Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2.

Immunization is expected to confer protection against infection and severe disease for vaccinees, while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies, we show that during a severe SARS-CoV2 Delta-variant outbreak in Delhi, 25.3% (95% CI 16.9 - 35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare-workers (HCW) were infected within a period of less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, IQR 374) or not (342 U/ml, IQR 497), as was induction of neutralization activity to wildtype. Most infections were unrecognized. The Delta-variant thus causes frequent unrecognized breakthrough infections in adequately immunized subjects, reducing any herd-effect of immunity, and requiring reinstatement of preventive measures such as masking.

A highly thermotolerant, trimeric SARS-CoV-2 receptor binding domain derivative elicits high titers of neutralizing antibodies

The Receptor Binding Domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We designed a trimeric, highly thermotolerant glycan engineered RBD by fusion to a heterologous, poorly immunogenic disulfide linked trimerization domain derived from cartilage matrix protein. The protein expressed at a yield of [~]80-100 mg/liter in transiently transfected Expi293 cells, as well as CHO and HEK293 stable cell lines and formed homogeneous disulfide-linked trimers. When lyophilized, these possessed remarkable functional stability to transient thermal stress of upto 100 {degrees}C and were stable to long term storage of over 4 weeks at 37 {degrees}C unlike an alternative RBD-trimer with a different trimerization domain. Two intramuscular immunizations with a human-compatible SWE adjuvanted formulation, elicited antibodies with pseudoviral neutralizing titers in guinea pigs and mice that were 25-250 fold higher than corresponding values in human convalescent sera. Against the beta (B.1.351) variant of concern (VOC), pseudoviral neutralization titers for RBD trimer were [~] three-fold lower than against wildtype B.1 virus. RBD was also displayed on a designed ferritin-like Msdps2 nanoparticle. This showed decreased yield and immunogenicity relative to trimeric RBD. Replicative virus neutralization assays using mouse sera demonstrated that antibodies induced by the trimers neutralized all four VOC to date, namely B.1.1.7, B.1.351, P.1 and B.1.617.2 without significant differences. Trimeric RBD immunized hamsters were protected from viral challenge. The excellent immunogenicity, thermotolerance, and high yield of these immunogens suggest that they are a promising modality to combat COVID-19, including all SARS-CoV-2 VOC to date.

COVID-19 Risk Stratification and Mortality Prediction in Hospitalized Indian Patients

The clinical course of coronavirus disease 2019 (COVID-19) infection is highly variable with the vast majority recovering uneventfully but a small fraction progressing to severe disease and death. Appropriate and timely supportive care can reduce mortality and it is critical to evolve better patient risk stratification based on simple clinical data, so as to perform effective triage during strains on the healthcare infrastructure. This study presents risk stratification and mortality prediction models based on usual clinical data from 544 COVID-19 patients from New Delhi, India using machine learning methods. An XGboost classifier yielded the best performance on risk stratification (F1 score of 0.81). A logistic regression model yielded the best performance on mortality prediction (F1 score of 0.71). Significant biomarkers for predicting risk and mortality were identified. Examination of the data in comparison to a similar dataset with a Wuhan cohort of 375 patients was undertaken to understand the much lower mortality rates in India and the possible reasons thereof. The comparison indicated higher survival rate in the Delhi cohort even when patients had similar parameters as the Wuhan patients who died. Steroid administration was very frequent in Delhi patients, especially in surviving patients whose biomarkers indicated severe disease. This study helps in identifying the high-risk patient population and suggests treatment protocols that may be useful in countries with high mortality rates.

Low uptake of COVID-19 prevention behaviours and high socioeconomic impact of lockdown measures in South Asia: evidence from a large-scale multi-country surveillance programme

BackgroundSouth Asia has become a major epicentre of the COVID-19 pandemic. Understanding South Asians awareness, attitudes and experiences of early measures for the prevention of COVID-19 is key to improving the effectiveness and mitigating the social and economic impacts of pandemic responses at a critical time for the Region. MethodsWe assessed the knowledge, behaviours, health and socio-economic circumstances of 29,809 adult men and women, at 93 locations across four South Asian countries. Data were collected during the national lockdowns implemented from March to July 2020, and compared with data collected prior to the pandemic as part of an ongoing prospective surveillance initiative. ResultsParticipants were 61% female, mean age 45.1 years. Almost half had one or more chronic disease, including diabetes (16%), hypertension (23%) or obesity (16%). Knowledge of the primary COVID-19 symptoms and transmission routes was high, but access to hygiene and personal protection resources was low (running water 63%, hand sanitisers 53%, paper tissues 48%). Key preventive measures were not widely adopted. Knowledge, access to, and uptake of COVID-19 prevention measures were low amongst people from disadvantaged socio-economic groups. Fifteen percent of people receiving treatment for chronic diseases reported loss of access to long-term medications; 40% reported symptoms suggestive of anxiety or depression. The prevalence of unemployment rose from 9.3% to 39.4% (P<0.001), and household income fell by 52% (P<0.001) during the lockdown. Younger people and those from less affluent socio-economic groups were most severely impacted. Sedentary time increased by 32% and inadequate fruit and vegetable intake increased by 10% (P<0.001 for both), while tobacco and alcohol consumption dropped by 41% and 80%, respectively (P<0.001), during the lockdown. ConclusionsOur results identified important knowledge, access and uptake barriers to the prevention of COVID-19 in South Asia, and demonstrated major adverse impacts of the pandemic on chronic disease treatment, mental health, health-related behaviours, employment and household finances. We found important sociodemographic differences for impact, suggesting a widening of existing inequalities. Our findings underscore the need for immediate large-scale action to close gaps in knowledge and access to essential resources for prevention, along with measures to safeguard economic production and mitigate socio-economic impacts on the young and the poor.

SARS-CoV-2 antibody seroprevalence and stability in a tertiary care hospital-setting

BackgroundSARS-CoV-2 infection has caused 64,469 deaths in India, with 7, 81, 975 active cases till 30th August 2020, lifting it to 3rd rank globally. To estimate the burden of the disease with time it is important to undertake a longitudinal seroprevalence study which will also help to understand the stability of anti SARS-CoV-2 antibodies. Various studies have been conducted worldwide to assess the antibody stability. However, there is very limited data available from India. Healthcare workers (HCW) are the frontline workforce and more exposed to the COVID-19 infection (SARS-CoV-2) compared to the community. This study was conceptualized with an aim to estimate the seroprevalence in hospital and general population and determine the stability of anti SARS-CoV-2 antibodies in HCW. MethodsStaff of a tertiary care hospital in Delhi and individuals visiting that hospital were recruited between April to August 2020. Venous blood sample, demographic, clinical, COVID-19 symptoms, and RT-PCR data was collected from all participants. Serological testing was performed using the electro-chemiluminescence based assay developed by Roche Diagnostics, in Cobas Elecsys 411. Seropositive participants were followed- upto 83 days to check for the presence of antibodies. ResultsA total of 780 participants were included in this study, which comprised 448 HCW and 332 individuals from the general population. Among the HCW, seroprevalence rates increased from 2.3% in April to 50.6% in July. The cumulative prevalence was 16.5% in HCW and 23.5% (78/332) in the general population with a large number of asymptomatic individuals. Out of 74 seropositive HCWs, 51 were followed-up for the duration of this study. We observed that in all seropositive cases the antibodies were sustained even up to 83 days. ConclusionThe cumulative prevalence of seropositivity was lower in HCWs than the general population. There were a large number of asymptomatic cases and the antibodies developed persisted through the duration of the study. More such longitudinal serology studies are needed to better understand the antibody response kinetics.