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The following information was supplied
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available in the Supplemental Files.
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LETTER TO THE EDITOR REGARDING “NEUROSURGERY SERVICES IN DR. SARDJITO
GENERAL HOSPITAL, YOGYAKARTA, INDONESIA, DURING THE COVID-19 PANDEMIC:

EXPERIENCE FROM A DEVELOPING COUNTRY”

Nishant Goyal1, JitenderChaturvedi1, P. Prarthana Chandra2, Amol Raheja3

From the 1Department of Neurosurgery, All India Institute of Medical Sciences, Rishikesh; 2Department of Neurosurgery,
Hamdard Institute of Medical Sciences & Research, New Delhi; and 3Department of Neurosurgery, All India Institute of
Medical Sciences, New Delhi, India To whom correspondence should be addressed: Nishant Goyal, M.Ch.
[E-mail: [email protected]] https://doi.org/10.1016/j.wneu.2020.10.117.

Letter: week decreased from 16 to roughly 9, during
We read with great interest the article by phase 2 of the pandemic. According to Manu-
Manusubroto et al,1 “Neurosurgery services in subroto et al,1 the decrease in elective
Dr. Sardjito General Hospital, Yogyakarta, procedures could be because of reduced spots
Indonesia, during the COVID-19 pandemic: in the ICU for neurosurgery patients as most
experi- ence from a developing country.” The beds were reserved for COVID-19 patients and
first patient with coronavi- rus disease 2019 poor availability of personal protective
(COVID-19) from Indonesia was reported on equipment (PPE) in the early phase of
March 2, 2020. As a response to the pandemic, breakdown. The improved PPE availability
the Indonesian Ministry of Health selected increased the safety of the procedure, which
several hospitals as the referral hospitals to explains the increased number of elective
handle COVID-19 cases. The authors’ surgical procedures after the second week of
institution, Dr. Sardijito General Hospital, was April 2020.
one of these referral hospitals due to the
availability of full-range intensive care unit (ICU) India is a lower middle-income country as
and isolation wards. In this article, the authors per the World Bank categorization.2 During
share their experience during the COVID-19 the lockdown, hospitals were prepared for the
pandemic in the special region of Yogyakarta in incoming tsunami of patients. Our hospital is
Indonesia and discuss their institute protocol for the largest referral tertiary care hospital in the
preoperative preparation and the impact of the Himalayan state of Uttarakhand, catering to a
pandemic on the neurosurgical workload in their population of over \11 million. Our response
hospital.1 to the pandemic was different from that of
Manusubroto’s institute in many aspects. In our
In the pre COVID-19 era, the Dr. Sardijito hospital, dedicated areas were defined in our
General Hospital had a long list of patients hospital as COVID-19 areas for COVID-19
waiting to undergo surgery and even tumor confirmed and COVID-19 suspect patients.
patients had to wait for up to 6 months for These had dedicated staff, posted there on a
operations. Cancellation or further rota- tion basis from various departments.3
postponement of these surgeries, as per There was no rule for hospital zoning in
recommendations by various bodies including Manusubroto’s institution.1 Initially, we adopted
Indonesian Society of Neurological Surgeons, the policy of postponement of elective cases.
would have resulted in further lengthening of Once the hospital had adequate testing facilities,
waiting periods and would have led to worsening PPE, and ICU equipment, the intake of elective
of patients’ conditions. Therefore they decided surgical patients was increased gradually. In our
against further postponement of surgeries during opinion, it is our duty to keep the elective
the pandemic. Despite this, the number of neurosurgical work going as well as to
emergency operations per week decreased from protect our health care workers against
4 to 2.4 and the number of elective surgeries per

contracting COVID-19 infection.4-7 During the result among 284 patients admitted under
period of lockdown in India (March 25 to May 31, neurosurgery.9 In our opinion, this COVID-19
2020), our surgical volume decreased from 111 testing policy along with strict
to 53, a decline of 52.3% while the number of quarantine/isolation rules have allowed us to
emergent surgeries remained the same (47 restrict the infection rate in our health care
cases), when compared with the same duration workers to an acceptable level, thus allowing
in 2019.8-10 Thus we were able to continue continued functioning in the hospital.3,9,31,32
providing emergency services even during the To date, we have had only 1 attending
lockdown, while most of the “nonemergent” neurosurgeon out of 8 testing positive for
cases had been postponed/cancelled. Similarly, COVID-19 and none of the 10 residents have
a large number of elective surgeries have been contracted COVID-19 infection.3
cancelled/postponed in hospitals across the
world as a response to the COVID-19 By mid-April 2020, the testing rate in Indonesia
pandemic.11-28 We have strictly regulated our was 130 tests per million population, one of the
outpatient department (OPD), resulting in lowest in the world. The shortage in the testing
substantial decline in the outpatient volumes.29 facilities might be the reason for the institute
Our policy has been to continue the emergent COVID- 19 testing protocol, described by
operations even during the peak of the lockdown Manusubroto et al.1 They seemed to rely
in the country as shown earlier. Still, there has heavily on COVID-19 related history;
been a decrease in the number of road traffic laboratory tests (neutrophil-to-lymphocyte ratio,
accident cases8 similar to the observations of C-reactive protein); and chest radiography.
Manusubroto et al.1 This may be attributed to Few patients underwent chest computed
decreased traffic on roads during the lockdown tomography (CT) and rapid test, measuring IgG
period. and IgM antibodies against COVID-19. In case
of a positive rapid test, they did a real-time
At our institute, we test all patients being polymerase chain reaction analysis. With this
admitted to the ward and test them again protocol of COVID-19 screening, there is a high
before surgery.3,8 Thus we consider every chance of missing asymptomatic individuals with
patient as a “suspected” COVID-19 patient. The COVID-19 infection. It would be interesting to
highly infective nature of the virus and high rate know if they are still following the same protocol
of asymptomatic/presymptomati carriers justifies at Dr. Sardijito General Hospital and how many
this policy. Doing 2 tests before surgery further COVID-19 infections have been detected by
reduces the false-negative result from 29% to them in patients and among their health care
8.4% as the sensi- tivity of the tests available is workers. In addition, we would be interested to
only 71%.30 If an emergent surgery does not know if they have noticed any increased
allow preoperative COVID-19 testing, the mortality in their patients, as patients with
patient is operated in dedicated COVID-19 perioperative COVID-19 infections have an
operation room with necessary COVID-19 increased rate of mortality (23.6%) and
precautions. Such a patient undergoes COVID- pulmonary infections (51.2%).9,30 An increase
19 testing postoperatively and is shifted to a non in mortality compared with the pre—COVID-
COVID-19 area if he or she tests negative. 19 era could indicate undetected asymptomatic
Between April and August 2020, we had COVID-19 infections in their patients.
detected 6 patients with positive a COVID-19

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THE IMPACT OF COVID-19 PANDEMIC ON PEDIATRIC SURGERY PRACTICE: A
CROSS-SECTIONAL STUDY

Gunadi, Yofizal Idham, Vincentia Meta Widya Paramita, Aditya Rifqi Fauzi, Andi Dwihantoro, Akhmad Makhmudi

Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas
Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta 55281, Indonesia

ABSTRACT
Background: Since the COVID-19 pandemic was declared by the World Health Organization on March
11, 2020, routine clinical practices were affected, including pediatric surgery services. We aimed to
compare pediatric surgery practices, including the number and types of surgery, either elective or
emergency surgeries and outpatient services, before the outbreak and during the COVID-19 pandemic
in our institution.
Material and methods: We retrospectively compared pediatric surgery practices, including elective and
emergency surgeries, and outpatient services between the previous one-year period (March 2019–
February 2020), the last three months of that period (December 2019–February 2020) before the
outbreak, and the three months (March–May 2020) during the COVID-19 pandemic in our hospital.
Results: The frequency of elective surgeries during the pandemic was lower than during the last three
months before the outbreak: 61 vs. 18 (~3-fold), 19 vs. 13 (~1.5-fold), 19 vs. 5 (~4-fold), and 30 vs. 15
(~2-fold) for digestive, neonate, urology and oncology cases, respectively. No laparoscopic procedures
were performed during the pandemic compared with the one-year period before the outbreak (0 vs. 16
cases). The frequency of all emergency pediatric procedures before and during the COVID-19
pandemic was similar (29 vs. 20 cases, respectively). Moreover, a declining trend was also clearly
apparent in the outpatient services during the pandemic compared with before the outbreak, both in the
new and the established patients.
Conclusions: The pediatric surgery practices in our institution have been severely affected by the
COVID-19 pandemic, including elective and outpatient services. This setback needs a comprehensive
strategy to avoid morbidity from the neglected elective surgeries during the pandemic, including the
proper comparison between the real risk of COVID-19 cross-infection and the benefits of elective
procedures.

Keyword: COVID-19 pandemic, Elective and emergency surgeries Indonesia, Outbreak, Outpatient services, Pediatric
surgery practices

1. INTRODUCTION patients with COVID-19 in Yogyakarta was
The World Health Organization (WHO) 1557 cases and 46 deaths [3]. Moreover,
declared COVID-19 as a worldwide instead of the lockdown, our provincial
pandemic on March 11, 2020 [1]. The first government applied the emer- gency
two cases of COVID-19 were identified in response for the COVID-19 policy [3]. Our
Indonesia on March 2, 2020 [2], while the hospital is a tertiary referral hospital that
first case in the Special Region of primarily serves urban and rural
Yogyakarta Province was announced on populations from the Special Region of
March 15, 2020 [3]. The total population of Yogyakarta Province, Indonesia [5–7].
Yogyakarta Province in the beginning of Accordingly, our hospital was assigned by
June 2020 is 3,882,288, while the pediatric the Ministry of Health of the Republic of
population is 997,159 [4]. Eventually, the Indonesia as a referral hospital for the
Special Region of Yogyakarta was indi- management of patients with COVID-19 in
cated to have local transmission of COVID- Yogyakarta Province during the pandemic
19 on April 22, 2020. Until September 6, by a public emergency edict. Recently,
2020, the total number of confirmed several studies showed that the COVID-19

pandemic affected pediatric surgery [8,9] but did not specifically analyze the
services[8–11]; however, the reports number and type of surgeries affected by
described the effect of the pandemic on the outbreak and
pediatric surgery practice in general

