Evaluation of a Hospitalized Pediatric COVID-19 Cohort from Indian National Clinical Registry of COVID-19.

OBJECTIVE: To evaluate the factors associated with mortality of a multicentric cohort of hospitalized COVID-19 patients, 0-18 y old, from 42 centers across India. METHODS: The National Clinical Registry for COVID-19 (NCRC) is an on-going prospective data collection platform enrolling COVID-19 patients diagnosed by real-time PCR or rapid antigen test. The data are collected in prestructured e-capture forms. The sociodemographic, clinical, laboratory, and hospital outcome data from 1st September 2020 to 20th February 2022 were analyzed. RESULTS: Of the 1244 enrolled hospitalized COVID-19 patients aged 0-18 y, 98 and 124 were infants and neonates, respectively. Only 68.6% children were symptomatic at admission, with fever being the most common symptom. Diarrhea, rash, and neurological symptoms were also noted. At least 1 comorbidity was present in 260 (21%) children. The in-hospital mortality rate was 6.2% (n = 67), the highest in infants (12.5%). Altered sensorium (aOR: 6.8, CI: 1.9, 24.6), WHO ordinal scale ≥ 4 at admission (aOR: 19.6, CI: 8.0, 47.8), and malignancy (aOR: 8.9, 95% CI: 2.4, 32.3) were associated with higher odds of death. Malnutrition did not affect the outcome. Mortality rates were similar across the three waves of the pandemic, though a significant shift towards the under-five group was observed in the third wave. CONCLUSION: This multicentric cohort of admitted Indian children showed that the COVID-19 was milder in children than adults, and the pattern was consistent across all waves of the pandemic.

Mortality audit of COVID-19 infection among children.

Background & objectives: As severe COVID-19 and mortality are not common in children, there is a scarcity of data regarding the cause of mortality in children infected with SARS-CoV-2. This study was aimed to describe the all-cause mortality and COVID-19 death (disease-specific mortality) in children with SARS-CoV-2 infection admitted to a paediatric COVID facility in a tertiary care centre. Methods: Data with respect to clinical, epidemiological profile and causes of death in non-survivors (0-12 yr old) of SARS-CoV-2 infection admitted to a dedicated tertiary care COVID hospital in north India between April 2020 and June 2021 were retrieved and analyzed retrospectively. Results: A total of 475 SARS-CoV-2-positive children were admitted during the study period, of whom 47 died [18 neonates, 14 post-neonatal infants and 15 children (1-12 yr of age)]. The all-cause mortality and COVID-19 death (disease-specific mortality) were 9.9 per cent (47 of 475) and 1.9 per cent (9 of 475), respectively. Underlying comorbidities were present in 35 (74.5%) children, the most common being prematurity and perinatal complications (n=11, 24%) followed by congenital heart disease (n=6, 13%). The common causes of death included septic shock in 10 (21%), COVID pneumonia/severe acute respiratory distress syndrome in nine (19%), neonatal illnesses in eight (17%), primary central nervous system disease in seven (15%) and congenital heart disease with complication in six (13%) children. Interpretation & conclusions: Our results showed a high prevalence of underlying comorbidities and a low COVID-19 death (disease-specific mortality). Our findings highlight that mortality due to COVID-19 can be overestimated if COVID-19 death and all-cause mortality in children infected with SARS-CoV-2 are not separated. Standardized recording of cause of death in children with SARS-CoV-2 infection is important.

Epidemiology, Clinical Profile, Intensive Care Needs and Outcome in Children with SARS-CoV-2 Infection Admitted to a Tertiary Hospital During the First and Second Waves of the COVID-19 Pandemic in India.

