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Published by manipal.mup, 2020-09-09 11:59:52

MUP's 190th publication - an evolving eBook "COVID-19: A Multidimensional Response"

MUP's 190th publication - an evolving eBook "COVID-19: A Multidimensional Response"

C VID-19

A Multidimensional Response

Edited by
N Udupa
Raviraja N S
Chiranjay Mukhopadhyay



C VID-19

A Multidimensional Response

Edited by
N Udupa
Raviraja N S
Chiranjay Mukhopadhyay

Manipal Universal Press (MUP) is a unit of the Manipal Academy of Higher
Education (MAHE) Trust and is committed to the dissemination of knowledge
generated within its vibrant academic environment and beyond.

Published by Manipal Universal Press (MUP)
5th Floor, Advanced Research Centre
Madhav Nagar, Manipal 576104 India
Tel: +91 820 2922954, 2922516
Website: mup.manipal.edu
E-mail: [email protected]

Title: COVID-19: A Multidimensional Response a
Editors: N Udupa, Raviraja N S and Chiranjay Mukhopadhyay
First Edition: September 2020

Cover page design: Jayashree M J, Manipal Universal Press, Manipal

The views and opinions expressed in this book are the editor’s and
contributor’s own and the publishers are not in any way liable for the same.

No part of this publication may be reproduced in any form without the prior
permission of the publisher in writing.

Foreword

Novel coronavirus disease (COVID-19) has been responsible for the current global
economic crisis as a result of its rapid spread across the world, swamping health systems
in its wake. Like with all new and emerging infections, there is a lot more to be known
about the causative organism, its pathogenicity, the natural history of the disease, host
factors, case management protocols, and immunoprophylaxis. It is in times like this
that an edited book with multiple authors drawn from various specialties stands out
as a beacon of light pushing back the dark shadows of ignorance and wrong beliefs
into oblivion. COVID-19 A Multidimensional Response jointly edited by Dr N Udupa, Dr
Chiranjay Mukhopadhyay, and Dr N S Raviraja is just what the doctor ordered!
It is all the more laudable that this eBook will continue to update and evolve as more and
more research findings get translated for human good and the mystery surrounding the
pandemic gets unravelled, strand by strand. I congratulate the individual contributors
to the chapters and the editors for this extraordinary effort in disseminating what is
known of date even as newer breakthroughs are happening by the hour, in the global
war against the virus.
Dr H Vinod Bhat
Executive Vice President
Manipal Academy of Higher Education
Manipal – 576 104, India

iii



Preface

‘If winter comes, can spring be far behind?’
Amid the cataclysmic COVID-19 pandemic that is ravaging communities and
cratering economies, we can take solace in Percy Bysshe Shelley’s redemptive
vision for the “Pestilence-stricken multitudes” in his acclaimed ‘Ode to the West
Wind’. Faced with a bleak, uncertain future, where “social distancing” might well
inure us to the plight of the poor and the most vulnerable, where isolationism
is running riot, this pandemic has quickly taken the form of the west wind that
is described as the ‘Wild Spirit, which art moving everywhere; destroyer and
preserver’. However, we must fall back on our ingenuity and resilience to start
the process of recuperation and renewal.
As of today, there are 15,296,926 confirmed cases of COVID-19 with 628,903
deaths reported from 216 countries, areas, or territories (24 July 2020; 04:30
GMT; WHO). In India, a total of 1,58,49,068 cumulative samples have been
tested (25 July 2020, 08:00 IST; MoHFW, GoI) in 1276 laboratories across the
country, which includes 384 private settings. The total number of confirmed cases
is 13,36,861 out of which 4,56,071 are active cases; 8,49,431 have been cured or
discharged and 31,358 have succumbed to the disease (25 July 2020, 08:00 IST;
MoHFW, GoI). Our state Karnataka is, unfortunately, one of the worst affected
states in India with a total confirmed case count of 85,870 including 52,799
active cases; 31,347 cured/discharged/migrated and 1,724 deaths (25 July 2020,
08:00 IST; MoHFW, GoI).
As the global picture of chaos and unmitigated suffering unfolds before our
eyes, the Yeatsian vision comes to mind, irremediably, ‘Things fall apart, the
centre cannot hold’. William Butler Yeats penned ‘The Second Coming’ against
the backdrop of the catastrophic First World War. Incidentally, his wife afflicted
by the Spanish flu of 1918-19, just had a brush with death. The superhuman
efforts of the COVID warriors at the forefront to alleviate the tribulations

