Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.

Importance: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. Objective: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. Design, setting and participants: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. Intervention: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). Main outcome measures: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O ₂ therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. Results: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7–13) (p=0.328). The median duration of O ₂ therapy was 8 days (IQR=6–12) in COPLA and 10 days (IQR=6–12) in SMT group (p=0.64). The PaO ₂ /FiO ₂ ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80–80)) were higher than SMT group (0 (IQR 0–80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. Conclusion and relevance: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. Trial registration number: NCT04425915 .

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

Mucormycosis is an infrequent but fatal illness that mainly affects patients with uncontrolled diabetes mellitus, diabetic ketoacidosis, solid and hematologic neoplasms, organ transplantation, chronic steroid intake, prolonged neutropenia, iron overload states, neonatal prematurity, severe malnutrition, and HIV. Many cases were reported across the world recently following the COVID-19 pandemic. Recent research has led to a better understanding of the pathogenesis of the disease, and global guidelines are now available for managing this serious infection. Herein, we comprehensively review the etiological agents, pathogenesis, clinical presentations, diagnosis, and management of mucormycosis.

A previous community-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in Delhi in January 2021 reported a seroprevalence of 50.52%. We conducted a repeat serosurvey to obtain a recent estimate of the seroprevalence of IgG SARS-CoV-2 in the general population of Delhi, India. This cross-sectional study was conducted from September 24 to October 14, 2021, in 274 wards of Delhi among 27,811 participants through a multistage sampling technique. The crude seroprevalence was 89.5% (95% CI 89.1, 89.8), weight for age and sex was 88% (95% CI 87.6, 88.4), and after adjustment for assay performance was estimated as 97.5% (95% CI 97.0, 98.0). On adjusted analysis, the odds of seroconversion in the participants vaccinated with at least one dose of either COVID-19 vaccine (Covishield/Covaxin) was more than four times compared to the unvaccinated ones (aOR 4.2 (3.8, 4.6)). 86.8% of the seropositive individuals had a SARS-CoV-2 signal/cut-off ≥4.0 although it was significantly lower in the pediatric age group. Post-second wave (August to October 2021), on average there were daily 39 new COVID-19 cases and 0.44 deaths which during Omicron driven the third wave in January to March 2022 increased to daily 4,267 cases and 11.6 deaths. A high prevalence of IgG antibodies against SARS-CoV-2 with likely higher antibody titres in the vaccinated compared to the unvaccinated groups with evidence of hybrid immunity in a majority of the population was protective against severe disease during transmission of subsequent omicron variants.

Background: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. Methods: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. Results: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.