OBJECTIVES: To compare the epidemiological, clinical profile, intensive care needs and outcome of children hospitalized with SARS-CoV-2 infection during the first and second waves of the pandemic. METHODS: This was a retrospective study of all children between 1 mo and 14 y, admitted to a dedicated COVID-19 hospital (DCH) during the first (1st June to 31st December 2020) and second waves (1st March to 30th June 2021). RESULTS: Of 217 children, 104 (48%) and 113 (52%) were admitted during the first and second waves respectively. One hundred fifty-two (70%) had incidentally detected SARS-CoV-2 infection, while 65 (30%) had symptomatic COVID-19. Comorbidities were noted in 137 (63%) children. Fifty-nine (27%) and 66 (30%) children required high-dependency unit (HDU) and ICU care respectively. Severity of infection and ICU needs were similar during both waves. High-flow oxygen (n = 5, 2%), noninvasive ventilation [CPAP (n = 34, 16%) and BiPAP (n = 8, 5%)] and invasive ventilation (n = 45, 21%) were respiratory support therapies needed. NIV use was more during the second wave (26% vs. 13%; p = 0.02). The median (IQR) length (days) of DCH stay among survivors was longer during the first wave [8 (6-10) vs. 5.5 (3-8); p = 0.0001]. CONCLUSIONS: Disease severity, associated comorbidities, PICU and organ support need and mortality were similar in the first and second waves of the pandemic. Children admitted during the second wave were younger, had higher proportion of NIV use and shorter length of COVID-19 hospital stay.

Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India.

OBJECTIVES: To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY: This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS: The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION: MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.

Changes Adopted in Asian Pediatric Hospitals during the COVID-19 Pandemic: A Report from the Pediatric Acute and Critical Care COVID-19 Registry of Asia

There is wide variation in the overall clinical impact of novel coronavirus disease 2019 (COVID-19) across countries worldwide. Changes adopted pertaining to the management of pediatric patients, in particular, the provision of respiratory support during the COVID-19 pandemic is poorly described in Asia. We performed a multicenter survey of 20 Asian pediatric hospitals to determine workflow changes adopted during the pandemic. Data from centers of high-income (HIC), upper middle income (UMIC), and lower middle income (LMIC) countries were compared. All 20 sites over nine countries (HIC: Japan [4] and Singapore [2];UMIC: China [3], Malaysia [3] and Thailand [2];and LMIC: India [1], Indonesia [2], Pakistan [1], and Philippines [2]) responded to this survey. This survey demonstrated substantial outbreak adaptability. The major differences between the three income categories were that HICs were (1) more able/willing to minimize use of noninvasive ventilation or high-flow nasal cannula therapy in favor of early intubation, and (2) had greater availability of negative-pressure rooms and powered air-purifying respirators. Further research into the best practices for respiratory support are warranted. In particular, innovation on cost-effective measures in infection control and respiratory support in the LMIC setting should be considered in preparation for future waves of COVID-19 infection.

Multisystem Inflammatory Syndrome in Children: Follow-Up of a Cohort from North India.

Multisystem inflammatory syndrome in children (MIC-S) is a hyperinflammatory manifestation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Information on the long-term outcome of MIS-C is limited. This study was conducted to describe the long-term outcome of MIS-C from a tertiary care center in North India. Children admitted with MIS-C from September 2020 to January 2021 were followed up after discharge until June 2021. The details during the acute phase (clinical features, investigations, treatment, and outcome) and follow-up (symptoms, echocardiographic findings, ongoing treatment, and outcome) were collected retrospectively. During the acute phase, 40 children presented at median (interquartile range [IQR]) age of 7 (5-10) years with fever, mucocutaneous, gastrointestinal, and respiratory symptoms. The majority (66.7%) of the children had positive SARS-CoV-2 serology and elevated inflammatory markers (C-reactive protein, procalcitonin, ferritin, D-dimer, and fibrinogen), lymphopenia, and thrombocytopenia. Eighty percent had shock, 72.5% had myocardial dysfunction (left ventricular ejection fraction <55%), and 22.5% had coronary artery dilatation or aneurysm. Treatment included pediatric intensive care unit admission (85%), intravenous immunoglobulin (100%), steroids (85%), aspirin (80%), vasoactive drugs (72.5%), and invasive mechanical ventilation (22.5%). Two (5%) children died because of refractory shock. Thirty-four children were followed up with until a median (IQR) of 5 (3-6) months. During the follow-up, a majority were asymptomatic, myocardial function returned to normal in all, and only one had coronary artery aneurysm. Prednisolone and aspirin were given for a median (IQR) of 3 (2-4) weeks and 4 (4-6) weeks after discharge, respectively. There was one readmission and no death during the follow-up. To conclude, the long-term outcome of MIS-C is generally favorable with resolution of cardiovascular manifestations (myocardial dysfunction and coronary artery changes) in the majority of children during follow-up.