only provided editorial comments [10] or services into two additional categories:
perspectives [11]. Therefore, we aimed to laparoscopic vs. nonlaparoscopic surgery.
compare pediatric surgery practices, The Medical and Health Research
including the number and types of surgery, Committee of our institution approved this
either elective or emergency surgeries and study (KE/FK/0653/EC/2020). Written
outpatient services, before the outbreak informed consent was obtained from all
and during the COVID-19 pandemic in our parents of the pediatric patients who
institution. visited/admitted to our hospital during the
previous one-year period (March2019 –
2. Material and Methods February 2020) before the outbreak and the
2.1 Patient Samples three months (March– May 2020) during
the COVID-19 pandemic. The work has
We retrospectively compared the pediatric been re- ported in line with the
surgery practices elective and emergency STROCSS criteria [12].
surgeries and outpatient services between
the previous one-year period (March 2019– 2.2 COVID-19 Assessment
February 2020), the last three months of The diagnosis of COVID-19 using real-time
that period (December 2019–February polymerase chain reac- tion (RT-PCR) in
2020) before the outbreak and the three the Special Region of Yogyakarta Province
months (March–May 2020) during the was con- ducted in five laboratories,
COVID-19 pandemic in our hospital. We including our institution.
chose the last three months before the
outbreak (December 2019 – February 3. RESULTS
2020) to compare the pediatric surgical 3.1 Elective surgeries
burden between the first three months of
the pandemic and just before the outbreak First, we compared the frequency and
in our institution. Moreover, in Indonesia, types of elective surgeries performed in our
there are no seasonal variations, and the all hospital. There was a significant decline in
school schedule from elementary until the number of elective surgeries in each
undergraduate school is started between type of surgery (Table 1 and Fig. 1). The
July and August every year. frequency of elective surgeries during the
We classified pediatric surgery patients’ pandemic was lower than those of the last
services in our hospital into four categories: three months before the outbreak: 61 vs. 18
digestive, neonates, urology and oncology. (~3-fold), 19 vs. 13 (~1.5-fold), 19 vs. 5 (~4-
Moreover, we also defined those patients’ fold), and 30 vs. 15 (~2-fold) for digestive,

neonate, urology and oncology cases, malformation (1vs.9), chordectomy and
respectively (Table 1). Subsequently, we urethroplasty (1 vs. 5) and excision and
compared the frequency of each surgical bleomycin sclerotherapy for lymphangioma
procedure of elective services according to (5 vs.12) (Table 2).
the disease (Table 2). Almost all surgical Moreover, none of the laparoscopic
procedures during the pandemic were procedures were performed during the
fewer than the last three months before the pandemic compared to the previous one
outbreak, such as pull-through for year before the outbreak (0 vs. 16 cases:
Hirschsprung disease (3vs.15 cases), laparoscopic anoplasty = 3, laparoscopic
anoplasty and stoma closure for anorectal

Fig. 1. Comparison of elective pediatric surgeries performed in our institution before and during the
COVID-19 pandemic from December 2019 to May 2020. The frequency of all elective surgeries during
the pandemic was approximately 1.5 – 4-fold lower than those of the last three months before the
outbreak, including digestive, neonate, urology and oncology cases.

appendectomy = 3, laparoscopic 3.2 Emergency Procedures
orchiopexy = 4, laparoscopic unroof- ing of The frequency of emergency pediatric
splenic cyst = 1, laparoscopic-assisted surgical procedures before and during the
transanal endorectal pull- through = 2, COVID-19 pandemic was similar (29 vs. 20
laparoscopic high ligation = 1, and cases, respectively) (Table 3 and Fig. 2).
laparoscopic chole- cystectomy = 2). Next, we compared the frequency of each
surgical procedure of emergency services
according to the disease (Table 4). Almost

all emergency procedures before and showed a declining trend in neonates and
during the outbreak were similar, including oncology cases as well, with approximately
laparotomy appendectomy (6 vs. 4 cases), 1.5 – 2-fold fewer of these surgical
laparotomy milking procedure for procedures performed during the outbreak
intussusception (3 vs. 2 cases), and compared to before the pandemic (Table
colostomy for ano rectal malformation (2 vs. 2). This difference might be related to the
4 cases). fact that many families were worried about
whether it is safe to bring their children to
3.3 Outpatient services the hospital [9,14]. Although still considered
A declining trend was clearly apparent in controversial, we avoided laparoscopic
the outpatients’ services during the procedures during the pandemic to
pandemic compared with before the minimize the risk of aerosol transmission,
COVID-19 outbreak (Fig. 3A). Next, we as recommended by a previous report [15].
divided the outpatient services into new and Several methods have been proposed to
estab lished patients. Similar decreasing reduce the risk of cross-infection of COVID-
trends were obtained (Fig. 3B). 4. 19 during laparoscopic surgery: a) properly
decreasing the pressure of
4. DISCUSSION pneumoperitoneum; 2) avoiding the
We are able to show the effect of the leakage of gas from the trocar places; and
COVID-19 pandemic on decreasing the 3) gradually eliminating the aerosol via
number of pediatric surgical services in our aspirator after pneumoperitoneum [8].
institution, including elective and outpatient While our data showed declining trends in
services. These declining trends might be the elective surgical cases, the number of
related to the fact that all non-urgent emergency procedures did not appear to be
elective surgeries were temporarily significantly affected by the pandemic
suspended to ensure adequate hospital (Table 3). Our findings were similar to those
capacity to respond to the rapid spikes in of a previous report [9]. The number of
COVID-19 cases and decrease the risk of laparotomies performed for perforated
nosocomial transmission of COVID-19 appendicitis was similar before and during
infection. This strictly enforced policy was the pandemic (Table 3). In the USA, some
applied in almost all hospitals around the hospitals applied non-operative
world that were affected by the COVID-19 management for acute appendicitis, while
pandemic, including Australia [13], Finland other institutions continued to perform
and other Nordic countries and the United routine appendectomies [9]. Notably, no
States of America (USA) [9]. Moreover, the consensus has been established yet for the
relative lack of medical resources due to management of acute appendicitis during
the increasing number of patients with the COVID-19 pandemic. The choice
COVID-19 and the accompanying between conservative treatment and
economic downturn might also influence emergency surgical procedures with
the management decisions for pediatric appendectomy depends on the resources
surgery patients [8]. It should be noted that of each institution [9]. Our government has
delay of surgery for “time-sensitive” and applied restrictions on travel between
urgent diseases in children might affect provinces and/or cities in the earlier period
their growth, development, and quality of of the pandemic. Moreover, many families
life [8]. Therefore, we still performed were worried about whether it is safe to
elective surgeries for neonates and bring their children to
oncology cases. However, our findings

Fig. 2. Comparison of emergency pediatric surgeries conducted in our hospital before and during the
COVID-19 pandemic from December 2019 to May 2020.

the hospital, as noted by other reports services [16]. Accordingly, our pediatric
[9,14]. These facts might affect our results. surgery division in our hospital has tried to
Since the COVID-19 pandemic might end in normalize our services as follows: each
months, on June 1, 2020, our government week, one major surgery will be performed
announced a “new normal” policy to start every Tuesday, while two or three minor
implement ing adaptations of the public’s procedures will be scheduled and
daily activities to the COVID-19 pandemic, conducted on another working day. These
including updated changes in health care policies started June 8, 2020. Furthermore,

it has been recommended that all pediatric 5. CONCLUSIONS
surgeons should contact each other and The pediatric surgery practices in our
benefit from the positive, synergistic ef fects institution have been severely affected by
from sharing experiences and best the COVID-19 pandemic, including elective
practices during the pandemic with other and outpatient services.
colleagues [9]. Although several studies
showed that the COVID-19 pandemic Conflicts Of Interest
affected pediatric surgery services [8–11], No potential conflict of interest relevant to
our study has the following strengths: we this article was reported.
specifically analyzed the number and type
of surgeries affected by the outbreak (vs. Funding
described the effect of the pandemic on This study was funded by Indonesian
pediatric surgery practice in general [8,9] Ministry of Research and
vs. editorial comments [10] vs. perspectives Technology/National Agency for Research
[11]). Notably, our findings are limited to and Innovation.
one pediatric surgical center. These facts
should be considered during the Consent
interpre tation of our study. Our findings Written informed consent was obtained
suggest that a comprehensive strategy is from the parents before joining the study. A
needed either by the hospital or health copy of the written consent is available for
district or regional pediatric surgeon review by the Editor-in-Chief of this journal
associa tion to avoid morbidity from on request.
neglected elective surgeries during the
pandemic, including the proper comparison Provenance And Peer Review
between the real risk of COVID-19 cross- Not commissioned, externally peer
infection and the benefits of elective reviewed.
procedures.

Fig. 3. Comparison of outpatient services in our hospital before and during the COVID-19
pandemic from March 2019 to May 2020. The frequency of all outpatients’ (A) and new and
established outpatients’ (B) services during the pandemic was lower than those of the previous
year before the outbreak.

Acknowledgement Heliyon 6 (2020), e03435.
We extend our thanks to all attending
physicians and nurses who have taken care 8. Y. Zhou, H. Xu, L. Li, X. Ren, Management
of our patients. We are also thankful to the
English editing service staff at our for patients with pediatric surgical disease
institution for checking the manuscript
grammar. Appendix A. Supplementary data during the COVID-19 epidemic, Pediatr.
Supplementary data to this article can be
found online at https://doi. Surg. Int. 36 (2020) 751–752.
org/10.1016/j.amsu.2020.09.020.
9. M. Davenport, M.P. Pakarinen, P. Tam, P.

Laje, G.W. Holcomb, From the editors: the

COVID-19 crisis and its implications for

pediatric surgeons, J. Pediatr. Surg. (2020),

https://doi.org/10.1016/j.jpedsurg.2020.04.0

09.

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Accessed on September 6, 2020. STROCSS Group, The STROCSS 2019

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/2017/08/02/32/jumlah-penduduk-menurut- (2019) 156–165.

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5. Kalim AS. Gunadi, N.Y.P. Budi, H.M. Hafiq, vid-19/Pages/elective-outpatient.aspx

A. Maharani, M. Febrianti, F. Ryantono, D. Accessed on June 6, 2020.

Yulianda, K. Iskandar, J.A. Veltman, 14. Children Hospital Los Angeles.

Aberrant expressions and variant screening https://www.chla.org/blog/hospital-

of SEMA3D in Indonesian Hirschsprung news/covid 19-information-patients-

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6. A. Makhmudi, R. Supanji, B.P. Putra, 2020.

Gunadi, The effect of APTR, Fn14 and 15. X. Ren, B. Chen, Y. Hong, et al., The

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Yulianda, A. Dwihantoro, Gunadi, Anorectal https://www.thejakartapost.com/news/2020/

malformation patients’ outcomes after 06/01/10 2-areas-with-zero-covid-19-cases-

definitive surgery using Krickenbeck allowed-to-start-new-normal.html Accessed

classification: a cross-sectional study, on June 6, 2020.

