Severe Acute Hepatitis of Unknown Etiology Presenting as Pediatric Acute Liver Failure: Analysis of Likely Etiology, Clinical Course and Outcome.

Adenovirus, adeno-associated virus, and severe acute respiratory syndrome-coronavirus-2 (SARS-COV2) have been recently implicated as probable causative agents of severe acute hepatitis of unknown etiology reported from most of Europe. High mortality and liver transplantation (LT) rates have been observed in those presenting with acute liver failure (ALF). Such cases have not been reported from the Indian subcontinent. We analyzed the etiologies, clinical course, and in-hospital outcomes of cases of severe acute hepatitis with ALF presenting to us between May and October 2022. A total of 178 children presented with severe acute hepatitis of known/unknown etiology including 28 presenting as ALF. Eight of them fulfilled the definition of severe acute hepatitis of unknown etiology presenting as ALF. Adenovirus was not associated with cases of ALF in these children. SARS-COV2 antibodies were detected in 6 (75%) of them. Children with severe acute hepatitis of unknown etiology presenting as ALF were young (median age 4 years), had hyper-acute presentation with a predominance of gastrointestinal symptoms, and a fulminant course with worse outcomes (native liver survival 25%). Expedited evaluation of these children for LT would be the key to management.

Current surge of COVID-19 infection in China and its impact on India.

BACKGROUND: COVID-19, the pandemic caused by the SARS-CoV-2, is a global health calamity and one of the greatest challenges faced by the humankind across the globe. The virus originated in Wuhan, China and spread rapidly to more than 200 countries/nations, affected more than 600 billion individuals and caused around 65 lakh deaths worldwide. Since the start of the pandemic, SARS-CoV-2 mutates and accumulates genetic variations which constantly resulted in the emergence of new variants. OBJECTIVE: The current article discusses about the new omicron sub variant BF.7, and how this BF.7 variant may pose risk in India, if it overrides the current COVID-19 circulating variants. CONTENT: The emergence and potential consequences of the circulating SARS-CoV-2 variants usually augment virus transmissibility and host immune evasion. The current spurt in COVID-19 infections in China which has alarmed people around the world, is believed to be driven by an omicron sub variant BF.7. Although India has been reporting a "steady decline" in COVID-19 cases, we need constant surveillance to keep a track of the new emerging variants in circulation. Keeping in mind, the new surge in COVID-19 cases across many nations, we discuss about the new variant and its possible impact on India.

Household transmission dynamics of COVID-19 among residents of Delhi, India: a prospective case-ascertained study.

Objective: The aim of this study was to observe the secondary infection rate and transmission dynamics of COVID-19 among household contacts, and their associations with various factors across four dimensions of interaction. Methods: This was a case-ascertained study among unvaccinated household contacts of a laboratory-confirmed COVID-19 case in New Delhi between December 2020 and July 2021. For this study, 99 index cases and their 316 household contacts were interviewed and sampled (blood and oro-nasal swab) on days 1, 7, 14, and 28. Results: The secondary infection rate among unvaccinated household contacts was 44.6% (95% confidence interval (CI) 39.1-50.1). The predictors of secondary infection among individual contact levels were: being female (odds ratio (OR) 2.13), increasing age (OR 1.01), symptoms at baseline (OR 3.39), and symptoms during follow-up (OR 3.18). Among index cases, age of the primary case (OR 1.03) and symptoms during follow-up (OR 6.29) were significantly associated with secondary infection. Among household-level and contact patterns, having more rooms (OR 4.44) and taking care of the index case (OR 2.02) were significantly associated with secondary infection. Conclusion: A high secondary infection rate highlights the need to adopt strict measures and advocate COVID-19-appropriate behaviors. A targeted approach for higher-risk household contacts would efficiently limit infections among susceptible contacts.

Co-infection of SARS-CoV-2 with other respiratory pathogens in patients with liver disease.