v

COVID-19 A Multidimensional Response

of the common man are a testament to the eternal promise enshrined in the
Bhagavad Gita that teaches us that whenever the delicate equilibrium of the
world is disrupted and anarchy is unleashed, it is time to lead from the front; it
is the time when utmost efforts have to be undertaken to restore equilibrium
and salvage the situation. In this context, ‘COVID-19 A Multidimensional
Response’ is an evolving e-book published by Manipal Universal Press with the
initiative and editorship of Dr N Udupa, Dr Raviraja N S and Dr Chiranjay
Mukhopadhyay, with excellent scientific contribution of experts in the field. The
book is a redemptive exercise in creating awareness with facts and figures about
the dreaded disease in these troubled times.
‘COVID-19 A Multidimensional Response’ informs us about the history
of the disease and origin of the organism; more so, it offers valuable insights
about pathogenicity, host factors, laboratory diagnosis, management,
immunoprophylaxis, newer advancements in research, innovation, and
implementation. The introduction by Dr Raviraja N S and Dr N Udupa has
briefly touched upon the emergence of COVID-19 pandemic along with the
history of previous pandemics since 1918 with a valid apprehension ‘that enough
efforts have not been taken to control or contain this disease’. In the following
chapters, scientific data and information elaborated upon by erudite experts lend
a comprehensive perspective to dispel the gloom surrounding the pandemic.
The interaction between the virus and the individual’s immune system is
dependent on multiple viral factors such as virus type, genomic mutations, viral
load, and viability of the virus in vitro as well as various human host factors such
as genetics (such as HLA genes), age, gender, nutritional status, neuroendocrine-
immune regulation, and physical status. Overall, the occurrence and progression
of the disease depend on the extent of exposure to the virus, the duration,
and severity of the disease, host immune response, and the propensity to
reinfection. Dr Sathishkumar Arumugam and his fellow researchers describe
the molecular anatomy of SARS-CoV-2, one of the human coronaviruses that
cause severe pneumonia. The lifecycle of SARS-CoV-2 in host cells and immune
dysregulation inside the human body is elucidated by Dr Chandrashekar U K.
The medical team engaged in the treatment of COVID-19 patients in Kasturba
Hospital, Manipal, and Dr TMA Pai Hospital, Udupi includes Dr Shashikiran
Umakanth, Dr Muralidhar Varma, Dr Nandakrishna, Dr Kavitha Saravu, and
Dr Kiran Chunduru. They discuss the clinical manifestations, risk factors, co-
morbidities, and management of COVID-19 based on various national and
international guidelines while keeping in mind patient safety. In the past few
months, the COVID-19 outbreak has underlined the importance of microbiology

