitis by AIOS:23
and virus particles can be present - Prior scheduled appointments for OPD Measures that the
in ocular secretions.1 A study in 522 ophthalmologists should undertake
hospitals across 30 provinces hospital routine OPD and OT should be during the COVID-19 pandemic
in China documented conjunctival postponed and rescheduled for four
congestion in 9 out of 1099 patients weeks at least.
(0.8%).18 Another retrospective study of
38 patients, RT-PCR onnasopharyngeal Table 1: Various studies showing correlation between Ocular features and
swabs of 28 (73%) patients tested COVID-19
positive for SARS CoV-2. Ocular
features of conjunctivitis, conjunctival Study Sample Ocular Features Positive Naso- Positive
hyperemia, epiphora and increased Size (Conjunctival congestion/ pharyngeal Conjunctival/
conjunctival secretion were seen in 12 Conjunctival Hyperemia/ swabs Tear Swabs
(31.57%) of which 9 (23.68%) tested Epiphora (RT-PCR) (RT-PCR)
positive on RT-PCR of nasopharyngeal
swab alone 2 (5.26%) patients tested Peng Y et al1 30 1 30 1
positive for both nasopharyngeal and
conjunctival swabs of RT-PC.19 A study Guan et al18 1099 9 1099 Not taken
Xia J et al20 of 30 confirmed cases of
COVID-19 reported only one positive Wu P et al19 38 12 28 11

Xia J et al*20 30 1 30 2

Zhang et al21 102 2 72 1

Zhou et al22 67 1 63 -

* Xia J et al had collected 2 samples from each patient i.e. conjunctival and tear sample

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COVID-19 Special

Table 2: Ocular Emergency (Signs/Symptoms) staff should follow the universal
precaution measures and use PPE
Injury to eye (chemical, thermal, Sudden loss of vision Thorough hand washing, preferably
mechanical) with the use of chlorhexidine alcoholic
Sudden onset of pain in eyes Acute red eye hand rub (0.5%–1% chlorhexidine
Acute onset lid lesions Sudden onset of diplopia in 80% ethyl alcohol, or a similar
Sudden onset of drooping of lids Sudden onset of Halos, floaters and or flashes product. The gloves, if used for high-risk
Photophobia Sudden onset discharge from eyes procedures, must be changed and hand
hygiene must be performed in between
Table 3: Ocular Emergencies H/o recent onset sudden vision loss- CRAO/ each contact with different patients.
Chemical Injury CRVO/VH/Retinal detachment Staff are strongly advised not to touch
Endophthalmitis their face-shield, eye protective wear,
Blunt/Perforating Trauma Expulsive choroidal haemorrhage mask, head, and neck region before a
Open globe injuries with or thorough and complete hand washing
without foreign body Exposed infected buckle procedure.24
Lid Trauma Orbital cases with vison loss/tumour
Angle closure glaucoma Corneal abrasion/ corneal FB (including Suspect and Probable categories: For
Neovascular glaucoma displaced contact lens)/corneal ulcer confirmed cases of COVID-19 patients,
Post-operative presence of attendant is deemed
IOP > 38 mmHg Patients requiring intravitreal injections contraindicated because of significant
Conjunctivitis (rule out fever with fresh bleed or those requiring for risk of cross infection. If any ophthalmic
as this may need screening for endophthalmitis consultation is required it should be
COVID hence need to be referred) completed within the quarantine ward.
If an outpatient presented with overt
For Staff- For Patients- symptoms and signs, referral to the
- All patients should be asked for - Patients must wear face mask or respiratory physicians and infection
control officers should be done. The
history of international travel or should cover their mouth and nose ophthalmic appointment should be
contact with covid positive patient. with a tissue while sneezing and avoided indefinitely until the status of
- Staff shall practice hand wash on coughing. infection is ascertained.
an hourly basis and immediately if - They should be educated not
contact with suspected patient or to believe in bogus news and For contacts and recovered patients
with contaminated surface. management protocols and rely on shortly discharged from hospital,
- Patient screening desk (PSD) should health care professionals only for infection control measures must
be functional with minimum and treatment and relevant guidelines be taken to prevent any sort of
experienced staff with best available for cure. transmission, i.e. by using PPE and
methods of Personal Protective - Self-medication should be should be worn all the time when
Equipment (PPE). discouraged. attending to these patients. Proper
- Before entering the waiting area, disposal of these equipments after use
chief complaints and history should A modified WHO cases classification is very important and it is strongly
be taken the by the staff at the PSD in scheme in handling eye patients can advised to practice hand hygiene after
order to sort the patients according also be used. Three categories of patients removal of PPE, mask & gloves.
to triage system. are recognized based on a triage system
- Reduce instances of hand to hand run by experienced nurses. They are A dedicated consultation room
transfer like handing over of bill/ the general, suspect, and probable with separate set of instruments is
old prescriptions and can shift to categories.24 required. An independent ventilatory
electronic prescription and billing generating a negative pressure with
- Avoid cash transaction and prefer Guidelines for the ophthalmologist lamellar downward airflow is highly
digital billing in handling such cases: advised. During the ophthalmic
General categories: In this category, examination,patients themselves are
irrespective of their COVID-19 status, required to put on the N-95 respirator
mask as well. Self-adhesive surgical
plastic sheets that are commonly used
during cataract surgery can be applied
directly but over the face and the
nostril areas, leaving behind the eyes

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COVID-19 Special

for examination preventing aerosol procedures, thorough lyclean done after each surgical procedure as
transmission.24 instruments before and after every per guideline by CDC.
new case - All staff coming in direct contact
Precautions during ophthalmic - Special handling of conjunctivitis and ophthalmologists should be
examination23 patients with non-contact gloves and encouraged to take a soap bath once
OPD plan- cotton buds, after triaging for any they reach home.
Patient screening desk- COVID-risk factors - Prophylaxis: ICMR has advised oral
- All the patients coming to hospital/ - All used items must be disposed in Hydroxychloroquine 400mg BD on
proper colour bins. day1, followed by 400 mg OD weekly
clinic are to be screened by the for 7 weeks.
experienced staff for ocular Figure 3: Image showing protective shield
emergency. Routine patients are for slit lamp Instrument sterilization and
to be counselled and requested to Precautions in Operating Room23 disinfection guidelines:25
follow up on later dates (4 weeks) - Any surgery if so, required should be Tonometer tip cleaning-The virus
causing COVID-19 is an enveloped
- All patients must pass through day care. virus and are much more susceptible
thermal scanner. - Routine screening should include to alcohol (70% conc.). If a tonometer
tip is cleaned with alcohol and allowed
- Self-evaluation questionnaire (for serology and Chest X-ray before each to dry in room air, solutions should
patients with fever, travel history surgery, if possible be effective at disinfecting tonometer
to affected countries, contact with a - Avoid surgeries off-hours or with an tips from SARS-CoV-2. Use single-use,
Covid 19 patient or family members incomplete team disposable tonometer tips if available.
of covid 19 patient) - Surgeon with expertise should Tips cleaned with diluted bleach remain
preferably do the surgery – quick and a safe and acceptable practice.
- Brief history and chief complaints of safe surgery.
patient - Prefer topical anaesthesia over local The current CDC recommendations
anaesthesia. Try to avoid GA unless for disinfectants specific to COVID-19
Waiting area- mandatory include:
- Should be less crowded. - PPE for all OT staff (HIV Kit for non- - Diluted household bleach (5
COVID-19 patients and a full-body
- Seating arrangement has to be such suit for COVID-19 patients and tablespoons bleach per gallon of
that at least 1-meter distance should suspects) water)
be between the patients - All universal precautions must be - Alcohol solutions with at least 70%
taken. alcohol.
- Minimum waiting time for patients - Stop positive ventilation in theatre - Common EPA registered
during procedure and for at least 20 household disinfectants currently
- Provision of hand sanitizer or hand minutes after the patient has left recommended for use against SARS-
washing. theatre CoV-2 include disinfecting wipes,
- One patient at a time and here should multi-surface cleaner + bleach, clean
- Open door practice for good be a 20-min time out between each up cleaner + bleach,professional
ventilation. surgery disinfectant spray, clean and fresh
- Disinfection of the OT should be multi-surface cleaner, disinfectant
- Display of information and max cover mist, Purell professional
education content (if available) surface disinfectant wipes and
more. The EPA offers a full list of
Examination Room- antimicrobial products expected to
- All non-essential procedures should be effective against COVID-19 based
on data for similar viruses.
be avoided, and patient explained
the need for more elaborate testing Economic impact
in future as feasible
Ophthalmologist contribution
- All slit lamps to have protective during the pandemic: as per the
shield acrylic/ plastic / X-ray sheets guidelines issued by MOHFW the
attached to prevent direct contact Ophthalmologists have been placed in
with the patients. Material used
should be cleaned with alcohol every
2 hourly. (Figure 3)

- Clean hands with sanitizers before
touching any equipment once
patient has been touched.

- While performing any contact

22 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

category D wherein they are categorized insufficient for protecting our other anytime soon to be at frontline. They
with medical specialities with limited patients in the clinic), and we now know say tough times don’t last, but tough
or no responsibilities of critically ill that healthy people well younger than people and tough organizations do.
patients wherein they can be called age 70 years are vulnerable and dying I am confident that we will emerge
for the management of non-critically (thus, age screening is insufficient). unscathed from this as well.
ill hospitalized patients in case of The rate of viral shedding and infection
exigencies under the supervision of a from asymptomatic individuals is much References
certified medical practitioner. higher than previously estimated.
Most centers have closed temporarily 1. Peng Y, Zhou YH. Is novel coronavirus
The health and economic burden levied whereas others are staffed by a skeleton disease (COVID 19) transmitted through
upon due to the COVID 19 pandemic crew of office staff, a retina doctor conjunctiva, J Med Virol, 2020 Mar 16.
has far fetched reputation. The viral ,glaucoma doctor & a cornea person
contagion is ravaging economies, on call but not seeing routine cases, 2. Li JO, Lam DSC, Chen Y, et al Novel
people and livelihoods. Globally, as most of Ophthalmic emergencies Coronavirus disease 2019 (COVID-19):
governments rich and poor are gasping involve these sub-specialties. Clinics The importance of recognising possible
for an effective coping strategy. An are being cleaned several times a day, early ocular manifestation and using
unprecedented crisis looms. And no one family members stay outside and only protective eyewear British Journal of
can see light at the end of the tunnel. the patient is allowed in the waiting Ophthalmology 2020;104:297-298.
“The world is staring down the barrel or examining room. Slit lamps are
of a recession. COVID-19’s scourge has fitted with homemade splash guards 3. Available from: https://en.wikipedia.
spared none, irrespective of sector, size although it provides a false sense of org/wiki/Li_Wenliang. [Last accessed on
and vintage “This is not a three week, security because newly published April 3, 2020].
one-month, or six-week phenomenon. research indicates that the COVID-19
This is going to run for quite some time. virus lives on plastic for 5 days and 4. Zhou P, Yang XL, Wang XG, et al. A
lingers in the air for hours.26 Significant pneumonia outbreak associated with a
While COVID-19 is a significant number of staff have been furloughed. new coronavirus of probable bat origin.
challenge for the entire healthcare But a staff person has been designated Nature. 2020;579(7798):270–273.
system, physician practices face a to keep close contacts with them so
unique set of issues themselves. They that they are available once the crisis 5. Wang C, Horby PW, Hayden FG, Gao
must balance between the acute needs gets over, patients are being contacted GF. A novel coronavirus outbreak of
of their patients, while also managing to assuage their fear & anxiety & global health concern. Lancet (London,
their staff through a major crisis. We encourage them for tele-consultation England) 2020;395:470 3
in Ophthalmology practice are affected with their consultant.
as most of our patients are geriatric Most doctors are hoping that this will 6. Gorbalenya, A.E., Baker, S.C., Baric, R.S. et
patients &unfortunately, they are the be a temporary slowdown of their al. The species Severe acute respiratory
ones most susceptible to die from the practices,as it’s human nature to assume syndrome-related coronavirus:
virus. The typical ophthalmologist in that relative normalcy will return classifying 2019-nCoV and naming it
India on average works nose-to-nose soon, so just hang in there. AIOS and SARS-CoV-2. Nat Microbiol 5, 536–544
with 50 patients a day. Before long, several other major physician groups
some of those noses could be loaded. (supported by FICCI) requested Finance (2020).
minister to provide dedicated financial
Our practices and our lives have support to all physicians and their 7. Backer Jantien A , Klinkenberg Don ,
changed dramatically from early to practices who are experiencing adverse Wallinga Jacco . Incubation period of
late March and continue to rapidly economic impact on their practices 2019 novel coronavirus (2019-nCoV)
evolve. Concerned about the rate of from suspending elective visits and infections among travellers from
spread, the high contagion factor procedures.” Wuhan, China, 20–28 January 2020.
and the high mortality rate in the As Ophthalmologists, we have our own Euro Surveill. 2020;25(5).
vulnerable population and with the concerns & worries. But it would be
prime directive of doing no harm,most myopic of us to just think about our 8. Kuba K.; Imai Y; Rao, S.Gao, et al. A
Ophthalmologists have cancelled all field. The bigger worry is the battle crucial role of angiotensin converting
elective procedures and non urgent between the human race and the virus enzyme 2 (ACE2) in SARS coronavirus–
visits at the Advisory of AIOS &strongly Let us brush up our medical school induced lung injury. Nat. Med. 2005,11,
worded March 18 letter from the knowledge as we can be called up 875–879.
AAO. Additionally, we now know that
infected patients do not always have a 9. Glowacka, I.; Bertram, S.; Muller; et al.
fever (thus, temperature screening is Evidence that TMPRSS2 Activates the
Severe Acute Respiratory Syndrome
CoronavirusSpike Protein for Membrane
Fusion and Reduces Viral Control by
the Humoral Immune Response. J.
Virol.2011, 85, 4122–4134.

