Search

Background: Repeated cross-sectional serosurveys in the same geographic area establish the trend of the evolving pandemic. We present the findings of the third round of a national serosurvey to estimate the seroprevalence of SARS-CoV-2 infection among the general population and health care workers of India. Methods: We conducted the third population-based serosurvey between Dec 18, 2020 and Jan 6, 2021 in the same 700 villages or wards from 70 districts in 21 states across India, which were selected for the first and second serosurveys. We enrolled from each district, at least 400 individuals aged ≥ 10 years from general population and 100 HCWs from sub-district level public health facilities. Serum samples from general population were tested for the presence of IgG antibodies against nucleocapsid (N) and spike protein (S1-RBD) of SARS-CoV-2 using the Abbott and Siemens assays respectively, whereas sera from HCWs were tested for anti-S1-RBD. For general population, sera positive for either of the antibodies were considered positive, while sera positive for anti-S1-RBD were considered as positive for HCW. Weighted seroprevalence estimates were adjusted for sensitivity and specificity of respective assays. Findings: Of the 28,598 sera from general population, 4585 (16%) had IgG antibodies against N, 6647 (23.2%) against S1-RBD and 7436 (26%) against either. The weighted and assay characteristic adjusted seroprevalence against either of the antibodies was 24.1 (95%CI: 23.0% to 25.3%). Seroprevalence was lower in rural areas (21.4%, 95% CI: 20.3% to 22.6%) compared to urban non-slum (29.4%, 95% CI: 26.9% - 32.1%) and slum areas (34.6%, 95% CI: 31.0% to 38.3%). Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI: 23.5% to 27.8%). Interpretation: Nearly one in four individuals aged 10 years or older from general population as well as HCWs were exposed to SARS-CoV-2 by December 2020 amounting to 271 million infections in India. Funding Statement: Indian Council of Medical Research Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no competing interests Ethics Approval Statement: The project was approved by Institutional Human Ethics Committee at ICMR-National Institute of Epidemiology.

Background: ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at Serum Institute of India Pvt Ltd (SIIPL) after technology transfer from AstraZeneca, was evaluated in this phase 2/3 immunobridging study. Methods: This observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). Two doses of vaccine (5 × 10¹⁰ viral particles) or placebo were given at 4-week intervals (+2-week window). Primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibodies 28 days after second dose (defined as lower 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. Anti-spike IgG response was assessed using a validated multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Findings: Between August 25 and October 31, 2020, n=1601 participants were enrolled: n=401 to the immunogenicity/reactogenicity cohort and n=1200 to the safety cohort. After two doses of SII-ChAdOx1 nCoV-19 or AZD1222, seroconversion rates for anti-spike IgG antibodies were 98·0% and 98·9%, respectively, with anti-spike IgG GMTs of 30 245·6 AU/mL (95% CI 26 794·0–34 141·8) and 28 558·3 AU/mL (23 479·3–34 735·8); SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·79–1·23). SAEs were reported in 15/1200 (1·3%, 95% CI 0·7–2·1), 2/300 (0·7%, 0·1–2·4) and 2/100 (2·0%, 0·2–7·0) participants who received SII-ChAdOx1 nCoV-19, placebo and AZD1222, respectively; none were causally related. SARS-CoV-2 infections were observed in 1·9% (n=22), 3·4% (n=10) and 2·0% (n=2) of the SII-ChAdOx1 nCoV-19, placebo and AZD1222 groups, respectively; none were severe. Interpretation: SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Trial Registration: This study was registered with number CTRI/2020/08/027170 Funding: SIIPL, Indian Council of Medical Research, AstraZeneca. Declaration of Interest: PSK, CB, AD, MG, US, DK, and BG are employees of SIIPL. JV and EJK are employees of AstraZeneca. All other authors declare no competing interests. Ethical Approval: The study was approved by the Drugs Controller General of India (DCGI) and the ethics committees of each study site.

Background: India has the second highest number of COVID-19 cases. We evaluated the progression of the pandemic across the lockdowns and phased reopening during the first wave in India at the district level. Methods: More than 100 million COVID-19 test results along with other parameters available in the Indian Council of Medical Research (ICMR) database during March-October, 2020, was used for the analysis. District was chosen as the unit of analysis, as it is the smallest unit of administration in India. The districts were stratified as high, moderate, and low case load districts, and data analysis was done for each phase of lockdown. Findings: Of the 110.5 million tests included in the analysis, 54.79 million tests were performed using molecular methods, 53.58 million by rapid antigen tests (RATs) and 2.13 million by the indigenous TruNat platform. Only 7.95 million (7.16%) tests were among symptomatic individuals. The positivity proportion among symptomatic individuals (22.6%) was significantly higher than asymptomatic individuals (8.6%). The tests conducted, and positivity proportions were significantly higher in high caseload districts and 58% of these tests were by molecular methods as opposed to only one-third in low case load districts. The proportion of ‘symptomatic contacts’ being tested increased significantly around the peak. Interpretation: Laboratory parameters, along with other demographic information, can help us better understand the spread of the pandemic in a country. Such information can be crucial to formulate and implement public health policies in any future waves of the pandemic. Funding: Indian Council of Medical Research (ICMR) Declaration of Interest: We declare no competing interests Ethical Approval: Approval from the ICMR Central Ethics Committee on Human Research (Ref. No. NCDIR/BEU/ICMR-CECHR/75/2020) was obtained for this study and no patient identifiers were accessed during analysis or reporting.

