Retrospective medical record review of all children admitted to the hospital between March 19, 2020 and August 7, 2020 was done. Approval of institutional ethics committee obtained. All children with reverse transcriptase-polymerase chain reaction (RT-PCR) positive for SARS-CoV-2 were studied.

As per institutional protocol, derived from national guidelines [1], every child requiring admission was tested by RT-PCR for SARS-CoV-2 from an Indian Council of Medical Research (ICMR) recognized laboratory. Children who tested positive were admitted to the isolation ward, specially created as per national guidelines [2]. Historical details and pre-existing co-morbidities were recorded. COVID-19 disease characterization was done as per guidelines [1]. Multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) were defined as per standard definition [3,4]. Institutional protocol of care created based on ICMR /GOI recommendations was followed. Some cases of MIS-C/KD included in this study have been previously published [5].

Laboratory investigations and imaging studies were carried as necessary. Therapeutic principles included general supportive therapy, active control of fever, respiratory support with oxygen and/or ventilation as necessary, vasoactive drugs in shock, and active monitoring of organ system dysfunctions. Remdesivir was given to children above 12 years of age with COVID-19 pneumonia. Younger children received it on compassionate grounds with risk explained and an informed consent taken. Intravenous immunoglobulin, pulse methyl-prednisolone, and anticoagulation with low-molecular-weight heparin were used as per protocol. Repeat testing for SARS-CoV-2 PCR and discharge criteria were followed as per guidelines [1]. Time taken to PCR negativity and duration of hospital stay was noted. Treatment outcomes were defined as discharged or died.

SARS-CoV-2 positive children in this cohort were classified into Group I comprising of previously healthy children, and Group II with children having co-morbidities like heart disease, diabetes, malignancy, malnutrition, renal, hepatobiliary, neurological, surgical/orthopedic conditions, etc. Variables were compared between the groups.

Statistical analyses: Data was entered in MS Excel, and coded and analyzed in statistical software STATA, version 10.1 (Stata Corp.). Pearson Chi-square test was used for assessing significance of association　between outcome (mortality/discharge) and exposure variables/predictors. Binomial　test for difference in　proportions was also used to compare proportions in sub-groups or categories in two groups. Student t-test or Mann–Whitney test was performed to assess significance of difference in means or medians in two independent groups. Binary multiple logistic regression model was applied to identify predictors of mortality accounting for the role of other factors, wherein adjusted odds ratio (OR) and 95% Confidence Intervals (CI) were estimated.　　A P value of <0.05 was considered statistically significant for all the comparisons.

Of 969 children admitted during the study period, 123 (12.8%) tested positive for SARS-CoV-2 including 16 (13%) extramural neonates. Five (4.1%) had a history of travel. The median (IQR) age at presentation was 3 (0.7–6.0) year with a male: female ratio of 1.36 (Table I).

The study highlights the clinical characteristics, disease progression, and outcome of 123 children admitted with COVID-19. As admitted children were enrolled, the data likely represents individuals from the moderate-to-severe end of the disease spectrum.

The proportion of previously healthy children was 62%. In a study from Columbia Pediatric COVID-19 management group co-morbidities defined as obesity, asthma, infancy or immune suppression were studied [6].Recent data from US studied chronic lung disease, cardiovascular disease and immune suppression as the common co-morbidities [7].Twenty seven (21.7%) children were asymptomatic comparable to the meta-analysis where 23% were asymptomatic [8]. Initial studies from China reported 4.1-50% cases to be asymptomatic, while 58% were asymptomatic in a study from Pune [9,10].Fever and respiratory symptoms were the common presenting symptoms as also found by others [8-10]. Atypical presentations like seizures (10.6%), gastrointestinal symptoms (12.2%) were more common in this series as compared to other studies[7,10,11]. More children in our cohort had severe disease as compared to only 1% as reported in recent retrospective study from China[12].Children with underlying hemato-oncological, renal or cardiac disorders had severe disease. Interestingly, the immune response of COVID-19, the MIS-C/KD was found more in Group I than Group II. This has been reported in other studies also[5,13].Presence of comorbidity dysregulates or blunts the immunological host responses causing severe infection but a hyper-inflammatory immune response like MIS-C/KD is not seen.

Need for intensive care in our series is similar to that reported in literature [14]. Adult studies suggest presence of co-morbidities as an important predictor of need for intensive care[15], which was not found by us. Children requiring mechanical ventilation (15.5%) were fewer than the cohort from USA [6,16] as we had more non-respiratory presentations.

A study of children from the European cohort concluded that neonates, male sex, pre-existing medical conditions, fever, lower respiratory tract infection, radiological changes of pneumonia or ARDS, and viral co-infection were associated with more severe course on univariate analysis; however, these were not correlated to mortality [11]. In our cohort, male sex, hypoxia (SpO2 <94%) on admission, need for respiratory support, inotropes, intensive care, length of hospital stay <10 days was significantly associated with mortality. Male gender has been associated with a higher risk of severe disease and mortality because of higher ACE-2 receptor expression [17]. On regression analysis, SpO2 <94% on admission and length of hospital stay of <10 days were predictors of mortality and not the presence of co-morbidities. This need to be corroborated with a bigger sample size. Experience from adult studies has shown mortality within 1 to 2 weeks of ICU admission [15].

As a retrospective study, certain important parameters like onset of symptoms from day of contact, source of infection, and exact duration of COVID-19 RT-PCR positivity in all children could not be assessed.

To conclude, pediatric COVID-19 although considered a mild illness, children with co morbidity manifest with severe disease. Male sex, hypoxia on admission, need for intensive care, ventilator support, inotrope, hospital stay of <10 days are predictors of mortality. Policy of testing all admitted children for COVID-19 helps identify and segregate the cases, provide protocol based care, characterize the severity, initiate prompt treatment and improve outcome.

Contributors: SR,SSP,SBP: conceived, designed the study, finalised the manuscript; SR,VG,RM, LRD,SBP,SSP,MB: data collection, data analysis; SR,VG,RM,LRD,SSP,SBP: Literature search, interpretation of data, writing manuscript. All authors approved the final manuscript.

Ethics clearance: Institutional Ethics Committee Bai Jerbai Wadia Hospital for Children; No. IEC-BJWHC/ 89/2020, dated 26 August, 2020.

Funding: None; Competing interests: None stated.

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