THE COVID-19 PANDEMIC IMPACT ON PEDIATRIC SURGERY RESIDENCY
PROGRAMS

Objective: The COVID-19 pandemic has had an institution serves as a pillar of educational
impact not only on clinical practices but also on training and academic awakening in our country.
residency programs as an important part of Now, our institution has 18 Faculties, one
hospital medical services. We investigated the Postgraduate School (master’s and doctoral
impact of the COVID-19 pandemic on the program), one Vocational School and 20
pediatric surgery residency program in our Residency Programs, including pediatric surgery
institution. training [5]. The pediatric surgery residency
program has been established in our institution
Results: A questionnaire was developed, since 2006 with a length of training of 5 years
consisting of 24 questions: a) the perspectives of [6]. Several reports have been published
residents about COVID-19 infection during their regarding the impact of COVID-19 on the
residency program; b) the learning process; c) residency programs; however, all studies were
academic evaluations; and d) residents' performed in developed countries [2, 3] or did not
suggestions to improve the quality of their comprehensively analyze what residents think
residency program during the outbreak. Most about the COVID-19 impact on their residency
(85.7%) pediatric surgery residents agreed that program [4]. Moreover, there is an uncertainty
elective surgeries should be postponed during when the COVID-19 pandemic will end, and the
the pandemic. Before the outbreak, almost all number of cases is increasing, particularly in our
(90.5%) residents used textbooks and journals as province of 2.960 cases and 78 deaths per
their primary sources of learning, while during October 10, 2020. Therefore, we aimed to
the outbreak, 71.4% of residents shifted to use investigate the impact of the COVID-19
online lectures either from the school or pandemic on the residency program in our
Association of Pediatric Surgeons. Interestingly, institution, particularly pediatric surgery training,
95.2% of participants agreed that they had more from the perspectives of residents.
time to complete their academic assignments
during the pandemic. In conclusions, the MATERIAL AND METHODS
pandemic has had a significant impact on the We developed and distributed a questionnaire to
development of pediatric surgery residency 21 pediatric surgery residents in our institution
programs. A comprehensive approach is needed during July 2020. Twenty-one residents were
to maintain the high standard of competence of registered from January 2015 – January 2020.
pediatric surgery without compromising our The questionnaire was developed by
safety from the COVID-19 infection risk. educators/attending pediatric surgeons. The
educators/attending pediatric surgeons convened
Keywords: COVID-19 pandemic, pediatric to designing the questions. The questionnaire
surgery, residency program consisted of 24 questions concerning: a) the
perspectives of residents about COVID-19
INTRODUCTION infection during their residency program (n = 5);
Since the World Health Organization (WHO) b) the learning process during the outbreak (n =
declared COVID-19 as a worldwide pandemic 12); c) academic evaluations (n = 6); and d) the
on March 11, 2020 [1], clinical practices have residents’ suggestions to improve the quality of
been severely affected worldwide. The their residency program during the outbreak (n =
residency program as a part of the clinical 1, open question) (Table 1). The Medical and
services itself has also been influenced by the Health Research Ethics Committee of our
outbreak [2, 3, 4]. institution approved this study
Our institution was oficially established in 1949 (KE/FK/0718/EC/2020). Written informed
as a national university. Considered as one of consent was obtained from all participants
the oldest universities in our country, our before joining in this study.









Results
Baseline Characteristics
The total number of pediatric surgery residents was 21, consisting of 14 males and 7 females (Table 2).
All residents (100%) completely responded to the questionnaire.

Perspectives Of Residents Concerning textbooks and journals. Only 23.8% of
COVID-19 Infection During The Residency participants still used textbooks and journals as
Program the primary sources of learning (Fig. 1b). During
Most pediatric surgery residents (85.7%) agreed the pandemic, we changed the morning reporting
that elective surgeries should be postponed of residents from off-line to online meeting. Most
during the pandemic because they (100%) residents (85.7%) considered the online morning
worried about getting infected with SARS-Cov-2 reports to be good; however, 71.4% of residents
during the surgical procedures. Most of them thought that off- line morning reports were better
(85.7% and 76.2%, respectively) thought that the than online meeting. About 95.2% of participants
number of elective and emergency surgeries agreed that live view surgery was very important
decreased by approximately 25-<75% and 25- to obtain the necessary skills’ competence of
<50%, respectively, during the pandemic (Fig. pediatric surgery during the outbreak. While
1a). 85.7% of subjects assumed that live view surgery
was important for all cases of elective and
Learning Process During The Outbreak emergency surgeries, 81% of residents felt that
Before the outbreak, almost all (90.5%) residents live view surgery was necessary only for
used textbooks and journals as their primary interesting cases (Fig. 1b).
sources of learning, while during the COVID-19 Approximately 71.4% of residents expressed that
pandemic, interestingly, 71.4% of residents used the restriction of resident number in the outpatient
online lectures either from the school or clinics during the outbreak did not hamper them
Association of Pediatric Surgeons in addition to from gaining the necessary skills; however, 43%

of participants said that the restriction of resident (vs. general questionnaire [2] or authors’
number during the ward rounds inhibited them perspective [4]).
from obtaining the needed skills (Fig. 1b). All residents are worried they will become infected
Accordingly, most residents (85.7%) thought that by COVID-19 during their residency program in
their competence was declining during the the hospital. Accordingly, they agreed that
pandemic. Some residents (43%) assumed that elective surgeries should be postponed during
virtual outpatient and ward round methods are the pandemic. When compared with the
necessary to obtain the necessary skills, importance of the residents safeguarding the
particularly for residents who were not on duty in well-being of their families from the possibility of
the hospital (Fig. 1b). getting cross-infected by COVID-19 due to the
residents’ potential exposure at the hospital, the
Academic Evaluation training program was no longer considered as
During the pandemic, 95.2% of participants important anymore for the residents [3].
agreed that they had more time to complete their Moreover, since the COVID-19 pandemic, we
academic assignments, including thesis have shifted our morning reporting from off-line
completion (42.8%), extended length of study to online meetings. Most residents are satisfied
(42.8%), and level up examination (71.4%). with the changes, although some residents
Moreover, 38.1% of participants thought that the thought that oPine morning reporting was better
pandemic would delay their taking the national to gain skills and knowledge than online
board examination (Fig. 1c). meetings (Fig. 1). Interestingly, approximately 5%
of residents used the virtual didactic methods for
Residents’ Suggestions To Improve The their learning process during the pandemic, while
Quality Of Their Residency Program During they never used it before the outbreak. The use
The Outbreak of virtual didactic methods is not common in
There were several suggestions from residents to pediatric surgery, at least in our institution. A
gain the needed skills and knowledge during the recent study suggested that virtual methods will
outbreak as follows: 1) virtual didactic methods; not substitute for conventional didactic
2) maintain and improve the quality of the online approaches, but they will give advantages for
learning process; 3) comprehensive scheduling residents to encourage their positive eagerness
for elective surgeries; and 4) gradually increase and enthusiasm [2].
the number of elective surgeries. We also evaluated the learning process
regarding the competence gained during the
Discussion pandemic. Our data showed that most residents
Here, we show that the pediatric surgery believe that their competence is declining during
residency program at our institution has been the pandemic. This finding might be associated
significantly affected by the COVID-19 with the fact that almost all elective surgical
pandemic. Our findings further confirmed cases were postponed during the pandemic.
previous reports [2, 3]. However, there are several Postponing elective surgeries occurred in every
novelties of our study: 1) pediatric surgery country affected by the COVID-19, including the
residency program (vs. plastic surgery training USA [3] and Australia [7]. Most residents agreed
[2]); developing country (vs. developed countries that live view surgery with virtual outpatient
[2, 3, 4]); 3) prospective design using services and ward rounds will be useful to solve
questionnaire (vs. retrospective design [3]); and this challenge.
4) comprehensively developed the questionnaire While there are limited activities to gain the skills
into four aspects that might affect the residency of pediatric surgery during the pandemic,
program: a) the perspectives of residents about intriguingly, most residents claimed that this
COVID-19 infection; b) learning process; c) outbreak gave them more time to finish their
academic evaluations; and d) residents’ academic assignments, including extended study
suggestions for residency program improvement time for level up examinations and completion of
their thesis. These advantages might be related

to the policy that restricted the number of All data generated or analyzed during this study
residents during the outpatient services, ward are included in the submission. The raw data are
rounds and surgical procedures. As a result, available from the corresponding author on
most of them stayed at home, and only a limited reasonable request.
number of rotating residents (i.e., three per round)
were allowed to perform residency tasks each Competing Interests
day in the hospital. The authors declared no potential conflicts of
One of the residents’ suggestions was to interest with respect to the research, authorship,
gradually increase the number of elective and/or publication of this article.
surgeries. This response reflects that it is not
clear whether the COVID-19 pandemic will end Funding
in a few months or even in the next few years, Indonesia Ministry of Research and
and as a proper response, our government Technology/National Agency for Research and
declared a “new normal” policy on June 1, 2020 Innovation.
to begin the adaptations of the daily activities to
the COVID-19 pandemic, involving clinical and Authors’ Contributions
surgical services [8]. Our pediatric surgery G, EP, AD, NA and AM conceived the study. G
services have adapted our scheduling practices drafted the manuscript, and EP, AD, NA and AM
as well starting critically revised the manuscript for important
intellectual content. NB, ASK, WW, FF, and AKT
Conclusions collected the data and G analyzed the data. All
The pandemic COVID-19 has had a significant authors have read and approved the manuscript
impact on the development of pediatric surgery and agreed to be accountable for all aspects of
residency programs. A comprehensive approach the work in ensuring that questions related to the
is needed to maintain the high standard of accuracy or integrity of any part of the work are
competence of pediatric surgery without appropriately investigated and resolved.
compromising our safety from the risk of COVID-
19 infection. Acknowledgement
We extend our thanks to all residents who
Limitations participated in this study. We are also thankful
Although the response rate of our study was for the English editing service staff at our
100%, a relatively small number of pediatric institution for checking the grammar of the
surgery residents involved in this study should manuscript.
be taken into consideration during interpretation
of our findings. Another limitation of our study References
was limited to the subjective opinion of the 1. World Health Organization. https:/
residents without objective support.
www.who.int/news-room/detail/27-04-2020-
Declarations who-timeline---covid- 19 Accessed on June
Ethics Approval And Consent To Participate 1, 2020.
The Medical and Health Research Ethics 2. Zingaretti N, Contessi Negrini F, Tel A,
Committee of our institution approved this study Tresoldi MM, Bresadola V,Parodi PC. The
(KE/FK/0718/EC/2020). Written informed Impact of COVID-19 on Plastic Surgery
consent was obtained from all participants Residency Training. Aesthetic Plast Surg.
before joining in this study. 2020:1-5.
3. Davenport M, Pakarinen MP,Tam P,et al
Consent To Publish (2020) From the editors: the COVID-19
Not applicable. crisis and its implications for pediatric
surgeons. J PediatrSurg https:/
Availability Of Data And Material doi.org/10.1016/j.jpedsurg.2020.04.009

4. Boyd CJ, Inglesby DC, Corey B, Greene BJ,

Harrington MA, Johnson MD, King TW,

Rais-Bahrami S, Tavana ML. Impact of

COVID-19 on Away Rotations in Surgical

Fields. J Surg Res. 2020;255:96-98.

5. Universitas Gadjah Mada. https:/

www.ugm.ac.id/en/about Accessed on

October 1, 2020.