10. Heurich, A.; Hofmann-Winkler, H.;
Gierer, et al. TMPRSS2 and ADAM17
Cleave ACE2 Differentially and Only
Proteolysis by TMPRSS2 Augments Entry
Driven by the Severe AcuteRespiratory
Syndrome Coronavirus Spike Protein. J.

www.dosonline.org/dos-times DOS Times - Volume 25, Number 4, January-February 2020 23

COVID-19 Special

Virol. 2014, 88, 1293–1307. from:https://eyewire.news/articles/ 25. American academy of ophthalmology,
aao-alert-coronavirus-updates-for- Important cornonavirus updates for
11. Van Doremalen N, Bushmaker T, Morris ophthalmologists/ [Last Accessed on 01 ophthalmologists. Available from:
DH, et al. Aerosol and Surface Stability April 2020]. https://www.aao.org/headline/alert-
of SARS-CoV-2 as Compared with SARS- important-coronavirus-context [Last
CoV-1. NEngl J Med. 2020 Mar 17. 18. Guan WJ, Ni ZY, Hu Y, et al. Clinical accessed on April 1, 2020]
characteristics of coronavirus disease
12. Otter JA, Donskey C, Yezli S, et al. 2019 in China. N Engl J Med. 2020 Feb 28 26. Periman, At Issue: How ophthalmologist
Transmission of SARS and MERS are handling COVID-19. Available
coronaviruses and influenza virus in 19. Wu P, Duan F, Luo C, et al. Characteristics from: https://www.healio.com /
healthcare settings: the possible role of Ocular Findings of Patients with ophthalmology/practicemanagement/
of dry surface contamination. J Hosp Coronavirus Disease 2019 (COVID news/online/%7B81fbced9-8f99-439b-
Infect. 2016 Mar;92(3):235-50. 19) in Hubei Province, China. JAMA bc3c-ad6e9431c321%7D/at-issue-
Ophthalmol. 2020 Mar 31. how-ophthalmologists-are-handling-
13. Grasselli G, Pesenti A, Cecconi M. covid-19 [Last accessed on 01 April 1,
Critical Care Utilization for the 20. Xia J, Tong J, Liu M, Shen Y, Guo D. 2020]
COVID-19 Outbreak in Lombardy, Italy: Evaluation of coronavirus in tears and
Early Experience and Forecast During an conjunctival secretions of patients with Corresponding Author:
Emergency Response. JAMA. 2020 Mar SARS-CoV-2 infection. J Med Virol 2020.
13. Dr. Jatinder Singh Bhalla
21. SunX,ZhangX,ChenXetal.Theinfection MS, DNB, MNAMS
14. Zhou F, Yu T, Du R, et al Clinical course evidence of SARS-COV-2 in ocular Senior Consultant & HOD (Ophthal)
and risk factors for mortality of adult surface: a single-center cross-sectional DDU Hospital, New Delhi
inpatients with COVID-19 in Wuhan, study. medRxiv 2020.02.26.20027938
China: a retrospective cohort study.
Lancet. 2020 Mar 28;395(10229):1054- 22. Zhou Y, Zeng Y, Tong Y, et al.
1062. Ophthalmologic evidence against the
interpersonal transmissionof 2019novel
15. Lu CW, Liu XF, Jia ZF. 2019 nCoV coronavirus through conjunctiva.
transmission through the ocular surface medRxiv 2020.02.11.20021956
must not be ignored. Lancet (London,
England) 2020;395:e39. 23. AIOS Operational Guidelines for
Ophthalmic Practice during COVID 19
16. American Academy of Ophthalmology, outbreak.Available from: https://www.
Coronavirus kills Chinese whistle medscape.com/viewarticle/926365 [Last
blower. Available from: https// www. accessed on 01 April 1, 2020]
aao.org/headline coronavirus kills
Chinese whistle blower Ophthalmol. 24. Chan WM, Liu DT, Chan PK, et al.
[Last accessed on April 3, 2020]. Precautions in ophthalmic practice
in a hospital with a major acute SARS
17. AAO Alert: Coronavirus Update outbreak: an experience from Hong
for Ophthalmologists. Available Kong. Eye 2006;20(3):283–289.

24 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

Virus of the Century, Corona:
An Ophthalmic Perspective

Tanu Singh DNB, Parul Ichhpujani MS
MS (Ophth), STT (Pediatric Ophth) PGIMER, WHO Fellow VR, MBA (Operations Research)
Deptt. of Ophthalmology, Government Medical College and Hospital, Chandigarh, India

Abstract: The novel corona virus or corona virus disease 2019 (Covid-19) has gradually become a worldwide pandemic of epic
proportions ever since its origin in Wuhan, China at the end of 2019, with the affected population increasing exponentially
every day. With the mechanism of spread mainly through droplets and fomites, the respiratory system is the most affected
by the disease, that has led to multiple deaths in thousands all over the globe. With the eye being an exposed organ, and the
structure of conjunctiva akin to mucous membrane, similar to what is found in the respiratory tracts, it could be a potential
target of the virus.
The present communication gives an ophthalmic perspective to the Covid 19 and highlights the precautionary measures to be
taken up in the management of ophthalmic patients, so as to protect the care givers along with patients’ management.
Keywords: Novel Corona virus; COVID-19; viral conjunctivitis; personal protective equipment (PPE); eye

Pandemic strikes advent of a mutant variety of this SARS cases have reported conjunctivitis
Corona virus disease 2019 (COVID-19) virus; SARS-Cov 2 or novel coronavirus like features at the presenting ocular
pandemic has created a havoc in the (nCov), this disease started in the city of symptoms in few of the corona positive
entire world, with latest whopping Wuhan, China, and eventually spread patients.
figures of 5,71,678 confirmed cases across continents. WHO declared In a recent reported case, one of the
across the world and a death tally of COVID-19 as a ‘Public Health Emergency experts while handling the cases of
26,494 by 28th March 2020.1 In India, a of International Concern’ (PHEIC) on 30th COVID-19 developed conjunctivitis and
total of 4037 cases including 107 deaths January 2020.6 eventually tested positive for the virus,
have been reported, so far (At the time which in hindsight actually incited
of writing this article).2 The most common presenting feature the probable ocular presentation
of this disease includes fever, dry of the disease. The aforementioned
Getting to know the Culprit cough, myalgia and less commonly, was wearing the N95 mask with no
COVID-19 essentially spreads through expectorant production, headache, adequate eye protective goggles and
human contacts via fomites or droplet, haemoptysis and diarrhoea.7 It would developed eye redness much before
with aerosol transmission being be interesting to understand the symptoms of pneumonia.8 While
another potential route of transmission. ophthalmological perspective of this analysing this case into perspective, it
It is essentially a respiratory disease potentially fatal disease and if there was advised that all healthcare workers
which leads to severe acute respiratory is any role of spread of the infection dealing with COVID-19 patients should
syndrome with involvement of the through involvement of the mucous additionally be wearing eye protective
respiratory mucous membrane. membrane of the eye. equipment and also that conjunctival
Coronaviruses are essentially the viruses swabs be taken in patients presenting
which affect birds and mammals.3 The Eye, an easy target with conjunctivitis to establish the
importance of coronaviruses in humans The conjunctiva and cornea are the possible role of virus.9 Liang et al. tried
was established with the outbreak seen most exposed parts of the eye to to elucidate the presence of the nCOV-
in 2003 as severe acute respiratory external environment, thus rendering 19 in the conjunctival sac with real time
syndrome (SARS-Cov)4, which was them as susceptible targets for the PCR. Of the 37 patients with pneumonia
later followed by another outbreak in virus infection. It is well known due to CoV 19, only 3 patients had
the form of Middle eastern respiratory that the conjunctiva is susceptible feature of conjunctival congestion.
syndrome (MERS-CoV).5 With latest to contamination by the infectious Of these 37 cases, 36 patients tested
droplets and other body fluids. Few

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COVID-19 Special

negative for the presence of nucleic acid Indian Front: The All India Ophthalmic or the patients having contact history
in the conjunctival secretions while society (AIOS) recommends protection with those having had a travel history.
one patient who tested positive for of mouth, nose and eyes while However, the recent WHO guidelines
the virus did not show presence of any providing ophthalmic care to patients aim at increasing the number of testing
conjunctival involvement.10 Thereby who could be potentially COVID-19 criteria and not necessarily including
raising serious doubts regarding the infested. On 24th March, 2020, the AIOS those with only a significant travel
actual mode of transmission and the recommended postponement of all history. At present, the diagnostic
potential role of the CoV in the eye. routine clinical practice including OPDs tests are based on identifying the viral
and elective surgeries for minimum genome by real time PCR using the
The pathogenesis involves binding of of 4 weeks. Besides, the healthcare material collected with nasal or throat
the virus to the human angiotensin personnel must compulsorily use swab and in some instances even
converting enzyme 2 receptors which personal protective equipments (PPEs) blood sample might be taken.16 Recent
are mostly expressed on the respiratory like masks and eye shields. addition to the diagnostic modality has
mucosa.11 The similar ACE 2 receptors been assessment of the seroconversion
are also expressed in the eye, and hence The emergency patients should only of the SARS-CoV2 and elucidating the
its role in the ocular manifestations. be allowed a maximum of 1 attendant. viral presence by measurement of the
However, these ACE receptors are seen Facilities like screening desks, thermal antibody titres.17 The blood parameters
in higher numbers in the posterior scans and hand wash areas must be show presence of high neutrophil count
structures of eye like retina and retinal available. Additionally, there must be an with lymphocytopenia. Also, there’s
pigment epithelium, when compared awareness drive to educate the patients increase in the inflammatory cytokines
to the anterior surfaces like cornea as well as the professional regarding and an altered renal function tests with
and conjunctiva.12 Hence, there have basic social distancing and personal increased blood urea and creatinine
been conflicting opinions regarding hygiene; maintenance of at least 1-meter levels.18
potential ocular involvement by the distance, minimizing hand to hand
virus.13 transfers of stuffs including money, and Developing Management
discouraging self- medication. Protocol: Biggest Challenge
How to save the eye and the Once confirmed, the next challenging
care providers? In terms of surgical practice, disposable aspect is the unavailability of the
International Front: The American gowns and linen should be preferred. defined treatment protocol of the
Academy of Ophthalmology (AAO) has Procedures like nasal endoscopy and disease. The therapeutic efforts mainly
come up with specific guidelines for DCR should be avoided. In the OPDs slit concentrate at the two distinct stages
clinical practice. A list of emergency lamp barriers or breath shields should of the disease. The first where the
procedures has been enlisted and be installed, usage of sanitizers and patients present with symptoms in
scientific recommendations have been PPEs should be compulsory, aerosol accordance with the viral load and
given to avoid routine clinical practice.14 generating procedures like NCT should the associated proportionate immune
be avoided until absolutely necessary. response towards it. The treatment
Multiple other ophthalmological Since conjunctivitis could be the 1st strategy at this stage concentrates
societies were consulted before the presentation of the COVID-19, therefore on the antiviral therapy along with
said lists were put forward. The basic such patients should only be seen symptomatic therapy. The late stages
premise for all these unprecedented in designated room with an isolated of the disease however, show presence
guidelines is the fact that the COVID-19 waiting room by a doctor specifically of an exaggerated host immune
pandemic is spreading like a wildfire posted for the same who uses complete response which needs to be combated
and the current world scenario calls set of PPEs.15 with an immunosuppressive targeted
for minimization of nascent cases therapy.19 The various drugs which
and human to human transmission. With the pandemic being uncertain target the viral attachment and entry
Additionally, the available healthcare the specific protective and practicing include hydroxychloroquine (HCQS),
resources should primarily be utilized guidelines have been changing all over promazine, camostat, nafamostat,
for fighting this pandemic and hence the world, but the importance of the while various antiviral drugs in current
routine clinical practice must take a most critical aspect of social distancing use are lopinavir, ritonavir, nelfinavir,
backseat. The AAO recommends only and personal hygiene cannot be cinancerin (protease inhibitors),
emergency care and the list prescribed emphasized more. remdesivir, ribavirin, sofosbuvir,
by the body along with the practitioner’s oseltamivir and zanamivir (nucleic acid
clinical judgement should be utilized Testing criteria: The testing criteria and protein synthesis inhibitors). The
to segregate routine from emergency in the developing nations usually last resort for the sick patients lies with
cases. focuses on testing the symptomatic the corticosteroids, IVIg and various
patients with a recent travel history