vi

COVID-19 A Multidimensional Response

laboratories in providing integrated, rapid, and accurate diagnosis and monitoring
of SARS-CoV-2. Dr Puneet Bhatt and Dr Chiranjay Mukhopadhyay emphasize
the importance of optimal laboratory diagnosis of SARS-CoV-2 and describe
the evolution, development, and implementation of a battery of sophisticated
laboratory tests in different clinical scenarios while touching upon the high
throughput and quality performance of the dedicated COVID laboratory in
MAHE.
Apart from regular patient management and laboratory diagnosis, there are other
important supportive functions related to patient care. Plasma therapy, as an
essential management technique, has been dwelt upon by Dr Shamee Shastry. Dr
Raviraja N S focuses on the relevant properties of mesenchymal stromal cells
along with the details of clinical trials underway to establish the safety and
efficacy of cell therapy in COVID-19 patients. Contributions in specialized
areas include the role of nanotechnology in management by Dr S Mutalik and
colleagues, management of pregnant women by Dr Shashikala Bhat, dental care
amidst the pandemic by Dr Aparna, safe management of endotracheal airway
by Dr Suresh Pillai and Dr Rohit Singh, risks and challenges of surgery by Dr
Rajesh Nair and Dr Girish Menon, and eye care during the COVID-19 pandemic
by Dr Manali Hazarika. In parallel perspectives, Dr Basavaraj highlights the
contribution of Ayurveda and other traditional methods for treating COVID-19
infected patients. Dr Atulya has contributed her knowledge about COVID-19 in
the veterinary world, and Dr Shridhar Dwivedi has thrown light on the ethical
dimensions of pandemic COVID-19 disease.
The book encompasses various multidimensional aspects related to relevant
research, drug discovery, policy, and public health in the context of the
COVID-19 pandemic. Dr Manjunatha M V from NIMHANS discusses the
progress and challenges of vaccine development. Dr Prashantha Naik elaborates
on the importance of telemedicine in connecting patients and doctors. The
topic of gut microbiota and infections is delineated by Dr M K Unnikrishnan
and his colleagues, to enlighten the readers on patterns in susceptibility and
vulnerability to SARS-CoV-2. Dr Yogendra Nayak deliberates on medicinal
chemists’ contribution to new antiviral drug discovery and development to fight
the pandemic. Dr Praveen Hugar from the Centre of Biocultural Studies explains
social distancing norms from an anthropological perspective.
WHO Director-General, Dr Tedros Adhanom Ghebreyesus commented that the
world is learning the hard way that health is not a luxury; it is the cornerstone
of security, stability, and prosperity (22 June 2020). Hence, it is imperative that

vii

COVID-19 A Multidimensional Response

countries not only respond with urgency but also invest in strong domestic health
systems and global health security because of the rapidly proliferating pandemic.
Keeping this in mind, Dr Piya Paul Mudgal and her team make the valid point
that social distancing, sanitization, and hygiene measures are going to be ‘the
vaccines’ to contain human to human transmission of COVID-19 until the time,
a safe and efficacious vaccine is developed. The million-dollar question is: When
are we going to get the vaccine? Dr Anitha J and her colleagues address the matter
of community spread and prevention and highlight the role of government
advisories meant for infection control and prevention in the community. Their
pertinent question ‘if the number of cases rise, has India efficiently utilized the
lockdown time to build the healthcare, quarantine, and testing facility?’ will be
answered in the days to come. Adding to this, Dr Helmut Brand and Dr Sanjay
Pattanshetty discuss health and foreign policy.
Some paradoxes continue to flummox us - What accounts for the huge differences
in death tolls between the most developed countries and developing countries
with relatively limited resources? Britain, Italy, and Spain have seen numerous
deaths, while Greece, Thailand, Vietnam, Cambodia, and Mongolia have scripted
their unique success stories. Economic powerhouse Germany has managed the
pandemic better than its neighbours. Also, critical questions remain: What role
do factors such as heat, humidity, genetic differences, immunity, or demographics
play? What role do cultural factors play? In a vast and populous country like India,
how can we contain the community spread effectively? How can one pinpoint
the cause of death in COVID-19 patients with co-morbidities or cases of mixed
infections? Will high antibody titers of the community be protective enough to
save the elderly? Detailed research in times to come might throw some light on
these vexed issues.
Leading Infectious Disease expert, Dr Anthony Fauci recently opined that
the outbreak in the US has not “even begun to see the end”. However, there
is cautious optimism that scientists will be able to create at least one safe and
effective vaccine by the end of the year or early 2021. While the world waits
with bated breath, Sarah Gilbert and Andrew Pollard from Oxford Vaccine trial
team, came out with the welcome news on 20th July 2020 that the pandemic
of SARS-CoV-2 might be curtailed by vaccination, as their vaccine candidate,
‘ChAdOx1 nCoV-19’ showed increased humoral and cellular immune response.
A great breakthrough indeed!
Let us revisit Shelley’s famed ‘Ode to the West Wind’ where the poet-seer asks
defiantly: ‘O Wind, if winter comes, can spring be far behind?’ In the context