6. Residency Program of Faculty of Medicine,

Public Health and Nursing, Universitas

Gadjah Mada. https:/

ppds.fk.ugm.ac.id/program-studi/ Accessed

on October 1, 2020.

7. AustraliaGovernment.https:/

www.health.nsw.gov.au/Infectious/covid-

19/Pages/elective- outpatient.aspx

Accessed on October 1, 2020.

8. Indonesian Government. https:/

www.thejakartapost.com/news/2020/06/01/

102-areas-with-zero- covid-19-cases-

allowed-to-start-new-normal.html Accessed

on October 1, 2020.

9. Gunadi, Idham Y, Paramita VMW, Fauzi AR,

Dwihantoro A, Makhmudi A. The Impact of

COVID-19 pandemic on pediatric surgery

practice: A cross-sectional study. Ann Med

Surg (Lond). 2020;59:96- 100.

VARIOUS RADIOLOGICAL FINDINGS IN PATIENTS WITH COVID-19: A CASE
SERIES

Theresia Riawati a,**, Wikan Indrarto b , Aditya Rifqi Fauzi c , William Widitjiarso c , Gunadi c,*

ADepartment of Radiology, Panti Rapih General Hospital, Yogyakarta, 55233, Indonesia
BDepartment of Child Health, Panti Rapih General Hospital, Yogyakarta, 55233, Indonesia
CFaculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, 55281,
Indonesia

ABSTRACT 1. INTRODUCTION
Introduction: Radiological evaluation of Severe Acute Respiratory Syndrome
suspected COVID-19 patients is required for Coronavirus 2 (SARS-CoV-2), which causes
early detection of thoracic involvement, Coronavirus Disease 2019 (COVID-19), has
particularly in emergency units, while waiting for become a global pandemic that infected nearly
definitive diagnosis by real-time reverse 11 million people and claimed 523,011 lives as
tran scription polymerase chain reaction (RT- of July 4, 2020 [1,2]. The first two cases in
PCR). Here, we report a case series of CXR Indonesia were declared on March 2, 2020.
findings in Indonesian pa tients with COVID-19 Since it was first announced in Indonesia,
in our institution. Presentation of cases: We COVID-19 cases have increased rapidly over
included 7 patients with COVID-19 confirmed by time, thus requiring continued attention. On July
RT-PCR, including 4 females and 3 males, with 5, Indonesia recorded 63,749 COVID-19
ages ranging from 36 to 71 years. All patients infections [3]. Until now, radiological
showed abnormal findings on CXR when examinations have an important role in the
admitted to the hospital, except one, composed management of COVID-19, especially for
of ground glass opacity (GGO) (n = 1), screening tests, working diagnosis and
consolidation (n = 3), and both (n = 2). Both and monitoring pneumonia [4,5]. Plain chest X-rays
one side of the lung were affected in three and (CXR) and computerized tomography (CT)
three (left side = 2; right side = 1) patients, scans are key radiological or imaging
respectively. Pneumonia degrees of mild, examinations in confirming COVID-19 diagnosis.
moderate and severe were observed in three, CT scans are reported to be more sensitive in
one, and two patients, respectively. All patients diagnosing COVID-19 than CXR [6]. However,
eventually recovered. Discussion: CXR is the its use is limited due to its expense and is not
most common radiological examination for widely available, especially in developing
patients with respiratory disorders, including countries. Therefore, CXR is considered more
COVID-19, and it is readily available in almost effective and useful for the initial screening and
all health care facilities. The imaging follow-up of patients with COVID-19 [7,8].
manifestation of COVID-19 is similar to viral Moreover, radiological evaluation of suspected
pneumonia but also has its own characteristics, COVID-19 patients is required for early detection
including GGO, consolidation, multiple plaque of thoracic involvement, particularly in
shadows, and interstitial changes that are mostly emergency units, while waiting for definitive
seen in peripherals and subpleural areas, as diagnosis by real-time reverse transcription
well as shadow infiltration in both lungs. polymerase chain reaction (RT-PCR) [9]. In
Conclusion: CXR showed various abnormality Indonesia, there is no consensus on the use of
findings in patients with COVID-19, including the chest CT scans for COVID-19 cases, but it
type, location, and degree of pneumonia. depends on the availability of tools, facilities,
Moreover, CXR is considered more effective and and human resources in most hospitals. Chest
useful for initial screening and follow up of the CT scanning is not recommended for screening
progress of patients with COVID-19 tests and in patients with mild and asymptomatic
symptoms but is indicated in patients with
Keywords: Abnormality findings COVID-19 Ground glass negative RT-PCR; however, they show
opacity Plain chest X-ray Thoracic CT scan

worsening clinical signs and severe pneumonia ceftazidime 1 gr and intravenous levofloxacin
with complications. Here, we report a case 500 mg, while she also received medication for
series of CXR findings in Indonesian patients her asthma.
with COVID-19. This study has been reported in Case 2: A 61-year-old female presented with
line with PROCESS criteria [10]. fever, shortness of breath, and cough.
Complaints of shortness of breath felt worse
2. PRESENTATION OF CASES starting 1 day before admission. The patient was
There were 7 patients diagnosed with COVID-19 brought to the emergency room, and a CXR was
according to positive RT-PCR results in our performed. The result showed consolidation in
hospital. They consisted of 4 females and 3 the basal lung sinistra (Fig. 2). The patient had
males, with ages ranging from 36 to 71 years. comorbid diabetes mellitus and chronic renal
Case 1: A 59-year-old female presented with failure. RT-PCR swab tests were performed, and
cough with phlegm, runny nose, fever, and the results were positive. The patient was
shortness of breath 3 days before admission. diagnosed with COVID-19, chronic kidney
The patient was taking self-medication using disease and diabetes mellitus. After admission,
decongestant drugs, but her complaints did not the pa tient received antibiotics and antiviral
improve. There was no history of traveling to therapy based on the COVID-19 Prevention and
areas with COVID-19 local transmission. A CXR Control guidelines by the Indonesian Ministry of
was performed, and the re sults showed bilateral Health, namely, oral hydroxychloroquine 200 mg
consolidation in the basal lung (Fig. 1). The twice daily and oral oseltamivir 75 mg twice
pa tient was then hospitalized with a diagnosis daily, oral moxifloxacin 400 mg, and
of bronchial asthma. Later, an RT-PCR test for intrave nous meropenem 1gr thrice daily for his
COVID-19 was performed, and the results were COVID-19, while she also received medication
positive. During treatment, the patient received for her chronic renal disease, hypertension, and
antibiotic therapy, namely, intravenous diabetes.

Fig. 1. Plain chest X-ray showed bilateral consolidation in the basal lung.

Fig. 2. Plain chest X-ray revealed consolidation in the basal lung sinistra.

Case 3: A 40-year-old male with complaints of was done, and the result was positive for
fever 11 days before admission, accompanied COVID 19. After admission, the patient received
by cough, runny nose, shortness of breath, antibiotics and antiviral ther apy based on the
dizziness, and nausea, came to our hospital. COVID-19 Prevention and Control guidelines by
The patient had a history of asthma, diabetes the Indonesian Ministry of Health, namely, oral
and hypertension that was controlled with hydroxychloroquine 200 mg twice daily and oral
routine medication. The patient had oseltamivir 75 mg twice daily, intravenous
comorbidities of diabetes mellitus and meropenem 1gr thrice daily, intravenous
hypertension. A CXR was performed, and the levofloxacin 500 mg, and intravenous imipenem
results showed ground glass opacities (GGOs) 500 mg four times a day for his COVID-19, while
in the periphery of the left lung and consolidation also receiving medication for his diabetes and
in the bilateral parahilar and paracardial regions hypertension
of the lung (Fig. 3). RT PCR swab examination

Fig. 3. Plain chest X-ray presented GGOs in the periphery of the left lung and consolidation in the
bilateral parahilar and paracardial regions of the lung

Case 4: A 48-year-old female presented with based on the COVID-19 Prevention and Control
fever 10 days before admission, accompanied guidelines by the Indonesian Ministry of Health,
by cough and vomiting. Her husband had a namely, oral lopinavir/ritonavir 400 mg/100 mg
history of traveling from a local transmission once daily, oral hydroxychloroquine 200 mg
area. The patient had co morbid diabetes twice daily, intravenous azithromycin 500 mg
mellitus. A CXR was done, showing the once daily, and oral oseltamivir 75 mg twice
appearance of GGO in the periphery of both daily (Insert Fig. 5 here). Case 6: A 57-year-old
lungs and multifocal consolidation para hilar and male came to our hospital without complaints.
paracardial in the right lung (Fig. 4). RT-PCR for He brought the RT-PCR COVID-19 swab
COVID-19 was done, and the results were results, which showed that he was positive. He
positive. After admission, the patient received had a history of traveling to the local
antibiotics and antiviral therapy based on the transmission area. The patient had no
COVID-19 Pre vention and Control guidelines by comorbidities. A CXR revealed consolidation in
the Indonesian Ministry of Health, namely, oral the basal right lung (Fig. 6). Patient was
lopinavir/ritonavir 400mg/100 mg once daily, hospitalized, and after admission, she received
intravenous levofloxacin 750 mg once daily, and antibiotics and antiviral therapy based on the
oral hydroxychloroquine 200 mg twice daily, and COVID-19 Prevention and Control guidelines by
intravenous meropenem 1gr thrice daily for her the Indonesian Ministry of Health, namely, oral
COVID 19 diagnosis, while also receiving azithromycin 500 mg once daily, oral
medication for the possibility of bacterial chloroquine 150 mg twice daily, oral
infection. Case 5: A 36-year-old female with the methisoprinol 1000 mg thrice daily, and oral
chief complaint of fever 4 days before oseltamivir 75 mg twice daily. Case 7: A 71-
admission. There was no history of contact with year-old male presented with a complaint of pain
suspected or confirmed COVID-19 patients. A in his right leg, and the patient asked to be
CXR showed GGO in the periphery of the left treated. The patient had a history of living with
lung. RT-PCR for COVID-19 was done, and the his children who did not comply with the COVID-
results were positive. After admission, the 19 pre vention health protocol. His CXR showed
patient received antibiotics and antiviral therapy cardiomegaly with

Fig. 4. Plain chest X-ray showed the appearance of GGO in the periphery of both the lung and
multifocal consolidation parahilar and paracardial in the right lung.

Fig. 5. Plain chest X-ray displayed GGO in the periphery of the left lung.

Fig. 6. Plain chest X-ray demonstrated consolidation in the basal right lung.

configuration of left ventricle hypertrophy (Fig. therapy based on the COVID-19 Prevention and
7). The patient had a history of diabetes mellitus. Control guidelines by the Indonesian Ministry of
The patient underwent an RT-PCR swab Health, namely, intravenous ceftazidime 1 gr
examination for COVID-19, and the results were thrice daily, oral azithromycin 500 mg twice
positive. He was treated with a diagnosis of daily, oral chloroquine 150 mg twice daily, and
COVID-19, anemia and diabetes mellitus, and oral oseltamivir 75 mg twice daily, while he also
dia betic ulcer on his left foot. After admission, received therapy for his diabetes and diabetic
the patient received anti biotics and antiviral ulcer

Fig. 7. Plain chest X-ray was within normal limits.

