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      Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India, June–July 2021: A population-based cross-sectional study

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      1 , * , 1 , 1 , 1 , 1 , 2 , 3 , 1 , 1 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 11 , 19 , 20 , 11 , 21 , 22 , on behalf of the ICMR serosurveillance group
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          Abstract

          Background

          India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).

          Methods and findings

          We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) 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 SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. 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% to 68.7%). Seroprevalence increased with age ( p < 0.001) and was not different in rural and urban areas ( p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.

          Conclusions

          Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As 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.

          Abstract

          Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India.

          Author summary

          Why was this study done?
          • Earlier nationwide COVID-19 serosurveys conducted in India indicated an increase in seroprevalence from 0.73% (95% CI 0.34% to 1.13%) in May–June 2020 to 6.6% (95% CI 5.8% to 7.4%) in September–October 2020 and 24.1% (95% CI 23.0% to 25.3%) in December 2020–January 2021.

          • India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above.

          • India witnessed a severe second wave of COVID-19 in March–June 2021.

          What did the researchers do and find?
          • The fourth nationwide serosurvey indicated that about two-thirds of India’s population aged ≥6 years had antibodies against SARS-CoV-2 by June–July 2021.

          • Seroprevalence increased with age, but was not different in urban slum, urban non-slum, and rural areas.

          • Seroprevalence was significantly higher among individuals who had received 2 doses of COVID-19 vaccine compared to unvaccinated individuals.

          • About 85% of healthcare workers working in district-level health facilities had antibodies against SARS-CoV-2.

          What do these findings mean?
          • The substantial seroprevalence of anti-SARS-CoV-2 antibodies in the Indian population should provide some measure of protection against future waves of COVID-19 in the country.

          • About one-third of the population in India did not have detectable antibodies against SARS-CoV-2 by June–July 2021. It is therefore necessary to accelerate the coverage of COVID-19 vaccination among adults.

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          Most cited references22

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          Adaptive immunity to SARS-CoV-2 and COVID-19

          The adaptive immune system is important for control of most viral infections. The three fundamental components of the adaptive immune system are B cells (the source of antibodies), CD4+ T cells, and CD8+ T cells. The armamentarium of B cells, CD4+ T cells, and CD8+ T cells has differing roles in different viral infections, and in vaccines, and thus it is critical to directly study adaptive immunity to SARS-CoV-2 to understand COVID-19. Knowledge is now available on relationships between antigen-specific immune responses and SARS-CoV-2 infection. While more studies are needed, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ T cells, and neutralizing antibodies all contribute to control of SARS-CoV-2, in both non-hospitalized and hospitalized cases of COVID-19. The specific functions and kinetics of these adaptive immune responses are discussed, as well as their interplay with innate immunity and implications for COVID-19 vaccines and immune memory against re-infection.
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            Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

            SARS-CoV-2 antibodies persist As the number of daily COVID-19 cases continues to mount worldwide, the nature of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. Wajnberg et al. used a cohort of more than 30,000 infected individuals with mild to moderate COVID-19 symptoms to determine the robustness and longevity of the anti–SARS-CoV-2 antibody response. They found that neutralizing antibody titers against the SARS-CoV-2 spike protein persisted for at least 5 months after infection. Although continued monitoring of this cohort will be needed to confirm the longevity and potency of this response, these preliminary results suggest that the chance of reinfection may be lower than is currently feared. Science, this issue p. 1227
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              SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)

              Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Funding Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.
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                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: SoftwareRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
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                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
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                Journal
                PLoS Med
                PLoS Med
                plos
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                10 December 2021
                December 2021
                : 18
                : 12
                : e1003877
                Affiliations
                [1 ] ICMR–National Institute of Epidemiology, Chennai, India
                [2 ] ICMR–National Institute for Research in Tuberculosis, Chennai, India
                [3 ] WHO Country Office for India, New Delhi, India
                [4 ] ICMR–National Institute of Cancer Prevention and Research, Noida, India
                [5 ] ICMR–National Institute of Occupational Health, Ahmedabad, India
                [6 ] ICMR–National AIDS Research Institute, Pune, India
                [7 ] ICMR–National JALMA Institute for Leprosy & Other Mycobacterial Diseases, Agra, India
                [8 ] ICMR–National Institute of Research in Tribal Health, Jabalpur, India
                [9 ] ICMR–National Institute of Cholera and Enteric Diseases, Kolkata, India
                [10 ] State TB Training and Demonstration Centre, Patiala, India
                [11 ] ICMR–Regional Medical Research Centre, Bhubaneswar, Bhubaneswar, India
                [12 ] ICMR–Regional Medical Research Centre, N. E. Region, Dibrugarh, India
                [13 ] ICMR–Regional Medical Research Centre, Gorakhpur, Gorakhpur, India
                [14 ] State TB Office, Dehradun, India
                [15 ] Government Medical College, Srinagar, Srinagar, India
                [16 ] State TB Training and Demonstration Centre, Thiruvananthapuram, India
                [17 ] ICMR–National Institute of Nutrition, Hyderabad, India
                [18 ] ICMR–Rajendra Memorial Research Institute of Medical Sciences, Patna, India
                [19 ] State TB Office, Hyderabad, India
                [20 ] National Tuberculosis Institute, Bangalore, India
                [21 ] ICMR–National Institute for Implementation Research on Non-Communicable Diseases, Jodhpur, India
                [22 ] Indian Council of Medical Research, New Delhi, India
                PLOS Medicine Editorial Board, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                ¶ Membership of the ICMR serosurveillance group is provided in the Acknowledgements.

                Author information
                https://orcid.org/0000-0002-1720-7628
                https://orcid.org/0000-0002-3547-1393
                https://orcid.org/0000-0002-9940-4878
                https://orcid.org/0000-0001-8788-2250
                https://orcid.org/0000-0002-6595-2251
                https://orcid.org/0000-0003-2207-3465
                https://orcid.org/0000-0002-1494-688X
                https://orcid.org/0000-0002-7799-271X
                https://orcid.org/0000-0003-3609-9797
                https://orcid.org/0000-0003-1550-8416
                https://orcid.org/0000-0002-8821-6097
                https://orcid.org/0000-0001-8996-8998
                Article
                PMEDICINE-D-21-03454
                10.1371/journal.pmed.1003877
                8726494
                34890407
                e77b10ce-4e60-4219-9218-76a0aa0f523b
                © 2021 Murhekar et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 August 2021
                : 29 November 2021
                Page count
                Figures: 1, Tables: 5, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001411, Indian Council of Medical Research;
                Award Recipient :
                MVM received the funding from Indian Council of Medical Research, New Delhi. The funders were involved in study design, and the decision to publish and preparation of the manuscript.
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                The authors confirm that, for IHEC-approved reasons, some access restrictions apply to the data underlying the findings. An individual may email to ICMR Data Repository office ( harpreets.hq@ 123456icmr.gov.in ) to request the data. Given the nature of these data, potential users will be asked to sign a data sharing agreement. This is not intended to restrict access, but to ensure that requests are for ethical research purposes and that any analyses undertaken will not compromise the confidentiality of individual participants, and are not for commercial purposes.
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