26 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

other cytokine blocking agent. All these 4. Loon SC, Lun K. SARS: a timely reminder. Guidelines-COVID19.pdf
drugs have a potential role at specific Br J Ophthalmol. 2013;97(9):1217–1218.
stages of viral infection, however, a 16. Li X, Geng M, Peng Y, Meng L, Lu S.
streamlined treatment regime to tackle 5. Chafekar A, Fielding BC. MERS- Molecular immune pathogenesis and
the disease is still to be established.20 CoV: understanding the latest diagnosis of COVID‑19. J Pharm Anal
Looking at the larger perspective to human coronavirus threat. Viruses. 2020.
combat this challenging disease would 2018;10(2):93.
be to eventually come up with a vaccine 17. Amanat F, Nguyen T, Chromikova
against SARS-CoV2, which would help 6. Organisation WH. Statement on the V, Strohmeier S, Stadlbauer D, Javier
to built in active immunity across a large second meeting of the international A, et al. A serological assay to detect
population. A lot in this field is going health regulations (2005) emergency SARS‑CoV‑2 seroconversion in humans.
around, with potential 41 different committee regarding the outbreak 2020.
vaccines being tested according to the of novel coronavirus (2019-nCoV).
latest WHO’s draft.21 RNA-1273 vaccine https://www.who.int/news-room/ 18. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou
has reached phase 1 of the clinical detail/30-01-2020-statement-on-the- CQ, He JX, et al. Clinical Characteristics
trials.22 Although the ongoing research second-meeting-of-the-international- of Coronavirus Disease 2019 in China. N
is robust, the destination still remains health-regulations-(2005)-emergency- Engl J Med 2020.
far-fetched and the price which we’ll committee-regarding-the-outbreak-of-
have to pay during this journey looks as novel-coronavirus-(2019-ncov). 2020 19. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou
alarming as one could think of. CQ, He JX, et al. Clinical Characteristics
7. Huang C, Wang YM, Li X, et al. Clinical of Coronavirus Disease 2019 in China. N
With the exponential rise in the number features of patients infected with 2019 Engl J Med 2020.
of cases in India, from an ophthalmic novel coronavirus in Wuhan, China.
perspective we need to be very Lancet 2020; published online Jan 24. 20. Shetty R, Ghosh A, Honavar SG, Khamar
meticulous regarding the prescribed P, Sethu S. Therapeutic opportunities
guidelines for eye care professionals 8. Yan A Chinese expert who came down to manage COVID-19/SARS-CoV-2
while handling the COVID-19 cases. with Wuhan coronavirus after saying infection: Present and future. Indian J
Since the evidence is scarce regarding it was controllable thinks he was Ophthalmol.2020 Mar 28.
ocular aspects of the COVID-19 we will infected through his eyes China: South
possibly get a better opportunity to China morning post. https://www. 21. WHO, DRAFT landscape of COVID‑19
elucidate the ocular presentation of the scmp.com/news/china/article/3047394/ candidate vaccines – 20 March 2020. 2020:
disease and the probable mechanism of chinese-expert-who-came-down-wuhan- Available from: https://www.who.int/
virulence, in due course of the pandemic. coronavirus-after-saying-it-was. 2020 blueprint/priority‑diseases/key‑action/
With the world in lockdown mode and novel‑coronavirus‑landscape‑ncov.
life at a standstill, the future is uncertain 9. Lu CW, Liu XF, Jia ZF. 2019-nCoV pdf?ua=1. [Last accessed on 2020 Mar 21].
with COVID-19 at its devastating worst; transmission through the ocular
and a better tomorrow will be built with surface must not be ignored. Lancet. 22. (NIAID), N.I.o.A.a.I.D., Safety and
collaboration of prevention, cure and 2020;395(10224):e39. Immunogenicity Study of 2019‑nCoV
prayers. Vaccine (mRNA‑1273) to Prevent
10. Liang L, Wu P. There may be virus in SARS‑CoV‑2 Infection. 2020: Available
References conjunctival secretion of patients with from: https://clinicaltrials.gov/ct2/
1. WHO Health Emergency Dashboard. COVID-19. Acta Ophthalmol. 2020 Mar show/NCT04283461. [Last accessed on
18. 2020 Mar 29].
[Accessed on 28 March 2020] available
from: https://experience.arcgis.com/ 11. Ge XY, Li JL, Yang XL et al. Isolation Corresponding Author:
experience/ 685d0ace5216 48f8a5 and characterization of a bat SARS-like
beeeee1b9125cd. coronavirus that uses the ACE2 receptor. Dr. Tanu Singh
2. Centers for Disease Control and Nature 2013; 503: 535– 8. Department of Ophthalmology
Prevention. Pandemic preparedness Government Medical College and Hospital,
resources. [Accessed on 5 April 2020]. 12. Choudhary R, Kapoor MS, Singh A, Chandigarh, India
Available from: https://www.cdc.gov/ Bodakhe SH. Therapeutic targets of
coronavirus/2019-ncov/php/pandemic- renin-angiotensin system in ocular
preparedness-resources. html disorders. J Curr Ophthalmol. 2016 Oct
3. Salata C, Calistri A, Parolin C, Palu 20;29(1):7-16.
G. Coronaviruses: a paradigm of new
emerging zoonotic diseases. Pathog Dis. 13. Qing H, Li Z, Yang Z, Shi M, Huang
2020;77(9), ftaa06. Z, Song J, Song Z. The possibility of
COVID-19 transmission from eye to
nose. Acta Ophthalmol. 2020 Mar 18

14. American Academy of Ophthalmology.
[Accessed on 2nd April] available from
https://www.aao.org/headline/alert-
important-coronavirus-context14.

15. All India Ophthalmic Socitey.[Accessed
on 2nd April 2020] available from
https://aios.org/pdf/AIOS-Operational-

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COVID-19 Special

Glaucoma Management in
COVID-19 Era

Suneeta Dubey, Monica Gandhi
Dr. Shroff’s Charity Eye Hospital, Delhi

Introduction Primary open angle glaucoma, ocular All the waiting points should have
hypertension, chronic angle closure facility for social distancing and
Glaucoma is a progressive optic glaucoma if well controlled on adequate points for hand sterilization.
neuropathy causing irreversible medication just requires continuation Covid 19 is highly contagious pathogen
visual field loss. On one hand it has of treatment and thus may not require and is transmitted directly or indirectly
the possibility of leading to blindness, a physical visit to the clinic. Suspected through contact with infected people.
but on the other hand the rate of and mild glaucoma also can be treated A distance of at least 1 meter has been
progression is very slow in most of conservatively. described as an area of risk.
the cases so the urgency of treatment
is more for reassurance than actual As with any other ophthalmology Staff reorganization and scheduling is
change in management plans. clinic, within the glaucoma clinic, necessary to have just adequate staff
measures can be broadly divided and not overcrowding and exposing
Corona virus disease COVID 19 can into OPD management, staff all of them to risk. Teams can be made
affect the lungs and airways and can protection, and environmental which operate on different days so that
lead to death if it escalates to severe precautions including disinfection there is no mixing of manpower and
acute respiratory syndrome. The elderly of equipment. one can isolate a part rather than the
patients and those with co morbidities entire hospital in case anyone is tested
have a greater risk. Many of our OPD protocols and procedures positive.
glaucoma patients fall in this category, There can be a system of pre - screening
thus in the current pandemic there is a done when the patient seeks an The registration staff should have
need to revisit the protocols to approach appointment to understand the chief proper protective masks and minimum
a patient with glaucoma. complaints to direct the patient for a interaction by having glass shield
physical or a teleconsult. If being given counters. Cash transaction can be
It is important to perform risk an appointment to come, they can be minimized by adopting digital methods
assessment and categorize patients as instructed to bring a maximum of one of payment.
low risk, moderate risk and high risk attendant and ensure that they will be
groups. wearing a mask The number of OPD rooms available
should be based on the number of
Low, moderate and high risk groups: If the patient arrives at the hospital patients expected so that minimum
Acute angle closure episode, sudden without an appointment triaging rooms are used. The movement of the
decrease in vision, pain and redness, should be done and they (attendant patient should be kept to a minimum,
postoperative complications like bleb also) should be asked a few pertinent the workup and consultation can take
leaks, blebitis or malignant glaucomas questions to rule out them being place in the same room. It is advisable
require urgent care. Secondary positive for COVID or at a greater risk to ask the attendant to wait outside the
glaucomas like uveitis, neovascular for being an asymptomatic carrier. A examination room.
glaucomas and traumatic glaucomas temperature test can be done by a non
can also be sight threatening or painful. contact thermometer. A declaration The doctor, optometrist and
One eyed patients could fall in the and consent form should be taken after paramedical staff should have proper
category where they may require early informing the patient. The patient and protective gear including head cap,
care. Pediatric glaucoma may require attendant should have face masks and face shield, face mask, waterproof long
urgent and immediate care which will be encouraged to wash their hands sleeved gowns and gloves. The slit lamp
be possible by a physical visit to the before entering the registration area. should have a barrier shield between
facility. the patient and observer. Eye goggles

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COVID-19 Special

can be used also. Avoid use of chin rest a contact number for queries and yy If available, use disposable occluders
paper for the slit lamp. educated to review only if necessary. to lower the risk of transmission of
infections
History taking should focus on very Ensure that all the instruments
pertinent questions to decrease and equipment used in glaucoma Inner surface of bowl of perimeter
unnecessary conversation. practice are properly disinfected using yy The inner surface of the bowl of the
standardized guidelines.
BCVA should be checked by starting perimeter is non-contact surface,
with the best expected achievable line Disinfection of Tonometer Probe it is advised not to clean the inner
and Applanation tonometry done with yy Household bleach is a solution surface, as it make alterations to the
proper sterilization techniques. Avoid surface & may negatively affect the
NCT for measurement as there is a risk of sodium hypochlorite which perimetric result.
of aerosol generation. A costlier, but generally contains 5% (50 g/litre or yy For dust visible in the cupola/ bowl,
good option, is I-care tonometer with a 50 000 ppm) available chlorine. it can be removed by gently wiping
disposable tip. Self tonometer is another yy To prepare 1:10 bleach solution with a soft cloth dampened slightly
option but has several limitations and is (which contains 0.5% chlorine with mild soapsuds like Colin,
not commonly practiced in India. concentration), add one volume of may be used for local cleaning in
household bleach (e.g. 1 litre) to nine emergencies, such as if spots have
A slit lamp examination is required and volumes of clean water (e.g. 9 litres) appeared due to patients’ sneezing.
gonioscopy done where indicated. In yy The solution should be prepared yy Do not rub the surface.
patients who have had a gonioscopy freshly every day in the morning and yy Cleaning it with other products
earlier, it may not be repeated unless discarded at the end of the day. might cause alterations to the
there is evidence of shallowing of the yy Before the beginning of the day, surface.
angle by SLE. Disposable gonioscopes dip the tonometer in 1:10 sodium yy Gonioscopes should be cleaned
are the futuristic approach. hypochlorite solution for 3-5 with mild soap and water after
minutes. every case
If goniscopy is done, immediately yy Fix the applanation tonometer to the
after the procedure the instrument slit lamp after disinfection Laser protocols and procedures
should be sterilized, do not leave it on yy Before starting to see a patient, clean Laser procedures are considered to be
the examination table for later. Optic the tip with alcohol swab (70% aerosol generating procedures. The
nerve head examination can be done by alcohol) vapors, smoke and particulate debris
noncontact lenses. yy Between every case, clean with produced during these procedures
alcohol swab. generate aerosols and can transmit viral
The plan of management should be – I care Tonometer- Change the infections.
discussed with the patient and after the
patient leaves the chamber the doctor probe (pin) after every case Consider YAG peripheral iridotomy
should wash their hands and then – Tonopen- Change the sleeve after (PI) only if absolutely necessary (To
complete the documentation and send resolve an acute angle closure attack. It
the prescription to the front desk where every case is advisable to defer it for primary angle
it can be given to the patient. closure suspects (PACS) or primary
Disinfection of Perimeters angle closure (PAC).
Hand hygiene is fundamental for all (Guidelines from HAAG STREET
and a minimum of 20 second hand wash DIAGNOSTICS) Full PPE including disposable gowns,
with soap and water is recommended. Overall cleaning of the outside gloves, face shields/eye protection
Alcoholic gels and solutions are also yy The outside of the perimeter can and N-95 masks are recommended for
considered effective provided the performing the procedure.
alcohol content is > 60%. be cleaned and disinfected using a
soft, lint-free cloth dampened with a Diagnostic protocols and
The slit lamp should be disinfected disinfectant or by alcohol swabs procedures
using 70 % alcohol wipes or sterillium yy Applied parts such as the eye Special diagnostic investigations like
solution before the next patient. occluder, patient response button, visual fields, OCT, HRT, GDx, fundus
forehead rest and chin rest as well photography or UBM should only be
The management plan should focus on as other parts such as the corrective advised when they are critical to clinical
medical rather than laser or surgical lenses they need to be disinfected decision making.
intervention where possible. Elective PRIOR to every examination by
surgery can be scheduled post COVID alcohol swab This is the time to base our treatment
control. The patient should be given