3. DISCUSSION can manifest earlier than clinical symptoms.
To date, confirmation of the diagnosis of COVID- Therefore, detecting the disease quickly and
19 requires viral nucleic acid detection from accurately is of great sig nificance, and imaging
throat swabs using RT-PCR, although this test is is playing a key role in preclinical screening [6,
considered only specific but not sensitive. 11]. CXR is the most common radiological
Current studies have shown that lung imaging examination for patients with respiratory

disorders, including COVID-19 [12]. Since it is and 2) it can be conducted at the bedside of
readily available in almost all health care patients, therefore minimizing the cross-infection
facilities, particularly in developing countries, risk in the radiology department [9].
and less expensive, CXR is considered more
effective and useful for initial screening and 4. CONCLUSIONS
follow-up of the progress of patients with CXR shows various abnormality findings in
COVID-19 [7,8]. The typical CXR in patients with patients with COVID-19, including the type,
COVID-19 is GGO. In addition, consolidation is location, and degree of pneumonia. Moreover,
usually multifocal, peripheral and bilateral, but in CXR is considered more effective and useful for
the early stages of the disease, it can be initial screening and follow-up of the progress of
unifocal and is most often seen in the inferior patients with COVID-19.
lobe of the right lung. Pleural effusion and hilar
lymphade nopathy are rare. This bilateral Consent
pulmonary involvement differentiates COVID-19 Written informed consent was obtained from the
from bacterial pneumonia [12]. These findings patient for publi cation of this case report and
are compat ible with our patients. Moreover, the accompanying images. A copy of the written
degree of pneumonia based on CXR consists of consent is available for review by the Editor-in-
no abnormality/normal, focal-unilateral/mild, Chief of this journal on request.
bilateral/moderate focal, and multifocal-
bilateral/severe [13]. Most of our patients with Provenance and peer review
COVID-19 showed bilateral, multifocal, and Not commissioned, externally peer-reviewed.
severe pneumonia. The imaging manifestation
of COVID-19 is similar to viral pneu monia but Declaration of competing interest
also has its own characteristics, such as multiple No potential conflict of interest relevant to this
plaque shadows and interstitial changes that are article was reported.
mostly seen in peripherals and subpleural areas,
as well as shadow infiltration in both lungs. In Appendix A. Supplementary data
severe cases, it can appear as a consolidation Supplementary data to this article can be found
with a “white lung” image [13]. Commonly seen online at https://doi.
patterns are GGO, with ill-defined margins, air org/10.1016/j.amsu.2021.01.030.
bron chograms, smooth or irregular interlobular
or septal thickening, and thickening of the Ethical approval
adjacent pleura, with predominance in the right Not applicable.
lower lobe [14]. These findings are quite similar
to the radiographic images of SARS infection Source of funding
[15], except SARS shows more unifocal rather The authors declare that this study had no
than bilateral involvement in COVID-19. Middle- funding source.
East Respiratory Syndrome (MERS) pneumonia
also shares similarities in subpleural and basilar Author contribution
airspace lesions, with extensive GGO and Theresia Riawati and Wikan Indrarto conceived
consolidation [16]. Even though CXR is less the study and approved the final draft. Gunadi
sensitive than CT scanning to diagnose COVID- and Aditya Rifqi Fauzi drafted the manuscript.
19, it has a significant role in the management of William Widtjiarso critically revised for important
the outbreak [17,18]. Additionally, CT scans intel lectual content. All authors read and
have a very low specificity to detect the peculiar approved the final draft. All authors facilitated all
findings of pneumonia due to COVID-19 [18,19]. project-related tasks.
Other ad vantages of CXR over CT scans are as
follows: 1) it is easier to operate the X-rays, Registration of research studies
particularly the procedure of disinfection that researchregistry5709.
should be per formed after each examination,

Guarantor 2018 statement: updating consensus preferred
Gunadi.
reporting of CasE series in surgery (PROCESS)
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THE USE OF TISDALE RISK SCORE DURING
HYDROXYCHLOROQUINE/CHLOROQUINE TREATMENTS ON COVID-19 PATIENTS

Anggoro Budi Hartopo1,3*, Ika Trisnawati2, Eko Budiono2, Brilliant Winona Jhundy1, Vita Yanti Anggraeni3

1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing Universitas Gadjah
Mada– Dr. Sardjito Hospital, Yogyakarta, Indonesia
2Division of Pulmonology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas
Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia.
3Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas
Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia.

ABSTRACT Tisdale moderate and low risks counterparts.
Background: The SARS-CoV-2 infection or The premature HCQ/CQ stop occurred in 1
COVID-19 disease caused significant morbidity subject (6.7%) with Tisdale moderate risk and 1
and mortality. Early reports showed clinical subject (6.7%) with Tisdale high risk.
improvement with hydroxychloroquine (HCQ) Conclusion: The Tisdale risk score stratification
and chloroquine (CQ). However, due to the was easily implemented in hospital as a tool to
concern of QTc interval prolongation, the strict guide in treatment decision and monitoring while
electrocardiogram monitoring was needed. The dealing with drugs potentially cause QTc
use of risk stratification score may help the prolongation, such as HCQ/CQ, in COVID-19
decision of this monitoring. Aims: The study patients.
purpose is to describe the use of Tisdale risk
score in patients with COVID-19 who received INTISARI
HCQ/CQ treatment. Methods: This was a Latar Belakang: Infeksi SARS-CoV-2 atau
prospective observational study. Subjects were penyakit COVID-19 menyebabkan angka
patients with the diagnosis of high-probability- kesakitan dan kematian yang bermakna.
COVID-19 and confirmed-COVID-19 receiving Laporan awal menunjukkan perbaikan klinis
HCQ/CQ as one of the treatments. The dengan terapi hidroksiklorokuin (HCQ) dan
demographic, medical history and laboratory klorokuin (CQ). Namun, karena permasalan
data were recorded. The Tisdale score was pemanjangan interval QTc, maka pengawasan
calculated based on baseline parameters and ketat dengan elektrokardiogram diperlukan.
the risk categories were divided into three Penggunaan skor stratifikasi risiko dapat
categories: low risk (score <7), moderate risk membantu keputusan tentang pengawasan ini.
(score 7-10) and high risk (score ≥11). The Tujuan: Tujuan penelitian adalah untuk
HCQ/CQ daily dose, cumulative dose, time of mendeskripsikan penggunaan skor risiko
administration, and duration were recorded. Tisdale pada pasien COVID-19 yang
Result: Forty-five subjects were analysed. Most mendapatkan terapi HCQ/CQ. Metode:
subjects were males (66.7%) at mean age 50.9 Penelitian ini merupakan penelitian
years. Most subjects were hospitalized due to observasional prospektif. Subjek adalah pasien
severe illness (44.4%). Medical comorbidity was dengan diagnosis high probability-COVID-19
mostly hypertension (31.1%). Most subjects had dan confirmed- COVID-19 yang mendapatkan
HCQ treatment (95.6%). Electrocardiogram HCQ?CQ sebagai salah satu pengobatan. Data
showed mostly sinus rhythm (97.8%). Mean QTc demografi, riwayat penyakit dan laboratorium
interval based Bazett formula was 413.1 ms. dikumpulkan. Skor Tisdale dihitung berdasarkan
Tisdale risk categories were low risk (57.8%), parameter dasar dan kategori risiko dibagi
moderate risk (31.1%) and high risk (11.1%). berdasarkan tiga kategori: risiko rendah (skor
Tisdale high risk had significantly lower <7), risiko sedang (skor 7-10) dan risiko tinggi
cumulative dose of HCQ/CQ and shorter (skor ≥11). Dosis harian HCQ/CQ, dosis
duration of HCQ/CQ treatment as compared to kumulativ, waktu pemberian dan durasi dicatat

dan dikumpulkan. Hasil: Empat puluh lima receiving HCQ/CQ was mandatory to detect
subjek dianalisis, sebagian besar laki-laki the potential fatal arrhythmia, namely QTc
(66.7%) dengan rerata usia 50,9 tahun. inteval >500 ms (narrow QRS), QTc interval
Sebagian besar subjek masuk dalam sakit berat ≥550 ms (wide QRS), QTc lengthening >60 ms
(44.4%). Komorbid utama adalah hipertensi and the presence of ventricular ectopy.7
(31.1%). Sebagian besar mendapatkan terapi However this approach was impractical, due to
HCQ (95.6%). Elektrocardiogram menunjukkan the restriction of hospital staff contacts with
irama sinus (97.8%). Rerata interval QTc patients. The Tisdale risk score was proposed to
berdasarkan formula Bazett adalah 413.1 be used as risk prediction score of drug-
millidetik. Kategori risiko Tisdale adalah risiko associated QTc prolongation, which could assist
rendah (57.8%), risiko sedang (31.1%) dan the selection and monitoring of patients.8,9
risiko tinggi (11.1%). Tisdale risiko tinggi Therefore, not all patients needed strict
mempunyai dosis kumulativ dan durasion electrocardiogram evaluation after selected by
HCQ/CQ yang lebih rendah dibandingkan Tisdale risk score. The studies aimed to
Tisdale risiko rendah dan sedang. Penghentian describe the use of Tisdale risk score in risk
HCQ/HQ lebih awal pada 1 subject (6.7%) stratification in patients with COVID-19 who
Tisdale risiko rendah dan 1 subject (6.7%) received HCQ/CQ treatment and to assess its
Tisdale risiko tinggi. Kesimpulan: Stratifikasi relation with HCQ/CQ cumulative dose and
skor risiko Tisdale secara mudah dapat duration.
diterapkan di rumah sakit sebagai sarana untuk
membimbing keputusan terapi dan pengawasan Methods
saat menggunakan obat-obatan yang berpotensi We conducted a prospective observational study
menyebabkan pemanjangan QTc, seperti at Dr. Sardjito Hospital, Yogyakarta, Indonesia
HCQ/CQ, pada pasien COVID-19. from March 2020 until August 2020. Subjects
were patients with the diagnosis of high-
Keywords: COVID-19; hydroxylchloroquine; risk probability-COVID-19 (SARS CoV2 PCR-
assessment negative result) andconfirmed-COVID-19 (SARS
CoV2 PCR-positive result) receiving HCQ/CQ as
Introduction one of the treatments. The use of HCQ/CQ was
The SARS-CoV-2 infection or COVID-19 based on the clinical decision by attending
disease had become a pandemic worldwide, physician according to hospital clinical practice
including in Indonesia.1 This disease has guideline at the time of this study. The inclusion
caused significant morbidity and mortality criteria were: patients’ age ≥18 years old,
throughout the world.1 Since the beginning of patients with diagnosis of high-probability
pandemic, Indonesia had increased numbers of COVID-19 or confirmed-COVID-19, patients who
patients without any known effective treatment.2 received HCQ/CQ treatment, patients who
Some early reports showed clinical hospitalized in hospital wards or ICU, and
improvement and faster coronavirus clearance patients who agreed to participate in this study.
with hydroxychloroquine (HCQ) and chloroquine The exclusion criteria were: the incomplete
(CQ).3,4,5 Although the evidence came from electrocardiogram recording and pregnant
non-randomized studies with small subjects, patients. The study protocol was approved by
W.H.O and Indonesian COVID-19 national Medical and Health Research Ethics Committee
protocols adopted CQ and HCQ as treatment of the Faculty of Medicine, Public Health and
modalities for COVID- 19.6,7 Despite its long Nursing Universitas Gadjah Mada – Dr. Sardjito
experience with HCQ/CQ as treatment for Hospital, Yogyakarta, Indonesia.
malaria, the warning of potential risk due to fatal The demographic, medical history and
arrhythmia limited its use and required strict laboratory data were recorded from medical
electrocardiogram monitoring.7 In the national record into an electronic case report form during
protocol released in April 2020, a daily admission. The Tisdale score was calculated
electrocardiogram monitoring in all patients based on baseline parameters and the risk