Respiratory illness caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was first documented in Wuhan, China, in December 2019, followed by its rapid spread across the globe. Accumulating evidence has demonstrated viral/bacterial co-infection in the respiratory tract could modulate disease severity and its outcome in COVID-19 infection. In this retrospective study, 300 chronic liver disease patients with radiologically confirmed lower respiratory tract infection were enrolled from September 2020 to December 2021. In all of them, along with SARS-CoV-2, other respiratory viral/bacterial pathogens were studied. In total, 23.7 % (n=71) patients were positive for SARS-CoV-2. Among the positive patients, 23.9 % (n=17) had co-infection with other respiratory pathogens, bacterial co-infections being dominant. The SARS-CoV-2 negative cohort had 39.7  % positivity (n=91) for other respiratory pathogens, the most common being those of the rhinovirus/enterovirus family. Ground glass opacity (GGO) with consolidation was found to be the most common radiological finding among SARS-CoV-2 positive co-infected patients, as compared to only GGO among SARS-CoV-2 mono-infected patients. Accurate diagnosis of co-infections, especially during pandemics including COVID-19, can ameliorate the treatment and management of suspected cases.

Current surge of COVID-19 infection in China and its impact on India

Background COVID-19, the pandemic caused by the SARS-CoV-2, is a global health calamity and one of the greatest challenges faced by the humankind across the globe. The virus originated in Wuhan, China and spread rapidly to more than 200 countries/nations, affected more than 600 billion individuals and caused around 65 lakh deaths worldwide. Since the start of the pandemic, SARS-CoV-2 mutates and accumulates genetic variations which constantly resulted in the emergence of new variants. Objective The current article discusses about the new omicron sub variant BF.7, and how this BF.7 variant may pose risk in India, if it overrides the current COVID-19 circulating variants. Content The emergence and potential consequences of the circulating SARS-CoV-2 variants usually augment virus transmissibility and host immune evasion. The current spurt in COVID-19 infections in China which has alarmed people around the world, is believed to be driven by an omicron sub variant BF.7. Although India has been reporting a "steady decline" in COVID-19 cases, we need constant surveillance to keep a track of the new emerging variants in circulation. Keeping in mind, the new surge in COVID-19 cases across many nations, we discuss about the new variant and its possible impact on India.

Neutralizing antibody responses to SARS-CoV-2: A population based seroepidemiological analysis.

This study (August-September 2021) estimated the seroprevalence of SARS-CoV-2 neutralizing antibodies in the general population of Delhi and correlated it with their anti-SARS-CoV-2 IgG levels. Samples were selected by simple random sampling method. The neutralizing capacity was estimated by performing a surrogate virus neutralization test (sVNT) (GenScript), Piscataway, NJ, USA. A total of 2233 (87.1%, 95% C.I. 85.7, 88.3) of the 2564 SARS-CoV-2 IgG seropositive samples had detectable SARS-CoV-2 neutralizing antibodies. In samples with S/CO â€‹≥ â€‹4.00, the neutralizing antibodies ranged from 94.5% to 100%. The SARS-CoV-2 neutralizing antibody seroprevalence strongly correlated with the S/CO range of IgG SARS-CoV-2 (r â€‹= â€‹0.62, p â€‹= â€‹0.002).

Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients.

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.

SARS-CoV-2 Seroprevalence in Delhi, India, During September-October 2021: A Population-Based Seroepidemiological Study.

Background 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. Methods 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. Results 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. Conclusion 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.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

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 O2 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 O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 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.

Identification of Potential Vaccine Candidates Against SARS-CoV-2 to Fight COVID-19: Reverse Vaccinology Approach.

Background: The recent emergence of COVID-19 has caused an immense global public health crisis. The etiological agent of COVID-19 is the novel coronavirus SARS-CoV-2. More research in the field of developing effective vaccines against this emergent viral disease is indeed a need of the hour. Objective: The aim of this study was to identify effective vaccine candidates that can offer a new milestone in the battle against COVID-19. Methods: We used a reverse vaccinology approach to explore the SARS-CoV-2 genome among strains prominent in India. Epitopes were predicted and then molecular docking and simulation were used to verify the molecular interaction of the candidate antigenic peptide with corresponding amino acid residues of the host protein. Results: A promising antigenic peptide, GVYFASTEK, from the surface glycoprotein of SARS-CoV-2 (protein accession number QIA98583.1) was predicted to interact with the human major histocompatibility complex (MHC) class I human leukocyte antigen (HLA)-A*11-01 allele, showing up to 90% conservancy and a high antigenicity value. After vigorous analysis, this peptide was predicted to be a suitable epitope capable of inducing a strong cell-mediated immune response against SARS-CoV-2. Conclusions: These results could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable, and effective platform to provide a timely countermeasure against this dangerous virus responsible for the COVID-19 pandemic.