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COVID-19 Special

on clinical evaluation rather than procedure preferably day care that Assess the need for a physical consult
machines. In many cases the demands least possible postoperative and give the option to the patient
diagnostic investigations are done for management, so that the postoperative but reiterate that being safe if also
documentation and for identifying visits can be minimized. important.
progression. With the slow progression Documentation is very critical and
rate of the disease, one would not miss Preoperative counseling plays a very should be done carefully and one must
much till the situation improves, so important role in making the patient try and be as detailed as possible.
keep the investigations to a minimum. and attendant understand the current
scenario and the risks involved. Summary Points:
One can choose to err on the side
of treatment. If there is a clinical Telemedicine and Tele consults yy Categorize patients in to low,
suspicion, it would not be wrong to moderate and high risk through tele-
start medical treatment with a suitable Telemedicine refers to a system where a consultation.
anti glaucoma medication based on facility with appropriate intra-structure
systemic condition of the patient. and diagnostic machines is run by yy Assess severity of glaucoma and
semiskilled staff. The patient visits associated co- morbidities. Cases
Advise patients to have adequate the clinic and the data is shared with a where there is danger of losing sight
supply of medicines and switching doctor at a different location. There can can be called for a consultation in the
and substitution may be needed if be a provision of a video chat with the hospital.
there is non-availability of certain patient to instill confidence, but because
brands. This should be done carefully of low bandwidth in such locations this yy Follow standardized disinfection/
if being done over teleconsults to avoid may not always be feasible. The doctor sterilization protocols for
documentation errors. assimilates the information and gives environmental cleaning and
opinion for further management. This disinfection of equipment, while
This choice can be revised after the could include prescription of medicines ensuring safety of staff and patients.
COVID 19 pandemic subsides and which are safe. But the main reason is
regular investigations are resumed. Of to identify patients who need referral yy Avoid use of NCT and other aerosol
course, the patient need to be counseled and thus can be guided to visit a nearby generating procedures like lasers.
and educated to understand the logic. facility equipped to deal with the
condition. Some clinics are equipped yy Operate if emergency and sight
Another point which requires attention with a robotic slit lamp and a real time saving, under all aseptic precaution.
is that if hydroxychloroquin is used to examination is also possible.
treat COVID 19, glaucoma specialists yy Postpone diagnostic and elective
may get requests to conduct visual field Tele-consultation is a subset of surgical procedures.
testing to monitor toxicity. These will telemedicine where the patient can call
be patients who are tested positive for the doctor and get consultation over yy Do not give into the need to generate
the virus thus will pose a threat to the the phone. This may involve sharing revenue and break protocols.
personnel involved. One option can be of photographs or making a video-
to do this test on a Sunday when the call. In glaucoma, since the signs and yy Patient counseling and reassurance
number of people in the facility will be symptoms are few, telephonically it is the key to improve compliance
very few. All prescribed precautions will may be impossible to make a definitive and prevent progression of the
be needed to deal with these patients. diagnosis particularly in a fresh patient. disease. If you assure your patients
These would have to be counseled based
OT protocols and procedures on the history and risk factors and a that they can reach out to you, they
Universal precautions for disinfection decision can be made as to when they will appreciate the care and come
of OT, protection of staff/ patient and need to be seen physically. back to you.
sterilization of instruments should
be followed as per guidelines. As In follow up patients, the important Suggested reading
with other ophthalmic specialties, thing is to listen and hear the patient.
surgeries should be performed wearing In many cases, the patient is looking for yy Mario R Romano, Alessio
full personal protective equipment. some reassurance and that can be done Montericcio, Clara Montalbano,
Extra precautions are required during if we patiently explain the situation and Raffaele Raimondi, Davide Allegrini,
aerosol generating procedures such as ask them to continue the previously Gabriella Ricciardelli, Martina Angi,
intubation, extubation, if the surgery prescribed medications. Try not to add Luca Pagano & Vito Romano (2020)
is performed in general anesthesia. another drug unless very sure because it Facing COVID-19 in Ophthalmology
Choose the quickest possible surgical can instill fear in the patients’ mind. department, Current Eye Research.

yy Preparedness among
Ophthalmologists: During and
Beyond the COVID-19

yy Pandemic 2020 Published by Elsevier
Inc. on behalf of the American

30 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

Academy of Ophthalmology
yy Guidelines for Disinfection and

Sterilization in Healthcare Facilities,
2008 William A. Rutala, Ph.D.,
M.P.H.1,2, David J. Weber, M.D.,
M.P.H.1,2, and the Healthcare
Infection Control Practices Advisory
Committee (HICPAC)
yy National Guidelines For Infection
Prevention And Control In
Healthcare Facilities By Ministry
Of Health And Family Welfare
Government Of India.

Corresponding Author:

Dr. Suneeta Dubey
Head of Glaucoma Services, Medical
Superintendent, Head of Quality Department
Shoff Charity Eye hospital, New Delhi

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COVID-19 Special

Retina Practice in Times of
COVID-19

Tanya Jain, Rahul Mayor
Dr Shroff’s Charity Eye Hospital, New Delhi

Introduction
The name COVID-19, which stands for
coronavirus disease 2019, was proposed
by the World Health Organization
(WHO) for a virus which has become a
global threat.1,2 The incubation period
of COVID-19 falls within 2 to 14 days.3
SARSCoV-2 is highly contagious and
has evolved into a global health threat
within weeks.4

Transmission Picture 1: Questionnaire for patients11
The virus is believed to spread Triage Of patients
primarily via person-to-person through
respiratory droplets produced when
an infected person coughs or sneezes.5
There is also evidence of asymptomatic
transmission.6,7

The risks of COVID-19 to
ophthalmologists and patients

Ophthalmologists may also be caught
off guard as conjunctivitis, though
uncommon, could be the first presenting
symptom of COVID-19, before the
appearance of other symptoms such as
cough and fever.8,9,10

The infection control measures
that must be implemented
They are based on a three-level
hierarchy of control measures:
1. Administrative control,
2. Environmental control and
3. The use of personal protective

equipment (PPE).

Administrative control Picture 2: Triage and appointment management of patients11
Questions you should ask to identify
patients with possible exposure to
SARS-CoV-2?

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COVID-19 Special

Prevention is better the cure- Picture 3: Judicious use of PPE according to the task being performed.12
(PPE- Protective personal
equipment) on the use of chloroquine or 4. Use screening questions and require
PPE is a major prevention strategy for hydroxychloroquine in COVID-19 temperature check on all patients
all doctors and staff. Picture 3 highlights patients. before bringing them into building.
the judicious use of PPR for various
procedures for ophthalmologists. The risk of irreversible maculopathy 5. All slit lamps to have acrylic/ plastic
at these higher doses for short / X-ray sheets attached so that the
Eye protection: To prevent mucous periods of time is unknown. Patients direct contact with the patients is
membrane exposure, ophthalmologists should be informed of the potential avoided
must use goggles with good adhesion to for macular toxicity before starting
the face. Alternatively, disposable face therapy. Until more is learned about 6. In the exam rooms, slit lamp/
shields should be used.12 the toxicity associated with current mouse/ keyboard/tablets will be
regimens, decisions should be made cleaned by optometry staff/ fellows/
Body protection: Long sleeved gowns on an individual basis, taking into doctors twice a day and in between
which could be plastic ones also : there consideration any pre-existing retinal patients as often as needed using
is no need for them to be sterile, but they disease. As in all cases, the Academy alcohol wipes
absolutely have to be waterproof.12 urges ophthalmologists to make
decisions guided by available scientific 7. Clean hands with sanitizers before
Hands protection: Glove usage is evidence.14 touching any equipment once
crucial, and it’s highly recommended patient has been touched
the usage of long gloves that cover up OPD Procedures15
to the cuff. Gloves must be changed 1. See only patients with emergent 8. While performing any contact
immediately following the care episode procedure like tonometry,
or the task undertaken.12 needs or those requiring frequent gonioscopy, keratometry, A scan, B
management, such as scheduled Scan, UBM, Humphrey Visual Fields,
Hand hygiene: it is a fundamental injections. This approach limits thoroughly clean instruments
for patients and doctors. The WHO exposure, enables patients with before and after every new case
encourages the use of alcoholic gel and urgent care needs to be seen and
solutions, although there is limited provides some continued income for 9. OPD –Trial frames, lenses to be
evidence that these are superior to hand the practice. wiped with alcohol swabs after
wash with water and soap in reducing 2. Emphasize to patients that non- doing refraction for each case.
viral load.12 urgent appointments are being All non-essential, non-critical
rescheduled but the practice is open examinations should be avoided
Respiratory protection: Respiratory should an emergency occur or when and patient explained need for more
protection is classified in three grades there are changes to their vision that elaborate testing in future as feasible
based on filter efficacy and face require care.
adhesion: filtering face piece (FFP) 1, 2 3. Pick a “safe” date to reschedule based 10. Special handling of conjunctivitis
and 3 (filter efficacy 80%, 94%, and 99% on your local or states guidelines. patients with non-contact gloves
respectively).12 and cotton buds, after triaging for
yy Surgical masks are recommended any COVID-risk factors

for patients and healthcare workers 11. Open door policy at all locations
in outpatient clinics in order (except operating room)
to reduce the viral load and to
prevent a potential viral spread by
asymptomatic COVID-19 carriers.
yy to attend to patients with suspected
or confirmed cases of coronavirus:
ophthalmologists need to wear at
least FFP2, while FFP3 is necessary
during slit-lamp examination.

Role of HCQ
The American Academy of
Ophthalmology has no opinion

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COVID-19 Special

Environmental cleaning14 Laser/ILO systems16 vital. For urgent surgical indications,
Contact lens must be cleaned with soap the risk of severe and permanent vision
The current CDC recommendations and water followed by drying with clean loss without immediate surgery is not
for disinfectants specific to COVID-19 tissue paper. Plastic wrap across the as high and treatment can be delayed.
include: front of the slit lamp delivery system as It is possible that, in following non-
shown in Picture 5. urgent, non-elective patients that their
1. Diluted household bleach (5 condition can worsen and the urgency
tablespoons bleach per gallon of Picture 5: Plastic wrap/cling wrap across increase. It is important that retina
water the slit lamp delivery system specialists are judicious with their use of
Injections the emergent and urgent designations.
2. Alcohol solutions with at least 70% The retina specialty is unique in
alcohol. ophthalmology in that a significant Examples of emergent surgical indications
percentage of clinic visits involve an may include:
3. Common EPA-registered intravitreal injection without which the yy Acute retinal detachment – macula
household disinfectants currently patient is at risk for permanent vision
recommended for use against loss. Patients most commonly in need attached
SARS-CoV-2 include Clorox brand of injection therapy are also at greatest yy Acute retinal detachment – macula
products (e.g., disinfecting wipes, risk of morbidity and mortality from
multi-surface cleaner + bleach, the COVID-19 infection including the detached in a monocular patient
clean up cleaner + bleach), Lysol elderly and those with a compromised yy Retained lens fragments with
brand products (e.g., professional immune system, particularly patients
disinfectant spray, clean and fresh with diabetes. It is important when elevated intraocular pressure not
multi-surface cleaner, disinfectant determining whether an upcoming controlled medically
max cover mist), Purell professional patient visit is essential, the retina yy Acute endophthalmitis with severe
surface disinfectant wipes and more. specialist weigh the risk of infection vision loss
exposure against the risk of vision loss yy Open globe injury with or without
Slit lamp systems13 without treatment. This determination an intraocular foreign body
To lower the risk of transmission via will vary by region and over time based yy Expulsive choroidal haemorrhage
droplets, protective shields (made of on the local prevalence of infection. yy Dense vitreous haemorrhage in
plastic) were installed on slit lamps as 17 Although no clear guidelines are monocular patient
shown in picture 4. available but patients with AMD/DME yy Exposed/infected scleral buckle or
receiving monthly injections could be other ocular implant
Picture 4: Protective shield for Slit lamp given their monthly dose of injections
and the vision loss is these irreversible Examples of urgent surgical indications
diseases as deemed by the specialists. may include:
Urgent surgeries yy Retinal detachment – macula
For emergent surgical indications given
by ASRS, the risk of permanent vision detached
loss without early intervention is high yy Retained lens fragment with
and access to the operating room is
medically controlled intraocular
pressure
yy Vitreous haemorrhage in which
a retinal tear or detachment is
suspected

(These indications could be considered
emergent if the patient is monocular or
extenuatingcircumstances arise)