categories were divided into three categories: descriptive analysis was performed to report the
low risk (score <7), moderate risk (score 7-10) characteristics of subjects. No hypothesis was
and high risk (score ≥11).9 The disease severity generated and tested in this study.
was determined based on the national protocol
classification and adopted by Dr. Sardjito Result
Hospital clinical practice.7 The HCQ/CQ daily Forty-five subjects were eligible in this study.
dose, cumulative dose, time of administration, Table 1 showed the characteristics of 45
and duration were in discretion of attending subjects in this study. Most subjects were males
physicians. Twelve-lead electrocardiogram was (66.7%) at mean age 50.9 years. The confirmed
obtained at baseline before HCQ/CQ using -COVID-19 was 51.1%. Most subjects were
standardized electrocardiograph machines, with hospitalized due to severe illness (44.4%).
standard 12-lead resting electrocardiogram, Medical comorbidities were mostly hypertension
paper speed of 25 mm/s, the amplitude of 10 (31.1%), diabetes mellitus (24.4%) and chronic
mm/V, and a sampling rate of 250 Hz. The kidney disease (11.1%). Mean bodymass index
measurement of QT interval was performed by was 25.2, and obesity (bodymass index > 25)
two cardiologists independently and manually by was 46.2%. Most subjects had HCQ treatment
standard calipers aided by computer. The QTc (95.6%). The electrocardiogram showed mostly
interval was calculated by the Bazett's formula. sinus rhythm (97.8%), with only 1 atrial
For statistics analysis, continuous data were fibrillation and 1 ventricular extrasystole. No
reported as mean±standard deviation significant arrhytmia found in electrocardiogram
(mean±SD) and categorical data were reported recording at baseline. The mean QTc interval
as count and percentage (n (%)). The based Bazett formula was 413.1 ms.



Table 2 showed that subjects with a Tisdale high risk had significantly lower cumulative dose of
HCQ/CQ and shorter duration of HCQ/CQ treatment as compared to Tisdale moderate and low risks
counterparts. The premature HCQ/CQ stop occurred in 1 subject (6.7%) with Tisdale moderate risk
and 1 subject (6.7%) with Tisdale high risk. None of subjects with Tisdale low risk underwent premature
HCQ/CQ stop.

Table 2.
The cumulative dose, duration and premature stop of HCQ/CQ based on Tisdale risk category

Discussion arrhytmia.7 However, since the restriction of
The result of our study indicated that among contact with patients and lack of dedicated
patients treated with HCQ/CQ due to COVID-19, electrocardiogram machine for pandemic, the
the Tisdale risk category had been used as an protocol requirement could not be fulfilled. The
easy and simple screening tool before ideal use of telemetry or portable device to
prescribing HCQ/CQ. The most common detect electrocardiogram could not be provided
subjects were those with Tisdale low risk by most hospitals. Therefore, the screening of
category. Among Tisdale high risk subjects, who fatal arrhytmia risk by Tisdale risk score was
were only a minority, the HCQ/CQ cumulative proposed and our study inditaed it was easily
dose and duration was significantly lower. One implemented.8 The majority of our subjects did
subject underwent premature HCQ/CQ stop in not undergo daily electrocardiogram, only those
Tisdale high risk subjects, whereas none in ICU was daily monitored.
experienced premature HCQ/CQ stop in Tisdale The HCQ and CQ are QTc-prolonging drugs
low risk subjects. During this study, the daily which create a threat of fatal arrhythmia and
electrocardiogram was not performed per- cardiac arrest.10,11 About 13% COVID-19
hospital clinical practice, due to pandemic patients had endure QTc prolongation due to the
restriction. illness itself.12 This also being aggravated by
During early COVID-19 pandemic, the use of the use antivirals, antibiotics and other
HCQ/CQ was one of the medications approved supportive drugs concomitantly or concurrently
by WHO and also by Indonesian authority.7 with HCQ/CQ. Tisdale et al. (2013) had
Similar to what had occurred in other parts of the identified several easily obtainable clinical
world, in Indonesia the use of HCQ/CQ for parameters and developed a risk score using
COVID-19 had been implemented in the these parameters to predict patients at highest
national protocol since April 2020.7 The risk for QTc interval prolongation during
Indonesian COVID-19 national protocol gave the hospitalization.9 This risk score was useful in
clear-cut requirement of daily electrocardiogram treatment decision and monitoring guidance
monitoring during HCQ/CQ treatment due to its (strict or loose) decisions during COVID-19
potential impact on QTc prolongation and letal pandemic in subjects taking HCQ/CQ.

Tisdale score calculation and risk score Meddeb L, Mailhe M et al.
stratification was feasible and can be Hydroxychloroquine and azithromycin as a
implemented in clinical practice. Our study had treatment of COVID-19: results of an open-
limitation that it did not assess the Tisdale risk label non-randomized clinical trial. Int J
score and risk stratification in subjects who did Antimicrob Agents, 56:105949.
not receive HCQ/CQ treatment. In conclusion, 6. WHO. Antiviral Drugs that are Approved or
the Tisdale risk score stratification was easily Under Evaluation for the Treatment of
implemented in our hospital as a tool to guide in COVID-19.vol. 19 47– 88
treatment decision and monitoring while dealing https://www.covid19treatmentguidelines.nih
with drugs potentially cause QTc prolongation, .gov/ on (2020).
such as HCQ/CQ, in COVID-19 patients 7. Burhan E, Susanto AD, Nasution SA,
Ginanjar E, Pitoyo CW, Susilo A, et al.
Acknowledgements 2020. Protokol Tatalaksana COVID-19,
Authors were grateful to: (1) Medic and edisi 1 April 2020. Perhimpunan Dokter
paramedic staffs at COVID-19 dedicated wards Paru Indonesia (PDPI) Perhimpunan
and ICU of Dr. Sardjito Hospital, Yogyakarta, Dokter Spesialis Kardiovaskular Indonesia
Indonesia, (2) Internal Medicine Residents at (PERKI) Perhimpunan Dokter Spesialis
COVID-19 dedicated wards and ICU of Dr. Penyakit Dalam Indonesia (PAPDI)
Sardjito Hospital, Yogyakarta, Indonesia, and Perhimpunan Dokter Anestesiologi dan
(3) Mr. Untara Vivi Chahya who provided Terapi Intensif Indonesia (PERDATIN)
electronic case report form. This research Ikatan Dokter Anak Indonesia (IDAI).
received funding from RSUP Dr. Sardjito, Jakarta: Indonesia.
Yogyakarta with contract number: 8. Laksono S, Hermanto DY, Iqbal M. 2020.
HK.02.03/XI.2/37465/2020 to Anggoro Budi How to manage QT prolongationin COVID-
Hartopo as Principal Investigator. 19 patients. Indonesian J Cardiol, 41:108-
111.
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5. Gautret P, Lagier JC, Parola P, Hoang VT,

DETERIORATION OF HEART RHYTHM DURING SHORT-TERM
HYDROXYCHLOROQUINE THERAPY FOR COVID-19: REPORT OF TWO CASES

Billy Aditya Pratama1,$, Brilliant Winona Jhundy1,$, Afik Maulana Rachman2, Vita Yanti Anggraeni2, Erika Maharani1, Ika
Trisnawati3, Eko Budiono3, Anggoro Budi Hartopo1,*

1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah
Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia
2Cardiology Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah
Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia
3Pulmonology Division, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah
Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia
These authors have contributed equally to this work and share first authorship

ABSTRACT
The rapid spread of the coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and
mortality globally. Hydroxychloroquine is one of the medications for eradicating COVID-19. Despite
concerns due to its potential cardiac toxicity, hydroxychloroquine is widely used in treating mild and
moderate COVID-19 pneumonia. In this case report, we report two cases of Indonesian adult patients
with suspected COVID-19 pneumonia who received hydroxychloroquine as part of the medications and
experienced deterioration of cardiac conduction which required stopping the drug prematurely. This
case report highlights the need for risk stratification, electrocardiogram monitor and QTc evaluation
before and during hydroxychloroquine therapy.

INTISARI
Penyakit koronavirus atau COVID-19 telah menyebabkan angka kesakitan dan kematian yang
bermakna di seluruh dunia. Hidroksiklorokuin merupakan salah satu pengobatan untuk mengeradikasi
COVID-19. Meskipun ada kewaspadaan tentang potensi toksisitas pada jantung, hidroksiklorokuin
secara luas digunakan untuk mengobati pneumonia COVID-19 ringan dan sedang. Pada kasus ini kami
melaporkan dua kasus pasien dewasa dari Indonesia dengan pneumonia curiga COVID-19 yang
mendapatkan pengobatan hidroksiklorokuin dan mengalami pemberatan konduksi jantung yang
menyebabkan dihentikannya pengobatan lebih awal. Kasus ini menitikberatkan perlunya stratifikasi
risiko, monitor elektrokardiogram dan evaluasi QTc sebelum dan selama pemberian terapi
hidroksiklorokuin.