The neglected pathogen: case reports of severe lower respiratory tract infection by human coronavirus 229E.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues, other previously ignored viruses must be taken into account as causes of severe acute respiratory distress, influenza-like illness and pneumonia. In this article, we report two cases of pneumonia in chronic liver disease patients where human coronavirus (HCoV) 229E was identified as the only infecting pathogen. Both the patients presented with fever, cough and respiratory distress, along with radiological findings suggestive of pneumonia. Multiplex real-time PCR for various respiratory viruses (FilmArray Respiratory Panel 2 plus) detected HCoV-229E in both cases. Both cases were managed with prophylactic antibiotics, steroids and supplemental oxygen therapy, after which they recovered completely and were discharged.

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study.

Since its advent, the pandemic has caused havoc in multiple waves due partly to amplified transmissibility and immune escape to vaccines. Delhi, India also witnessed brutal multiple peaks causing exponential rise in cases. Here we had retrospectively investigated clade variation, emergence of new lineages and varied clinical characteristics during those three peaks in order to understand the trajectory of the ongoing pandemic. In this study, a total of 123,378 samples were collected for a time span of 14 months (1 June 2020 to 3 August 2021) encompassing three different peaks in Delhi. A subset of 747 samples was processed for sequencing. Complete clinical and demographic details of all the enrolled cases were also collected. We detected 26 lineages across three peaks nonuniformly from 612 quality passed samples. The first peak was driven by diverse early variants, while the second one by B.1.36 and B.1.617.2, unlike third peak caused entirely by B.1.617.2. A total of 18,316 mutations with median of 34 were reported. Majority of mutations were present in less than 1% of samples. Differences in clinical characteristics across three peaks was also reported. To be ahead of the frequently changing course of the ongoing pandemic, it is of utmost importance that novel lineages be tracked continuously. Prioritized sequencing of sudden local outburst and community hot spots must be done to swiftly detect a novel mutation/lineage of potential clinical importance. IMPORTANCE Genome surveillance of the Delhi data provides a more detailed picture of diverse circulating lineages. The added value that the current study provides by clinical details of the patients is of importance. We looked at the shifting patterns of lineages, clinical characteristics and mutation types and mutation load during each successive infection surge in Delhi. The importance of widespread genomic surveillance cannot be stressed enough to timely detect new variants so that appropriate policies can be immediately implemented upon to help control the infection spread. The entire idea of genomic surveillance is to arm us with the clues as to how the novel mutations and/or variants can prove to be more transmissible and/or fatal. In India, the densely populated cities have an added concern of the huge burden that even the milder variants of the virus combined with co-morbidity can have on the community/primary health care centers.

Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers.

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.

Global metabolome profiling of COVID-19 respiratory specimen using high-resolution mass spectrometry (HRMS).

Here we describe a protocol for identifying metabolites in respiratory specimens of patients that are SARS-CoV-2 positive, SARS-CoV-2 negative, or H1N1 positive. This protocol provides step-by-step instructions on sample collection from patients, followed by metabolite extraction. We use ultra-high-pressure liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS) for data acquisition and describe the steps for data analysis. The protocol was standardized with specific customization for SARS-CoV-2-containing respiratory specimens. For complete details on the use and execution of this protocol, please refer to Maras et al. (2021).

Protocol for global proteome, virome, and metaproteome profiling of respiratory specimen (VTM) in COVID-19 patient by LC-MS/MS-based analysis.

In this protocol, we describe global proteome profiling for the respiratory specimen of COVID-19 patients, patients suspected with COVID-19, and H1N1 patients. In this protocol, details for identifying host, viral, or bacterial proteome (Meta-proteome) are provided. Major steps of the protocol include virus inactivation, protein quantification and digestion, desalting of peptides, high-resolution mass spectrometry (HRMS)-based analysis, and downstream bioinformatics analysis. For complete details on the use and execution of this profile, please refer to Maras et al. (2021).

Second Wave of the COVID-19 Pandemic in Delhi, India: High Seroprevalence Not a Deterrent?