viii

COVID-19 A Multidimensional Response

of these pestilential times, if there is but a sense of well-being illumined by
knowledge, can there be any hurdles to our vanquishing the illness and celebrating
the joyous arrival of spring? Like the seeds sown deep within the ground, once
forgotten, will give rise to a generation stronger than ever before. The west wind,
just like the pandemic, is a chance for a clean slate, a driving force for change
and rejuvenation in the human and natural world. We must reaffirm our faith in
the vision of ‘Kavi Guru’ Rabindranath Tagore for a new and awakened India,
a vision fortified by our valiant fight for freedom from colonial shackles that
remains as relevant as ever, during our battle for survival against the COVID-19
pandemic. If the mind is without fear, the head is held high, and knowledge is
free, our tireless striving will stretch its arms towards the perfect vision of well-
being and will lead us towards ever-widening thought and action.
‘COVID-19 A Multidimensional Response’ is the reflection of our vision,
thought and action occasioned by the pandemic.


ix



Content

1 COVID-19 an Uncalled-for Pandemic – An Introduction 1

2 Epidemiology of COVID- 19 5

3 Community Spread and Public Health Prevention 41

4 Biology of Severe Acute Respiratory Syndrome 66
Coronavirus-2

5 COVID-19 Laboratory Diagnosis: Challenges & 90
Conundrums

6 Pathogenesis and Pathophysiology of COVID-19 124

7 Clinical Manifestations and Diagnosis of COVID-19 137

8 COVID 19– Risk factors and comorbidities 150

9 Clinical and Therapeutic Management in COVID-19 158

10 Convalescent Plasma Therapy for COVID-19 Patients 188

11 Mesenchymal Stromal Cell Therapy for Novel Corona 198
Virus Disease 2019 (COVID-19) Patients

12 Gut microbiota and infections: Patterns in Susceptibility 210
and Vulnerability to Corona Virus

13 COVID-19: Drug Discovery and Development 223

14 Vaccine Development Against SARS-CoV2: The Road 238
Blocks and the Way Ahead

15 Role of Nanotechnology in the Management of COVID 19 255

xi

COVID-19 A Multidimensional Response 266
274
16 Novel Coronavirus Impacts – Role of Telemedicine 297
17 Pregnancy, Childbirth And Puerperium in the 310
318
COVID Era and Beyond 337
18 Dentist Care for COVID-19 Patients 350
19 Safe Management of Covid-19 Patients – An ENT Airway 358
368
Perspective 379
20 Eye Care Services In The COVID Era : Forging A New
392
Destiny 409
21 Surgery During COVID-19 – Risks, Challenges and the

Way Forward
22 Health in Foreign Policy in the Context of COVID-19
23 Role of Ayurveda for Treating COVID 19 Infected

Patients
24 Covid-19: Lessons from the Veterinary World
25 Ethical Dimensions of COVID 19 Pandemic
26 Non Pharmacological Interventions for prevention of

COVID-19
27 An Overview of Multisystem Inflammatory Syndrome in

Children
28 Social Distancing Laden with Stigma: An Anthropological

Insight
29 We Tried Everything, But Was It A Miss or Hit;