Keywords: Covid-19; hydroxychloroquine; electrocardiography; cardiac arrhythmia;

INTRODUCTION that he had high probability score. The physical
Coronavirus 2019 (COVID-19) is a new examinations were as follows: fully conscious,
infectious disease that is spreading rapidly body temperature 36.8ºC, blood pressure
around the world and becoming a pandemic 130/90 mmHg, tachycardia (120 beats/min
disease.1,2 The clinical manifestations of (bpm)) and tachypnea (28 times/min) and
COVID- 19 are symptoms related to the peripheral oxygen saturation 98% at 3 liters/min
respiratory tract which include fever, cough, sore nasal cannula. Lung physical examination found
throat, weakness and other complications rough crackles in both lung fields. Heart
related to pneumonia and respiratory distress examination showed a cardiomegaly. Abdominal
syndrome.3 In early studies, hydroxychloroquine and extremity examinations were within normal
(HCQ) has been touted as a promising therapy finding. The laboratory tests showed hemoglobin
for COVID-19 for showing increasing viral of 11.2 g/dL, leukocytes 18,900 cells/mm3,
clearance and clinical improvements.4 In platelets cells 648,000 /mm3, glutamic-
Indonesia, HCQ, alone or in combination with oxaloacetic transaminase 48 g/dL, glutamic-
azithromycin or other antiviral and supportive pyruvic transaminase 42 g/dL, creatinine 0.7
drugs, has been used to treat suspected and g/dL, sodium 132 meq/L, potassium 4.9 meq/L,
confirmed cases of COVID-19.5 Since its chloride 100 meq/L, hs-CRP 135 mg/L, ferritin
approval in 1955, there have been post-market 596 mg/dL, procalcitonin 0.48 ng/mL, hs-
reports of corrected QT (QTc) interval troponin I 7.3 ng/L and NT-pro BNP 344.7
prolongation that may lead to lethal arrhythmias pg/mL. Blood gas analysis: pH 7.4, pO2 90%,
like torsades de pointes (TdP).6-9 pCO2 31.2%, SO2 98%, HCO3 23, BE -0.6,
Studies evaluating HCQ in COVID-19 patients AaDO2 84.6, PO2 / FiO2 316.2.
reported that 2 out of 189 patients developed The ECG examination showed sinus
ventricular arrhythmia and other 2 patients tachycardia, normal axis, first-degree
developed atrioventricular block and left bundle atrioventricular block, left ventricular hypertrophy
branch block.10 However, if HCQ is proven to (figure 1). The calculation of QTc was 480 ms
be lifesaving for COVID-19 patients, evaluating (Bazett’s formula) (figure 1). The Tisdale score
the QT interval to mitigate the risk of lethal on admission of this patient was 12 (loop
arrhythmias will be critical. In this case report, diuretics use: 1, admission QTc ≥450 ms: 2, ≥ 2
we report a case of adult Indonesian patients QTc-prolonging drugs: 6 and heart failure: 3)
suspected COVID-19 pneumonia who received and classified as high risk category (table 1).
HCQ as one of medications. During course of The chest x-ray examination indicated
treatment, the electrocardiogram (ECG) showed cardiomegaly and pneumonia in the right lung
deterioration of cardiac conduction, one patient (figure 2).
developed a prolonged QTc interval >500 ms The patient was consulted to Internist-
and one patient experienced deterioration of Pulmonologist and was assessed as suspected
atrioventricular block, which required stopping COVID-19 pneumonia with moderate severity
the drug. and heart failure and hypertension as
comorbidities. The patient was performed
CASE REPORT 1 nasopharyngeal swabs twice in consecutive
A 26-year-old male was brought to the days. The patient was treated in the COVID-19
Emergency Unit of Dr. Sardjito Hospital, dedicated ward and given treatment with
Yogyakarta, Indonesia with the main complaints intravenous cefriaxon 1 gram b.i.d., intravenous
of dry cough, shortness of breath and fever. The furosemide 20 mg q.i.d., oral candesartan 8 mg
complaints were felt for 7 days. The patient had q.i.d., oral slow release KCl 1 tablet q.i.d, oral
a history of pulmonary tuberculosis treatment azythromycin 500 mg q.i.d, and intravenous
and hypertension, with irregular treatments. No vitamin C 400 mg/8 hours. The oral HCQ was
history of the beta blocker or digitalis use given as 400 mg b.i.d for day 1 followed by 400
(antiarrhythmia drugs). On admission, the mg q.i.d for the next days.
hospital screening score for COVID-19 indicated The ECG evaluation after 3 hours second dose

of HCQ showed sinus tachycardia, high-degree CASE REPORT 2
atrioventricular block with junctional escape beat A 48-year-old woman presented to the
and left bundle branch block (figure 3). At that emergency room of Dr. Sardjito Hospital,
time, the patient did not have any additional Yogyakarta, Indonesia with a four- day history of
complaints. The vital signs were as follows: fever and multiple episodes of vomiting before
blood pressure 170/60 mmHg, pulse 58 bpm, admission. The patient specifically denied
breathing rate 26 times/min, and body having a history of flu-like symptoms, dyspnea,
temperature 36.8 ºC. Because there was an and any history of comorbidities. She further
alteration in ECG from first-degree denied any diuretic treatments, laxative
atrioventricular block degenerating into high- medication, or ingestion of any other medication.
degree atrioventricular block and left bundle On admission, the hospital screening score for
branch block with prolonged QTc interval, the COVID-19 indicated that he had high probability
Cardiologist was consulted. The deteriorating score.
atrioventricular block in this patient was The physical examinations were as follows: fully
considered to be due to the effect of HCQ, conscious, body temperature 36.6ºC, blood
especially in combination with azythromycin. pressure 80/40 mmHg, tachycardia (109 bpm)
Another possibility was the acute viral/bacterial and tachypnea (22 times/min) and peripheral
myocarditis. The results of PCR SARS-CoV-2 oxygen saturation 96% at 3 liters/min nasal
from nasopharyngeal swabs were twice negative cannula. Clinical laboratory findings at the time
(on day 0 and day +1). Therefore, the of admission showed hypokalemia (potassium
Cardiologist decided to discontinue HCQ and level 2.7 mmol/L). Other laboratory examinations
the patient was put on continuous heart monitor were as follows: thrombocyte 46.000/μL,
apparatus. No steroids or antiinflammation were lymphocyte 7.5 %, albumin 2.51 g/dL, glutamic
added. aspartate transaminase 46 U/L, blood urea
On day+1, the ECG evaluation (24 hours after nitrogen 34.7 mg/L, creatinine 2.58 mg/dL,
HCQ termination) showed sinus tachycardia, procalcitonine >200 ng/mL, and C-reactive
second-degree atrioventricular block Mobitz type protein >150 mg/L. Other laboratory tests were
II, left ventricle hypertrophy and QTc 380 ms normal. Thorax radiology showed bilateral
(Bazett’s formula) at heart rate of 110 bpm pneumonia and cardiomegaly (Figure 7). Her
(figure 4). The complaints of progressing initial ECG showed sinus rhythm with QTc
shortness of breath, chest pain, dizziness or interval of 423 ms according to Bazett’s formula
palpitations were not found. On day+2, the ECG and low voltage in precordial leads (Figure 8).
showed sinus tachycardia, first-degree The patient was assessed to be in septic shock,
atrioventricular block, left ventricular pneumonia suspected of COVID-19 and
hypertrophy, and QTc 352 ms (Bazett’s formula) hypokalemia. She was given titrating dose of
at heart rate of 110 bpm (figure 5). The patient norepinephrine 0.05 µg/kg/min, oral HCQ 200
felt better and clinical condition improved. On mg b.i.d, oral oseltamivir 150 mg b.i.d, KCl 25
day+3 until day+5, the patient clinical condition mEq infusion over 24 hours, meropenem 1 gr
improved and uneventful. The subjective and per 12 hours per- iv, vitamin C 1000 gr b.i.d, and
objective parameters for pneumonia and heart selenium 400 mcg q.i.d. The Tisdale score was
failure were improved. The daily ECG evaluation moderate risk (table 1). The ECG monitor and
showed sinus tachycardia and first-degree QTc evaluation was performed daily. On the
atrioventricular block. On day+7, the ECG day+1, her ECG showed sinus rhythm with QTc
evaluation was sinus tachycardia (120 time/min), interval of 460 ms (Bazett’s formula) at heart
PR interval 200 ms and left ventricular rate of 70 bpm (Figure 9). On the day+2, her
hyperthrophy and QTc 380 ms (Bazett’s ECG showed sinus rhythm with QTc interval of
formula) at heart rate of 110 bpm (figure 6). The 581 ms (Bazett’s formula) at heart rate of 75
patient was stable and discharge home. The bpm (Figure 10). On the day+3, her ECG
cardiac abnormality would be followed up on showed sinus rhythm with QTc interval of 537
outpatient setting after discharge.

ms (Bazett’s formula) at heart rate of 64 bpm hypoventilation, bradycardia, arrhythmia and
(Figure 11). Her potassium level on the day+3 seizures.13 Hydroxychloroquine is quickly
was 3.17 mmol/L. At the beginning, the decision absorbed from gastrointestinal tract and usually
was to administer HCQ for five days; however, it within the first 1–3 hour later the onset of
was stopped prematurely owing to a prolonged symptoms develop.13 The duration of its effect
QTc > 500 ms and an interval increased by is short-lived, usually no more than 24 hour.13
more than 60 ms compared to baseline. Her Acute chloroquine poisoning effect has been
norepinephrine treatment was stopped on the reported to slow the atrioventricular conduction
day+7. Other medications were continued based (prolonged PR interval), in addition to its effects
on clinical conditions. The PCR detection of on QT interval prolongation, T wave inversion
SARS-CoV-2 from two nasopharyngeal swabs and ST-segment depression.14 Usually
showed negative results and she was atrioventricular block occurred in chronic usage
discharged from the hospital without any of chloroquine.15 This acute toxicity effect
remaining complaints after eleven days of occurs after ingestion of high-dose chloroquine
hospitalization. or HCQ. However, the underlying cause such as
DISCUSSION heart failure or previous arrhytmia may
The management strategy of COVID-19 therapy precipitate ECG abnormality even in lower dose.
is still a challenge today. A report of studies The acute myocarditis may also the reason for
which stated that hydroxycloroquine alone or in deterioration of atrioventricular conduction, this
combination with azithromycin would cause a was based on elevated hs-CRP levels, slightly
reduction in viral shedding from COVID-19.4,11 increased hs- troponin I and signs of acute heart
In cohort of 90 patients with COVID- 19, HCQ failure. The patient had previous history of
alone or in combination with azithromycin pose hypertension and tuberculosis short medication.
increased risk to develop prolongation of The incidence of high-degree AV block due to
corrected QT interval.7 In patient with underlying acute myocarditis was 1.1%, and Asian race has
cardiac condition infected with COVID-19 or preponderance.16 Acute inflammation
cardiac involvement due to COVID-19, the permeates into the atrioventricular node and
preponderance of cardiac complication is infra-Hisian conduction system make transitory
greater.7 In the first case, the combination of atrioventricular conduction blockade and bundle
azithromycin 500 mg q.i.d and HCQ 400 mg branch blockade which will resolve during the
b.i.d per oral was administered on day 0. On convalescence course.16 Since SARS-CoV-2
admission, the Tisdale score indicated high risk PCRs were negative, the use of HCQ was
to develop QTc prolongation. The American terminated and other treatment for underlying
College of Cardiology (ACC) issued guidelines cause and cardiac monitoring were continued.
that the use of azithromycin and/or HCQ for The improved atrioventricular conduction after
COVID-19 need concomitant ECG monitoring of stopping HCQ was observed. However, due to
QTc interval and adjusting the dose according to hospital constraint due to COVID-19 pandemic,
the QTc interval.12 Based on this guidance, we could not perform cardiac disease work-up,
after 3 hours from the second dose of HCQ we such echocardiography and cardiac imaging in
evaluated ECG and found the deterioration of this patient during current admission. After
first-degree atrioventricular block become high- seven days hospitalization, the patient condition
degree atrioventricular block and left bundle was improved uneventful.
branch block after ingestion of azithromycin 500 In the second case, the patient received HCQ
mg and HCQ 800 mg oral loading. The QTc due to suspected COVID-19. In this case,
interval during high-degree atrioventricular block meropenem was chosen over azithromycin as
was prolonged. After stopping the HCQ, the the antibiotic is often used for empirical
ECG returned to baseline. We speculated that treatment of infections in critically ill patients with
HCQ worsened the atrioventricular blockade in acute kidney injuries.17 This patient has an
this patient. increased creatinine of 2.58 mg/dL on
Acute HCQ toxicity can manifest as admission, which returned to 0.6 mg/dL on the