Background We report the findings of a large follow-up, community-based, cross-sectional serosurvey and correlate it with the coronavirus disease (COVID-19) test-positivity rate and the caseload observed between the peaks of the first and the second wave of the COVID-19 pandemic in Delhi, India. Methodology Individuals aged five and above were recruited from 274 wards of the state (population approximately 19.6 million) from January 11 to January 22, 2021. A total of 100 participants each were included from all wards for a net sample size of approximately 28,000. A multistage sampling technique was employed to select participants for the household serosurvey. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies were detected by using the VITROS® (Ortho Clinical Diagnostics, Raritan, NJ, USA) assay (90% sensitivity, 100% specificity). Results Antibody positivity was observed in 14,298 (50.76%) of 28,169 samples. The age, sex, and district population-weighted seroprevalence of the SARS-CoV-2 IgG was 50.52% (95% confidence interval [CI] = 49.94-51.10), and after adjustment for assay characteristics, it was 56.13% (95% CI = 55.49-56.77). On adjusted analysis, participants aged ≥50 years, of female gender, housewives, having ever lived in containment zones, urban slum dwellers, and diabetes or hypertensive patients had significantly higher odds of SARS-CoV-2 antibody positivity. The peak infection rate and the test-positivity rate since October 2020 were initially observed in mid-November 2020, with a subsequent steep declining trend, followed by a period of persistently low case burden lasting until the first week of March 2021. This was followed by a steady increase followed by an exponential surge in infections from April 2021 onward culminating in the second wave of the pandemic. Conclusions The presence of infection-induced immunity from SARS-CoV-2 even in more than one in two people can be ineffective in protecting the population. Despite such high seroprevalence, population susceptibility to COVID-19 can be accentuated by variants of concern having the ability for rapid transmission and depletion of antibody levels with the threat of recurrent infections, signifying the need for mass vaccination.

SARS-Coronavirus-2 seroprevalence in asymptomatic healthy blood donors: Indicator of community spread.

BACKGROUND: The Corona virus disease 2019 (COVID-19) pandemic caused by SARS -Corona virus-2 (SARS-CoV-2) has been a major concern the world over. Serological surveillance is an important tool to assess the spread of infection in the community. This study attempted to assess the prevalence of antibodies to SARS-CoV-2 among blood donors in Delhi, India during the pre-vaccination period. METHODS: Seroprevalence of SARS-CoV2-2 IgG antibodies were determined in blood donors reporting to the Department of Transfusion medicine at a tertiary care hepatobiliary center, in India from September to October 2020. The SARS-CoV-2 IgG antibodies against spike subunit 1 protein were measured using the enhanced chemiluminescence method. RESULTS: A total of 1066 blood donors were screened. The overall seropositivity for SARS-CoV-2 IgG antibodies was 27.57 % (294/1066). The highest seropositivity was seen in the age group 26-35 years, 46.6 % (137/492), followed by 18-25 years, 28.2 % (83/260), 36-45 years, 19.4 % (57/244), and more than 45 years, 5.8 % (17/70). The seropositivity in the donors who had donated blood previously was 26.1 % (189/723). There was no statistically significant difference amongst seroprevalence in the blood groups, AB blood group (32.6 %, 95 % CI 23.02-43.3), group B (27.2 %, 95 % CI 22.8-32.09 %), group A (27.1 %, 95 % CI 21.8-32.9 %), and group O (27.02 %, 95 % CI 22.3-32.1 %) (p 0.539). CONCLUSIONS: There was significantly higher seropositivity for SARS-CoV-2 antibodies in the voluntary healthy blood donors indicating community spread and large number of asymptomatic cases in Delhi. Higher seroprevalence in younger adults indicated increased exposure to the virus and lack of COVID appropriate behaviour.

Syndromic approach to SARS-CoV-2 detection using QIAstat-Dx SARS-CoV-2 panel from clinical samples.

The QIAstat-Dx SARS-CoV-2 panel is a multiplex cartridge based assay based on real time PCR which can detect 17 respiratory viruses, including the novel coronavirus SARS-CoV-2. A syndromic approach is the need of the hour for COVID-19 diagnostics among patients presenting with respiratory symptoms. The present study was done to evaluate 120 archived respiratory clinical specimens for SARS-CoV-2 on the SARS-CoV-2 panel. Further, 27 specimens were tested for other respiratory viruses, in comparison with the BioFire RP1.7 platform. The sensitivity and specificity for SARS-CoV-2 on SARS panel was found to be 90.00 % and 100 % respectively, indicating good diagnostic accuracy. The positive predictive value was found to be 100 %, negative predictive value was found to be 99.93 % and accuracy was 99.93 %. Detection of other respiratory viruses observed a concordance of 77.7 %. Despite advantages of speed, minimal expertise and accurate results; significant costs and discrepancies at Ct >35 remain important limitations of the SARS panel.