Examples of non-urgent, non-elective
surgical indications may include***:
yy Macular hole
yy Dislocated intraocular implant lens
yy Diabetic vitreous haemorrhage

with no macula-threatening retinal
detachment

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COVID-19 Special

yy Retained silicone oil measures, environmental measures Davide Allegrini, Gabriella Ricciardelli,
yy Macular epiretinal membrane/ and using appropriate PPE we can all Martina Angi, Luca Pagano & Vito
overcome these times. Romano (2020) Facing COVID-19 in
Vitreomacular traction Ophthalmology department, Current
References Eye Research.
Precautions during surgery15 1. WHO Director-General’s remarks at 13. Ma X, Lin J, Fang S. Precautions in
1. All surgeries must be day care unless ophthalmic practice in a hospital with
the media briefing on 2019- nCoV on the risk of COVID-19: experience from
the medical conditions or the Govt 11 February 2020. (2020) World Health China. Acta Ophthalmologica. 2020;.
of India rules strictly mandate Organization. 14. Important coronavirus updates for
admission. ophthalmologists [Internet]. American
2. Avoid surgeries off-hours or with an 2. COVID-19. (2020) World Health Academy of Ophthalmology. 2020 [cited
incomplete team Organization. Accessed 18 Feb 2020 19 April 2020]. Available from: https://
3. Faculty or senior fellows or senior www.aao.org/headline/alert-important-
residents should preferably do the 3. Symptoms of Coronavirus Disease 2019. coronavirus-context
surgery – quick and safe surgery is (2020) Centers for Disease Control and 15. [Internet]. Aios.org. 2020 [cited 19 April
warranted Prevention. 2020]. Available from: https://aios.org/
4. Choose the quickest possible pdf/AIOS-Operational-Guidelines-
surgical procedure 4. Guan W-J, Ni Z-Y, Hu Y, Liang W-H, COVID19.pdf
5. Prefer topical anaesthesia over local Ou C-Q, He J-X, Liu L, Shan H, Lei C-L, 16. Video from Sankara eye hospital,
anaesthesia Hui DS, Du B, Li L-J, Zeng G, Yuen K-Y, Bangalore.
6. Try to avoid GA unless mandatory,If Chen R-C, Tang C-L, Wang T, Chen P-Y, 17. [Internet]. Asrs.org. 2020 [cited 19 April
emergency operation under Xiang J, Li S-Y, Wang J-L, Liang ZJ, Peng 2020]. Available from: https://www.
general anaesthesia is inevitable, Y-X, Wei L, Liu Y, Hu Y-H, Peng P, Wang asrs.org/content/documents/asrs-
ophthalmologists should work J-M, Liu J-Y, Chen Z, Li G, Zheng Z-J, Qiu emergenturgentorprocedures.1.pdf
closely with anaesthetists and S-Q, Luo J, Ye C-J, Zhu S-Y, Zhong N-S
internal physicians to ensure (2020) Clinical characteristics of 2019 Corresponding Author:
COVID-19 rapid test is done for novel coronavirus infection in China.
fever and TOCC positive cases medRxiv: 2020.2002.2006.20020974. Dr. Tanya Jain
before proceeding under general MBBS, DNB, FICO
anaesthesia 5. Coronavirus disease 2019 Situation Vitreoretina Fellow
7. PPE for all OT staff (HIV Kit for non- Report - 25. (2020) World Health Dr. Shroff Charity Eye Hospital, New Delhi
COVID-19 patients and a full-body Organization.
suit for COVID-19 patients and
suspects) 6. Coronavirus kills Chinese whistleblower
8. Minimum number of staff in the OT ophthalmologist. (2020) American
9. Stop positive ventilation in theatre Academy of Ophthalmology. https://
during procedure and for at least www.aao.org/ headline/coronavirus-
20 minutes after the patient has left kills-chinese-whistleblower-
theatre ophthalmol.
10. Smoke evacuation for diathermy
11. Aerosol generating procedures 7. Community transmission nejm study
such as intubation, extubation,
bag masking, electrocautery 8. Chang D, Xu H, Rebaza A, Sharma L, Dela
should be done by anaesthetist Cruz CS (2020) Protecting health-care
and the surgeon while wearing full workers from subclinical coronavirus
personnel protective infection.

Conclusion 9. Zhou Y, Zeng Y, Tong Y, Chen C (2020)
Such unprecedented times need for Ophthalmologic evidence against the
extra-ordinary measures and utmost interpersonal transmission of 2019
care for our patients. By taking utmost novel coronavirus through conjunctiva.
important and urgent administrative medRxiv:2020.2002.2011.20021956.

10. Lu CW, Liu XF, Jia ZF (2020) 2019-nCoV
transmission through the ocular surface
must not be ignored. Lancet (London,
England).

11. Lai, T.H.T., Tang, E.W.H., Chau, S.K.Y.
et al. Stepping up infection control
measures in ophthalmology during
the novel coronavirus outbreak: an
experience from Hong Kong. Graefes
Arch Clin Exp Ophthalmol (2020).

12. Mario R Romano, Alessio Montericcio,
Clara Montalbano, Raffaele Raimondi,

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COVID-19 Special

Advisory on the use of Hydroxy-
Chloroquine in COVID-19 in India
and other Countries

Namrata Sharma1, Jatinder Singh Bhalla2, Rakesh Verma2
1Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
2Department of Ophthalmology, DDU Hospital, New Delhi, India

No drugs are currently approved for the similar surface receptor ACE2, essential for the membrane fusion. It is
Coronavirus Disease-2019 (COVID-19), it is believed that chloroquine can believed that both the agents could be
although some have been tried. In view also interfere with ACE2 receptor effective tools against SARS-CoV-1 and
of recent studies and discussion on glycosylation thus prevents SARS- SARS-CoV-2.5,6
chloroquine and hydroxychloroquine CoV-2 attachment to the target
(HCQ), we have reviewed existing cells.1,2,3,4 Data shows HCQ effectively inhibited
literature and relevant websites 3. It also inhibits the quinone both the entry, transport and the post-
regarding these drugs and COVID-19. reductase-2, which is involved entry stages of SARS-CoV-2, similar to
in sialic acid biosynthesis (an the chloroquine and one study found
Studies of chloroquine and acidic monosaccharides of cell HCQ to be a more potent agent than
hydroxychloroquine conducted transmembrane proteins required chloroquine in inhibiting SARS-CoV-2
in vitro for ligand recognition) that makes in vitro.7,8
Experimental studies have suggested this agent a broad antiviral agent.
that chloroquine is a proven anti- It is important to note that both Addition of hydroxyl molecule makes
malarial drug that has the capability human coronavirus HCoV-O43 and HCQ less permeable to blood-retinal
of inhibiting the replication of orthomyxoviruses uses sialic acid barrier and allows faster clearance
several intracellular micro-organisms moieties as a receptor. from retinal pigment cell, thereby
including coronaviruses in vitro. It has 4. Chloroquine changes the pH of suggesting a lesser risk of retinal
been increasingly learnt that the anti- lysosomes and likely inhibits toxicity with HCQ, as compared to
viral and anti-inflammatory activities cathepsins, that leads to the chloroquine.9 Furthermore, the narrow
of chloroquine may have a role in formation of the autophagosome therapeutic and safety index margin
the treatment of patients with novel which cleaves SARS-CoV-2 spike with chloroquine makes HCQ a safer
COVID-19. protein. option than chloroquine.
1. Chloroquine increases endosomal 5. Chloroquine through the inhibition
of MAP-kinase interferes with SARS- An additional issue to be considered in
pH and interferes with the CoV-2 molecular crosstalk, besides severely sick patients is cytokine storm
glycosylation of cellular receptor altering the virion assembly, budding associated with disease severity of
of SARS-CoV and thereby it has the and interfering with the proteolytic SARS-CoV-2.10 The significant decrease
potential to block viral infection.1 processing of the M protein.1,3 in the production of pro-inflammatory
2. Previous experimental studies have markers and cytokines with HCQ has
also demonstrated that chloroquine Since the structure and mechanism made this agent a successful disease
has potent anti-SARS-CoV-1 effects of action of chloroquine and modifying anti-inflammatory agent in
in vitro, primarily attributable to a hydroxychloroquine (HCQ) are exactly the treatment of various autoimmune
deficit in the glycosylation receptors same except an additional hydroxy diseases including rheumatoid arthritis,
at the virus cell surface, so that it moiety in one terminal in HCQ, both systemic lupus erythematosus and
cannot bind to the angiotensin- act as a weak base that can change the Sjogren’s syndrome. Long-term clinical
converting enzyme 2 (ACE2) pH of acidic intracellular organelles safety profile of HCQ is better than
expressed in lung, heart, kidney and including endosomes/lysosomes, that of chloroquine, that allows higher
intestine. Since SARS-CoV-2 utilizes daily dose of HCQ with less drug-drug
interactions.

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COVID-19 Special

Table 1: Available Guidelines for various countries (as of March 21, 2020) in the treatment of COVID-19 for Chloroquine
and Hydroxychloroquine.11,12,13,14,15,16,17,18,19

Study/Guidelines/Country Dose (adults)

Expert consensus from Department of Science Chloroquine phosphate 500 mg BID for 10 days.
and Technology and Health Commission of
Guangdong province, China12

Central Clinical Task Force, Korea13 Moderate to severe COVID-19:
Lopinavir 400 mg/Ritonavir 100 mg BID or Chloroquine 500 mg orally per
day or Hydroxychloroquine 400 mg orally per day for 7–10 days.

Centre for Disease Control and Prevention, URTI plus positive PCR:
Atlanta, MICC Version 1 (March 12, 2020)14 yy Chloroquine phosphate 500 mg BID for 5 days.
yy Oseltamivir 150 mg BID for 5 days.

COVID-19 Pneumonia:
yy Chloroquine phosphate 500 mg BID for 5 days plus Darunavir 800 mg/

Cobicistat 150 mg OD for 2 weeks.
yy Atazanavir 400 mg OD for 2 weeks plus Oseltamivir 150 mg BID for 5 days.

The Dutch Center of Disease Control15 600 mg of Chloroquine base followed by 300 mg after 12 h on day 1, then
300 mg - 2/day per person on days 2–5.

Italian Society of Infectious and Tropical Mild to moderate COVID-19:
Diseases (Lombardy Section)16 Lopinavir/ritonavir plus Chloroquine 500 mg - 2/day or
Hydroxychloroquine 200 mg per day for 10 days.

Severe or critical COVID-19:
Remdesivir plus Chloroquine 500 mg - 2/day or Hydroxychloroquine 200
mg per day for 10–20 days.

Mount Sinai Health System, Canada17 Moderate to severe COVID-19:
Hydroxychloroquine 400 mg BID x 2 doses then 12 h later start 400 mg OD
for 5–10 days.

Surviving Sepsis Campaign, The Society of Insufficient evidence to issue a recommendation on the use of chloroquine
Critical Care Medicine and the European or hydroxychloroquine in critically ill adults with COVID-19 at this point
Society of Intensive Care Medicine18 of time.

Clinical guidance for patients with suspected Mild/Moderate/Severe COVID-19:
or confirmed COVID-19 in Belgium19 Hydroxychloroquine 400 mg at diagnosis, 400 mg 12 h later, followed by
200 mg BID for 5 days,
Or,
Chloroquine 600 mg at diagnosis and 300 mg 12 h later followed by 300
mg BID for 5 days (Consider lopinavir 400 mg/ritonavir 100 mg BID for 14
days as a second choice only if HCQ and chloroquine is contraindicated,
provided it can be administered within 10 days after onset of symptoms)

Critical COVID-19:
Remdesivir 200 mg loading dose i.v within 30 min followed by 100 mg
OD for 2–10 days (Hydroxychloroquine is second option if Remdesivir is
unavailable)

Clinical guidance for patients with suspected Mild/moderate/severe COVID-19:
or confirmed COVID-19 in Netherland19 Chloroquine 600 mg on day 1, then 300 mg BID for 5 days (lopinavir/
ritonavir as second option)

Critical COVID-19:
Remdesivir for 10 days plus chloroquine for 5 day

Gautret et al., Marseille, France11 Hydroxychloroquine 200 mg TID for 10 days.

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COVID-19 Special

OD-once daily, BID-twice daily, TID- 3. The high- risk contacts of a Key Considerations :
thrice daily, URTI- upper respiratory positive case placed under chemo yy The drug has to be given only on the
tract infection, PCR-polymerase chain prophylaxis, should remain in home
reaction, i.v - intravenous. quarantine while on prophylactic prescription of a registered medical
therapy. practitioner
It is emphasized that India is following yy Advised to consult with a physician
ICMR Guidelines. 4. The drug should only be given on the for any adverse event or potential
prescription of a registered medical drug interaction before initiation of
Advisory on the use of hydroxy- practitioner. The contraindications medication
chloroquine as prophylaxis for mentioned should strictly be yy The prophylactic use of
SARS-CoV2 infection followed. hydroxychloroquine to be coupled
The All India Ophthalmological with the pharmacovigilance
Society recommends the use of 5. Apart from the symptoms for adverse drug reactions
hydroxy-chloroquine for prophylaxis of COVID -19 (fever, cough, through self- reporting using the
of SARS -CoV-2 infection for high-risk breathing difficulty), if the person Pharmacovigilance Program of India
population as advised by the Indian on chemoprophylaxis develops (PvO)helpline/app
Council of Medical research (ICMR). and other symptoms, he should yy If anyone becomes symptomatic
immediately seek medical treatment while on prophylaxis he/she should
The protocol recommended by the of the medical practitioner who has immediately contact the health
National Task Forces has been approved prescribed the chemoprophylaxis. facility, get tested as per national
by the Drug Controller General of guidelines and follow the standard
India for restricted use in emergency The National task force of COVID treatment protocol
situations. -19 recommends the use of hydroxy yy All asymptomatic contacts of
- chloroquine for prophylaxis of laboratory-confirmed cases should
Recommendation has been given by SARS -CoV-2 infection for selected remain in home quarantine ad per
ICMR for the use of hydroxy-chloroquine individuals as follows : the national guidelines, even if they
as prophylaxis for SARS-CoV2 infection are on prophylactic therapy
and not as the treatment for the same as Eligible Individuals: yy Simultaneously, proof of concept
the existing evidence regarding its use as yy Asymptomatic healthcare workers and pharmacokinetics studies be
treatment is inadequate. Furthermore, taken up expeditiously
it is causing side effects in patients involved in the care of suspected or
with arthritis and systemic lupus confirmed cases of COVID -19 References
erythematosus (SLE), who routinely 1. Wang, R. Cao, L. Zhang, X. Yang, J. Liu,
use the drug to control their symptoms. yy Asymptomatic household contacts
Moretrials are required to investigate of laboratory-confirmed cases M. Xu, et al.Remdesivir and chloroquine
whether hydroxychloroquinecould be effectively inhibit the recently emerged
efficacious as a treatment of the disease. Dose: novel coronavirus (2019-nCoV) in
yy Asymptomatic healthcare workers vitroCell Res.2020.
While following the above 2. C.C. Lai, Y.H. Liu, C.Y. Wang, Y.H.
recommendations, all should take note involved in the care of suspected or Wang, S.C. Hsueh, M.Y. Yen, et al.
of the following: confirmed cases of COVID -19: 400 Drug treatment options for the 2019-
mg twice a day on Day 1, followed new coronavirus (2019-nCoV) Biosci
1. Placing of healthcare workers under by 400 mg once weekly for next 7 Trends.2020.
chemoprophylaxis should not instill weeks, to be taken with meals 3. P. Colson, J.M. Rolain, D.
sense of false security. They should RaoultChloroquine for the 2019
follow all prescribed public health yy Asymptomatic household contacts novel coronavirusInt J Antimicrob
measures such as frequent washing of laboratory-confirmed cases: 400 Agents.2020.
of hands, respiratory etiquettes, mg twice a day on Day 1, followed 4. N. Zhou, T. Pan, J. Zhang, Q. Li, X. Zhang,
keeping a distance of minimum by 400 mg once weekly for the next 3 C. Bai, et al. Glycopeptide antibiotics
1m and use of Personal protective weeks; to be taken with meals potently inhibit cathepsin L in the late
equipment (wherever applicable). endosome/lysosome and block the entry
Exclusion/Contraindications: of Ebola virus, middle east respiratory
2. They should self - monitor their yy The drug is not recommended for syndrome coronavirus (MERS-CoV),
health and report to health and severe acute respiratory syndrome
authorities immediately in the event prophylaxis in children under 15 coronavirus (SARS-CoV) J Biol Chem.
of them being symptomatic. years of age 2016;291:9218e32

