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.

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.

Probiotics and Coronavirus disease 2019: think about the link.

The pandemic of Coronavirus disease 2019 (COVID-19) is rapidly progressing, causing significant morbidity and mortality. Various antiviral drugs, anti-inflammatory drugs and immunomodulators have been tried without substantial clinical benefits. The severe and critical cases of COVID-19 disease are characterised by gut microbiome dysbiosis, immune dysregulation, hyper-inflammation and hypercytokinaemia (cytokine storm). Therefore, the strategies which target these pathophysiological processes may be beneficial. Probiotics are one such strategy that exerts beneficial effects by manipulation of the gut microbiota, suppression of opportunistic pathogens in the gut, decreasing translocation of opportunistic organisms, activation of mucosal immunity and modulation of the innate and adaptive immune response. Probiotics are the potential candidates to be tested in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, safe and economical to use.

Updated Management Protocol for Multisystem Inflammatory Syndrome in Children (MIS-C).

The multisystem inflammatory syndrome in children (MIS-C) is a post-viral immunological or hyper-inflammatory complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection commonly seen in older children, who commonly present with fever, multi-systemic involvement including myocardial dysfunction and shock, and hyper-inflammation. The treatment of MIS-C is adapted from the treatment of other immunological or hyper-inflammatory conditions and these treatment protocols are not uniform across the globe, and more so, in India. We propose a uniform management protocol for MIS-C based on our experience of treating MIS-C cases, available evidence till now, and recent guidelines. The aims are to identify children with MIS-C with high sensitivity, recognize other infections or inflammatory processes, stratify treatment based on severity, and manage hyper-inflammatory syndrome.

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.

Acral Gangrene: Ugly Cousin of "COVID Toes" in Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2?

A spectrum of dermatologic manifestations has been reported in multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. We report 2 patients with multisystem inflammatory syndrome in children and severe cardiovascular dysfunction who developed acral gangrene. Both responded well to therapy and recovered in the follow-up.

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.

Clinicolaboratory Profile, Treatment, Intensive Care Needs, and Outcome of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2: A Systematic Review and Meta-analysis.

This study was aimed to summarize the current data on clinicolaboratory features, treatment, intensive care needs, and outcome of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2; PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C). Articles published in PubMed, Web of Science, Scopus, Google Scholar, and novel coronavirus disease 2019 (COVID-19) research database of World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) database, and Cochrane COVID-19 study register between December 1, 2019 and July 10, 2020. Observational studies involving patients <21 years with PIMS-TS or MIS-C were reported the clinicolaboratory features, treatment, intensive care needs, and outcome. The search identified 422 citations and finally 18 studies with 833 participants that were included in this study, and pooled estimate was calculated for parameters of interest utilizing random effect model. The median age was 9 (range: 8-11) years. Fever, gastrointestinal symptoms, rash, conjunctival injection, and respiratory symptoms were common clinical features. Majority (84%) had positive SARS-CoV-2 antibody test and only one-third had positive reverse transcript polymerase chain reaction (RT-PCR). The most common laboratory abnormalities noted were elevated C-reactive protein (CRP), D-dimer, procalcitonin, brain natriuretic peptide (BNP), fibrinogen, ferritin, troponin, interleukin 6 (IL-6), lymphopenia, hypoalbuminemia, and thrombocytopenia. Cardiovascular complications included shock (65%), myocardial dysfunction (61%), myocarditis (65%), and coronary artery abnormalities (39%). Three-fourths of children required admission to pediatric intensive care unit (PICU) where they received vasoactive medications (61%) and mechanical ventilation (25%). Treatment strategies used included intravenous immunoglobulin (IVIg; 82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). Mortality for patients with PIMS-TS or MIS-C was low ( n = 13). In this systematic review, we highlight key clinical features, laboratory findings, therapeutic strategies, intensive care needs, and observed outcomes for patients with PIMS-TS or MIS-C. Commonly observed clinical manifestations include fever, gastrointestinal symptoms, mucocutaneous findings, cardiac dysfunction, shock, and evidence of hyperinflammation. The majority of children required PICU admission, received immunomodulatory treatment, and had good outcome with low mortality.

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.