Impact of Recent SARS-CoV-2 Infection on the Course and Severity of Dengue in Children: A Prospective Observational Study from North India.

In 2020, a considerable overlap occurred between the COVID-19 pandemic and seasonal dengue transmission in India. This study aimed to evaluate the effects of acute or recent infection with SARS-CoV-2 on the course and outcomes of dengue fever in children. We prospectively enrolled 44 children with a clinical and laboratory diagnosis of dengue fever. Assessment of acute and recent SARS-CoV-2 infection was done using reverse transcription-polymerase chain reaction and IgG antibody through ELISA. Children were grouped based on evidence of SARS-CoV-2 exposure and clinical severity, and outcomes were compared. The median age of the study cohort was 96 months (interquartile range [IQR]: 69-129 months). Fever (98%), vomiting (78%), abdominal pain (68%), hepatomegaly (68%), and edema (32%) were the common features. About two-thirds (N = 30) had severe dengue; 20 (45%) had dengue shock. Liver dysfunction (58%) and acute kidney injury (25%) were other major organ dysfunctions. Nineteen (43%) children stayed in the pediatric intensive care unit for a median duration of 5 days (IQR: 2-11 days). None had acute SARS-CoV2 infection; however, IgG against SARS-CoV-2 was detected in 15 (34%) cases. Children with recent exposure to SARS-CoV-2 showed a trend toward a lower incidence of acute kidney injury, fewer organ dysfunctions, and a lower frequency of invasive ventilation. Four children (9%) died; none of the deaths were in the SARS-CoV-2-exposed group. The present study exposes preliminary evidence that dengue fever might follow a less severe course in children with recent exposure to SARS-CoV-2 infection. However, it is pertinent to understand the antigenic similarity and cross-protective antibody response between the two viruses and their clinical relevance.

Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience from North India.

OBJECTIVES: To describe the intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C). METHODOLOGY: This retrospective study was conducted in the pediatric emergency, pediatric intensive care unit (PICUs) and the coronavirus disease 2019 (COVID 19) hospital of a tertiary teaching and referral hospital in North India over a period of 5 months (September 2020 to January 2021). Clinical details, laboratory investigations, intensive care needs, treatment and short-term outcome were recorded. RESULTS: Forty children with median interquartile range age of 7 (5-10) years were enrolled. The common clinical features were fever (97.5%), mucocutaneous involvement (80%), abdominal (72.5%) and respiratory (50%) symptoms. Shock was noted in 80% children. Most cases (85%) required PICU admission where they received nasal prong oxygen (40%), non-invasive (22.5%) and invasive (22.5%) ventilation and vasoactive drug support (72.5%). The confirmation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposure was in the form of positive serology (66.7%), reverse transcriptase polymerase chain reaction (10%), and contact with SARS-CoV-2 positive case (12.5%). The common echocardiographic findings included myocardial dysfunction (ejection fraction <55%; 72.5%), and coronary artery dilatation or aneurysm (22.5%). The immunomodulatory treatment included intravenous immunoglobulin (2 g/kg) (100%) and steroids (methylprednisolone 10-30 mg/kg/day for 3-5 days) (85%). Aspirin was used in 80% and heparin (low molecular weight) in 7.5% cases. Two children died (5%) and median duration of PICU and hospital stay in survivors were 5 (2-8) and 7 (4-9) days, respectively. Children with shock showed higher total leucocyte count and higher rates of myocardial dysfunction. CONCLUSION: Cardiovascular involvement and shock are predominant features in severe disease. Early diagnosis can be challenging given the overlapping features with other diagnoses. A high index of suspicion is warranted in children with constellation of fever, mucocutaneous, gastrointestinal and cardiovascular involvement alongwith evidence of systemic inflammation and recent or concurrent SARS-CoV-2 infection. The short-term outcome is good with appropriate organ support therapies and immunomodulation.

Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China.

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.

Biomarkers in COVID-19: An Up-To-Date Review.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) poses several challenges to clinicians. Timely diagnosis and hospitalization, risk stratification, effective utilization of intensive care services, selection of appropriate therapies, monitoring and timely discharge are essential to save the maximum number of lives. Clinical assessment is indispensable, but laboratory markers, or biomarkers, can provide additional, objective information which can significantly impact these components of patient care. COVID-19 is not a localized respiratory infection but a multisystem disease caused by a diffuse systemic process involving a complex interplay of the immunological, inflammatory and coagulative cascades. The understanding of what the virus does to the body and how the body reacts to it has uncovered a gamut of potential biomarkers. This review discusses the different classes of biomarkers - immunological, inflammatory, coagulation, hematological, cardiac, biochemical and miscellaneous - in terms of their pathophysiological basis followed by the current evidence. Differences between children and adults are highlighted. The role of biomarkers in the diagnosis and management of Multisystem Inflammatory Syndrome in Children (MIS-C) is reviewed. The correlation of biomarkers with clinical and radiological features and the viral load, temporal evolution and the effect of treatment remain to be studied in detail. Which biomarker needs to be evaluated when and in whom, and how best this information can contribute to patient care are questions which currently lack convincing answers. With the evidence currently available broad guidelines on the rational use of available biomarkers are presented. Integrating clinical and laboratory data, monitoring trends rather than a single value, correlating with the natural course of the disease and tailoring guidelines to the individual patient and healthcare setting are essential.

Multidimensional dynamic healthcare personnel (HCP)-centric model from a low-income and middle-income country to support and protect COVID-19 warriors: a large prospective cohort study.

OBJECTIVES: Healthcare personnel (HCP) are at an increased risk of acquiring COVID-19 infection especially in resource-restricted healthcare settings, and return to homes unfit for self-isolation, making them apprehensive about COVID-19 duty and transmission risk to their families. We aimed at implementing a novel multidimensional HCP-centric evidence-based, dynamic policy with the objectives to reduce risk of HCP infection, ensure welfare and safety of the HCP and to improve willingness to accept and return to duty. SETTING: Our tertiary care university hospital, with 12 600 HCP, was divided into high-risk, medium-risk and low-risk zones. In the high-risk and medium-risk zones, we organised training, logistic support, postduty HCP welfare and collected feedback, and sent them home after they tested negative for COVID-19. We supervised use of appropriate personal protective equipment (PPE) and kept communication paperless. PARTICIPANTS: We recruited willing low-risk HCP, aged <50 years, with no comorbidities to work in COVID-19 zones. Social distancing, hand hygiene and universal masking were advocated in the low-risk zone. RESULTS: Between 31 March and 20 July 2020, we clinically screened 5553 outpatients, of whom 3012 (54.2%) were COVID-19 suspects managed in the medium-risk zone. Among them, 346 (11.4%) tested COVID-19 positive (57.2% male) and were managed in the high-risk zone with 19 (5.4%) deaths. One (0.08%) of the 1224 HCP in high-risk zone, 6 (0.62%) of 960 HCP in medium-risk zone and 23 (0.18%) of the 12 600 HCP in the low-risk zone tested positive at the end of shift. All the 30 COVID-19-positive HCP have since recovered. This HCP-centric policy resulted in low transmission rates (<1%), ensured satisfaction with training (92%), PPE (90.8%), medical and psychosocial support (79%) and improved acceptance of COVID-19 duty with 54.7% volunteering for re-deployment. CONCLUSION: A multidimensional HCP-centric policy was effective in ensuring safety, satisfaction and welfare of HCP in a resource-poor setting and resulted in a willing workforce to fight the pandemic.