yy The drug is contraindicated in
person with known cases of
retinopathy, known hypersensitivity
to hydroxychloroquine, 4
aminoquinoline compounds

38 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

5. P. Colson, J.M. Rolain, J.C. Lagier, P. of patients infected with 2019 novel conditions/2019-novel-coronavirus-
Brouqui, D. Raoult Chloroquine and coronavirus in Wuhan, China. 2019-ncov
hydroxychloroquine as available Lancet.2020;395(10223):497-506. 17. https://www.esicm.org/ssc-covid19-
weapons to fight COVID-19. Int J guidelines/
Antimicrob Agents. 2020:105932. 11. Zhonghua Jiehe. He Huxi Zazhi 18. Interim clinical guidelines for patients
Multicenter collaboration group of suspected of/confirmed with COVID-19
6. C. Biot, W. Daher, N. Chavain, T. Department of Science and Technology infection https://epidemio.wivisp.be/
Fandeur, J. Khalife, D. Dive, et al. Design of Guangdong Province and Health ID/Documents/Covid19/COVID19_
and synthesis of hydroxyferroquine Commission of Guangdong Province InterimGuidelie Treatment_ENG.pdf
derivatives with antimalarial and for chloroquine in the treatment of 19. Recommendation of National Taskforce
antiviral activities. J Med Chem. novel coronavirus pneumonia. Expert for use of Hydroxychloroquine as
2006;49:2845-2849 consensus on chloroquine phosphate prophylaxis for Covid 19.
for the treatment of novel coronavirus
7. J. Liu, R. Cao, M. Xu, X. Wang, H. Zhang, pneumonia.Chinese Journal of Corresponding Author:
H. Hu, et al.Hydroxychloroquine, a Tuberculosis and Respiratory Diseases,
less toxic derivative of chloroquine, 2020;43(03):185-88. Dr. Namrata Sharma MD, DNB, MNAMS
is effective in inhibiting SARS-CoV-2 Cornea, Cataract & Refractive surgery services
infection in vitro Cell Discov.2020;6:16. 12. Korea biomedical review website Dr. Rajendra Prasad Centre for Ophthalmic
http://www.koreabiomed.com/news/ Sciences, All India Institute of Medical Sciences,
8. X. Yao, F. Ye, M. Zhang, C. Cui, B. Huang, articleView.html?idxno=7428 New Delhi, India.
P. Niu, et al. In vitro antiviral activity and
projection of optimized dosing design of 13. https://www.medcampus.io/mnotes/
hydroxychloroquine for the treatment protocol-for-treatment-of-confirmed-
of severe acute respiratory syndrome covid-19 5e5e2781e86c5d0001f77303
coronavirus 2 (SARS-CoV-2) Clin Infect
Dis.2020. 14. https://lci.rivm.nl/covid-19/bijlage/
behandeladvies
9. M.F. Marmor, U. Kellner, T.Y. Lai, R.B.
Melles, W.F. MielerAmerican academy 15. http://www.simit.org/medias/1555-
of ophthalmology. Recommendations covid19-linee-guida-trattamento-
on screening for chloroquine and 01mar.pdf
hydroxychloroquine retinopathy (2016)
16. Mount Sinai health system treatment
10. C. Huang, Y. Wang, X. Li, L. Ren, J. guidelines for SARS-CoV-2 infection
Zhao, Y. Hu, et al.Clinical features (COVID19) https://www.mountsinai.
org/health-library/diseases-

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COVID-19 Special

Vaccines for COVID-19

Manpreet Bhalla MD1, Jaideep Singh Bhalla MBBS2
1Senior Consultant Microbiologist, National Institute of TB & Respiratory Diseases (NITRD), New Delhi
2Maulana Azad Medical College, New Delhi

The world experienced the outbreaks Let us understand some of the advanced vaccine technology, are
of coronavirus infection that threaten differences between SAS Cov, MERS expected to give us more knowledge on
global pandemic in 2002-2003 by Severe CoV& SARS CoV 2 infections.2 the pathogen itself, including the host
Acute Respiratory Syndrome (SARS) The rapid genomic sequencing and immune response as well as the plan
and in 2011 by Middle East Respiratory open access data, together with for therapeutic vaccines in the near
Syndrome (MERS). In both cases, future.3
the causative agents (SARS-CoV and
MERS-CoV, respectively) were newly Figure 1: The origins and intermediate hosts of SARS-CoV-2, SARS-CoV, and MERS-CoV.
identified coronavirus in the genus
Betacoronavirus with zoonotic origin.
At the end of 2019, outbreak of another
coronavirus that causes respiratory-
related illness was reported in Wuhan,
Hubei, China, a disease now officially
called “the Corona Virus Disease 2019;
COVID-19”. The coronavirus that is
the causative agent of this respiratory
disease was identified and its genome is
fully sequenced.1 The genomic sequence
of SARS-CoV-2 showed similar, but
distinct genome composition of SARS-
CoV and MERS-CoV.

Table 1: SARS-CoV MERS-CoV SARS-CoV-2

Demographic November 2002/ June 2012/ December 2019/
Date/Plate first detected Guangdong china Jeddah, Saudi Arabia Wuhan, china

Age, years (range) 39.9 (1-91) 56 (14 to 94) <1 to > 80
Confirmed cases 8,096 2,494 I,925,138 (AS ON 13.4.20)
Mortality rate
Host pathogen interaction 744 (9.19%) 858 (34.4%) 2,126 (2.8%)
Possible natural reservoir
Possible intermediate host Bat Bat Bat
Predominant cellular Palm civets Camel Pangolin
receptor Dipeptidyl peptidase 4 (DPP4,
Emerging characteristic ACE2 also known as CD26) ACE2
Number of affected country
Reproductive number, Ro 29 27 206
Epidemic doubling time 1.4-5.5 <1 2.2-2.6
4.6 to 14.2 days 90
(depending upon setting) 6.4

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COVID-19 Special

In addition, we need to build a system phase 3 trials and secure regulatory 2.2-2.6, with an epidemic doubling time
that can develop safe, effective vaccines approval for coronavirus vaccines, of 6.4 days.5,18 This implies that, in order
and antivirals, get them approved, and still more funding will be needed to reduce Ro˂ 1, more than half of the
and deliver billions of doses within to improve disease surveillance and current infection must be prevented or
a few months after the discovery of a response. controlled.19 Comparing with SARS-
fast-moving pathogen. That’s a tough CoV and MERS-CoV which R0 were ˂ 1
challenge that presents technical, Government funding is needed because and 1.4-2.5, respectively, it implies that
diplomatic, and budgetary obstacles, as pandemic products are extraordinarily SAR-CoV-2 is more contagious than
well as demanding partnership between high-risk investments; public funding MERS-CoV and may cause an epidemic
the public and private sectors. But all will minimize risk for pharmaceutical or even a pandemic if transmission is
these obstacles can be overcome.4 companies and get them to jump in with uncontrolled.6,7
both feet. In addition, governments and
One of the main technical challenges for other donors will need to fund — as a Immunopathology of COVID-19
vaccines is to improve on the old ways global public good — manufacturing The pathogenesis of COVID-19 is still
of manufacturing proteins, which are facilities that can generate a vaccine under investigation. For most patients,
too slow for responding to an epidemic. supply in a matter of weeks. Finally, COVID-19 might affect only the
We need to develop platforms that are governments will need to finance lungs. The primary mode of infection
predictably safe, so regulatory reviews the procurement and distribution of is human-to-human transmission
can happen quickly, and that make vaccines to the populations that need through close contact, which occurs
it easy for manufacturers to produce them. via spraying droplets from infected
doses at low cost on a massive scale. individual through their cough or
Billions of dollars for antipandemic sneeze. COVID-19 has a probable
Another technical challenge involves efforts is a lot of money. But that’s the asymptomatic incubation period
constructs based on nucleic acids. These scale of investment required to solve between 2-14 days during which the
constructs can be produced within the problem. And given the economic virus can be transmitted.8
hours after a virus’s genome has been pain that an epidemic can impose —
sequenced; now we need to find ways to we’re already seeing how Covid-19 Most common symptoms of COVID-19
produce them at scale. can disrupt supply chains and stock are fever, fatigue, and respiratory
markets, not to mention people’s lives symptoms, including cough, sore throat
Beyond these technical solutions, — it will be a bargain. and shortness of breath. Although
we’ll need diplomatic efforts to drive diarrhea was presented in about 20-
international collaboration and data Finally, governments and industry will 25% of patients with SARS and MERS,
sharing. Developing antivirals and need to come to an agreement: during a intestinal symptoms were rarely
vaccines involves massive clinical trials pandemic, vaccines and antivirals can’t reported in patients with COVID-19.9,10
and licensing agreements that would simply be sold to the highest bidder. Most patients also developed
cross national borders. We should make They should be available and affordable lymphopenia and pneumonia with
the most of global forums that can help for people who are at the heart of the characteristic pulmonary ground glass
achieve consensus on research priorities outbreak and in greatest need.5 opacity changes on chest CT.9,10 At
and trial protocols so that promising present, the mortality rate of COVID-19
vaccine and antiviral candidates can Host-Pathogen Interaction: worldwide is approximately 2.4%
move quickly through this process. Emerging Profiles of SARS-CoV-2 which are caused by multi-organ failure
These platforms include the WHO Infection especially in elderly people and people
R&D Blueprint, the International Concept of Ro & Epidemic Doubling with underlying health conditions such
Severe Acute Respiratory and Emerging Time as hypertension, cardiovascular disease
Infection Consortium trial network, As SAR-CoV-2 is a novel human- and diabetes.1
and the Global Research Collaboration infecting pathogen, recent studies have
for Infectious Disease Preparedness. attempted to define more accurate Innate Immune Responses to SARS-
The goal of this work should be to get infection situation and to forecast the CoV-2 Infection: Gaining Insight
conclusive clinical trial results and outbreak in the near future. By using from Strategies used by SARS-CoV
regulatory approval in 3 months or less, a mathematical model to calculate the and MERS-CoV
without compromising patients’ safety. basic reproductive number, Ro , which In one report where 99 cases in
is the average number of people that one Wuhan were investigated, increased
Then there’s the question of funding. infected individual will pass the virus total neutrophils (38%), reduced total
Budgets for these efforts need to be on to. If Ro is ˃1, continued transmission lymphocytes (35%), increased serum
expanded several times over. Billions can occur. Ro of SAR-CoV-2 ranged from IL-6 (52%) and increased c-reactive
more dollars are needed to complete