Management of Deadly COVID-19 -An Overview
30 Pediatric Care for children affected by COVID 19 viral

disease

xii

Dr N Udupa, M Pharm PhD is Professor, Department of Pharmaceutics and Former Principal,
Manipal College of Pharmaceutical Sciences, MAHE, Manipal, Karnataka, India. Dr N Udupa
received his PhD in 1987 from Banaras Hindu University, Varanasi, India. After serving in Pharma
Industry for eight years, he has been working in academics for the last 30 years. He served as
Director- Research (Health Sciences), Manipal Academy of Higher Education (MAHE), Manipal
for seven years. Dr N Udupa is a prolific researcher and author with more than 500 research
and review articles, over 400 presentations in national and international conferences. He has
authored about 15 books and has been on the editorial boards and advisory bodies of several
reputed journals. He is a life member of some 20 associations and societies and has nine Indian
patents to his credit. He has won many awards for his outstanding contributions in Pharmaceutical
Research and Education and the most recent awards include 43rd Annual Aryabhata International
Award 2017 for his contribution to the field of Medicine from Aryabhata Cultural Organization
(Regd.) and Life Time Achievement Award 2019 by Association of Pharmaceutical Teachers of
India (APTI), India. He has served as Convener-Scientific Services of the Indian Pharmaceutical
Congress Association from 2010 to 2012.

Dr Raviraja N Seetharam is an outstanding scientist and business development professional hav-
ing more than 25 years of research experience in diverse areas of biology/biopharma. He ob-
tained a master’s degree in Biosciences and secured a PhD in Biosciences (Microbiology), both
from Mangalore University. Later he pursued an MBA in Operations Management. He pursued
postdoctoral training at Mount Allison University, Canada, and Albert Einstein College of Medi-
cine, New York, USA. Later he was promoted as faculty at Albert Einstein College of Medicine
and Montefiore Medical Centre, New York. Dr Ravi joined MEMG group company, Stempeutics
Research, in 2010 and worked there for ten years as centre head. Recently, he joined MAHE as the
Director of Corporate Relations.

Dr Ravi hails from Neelavara village of Udupi district. He is married to Purnima, who is a software
engineer and an artist. He is blessed with a daughter and a son who are pursuing their schooling.

Dr Chiranjay Mukhopadhyay MD, PDCC (ID), PhD is a Clinical Microbiologist, Clinician Scientist,
and Infectious Diseases Specialist researching tropical bacterial infections with a special interest in
Melioidosis and global infection including Antimicrobial Resistance and Diagnostic Stewardship.

Dr Mukhopadhyay is the Professor in the Department of Microbiology, Associate Dean of Kasturba
Medical College, and Director of Manipal Institute of Virology, MAHE. He holds Dr TMA Pai Endowment
Chair on ‘Emerging Tropical Bacterial Diseases’ and Centre for Emerging and Tropical Diseases. He is
also the Chief of Department of Infection Control and Management, Kasturba Hospital. He was the
Chairman of the Hospital Infection Control Committee, Coordinator of Research Cell, and Head of the
Department of Microbiology.

Dr Mukhopadhyay is known internationally for his extensive research work on the emerging infectious
disease Melioidosis. He is the lead member of the International Melioidosis Network and leader
of the Indian Melioidosis Research Forum. He has more than 150 publications, multiple national
and international grants, prestigious awards from the Government of India, and distinguished
collaborations across the world.

COVID-19 disease is caused by the SARS-CoV-2 virus, first detected in
November-December 2019 in Wuhan, China. Thus far, more than 7 million
people have been infected with the novel coronavirus across the globe,
and the count is increasing with every passing day. Even though it causes
severe respiratory problems, the majority of patients show mild symptoms,
and pathogenesis is under investigation. Although several drugs are being
developed and many of them are undergoing clinical trials, currently there
are no approved drugs/vaccines to cure this disease. Personal hygiene and
social distancing are important means to prevent the spread of this disease.
With the advancements in scientific research, humankind is hoping to
find a potent drug/vaccine for this disease at the earliest. The health care
professionals and scientific community are at their maximum in combating
this viral infection. In this book, an attempt is made to compile various aspects
of COVID-19 in a single platform, which include aetiology, epidemiology,
its clinical manifestations, diagnosis, pathological, clinical and therapeutic
facets, comorbidities, risk factors, and the essential precautionary measures.
This book comprises around 29 chapters contributed by various experts
from research and clinical backgrounds.

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