Clinical Profile, Hospital Course and Outcome of Children with COVID-19.

OBJECTIVES: To describe the epidemiological and clinical characteristics and outcome of hospitalized children with COVID-19 during the initial phase of the pandemic. METHODS: This was a cross-sectional descriptive study conducted at the dedicated COVID-19 hospital of a tertiary care referral center in North India. Consecutive children aged 14 y or younger who tested positive for SARS-CoV-2 by RT-PCR from nasopharyngeal swab between 1 April 2020 and 15 July 2020 were included. RESULTS: Of 31 children with median (IQR) age of 33 (9-96) mo, 9 (29%) were infants. About 74% (n = 23) had history of household contact. Comorbidities were noted in 6 (19%) children. More than half (58%) were asymptomatic. Of 13 symptomatic children, median (IQR) duration of symptoms was 2 (1-5.5) d. Fever (32%) was most common followed by cough (19%), rapid breathing (13%), diarrhea (10%) and vomiting (10%). Severe [n = 4, 13%] and critical [n = 1, 3%] illnesses were noted more commonly in infants with comorbidities. Three (10%) children required PICU admission and invasive ventilation; one died. Median (IQR) length of hospital stay was 15 (11-20) d. Follow up RT-PCR before discharge was performed in 17 children and the median (IQR) duration to RT-PCR negativity was 16 (12-19) d. CONCLUSIONS: In the early pandemic, most children with COVID-19 had a household contact and presented with asymptomatic or mild illness. Severe and critical illness were observed in young infants and those with comorbidities.

Changes Adopted in Asian Pediatric Hospitals during the COVID-19 Pandemic: A Report from the Pediatric Acute and Critical Care COVID-19 Registry of Asia.

There is wide variation in the overall clinical impact of novel coronavirus disease 2019 (COVID-19) across countries worldwide. Changes adopted pertaining to the management of pediatric patients, in particular, the provision of respiratory support during the COVID-19 pandemic is poorly described in Asia. We performed a multicenter survey of 20 Asian pediatric hospitals to determine workflow changes adopted during the pandemic. Data from centers of high-income (HIC), upper middle income (UMIC), and lower middle income (LMIC) countries were compared. All 20 sites over nine countries (HIC: Japan [4] and Singapore [2]; UMIC: China [3], Malaysia [3] and Thailand [2]; and LMIC: India [1], Indonesia [2], Pakistan [1], and Philippines [2]) responded to this survey. This survey demonstrated substantial outbreak adaptability. The major differences between the three income categories were that HICs were (1) more able/willing to minimize use of noninvasive ventilation or high-flow nasal cannula therapy in favor of early intubation, and (2) had greater availability of negative-pressure rooms and powered air-purifying respirators. Further research into the best practices for respiratory support are warranted. In particular, innovation on cost-effective measures in infection control and respiratory support in the LMIC setting should be considered in preparation for future waves of COVID-19 infection.

Novel Coronavirus 2019 (2019-nCoV) Infection: Part I - Preparedness and Management in the Pediatric Intensive Care Unit in Resource-limited Settings.

First reported in China, the 2019 novel coronavirus has been spreading across the globe. Till 26 March, 2020, 416,686 cases have been diagnosed and 18,589 have died the world over. The coronavirus disease mainly starts with a respiratory illness and about 5-16% require intensive care management for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Children account for about 1-2% of the total cases, and 6% of these fall under severe or critical category requiring pediatric intensive care unit (PICU) care. Diagnosis involves a combination of clinical and epidemiological features with laboratory confirmation. Preparedness strategies for managing this pandemic are the need of the hour, and involve setting up cohort ICUs with isolation rooms. Re-allocation of resources in managing this crisis involves careful planning, halting elective surgeries and training of healthcare workers. Strict adherence to infection control like personal protective equipment and disinfection is the key to contain the disease transmission. Although many therapies have been tried in various regions, there is a lack of strong evidence to recommend anti-virals or immunomodulatory drugs.