Background: India witnessed a severe second wave of COVID-19 during March and June 2021. We did the fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged >=6 years and health care workers (HCWs). Methods: We did a cross-sectional study between 14 June and 6 July 2021 in 700 clusters in the same 70 districts across 21 states/Union Territory. From each district, a minimum of 400 individuals aged >=6 years from general population and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test adjusted seroprevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein along with 95% CI. Findings: Of the 28,975 sera tested, the weighted and test adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged >=6 years was 67.6% (95% CI: 66.4 – 68.7). The seroprevalence increased with age and was not different in rural and urban areas. Compared to unvaccinated adults (62.3%, 95% CI: 60.9 – 63.7), seroprevalence was significantly higher among individuals who received one (81.0%, 95% CI: 79.6 - 82.3) and two doses (89.8%, 95% CI: 88.4 - 91.1). The seroprevalence of IgG antibodies among 7,252 health care workers was 85.2% (95% CI: 83.5 - 86.7). Interpretation: Nearly one third of the population is still seronegative. It is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions. Funding: Indian Council of Medical Research. Declaration of Interest: None to declare. Ethical Approval: The Institutional Human Ethics Committee of the ICMR National Institute of Epidemiology, Chennai approved the study protocol.

Background: The first round of national serosurvey in India was conducted in May-June 2020 among adults from 21 States. The second serosurvey was conducted in August-September 2020 to estimate the nationwide seroprevalence for SARS-CoV-2 infection in the general population aged ten years and above. Methods: The household serosurvey was conducted among individuals aged ten years and above in the same 700 villages and wards from 70 districts selected during the first serosurvey. Blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. In order to compare the adult seroprevalence between the two surveys, we randomly selected one adult serum sample from each household. Findings: The weighted and adjusted prevalence of infection among 29,082 individuals aged ten years and above was 6·6% (95% CI: 5·8% - 7·4%). The seroprevalence among adults was 7·1% (95% CI: 6·2% – 8·2%). Seroprevalence was similar across age groups, sex, and occupation. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74·3 million infections in the country, with 26 – 32 infections for every reported COVID-19 case by August 2020. Interpretation: Nearly one in 15 individuals aged ten years and above had SARS-CoV-2 infection by August 2020. The adult seroprevalence increased ten times between May and August 2020. Lower infection to case ratio in August compared to May reflects a substantial increase in testing across the country. Funding: The study was funded by the Indian Council of Medical Research, New Delhi, India. The study sponsor was involved in reviewing the study design, writing of the manuscript and the decision to submit the paper for publication. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The authors obtained written informed consent from individuals aged 18 years and older. We obtained assent from children aged between 10–17 years, and written informed consent from their parents or guardians prior to the survey. The Central Ethics Committee of Health Research of Indian Council of Medical Research and the Institutional Human Ethics Committee of ICMR-National Institute of Epidemiology, Chennai approved the study protocol.

Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a Toll-Like Receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or 6 μg with alum (Algel). Methods: We conducted a double-blind, randomised, multicentre, controlled phase 1 clinical trial to evaluate the safety and immunogenicity of BBV152. A total of 375 healthy adults Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation were randomised equally to receive three vaccine formulations (n=100 each) prepared with 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel, and an Algel only control arm (n=75). Two intramuscular doses of vaccines were administered (twoweeks apart). Primary outcomes were reactogenicity and safety. Secondary outcome was seroconversion (≥4-fold above baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. Findings: Among 827 participants screened between July 13 and July 30, 2020, 375 participants were randomised. After both doses, the proportion (95%CI) of solicited local and systemic adverse reactions were 17% (10·5, 26·1), 21% (13·8, 30·5), 14% (8·1, 22·7), and 10% (6·9, 23·6) in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, 6 μg with Algel, and control groups, respectively . The most common solicited adverse events were injection site pain, headache, and fatigue. All solicited adverse events were mild (43, 69·3%) or moderate (19, 30·7%) and were more frequent after the first dose. One serious adverse event was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with AlgelIMDG, 6 μg with Algel-IMDG and 6 μg with Algel groups, respectively. CD4 + and CD8 + T cell responses were detected in a subset from both Algel-IMDG groups. Interpretations: BBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted. Trial Registration Number: Clinicaltrials.gov : NCT04471519 Funding: This work was supported and funded by Bharat Biotech International Limited. Conflict of Interest: This work was supported and funded by Bharat Biotech International Limited. All authors are employees of one of the above-mentioned organisations, with no stock options or incentives. Co-author- K.E is the Chairman and Managing Director of Bharat Biotech. Ethical Approval: The trial was conducted across 11 sites in 9 states in India. The trial was approved by the National Regulatory Authority (India) and the respective Ethics Committees and was conducted in compliance with all International Council for Harmonization 114 (ICH) Good Clinical Practice guidelines.