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COVID-19 Special

protein (84%) were observed.13 In Figure 2. Proposed host immune responses during SARS-CoV-2 infection
addition, the study of 41 hospitalized
patients with high-levels of type I IFN response will suppress Dysregulated type I IFN and
proinflammatory cytokines including inflammatory monocyte-macrophages
IL-2, IL-7, IL-10, G-CSF, IP-10, MCP-1, viral replication and dissemination are the main cause of lethal pneumonia.
MIP-1A, and TNFα were observed in the Individuals susceptible to CoVID19
COVID-19 severe cases.9 These findings But Virus may dampen anti-viral IFN are those with underlying diseases,
are in line with SARS and MERS in responses resulting in uncontrolled including diabetes, hypertension, and
that the presence of lymphopenia and viral replication → influx of neutrophils cardiovascular disease.10 In addition,
“cytokine storm” may have a major role and monocytes/macrophages → no severe cases were reported in
in the pathogenesis of COVID-19.11,12,13 hyperproduction of pro-inflammatory young children, when innate immune
This so-called “cytokine storm” can cytokines → cytokinestorms response is highly effective.
initiate viral sepsis and inflammatory- → immunopathology of lung
induced lung injury which lead to other (Pneumonitis/ARDS) → Specific Th1/ Why Different Response at
complications including pneumonitis, Th17 may be activated and contribute Different Ages
acute respiratory distress syndrome to exacerbate inflammatory responses In children, there is earlier innate
(ARDS), respiratory failure, shock, → B cells/plasma cells produce SARS- response to IFN γ th1 response →
organ failure and potentially death.1,11,12 CoV-2 specific antibodies that may help inhibition of viral replication → very
neutralize viruses.4 few symptoms that clear quickly. In
Effective innate immune response older population response is different as
against viral infection relies heavily on For SARS-CoV and MERS-CoV, the blocking STAT 1 Protein interferes with
the interferon (IFN) type I responses and response to viral infection by type I IFN γth1 → Virus replication unchecked
its downstream cascade that culminates IFN is suppressed/Dampened. The viral → Cytokine storm → Pneumonia &
in controlling viral replication and proteins involved in the modulation ARDS. These facts strongly indicate that
induction of effective adaptive immune of this host type I IFN response are innate immune response is a critical
response. While SARS-CoV and SARS- both structural proteins (such as M, factor for disease outcome.
CoV-2 seem to share the entry receptor N) and non-structural proteins (ORF
of ACE2, MERS-CoV uses dipeptidyl proteins). SARS-CoV2 shares overall Adaptive Immune Responses:
peptidase (DPP)-4 as a specific receptor. genomic similarity with SARS-CoV or A Clue for Future Vaccine
MERSCoV, approximately 79% and Development?
Recognition of Virus Invasion 50%, respectively & in amino acid Th1 type immune response plays
To mount an antiviral response, innate sequencing, 68% similarity with that a dominant role in an adaptive
immune cells need to recognize the of SARS-CoV. So can speculate that immunity to viral infections. Helper T
invasion of the virus, often by pathogen SARS-CoV-2 utilizes similar strategies cells orchestrate the overall adaptive
associated molecular patterns (PAMPs). to modulate the host innate immune response, while cytotoxic T cells are
For RNA virus such as coronavirus, it response, especially in dampening the
is known that PAMPs in the form of type I IFN response.14
viral genomic RNA or the intermediates
during viral replication are recognized
by either the endosomal RNA receptors
and the cytosolic RNA sensor. This
recognition event leads to activation
of the downstream signalling cascade,
leading to responses including type I IFN
and other pro-inflammatory cytokines
and comprise the first line defense
against viral infection at the entry site.
Successful mounting of this type I IFN
response should be able to suppress
viral replication and dissemination at
an early stage.11,12

Aerosolized uptake of SARS-CoV-2
leads to infection of ACE2 expressing
target cells (alveolar type 2 cells /
unknown target cells) → successful

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COVID-19 Special

essential in killing of viral infected cells. viral structural proteins, it will be Prophylactic Vaccines: Is it
Humoral immune response, especially informative to map those epitopes possible?
production of neutralizing antibody, identified with SARS-CoV/MERS- Based on knowledge from SARS and
plays a protective role by limiting CoV with those of SARS-CoV-2. If MERS vaccines development path,
infection at later phase and prevents overlapping epitopes among the three several research groups have been
reinfection in the future. viruses can be identified, it will be able to start SAR-CoV-2 vaccine
beneficial for application in passive development within only a few weeks
SARS-CoV infection induces immunization using convalescent after the outbreak. The target antigen
seroconversion as early as day 4 after serum from recovered SARS or MERS selection and vaccine platform are
onset of disease and was found in patients. probably based on SARS-CoV and MERS-
most patients by 14 days. Long lasting CoV vaccine studies, summarized in
specific IgG and neutralizing antibody Potential Immune Evasion Table 2. Full-length spike (S) or S1 which
are reported as long as 2 years after Mechanisms contains receptor binding domain
infection.31 For MERS-CoV infection, Coronaviruses are particularly adapted (RDB) might be considered as a good
seroconversion is seen at the second or to evade immune detection and dampen. vaccine antigen because it could induce
third week of disease onset. A limited This partly explains why they tend to neutralizing antibodies that prevent
serology details of SARS-CoV-2 was have a longer incubation period, 2-11 host cell attachment and infection.17,18,19
reported. In a preliminary study, one days on average compared to influenza, Table 2 describes the selected antigens
patient showed peak specific IgM at day 1-4 days.16 The longer incubation and platforms that have been tested for
9 after disease onset and the switching period is probably due to their immune SARS-CoV and MERS-CoV in clinical
to IgG by week 2.15 evasion properties, efficiently escaping and preclinical studies.
host immune detection at the early
Because most epitopes identified stage of infection. Interestingly, as summarized in the
for both viruses concentrate on the Table 2, nucleic acidbased DNA vaccine,

Vaccine Immunogen Phase Advantage Disadvantage
platform yy Efficient delivery system required
DNA Full- length Spike, or S1 Phase 1,2 yy Rapid production yy Induce lower immune responses
yy IM follow by (NCT 03721718) yy Easy design and manipulation
yy Induced both B and T cells when compare with live vaccine
electroporation Phase 1 yy Various innoculation routes may
(NCT 03399578, responses
Viral vector Full- length Spike, or S1 NCT 03615911) yy Excellence in immune induction produce different immune responses
Subunit yy Vector used: ChAd or Preclinical yy Possible TH2 bias
yy High safety profile yy Need appropriate adjuvants
Virus- like MVA yy Consistent production yy Cost-effectiveness may vary
particle yy Can induce cellular and humoral
Inactivated Full length spike, S1, yy Require optimum assembly condition
RDB, nucleocapsid immune responses
yy Formulated with yy Possible cause hypersensitivity
Preclinical yy Multimetric antigen display yy Possible Th2-bias
various adjuvants yy Preserve virus particle structure
and/or fused with Fc yy Risk of reversion to a virulent strain
Preclinical yy Preserve virus particle structure yy Cold chain required
RDB,S or Coexpressing Preclinical yy Rapid development yy Not suitable or sensitive population
of S1,M, and E yy Excellence in neutralizing Ab
yy Produced in such as infants, immunocompromised
induction or elderly individuals
baculovirus yy Can be formulated with various

Whole virus adjuvant
yy Inactivated by
yy Excellence in induction of T and
formaldehyde or B cell responses
gamma irradiation
yy Site- directed mutagenesis can be
Live- Mutant MERS-CoV tailer made
attenuated and SARS-CoV or
virus recombination with
other live attenuated
virus

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COVID-19 Special

showed the most advance platform its interaction with the host immune IgG and neutralizing antibodies. The
in response to emerging pathogens. responses may help provide a clearer induced cellular immune response
Moreover, during Zika virus outbreak, picture of how the pathogen causes involved increased CD3+CD4+ and
DNA vaccine was the first vaccine diseases in some individuals while most CD3+CD8+ T cell responses that
candidate that entered clinical trial infected people only show mild or no produced IFN-γ, TNF-α, IL-2, or both
(NCT02809443)44 (less than 1-year symptoms at all. In addition, the study IFN-γ and TNF-α. On March 3, 2020,
after the outbreak). According to the of the immune correlates of protection Inovio Pharmaceutical, Inc. announced
current technological advancement, and the long-term immune memory they had designed the DNA vaccine
mRNA vaccine, another nucleic acid- from convalescent individuals may help called INO-4800 to be planned for
based vaccine, has been considered as in design prophylactic and therapeutic human trials in the United States in
disruptive vaccine technology. Recent measures for future outbreak of similar April.25
mRNA vaccine designs have improved coronaviruses.
stability and protein translation Protein-Based Vaccines: vaccine
efficiency thus it could induce robust Antiviral vaccines generally fall into one comprises an S protein immunogen. It
immune responses.20,21 Delivery system of the following types: inactive or live- induced high levels of anti-SARS-CoV
such as lipid nanoparticle, LNP was attenuated viruses, virus-like particle IgG2a or IgG2b antibody responses and
also well-optimized.32 Within two (VLP), viral vectors, protein-based, neutralizing antibody responses.26
months of the SAR-CoV-2 outbreak, at DNAbased, and mRNA-based vaccines.
least 37 biopharmaceutical companies There are 363 patents in the CAS Virus-like Particle Vaccines: an
or academic sectors are in the race content collection related to vaccine immunogenic composition composed
to develop the prophylactic vaccine development to prevent viral disorders/ of MERS-CoV nanoparticle VLPs
by using several platforms including diseases, including SARS and MERS. containing at least one trimer of a S
mRNA, DNA, adenoviral vector and Of these, 175 patents disclose vaccines protein. This VLP preparation induced a
recombinant protein. In order to make for non-coronaviruses that may have neutralizing antibody response in mice
SAR-CoV-2 vaccine possible, gathering relevance to SARS and MERS, while and transgenic cattle.27
of important information for vaccine 188 patents are directly associated with
development and evaluation should anti-SARS and anti-MERS vaccines with mRNA-Based Vaccines: The potential
be well defined. This includes finding a demonstrated immune response.23 advantages of an mRNA approach
target antigen(s), immunization route, to prophylactic vaccines include the
correlated-immune protection, animal It was reported that viral S protein ability to mimic natural infection
models, scalability, production facility, subunit vaccines produced higher to stimulate a more potent immune
target product profile (TPP), outbreak neutralizing antibody titers and response as well as the ability to
forecasting and target population. more complete protection than live- combine multiple mRNAs into a single
International collaboration as well as attenuated SARS-CoV, full-length S vaccine. Vaccines comprising mRNA
technology transfer between experts protein, and DNA-based S protein encoding at least one antigen of a MERS
will also help SARS-CoV-2 vaccine vaccines.24 Unsurprisingly, about half of coronavirus, preferably a S protein or
development quickly move forward. In the patents focussed on protein vaccines a S protein fragment (S1), an envelope
order to speed up the available vaccine comprising the S protein subunit protein (E), a membrane protein (M),
during ongoing outbreak, preclinical vaccine and vaccines specifically or a nucleocapsid protein (N), all were
studies of SAR-CoV-2 vaccine candidates targeting the receptor binding domain effective in inducing an antigen-specific
may need to be performed in parallel (RBD) of the S1 subunit of the viral S immune response.28
with clinical trials. However, before protein. Collectively, S protein/gene is
entering clinical testing, the regulatory the preferred target site in SARS/MERS Human Convalescent Serum
agencies must assess the production vaccine development, and the same Is Another option for prevention
process and preclinical information to strategy can be potentially useful in and treatment of COVID-19 disease.
ensure volunteers’ safety.22 By looking at developing SARS-CoV-2 vaccines. It could be rapidly available when
the similarities and differences between there are sufficient numbers of people
the current SARS-CoV-2 and the Attenuated Virus Vaccines: The who have recovered and can donate
previous outbreak of SARS and MERS, attenuated MHV virus exhibited immunoglobulin-containing serum.
a striking similarity emerges with reduced replication in mice at day five
some unique features of its own. As the following intracerebral inoculation. Blood drawn from an individual
COVID-19 causes serious public health who has recovered from COVID-19
concerns across Asia and on the blink to DNA Based Vaccines: The consensus is screened for virus-neutralizing
affect world population, investigation spike protein significantly induced antibodies. Following identification of
into the characteristics of SARS-CoV-2, both humoral and cellular immune those with high titers of neutralizing
responses, including increased titers of antibody, serum containing these

