ABSTRACT
A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.
Subject(s)
COVID-19ABSTRACT
The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 ug/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.
Subject(s)
Coronavirus Infections , Adenocarcinoma, Bronchiolo-Alveolar , Bronchopneumonia , COVID-19 , Virus Diseases , Acute Lung InjuryABSTRACT
OBJECTIVEThis study was designed to study affect of COVID 19 pandemic on lifestyle of young adults and adolescent. METHODOnline survey, was conducted in about 1000 respondents in the age group of 13-25 years. RESULTSQuestionnaire based survey showed mean sleeping duration changing from 6.85hours to 8.17hours, average screen time becoming 5.12hours from 3.5hours, 51.9% subjects experiencing increased stress levels, 76.4% subjects experiencing increased food intake and 38.6% subjects had decreased levels of physical activity as per self-monitoring. CONCLUSIONThese changes might have long lasting effect on their physical, mental and social health and need counteractive measures to help young people lead a healthy lifestyle during the epidemic and beyond.
Subject(s)
COVID-19ABSTRACT
Introduction The coronavirus disease 2019(COVID-19) is caused by the virus SARS-CoV-2 and is declared as a global pandemic by the World Health Organization (WHO). Various hematological parameters alteration has been documented in the Chinese literature in SARS-Cov-2 infection. However, there is a need for research to evaluate the pattern of the hematological parameters of COVID-19 patients in the Indian population. Aims & Objectives: The objective of the study is to see the Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), and other hematological parameters alteration of COVID-19 patients along with their clinical course in the Indian scenario. Methods: A single-center prospective study of 32 patients with laboratory-confirmed COVID-19 admitted to Super Speciality Pediatric Hospital & Post Graduate Teaching Institute NOIDA, from March to April, were enrolled for the study. The demographic data, the clinical status of the patients during admission and follow up, baseline, and follow up hematological findings were recorded. Statistical analysis of the data was carried out, and relevant findings were presented. Results: Demographic characterization shows a mean age of 37.7 years, male (41.9%), female (58.1%)with the majority of patients are mildly symptomatic to asymptomatic(93%). The CBC values and NLR, PLR at baseline between the male and the female patients, are not showing any statistically significant difference as the 95% C.I. A statistically significant increment in the lab parameters is observed in follow-up visits. Conclusion: The majority of the patients are younger and have mild clinical presentation with female predominance. Pediatric cases have mild symptomology. Baseline CBC findings show mild neutrophilia, lymphopenia, eosinopenia, and normal to mild thrombocytopenia. An increase in CBC parameters, NLR was noted in follow up cases. Anemia was not noted in baseline CBC and in the follow-up group. A onetime PLR is not indicative of disease progression. Key words: Corona virus,COVID-19,CBC,NLR,PLR