third day of treatment. It was highly likely that Hydroxychloroquine has a half-life of 40–50
she experienced acute kidney injury upon days.25 Multiple drugs being used for the
admission. In previous experimental studies, treatment of COVID-19 are CYP3A4 inhibitors
HCQ attributed to a deficit in the glycosylation which can significantly increase serum
receptors of the virus cell, thus can decrease the concentration of CQ and HCQ. In particular, the
affinity of the virus to angiotensin- converting combination of both drugs and lopinavir/ritonavir
enzyme 2 (ACE2) receptors expressed in the or umifenovir/ritonavir is contraindicated
lung, heart, kidney, and intestine.18 HCQ as an because they are a major inhibitor of CYP3A4,
antiinflammatory therapy can significantly thus can further prolong the QT interval.26 In the
reduce the proinflammatory markers and second case, the patient only received
cytokines in severe SARS- Cov-2 patients that oseltamivir, another antiviral that did not
experience cytokine storms (3). HCQ has less interfere with CYP3A4, so the probability of
toxic metabolites than CQ; however, both of polypharmacy-induced QT interval can be
them can cause side effects like nausea, eliminated.
anorexia, skin exanthema, or other more severe The national protocol and the ACC guideline
forms like retinopathies or cardiac propose criteria for dose reduction or drug
arrhythmias.19,20 In the second case, even discontinuation of HCQ if: the QTc after HCQ
though the patient experienced vomiting and administration increased to greater than 500 ms
nausea before admission, she denied another when the baseline QTc is less than 500 ms, the
vomiting after HCQ administration and she did difference between the baseline and evaluation
not have any other complaints. QTc is greater than 60 ms.5,12 Previous reports
Hydroxychloroquine can block the inward showed that QTc interval changes of COVID-19
potassium channel, which further delay the patients treated with HCQ occurred between the
phase 3 repolarization of the cardiac action third and fourth days.26 In the second case, the
potential seen in the ECG as prolonged QT QTc changes started to increase on the
interval with subsequent risk of torsade des Adasdasdas day+1 and progressing into
pointes, ventricular fibrillation, and sudden significant increased on the remaining day.
cardiac death.20 The QTc interval was proposed The exact cause of the QTc prolongation is
because QT interval is influenced by heart rate, difficult to identify for certain. In the second
whereas a higher heart rate produces a shorter case, the ECG was normal and the QTc interval
QT interval and vice versa.21 Bazett’s formula prior to HCQ administration was normal even
has been used most often because of its though the potassium level was below 3 mmol/L
simplicity to estimate the QT interval.22 The and the QTc interval was progressively
QTc interval below 440 ms is considered prolonged during HCQ administration
normal, while between 440 to 460 ms and eventhough the potassium level was corrected
between 440 to 470 are considered borderline in above 3 mmol/L. Thus, a drug-induced QT
men and women, respectively.23 Arrhythmias prolongation was suspected, and since the
occur more frequently if the value is above 500 patient was not given other medications known
ms.23 A study analyzing patients with long QT to be associated with prolonged QT interval,
syndrome reported that there is 20% risk of HCQ was suspected as the cause.
syncope or sudden death in patients with QTc Even in normal ECG, HCQ pose risk to develop
interval below 446 ms and 70% risk of syncope arrhytmia. Tisdale et al. made a scoring system
or sudden death in patients with QTc interval to stratify risk of QT prolongation in patients
above 498 ms.24 In the second case, the QTc receiving drugs with potential QTc
interval progressively rose during shortterm prolongation.12 The incidence of QTc interval
HCQ therapy, at which time the patient did not prolongation in the low (score <7), moderate
make any complaints and did not experience (score 7-10), and high (score ≥ 11) is 15%,
syncope. However, the HCQ therapy was 37%, and 73% respectively.12 In the second
stopped immediately for safety reasons such case, the patient was female; her baseline
that preventing from TdP. potassium was lower than 3.5 mEq/L; she was

in septic shock and received 1 QTc prolongation
drug; her total score was 9 and fell to moderate
risk, meaning that she had more risk of QT
prolongation. However, considering the risks
and benefits, HCQ was still given with daily ECG
monitoring. This case highlights the need for risk
stratification by Tisdale scoring, ECG monitoring
and QTc evaluation based on the risk of QT
prolongation during HCQ therapy alone, in
combination, or during other QT prolonging
antiviral drugs in COVID-19 patients.
We have reported two cases with the early
cardiac adverse effect of short-term usage of
hydroxychloroquine with manifestation of
progressing atrioventricular blockade from first-
degree into high-degree atrioventricular block
and progressing QTc prolongation, which were
reversible after drug discontinuation. These
events occurred in patient with baseline
moderate to high risk Tisdale scores. The ECG
recording and QTc monitoring and scoring
system, such as Tisdale score, need to be
implemented in patient taking HCQ alone or in
combination.

CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest. The patients had signed an informed
consent form to publish the case as anonymous case report.
ACKNOWLEDGEMENT
Authors express sincere gratitude to Residents of Internal Medicine in the wards of Dr. Sardjito General
Hospital for their assistance during data collection. This manuscript received funding from RSUP Dr.
Sardjito, Yogyakarta with contract number: HK.02.03/XI.2/37465/2020 to Anggoro Budi Hartopo as
Principal Investigator.

Figure 1. A 12-lead ECG (upper) and strip (lower) showed sinus tachycardia, normal axis, first-degree
atrioventricular block, and left ventricular hypertrophy (poor R wave progression , Sokolow-Lyon voltage
criteria) and QTc was 480 ms (Bazett’s formula).

Figure 2. The chest x-ray examination showed cardiomegaly and pneumonia in the right lung (AP
projection).

Figure 3. A 12-lead ECG (upper) and strip (lower) showed sinus tachycardia, high-degree atrioventricular
block with junctional escape beat and left bundle branch block and QTc 600 ms (Bazett’s formula).

Figure 4. A 12-lead ECG (upper) and strip (lower) showed sinus tachycardia, second-degree
atrioventricular block Mobitz type II and QTc 380 ms (Bazett’s formula)

Figure 5. A 12-lead ECG (upper) and strip (lower) showed showed sinus tachycardia, first-degree

atrioventricular block, left ventricular hypertrophy, and QTc 352 ms using Bazett’s formula (heart rate of
110 bpm)

Figure 6. ECG just before discharge, showing sinus tachycardia, PR interval 200 ms, left ventricular
hypertrophy and QTc 380 ms using Bazett’s formula (heart rate at 110 bpm).

Figure 7. Chest x-ray of patient on admission showing multiple infiltrates in right and left lung and
cardiomegaly.

Figure 8. ECG prior to starting HCQ (day 0) with measured QT of 360 ms, calculated QTc of 423 ms
using Bazett’s formula (heart rate at 83 bpm).

Figure 9.ECG on day+1, showing measured QT of 426 ms, calculated QTc of 460 ms using Bazett’s
formula (heart rate 70 bpm).

Figure 10. ECG on day+2, showing measured QT of 520 ms, calculated QTc of 581 ms using Bazett’s
formula (heart rate 75 bpm).

Figure 11. ECG on day+3, showing measured QT of 520 ms, calculated QTc of 537 ms using Bazett’s
formula (heart rate 64 bpm).

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DIABETES MANAGEMENT AND SPECIfiC CONSIDERATIONS FOR PATIENTS
WITH DIABETES DURING CORONAVIRUS DISEASES PANDEMIC: A SCOPING

REVIEW

Anggi Lukman Wicaksanaa, b, *, Nuzul Sri Hertanti c, Astri Ferdianac, d, Raden Bowo Pramonoe, f

aDepartment of Medical Surgical Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
bThe Sleman Health and Demographic Surveillance System (HDSS), Universitas Gadjah Mada, Yogyakarta, Indonesia
cCenter for Tropical Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
dFaculty of Medicine, University of Mataram, West Nusa Tenggara, Indonesia
eDepartment of Internal Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

fDr. Sardjito General Hospital, Yogyakarta, Indonesia

ABSTRACT
Background And Aims: The global pandemic of coronavirus (COVID-19) affects almost all countries in
the world, which potentially alter diabetes management. Many diabetes patients are experiencing
barrier of care due to the policy related to COVID-19. This article aims to review the current evidence
on diabetes management and specific considerations during the COVID-19 pandemic for people living
with diabetes. Methods: We conducted a scoping review in PubMed, Science Direct, DOAJ and
Microsoft Academics databases from January 1 to April 17, 2020. Searching terms included “COVID-
19”, “severe acute respi- ratory syndrome coronavirus 2”, and “Diabetes Mellitus” were used. Only
scientific articles discussing diabetes management and specific considerations were selected and
extracted.
Results: A total of 7 articles was selected in the analysis. Most were published in diabetes journals
(85.71%). All articles (100%) discussed diabetes management and 71.43% of them provided diabetes
care in specific considerations. We discussed issue of diabetes management in glycemic control and
moni- toring, dietary intake, physical activity, medication, education and prevention of COVID-19
infection that applicable for diabetes patients. In addition, specific considerations explored caring for
diabetes in children and adolescents, pregnancy, elderly, emergency or critical care, to offer certain
concern for raising the awareness.
Conclusions: This review specifies a summary of diabetes management as well as the particular con-
siderations to care people living with diabetes during COVID-19 pandemic. Patients, health care pro-
viders, and policy makers could take advantage of the review to assist diabetic people passing through
COVID-19 pandemic session with optimum glycemic outcome.

Keyword : COVID-19,Diabetes, Diabetes management Pandemic, Scoping review Special consideration