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COVID-19 Special

virus-neutralizing antibodies can be 4. Wu, Y.Compensation of ACE2 function Perl TM, Nelson KE, Cummings DA.
administered in a prophylactic manner for possible clinical management. Virol. Incubation periods of acute respiratory
to prevent infection in high-risk Sin. 2020 viral infections: a systematic review.
cases, such as vulnerable individuals Lancet Infect Dis. 2009;9:291-300.
with underlying medical conditions, 5. Covid 19 -Navigating the Uncharted
health care providers, and individuals .Anthony S. Fauci,., H. Clifford Lane,., 17. Al-Amri SS, Abbas AT, Siddiq LA,
with exposure to confirmed cases of and Robert R. Redfield,.N Engl J Med Alghamdi A, Sanki MA, Al-Muhanna
COVID-19. Additionally, convalescent 2020; 382:1268-1269 MK, et al. Immunogenicity of Candidate
serum could potentially be used in MERS-CoV DNA Vaccines Based on the
individuals with clinical disease to 6. Tian-Mu Chen, Jia Rui, Qiu-Peng Wang et Spike Protein. Sci Rep. 2017;7:44875.
reduce symptoms and mortality.30 al. A mathematical model for simulating
the phase-based transmissibility of a 18. Du L, He Y, Zhou Y, Liu S, Zheng BJ,
Summary novel coronavirus ;Infectious Diseases Jiang S. The spike protein of SARS-CoV-
Since vaccines are crucial for prevention of Poverty volume 9, Article number: 24 -a target for vaccine and therapeutic
ofcoronavirus-relatedepidemicdiseases (2020) development. Nat Rev Microbiol.
in the future, it is reassuring that a 2009;7:226-36.
number of innovative strategies like 7. Chen N, Zhou M, Dong X, Qu J, Gong
genome based technologies are already F, Han Y, et al. Epidemiological and 19. Du L, Zhao G, He Y, Guo Y, Zheng BJ,
being deployed. Four MERS coronavirus clinical characteristics of 99 cases of Jiang S, et al. Receptor-binding domain
DNA vaccine candidates began phase 1 2019 novel coronavirus pneumonia of SARS-CoV spike protein induces long-
clinical trials in September of 2019, and in Wuhan, China: a descriptive study. term protective immunity in an animal
Moderna Inc. released its first batch of Lancet. 2020;395:507-13. model. Vaccine. 2007;25:2832-8
mRNA-1273 in February of 2020, which
is an mRNA vaccine against SARSCoV-2 8. Center for Disease Control and 20. Pardi N, Hogan MJ, Porter FW,
ready for phase 1 study in the United Prevention [Internet]. Atlanta: CDC; Weissman D. mRNA vaccines - a new
States.29 c2020 [cited 2020 Feb 10]. Symptoms of era in vaccinology. Nat Rev Drug Discov.
Novel Coronavirus (2019-nCoV) 2018;17:261-79.
The pandemic, will probably have
peaked and declined before a vaccine 9. Wu F, Zhao S, Yu B, Chen YM, Wang 21. Maruggi G, Zhang C, Li J, Ulmer JB,
is available”. A vaccine could still W, Song ZG, et al. A new coronavirus Yu D. mRNA as a Transformative
save many lives, especially if the virus associated with human respiratory Technology for Vaccine Development to
becomes endemic or perennially disease in China. Nature [Preprint]. 2020 Control Infectious Diseases. Mol Ther.
circulating – like flu – and there are [cited 2020 Feb 16]: [19 p.]. 2019;27:757-72.
further, possibly seasonal, outbreaks.
But until then, our best hope is to 10. Huang C, Wang Y, Li X, Ren L, Zhao J, 22. Thomas SJ, L’Azou M, Barrett AD,
contain the disease as far as possible. To Hu Y, et al. Clinical features of patients Jackson NA. Fast-Track Zika Vaccine
repeat the sage advice: wash your hands infected with 2019 novel coronavirus in Development - Is It Possible? N Engl J
& maintain social distancing. Wuhan, China. Lancet. 2020;395:497– Med. 2016;375:1212-6.
506.
References 23. Cynthia Liu et al. Research and
11. Nicholls JM, Poon LL, Lee KC, Ng WF, Lai Development on Therapeutic Agents
1. Wu F, Zhao S, Yu B, Chen YM, Wang ST, Leung CY, et al. Lung pathology of and Vaccines for COVID-19 and Related
W, Song ZG, et al. A new coronavirus fatal severe acute respiratory syndrome. Human Coronavirus Diseases. ACS
associated with human respiratory Lancet. 2003; 361:1773-8. Cent. Sci. 2020, 6, 315-331.
disease in China. Nature [Preprint]. 2020
[cited 2020 Feb 16]: [19 p.]. 12. Mahallawi WH, Khabour OF, Zhang Q, 24. Yong CY, Ong HK, Yeap SK, Ho KL, Tan
Makhdoum HM, Suliman BA. MERS- WS. Recent Advances in the Vaccine
2. Eakachai Prompetchara,Chutitorn CoV infection in humans is associated Development Against Middle East
Ketloy, Tanapat Palaga; Immune with a pro-inflammatory Th1 and Th17 Respiratory Syndrome -Coronavirus.
responses in COVID-19 and potential cytokine profile. Cytokine. 2018;104:8- Front Microbiol. 2019;10:1781.
vaccines: Lessons learned from SARS 13.
and MERS epidemic. Asian Pac J Allergy 25. Inovio Accelerates Timeline for
Immunol 2020;38:1-9. 13. Wong CK, Lam CW, Wu AK, Ip WK, Lee COVID-19 DNA Vaccine INO-4800 http://
NL, Chan IH, et al. Plasma inflammatory www.prnewswire.com/news-releases/
3. Lu R, Zhao X, Li J, Niu P, Yang B, Wu cytokines and chemokines in severe inovio-accelerates-timeline-for-covid-
H, et al. Genomic characterisation and acute respiratory syndrome. Clin Exp 19-dna-vaccine-ino-4800-301015031.
epidemiology of 2019 novel coronavirus: Immunol. 2004;136:95-103. html
implications for virus origins and receptor
binding. Lancet. 2020;395:565-74. 14. de Wit E, van Doremalen N, Falzarano 26. GlaxoSmithKline press release on
D, Munster VJ. SARS and MERS: recent 2/24/20. https://www.gsk. com/en-gb/
insights into emerging coronaviruses. media/press-releases/clover-and-gsk-
Nat Rev Microbiol. 2016;14: 523-34. announce-researchcollaboration-to-
evaluate-coronavirus-covid-19-vaccine-
15. de Wit E, van Doremalen N, Falzarano candidatewith-pandemic-adjuvant-
D, Munster VJ. SARS and MERS: recent system.
insights into emerging coronaviruses.
Nat Rev Microbiol. 2016;14: 523-34. 27. Novavax press release on 2/26/20.
http://ir.novavax.com/ news-releases/
16. Lessler J, Reich NG, Brookmeyer R,

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news-release-details/novavax-advances- 30. Arturo Casadevall and Liise-anne Corresponding Author:
developmentnovel-covid-19-vaccine. Pirofski .The convalescent sera option
for containing COVID-19. J Clin Invest. Dr. Manpreet Bhalla MD
28. Moderna press release on 2/24/2020. 2020;130(4):1545–1548. Dept. of Microbiology, National Institute of TB
https://investors. modernatx.com/news- and Respiratory Diseases, Sri Aurobindo Marg,
releases/news-release-details/moderna- 31. Liu W, Fontanet A, Zhang PH, Zhan L, Xin New Delhi - 110030, India
shipsmrna-vaccine-against-novel- ZT, Baril L, et al. Two-year prospective
coronavirus-mrna-1273. study of the humoral immune response
of patients with severe acute respiratory
29. Modjarrad, K.; Roberts, C. C; Mills, K. syndrome. J Infect Dis. 2006;193(6):792-
Tet al. Safety and immunogenicity of an 5.
anti-Middle East respiratory syndrome
coronavirus DNA vaccine: a phase 1, 32. Reichmuth AM, Oberli MA, Jaklenec A,
open-label, single-arm, doseescalation Langer R, Blankschtein D. mRNA vaccine
trial. Lancet Infect. Dis. 2019, 19 (9), delivery using lipid nanoparticles. Ther
1013-1022 Deliv. 2016;7(5):319-34.

46 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times

COVID-19 Special

Teleophthalmology and
Telemedicine: Getting Practice
Ready in the Changing Scenario

Jatinder Bali
MS (Ophth), STT (Pediatric Ophth) PGIMER, WHO Fellow VR, MBA (Operations Research)
NPC, North Delhi Municipal Corporation, Delhi

Telemedicine over telephone wires. In 1965 television and health-related services including
was used to facilitate consultations medical care, provider and patient
Telemedicine refers to the remote between specialists at a psychiatric education, health information services,
diagnosis and treatment of patients institute and general practitioners at and self- care via telecommunications
by means of telecommunications a state mental hospital. The term was and digital communication
technology. Telemedicine, coined in the used to describe the use of Information technologies.” Telemedicine is the
seventies means “healing at a distance.” and Communications Technology clinical service delivered by a medical
The World Health Organization to improve patient outcomes by practitioner while telehealth is a
adopted a broad description stating, increasing access to care and medical broader term for health and health
“The delivery of health-care services, information. Four elements common related services aimed at health
where distance is a critical factor, by to all definitions of telemedicine are preservation and health promotion in
all health-care professionals using giving clinical support, overcoming addition to telemedicine.
information and communications physical separation using various types
technologies for the exchange of of ICT to improve health outcomes. Teleophthalmology
valid information for diagnosis, Telemedicine has now been licensed Teleophthalmology is a branch of
treatment and prevention of disease by the National Medical Council to telemedicine delivering eye care
and injuries, research and evaluation, become a clinical service from 2020. using digital medical equipment and
and the continuing education of telecommunications technologies as
health-care workers, with the aim of Telehealth well as adjunctive activities. Patients
advancing the health of individuals NEJM Catalyst defines telehealth as can access eye specialists overcoming
and communities.” In 1906 Einthoven “The delivery and facilitation of health distances, ophthalmic diseases are
transmitted electrocardiograph data

Figure 1: Teleophthalmology Workflow Schematic Figure 2: Workflow from the Servers in both Synchronous and
Asynchronous Teleophthalmology
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DOS Times - Volume 25, Number 4, January-February 2020 47

COVID-19 Special

screened, diagnosed and monitored. It attempted to provide patient screening Telemedicine Practice Guidelines
may also be used for distance learning and appropriate referral to experts upto
though this is not explicitly laid down in recent times. Follow-up systems are On 25 March, 2020 new Telemedicine
the policy recently enunciated. Reports more recently in use. Practice Guidelines were issued for
from diabetic retinopathy, retinopathy telemedicine practice for Medical
of prematurity, macular degeneration, Background to the Guidelines Practitioners to be appended as
strabismus and adnexal eye diseases and Schedule V of the MCI Act Schedule V in the Indian Medical
seem to indicate beneficial use. Council Act 1956. These guidelines
Teleophthalmology was associated lay down the norms and standards
Teleophthalmology: with similar desired clinical outcomes for patients and practitioners using
Synchronous Versus to the traditional face-to-face system. telemedicine. For the purpose of the
Asynchronous However, there was a lot of fear and schedule telemedicine includes all
Teleophthalmology services can be uncertainty regarding the legitimacy channels of communication with the
synchronous or asynchronous: of telemedicine as the support of clear patient that leverage Information
guidelines and regulatory framework Technology platforms namely Voice,
yy Synchronous teleophthalmology was non-existent. An adverse judgment Audio, Text and Digital Dat.
refers to real-time interaction of the Hon’ble High Court of Bombay in
using standard telemedicine 2018 which was stayed in the Supreme The guidelines specifically explicitly
technologies like video-conferencing Court left the Medical Associations exclude the specifications for hardware
synchronously for consultations. crying for clear guidelines. The or software, infrastructure building
usual work flow of taking history of & maintenance, data management
yy Asynchronous teleophthalmology illness, physical examination, going systems, standards and interoperability
refers to transmission of captured through investigations and arriving of the platforms, digital technology
data for review at a later time. It at a diagnosis leads to a management use to conduct surgical or invasive
is also called “store-and-forward” strategy culminating in a prescription procedures remotely, research and
method wherein the ocular images for the treatment advised. The practice evaluation and continuing education of
captured and history elicited can be of telemedicine alters some or all parts health- care workers and consultations
reviewed at a different time at the of the work flow and hence it was easy to outside the territorial jurisdiction of
same or at different location. cry negligence for a litigant. Therefore, India.
all physician bodies wanted a clear
Video capture by web cameras or twain mandate in favor of a teleconsultation. Online Program in Telemedicine
acquire devices can be used for history. There were no legislations or guidelines
on the practice of telemedicine using The guidelines envisage an online
External eye can be examined by video, phone and internet based program in telemedicine which all
standard digital stills or video camera. platforms like apps and chat platforms. registered medical practitioners
The existing provisions under the Indian intending to provide online consultation
Anterior segment examination is done Medical Council Act, 1956, the Indian will need to complete within 3 years of
using slit lamp connected to a camera. Medical Council (Professional Conduct, its notification. In the interim period,
Etiquette and Ethics Regulation 2002), the principles mentioned in these
Posterior segment or retina can be Drugs &Cosmetics Act, 1940 and guidelines only will be followed. After
examined using a fundus camera. Rules 1945, Clinical Establishment that undergoing and qualifying the
(Registration and Regulation) Act, prescribed course will be essential prior
The image can be transferred over 2010, Information Technology Act, to practice of telemedicine.
dedicated network or the Internet to a 2000 and the Information Technology
physician for immediate examination, (Reasonable Security Practices and All modes of communication have
or for storage and later review. Ideally, Procedures and Sensitive Personal Data been included in the guidelines like
the image is should encrypted or or Information) Rules 2011 primarily Video (Telemedicine facility, Apps,
anonymized for transmission, to protect governed the practice of medicine and Video on chat platforms, Skype/
patient confidentiality especially so information technology. There were Face time etc.) Audio (Phone, VOIP,
in asynchronous transmission. Image grey areas and gaps in legislation. Apps etc.), Text Based: Telemedicine
capture, compression, enhancement, Uncertain rules posed a risk for both the chat based applications (specialized
edge-detection and other processing doctors and their patients. Some nations telemedicine smartphone Apps,
activities can be conducted before treated non-legislated guidelines as Websites, other internet-based
viewing. Image evaluation is done by professional norms to be followed by systems etc.), General messaging/ text/
the ophthalmologist or subspecialty medical practitioners in this regard. chat platforms (WhatsApp, Google
trained staff or artificial intelligence. Hangouts, Facebook Messenger etc.)
Most of the teleophthalmology services and Asynchronous (email/ Fax etc.)

48 DOS Times - Volume 25, Number 4, January-February 2020 www.dosonline.org/dos-times


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