Community prevalence of antibodies to SARS-CoV-2 and correlates of protective immunity in an Indian metropolitan city
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Abstract
Objectives
To assess seroprevalence of anti-SARS-CoV-2 antibodies in a densely populated urban Indian settings and its implications for disease trends and protective immunity.
Design
Cross-sectional sero-epidemiological survey linked with administrative reporting of COVID-19 testing data.
Settings
Pune city in western India
Main outcome measure
Prevalence of anti-SARS-CoV-2 spike protein antibodies were estimated and along with correlates of virus neutralisation and other immune and inflammatory markers.
Results
Seropositivity was extensive (51·3%; 95%CI 39·9 to 62·4) but varied widely in the five localities tested, ranging from 35·8% to 66·4%. Seropositivity was higher in crowded living conditions in the slums (OR 1·91), and was lower in those 65 years or older (OR 0·59). The infection-fatality ratio was estimated at 0.21%. Post survey, COVID-19 incidence was lower in areas noted to have higher seroprevalence. Substantial virus-neutralising activity was observed in seropositive individuals, but with considerable heterogeneity in the immune response and possible age-dependent diversity in the antibody repertoire.
Conclusion
Despite crowded living conditions having facilitated widespread transmission, the variability in seroprevalence in localities that are in geographical proximity indicates a heterogenous spread of infection. Declining infection rates in areas with high seropositivity suggest population-level protection. It is also supported by substantial neutralising activity in asymptomatically infected individuals. This is the first report of a significantly high proportion of protective immune response among asymptomatic individuals in the population. The heterogeneity in antibody levels and neutralisation capacity indicates the existence of immunological sub-groups of functional interest.
Trial registration
Registered with the Clinical Trials Registry of India (CTRI/2020/07/026509)
Article activity feed
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SciScore for 10.1101/2020.11.17.20228155: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: The study team visited selected households and after written informed consent, five ml of peripheral venous blood was collected.
IACUC: Ethical considerations: The study was approved by the Institutional Ethics Committee of SPPU (SPPU/IEC/2020/82), IISER Pune (IECHR/Admin/2020/005) and THSTI (THS1.8.1(106)) and the Institutional Biosafety Committees of IISER Pune and THSTI.Randomization Five subwards were randomly selected from among the 13 subwards (∼400,000 population) classified as high incidence settings for a sero-epidemiological survey. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication n… SciScore for 10.1101/2020.11.17.20228155: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: The study team visited selected households and after written informed consent, five ml of peripheral venous blood was collected.
IACUC: Ethical considerations: The study was approved by the Institutional Ethics Committee of SPPU (SPPU/IEC/2020/82), IISER Pune (IECHR/Admin/2020/005) and THSTI (THS1.8.1(106)) and the Institutional Biosafety Committees of IISER Pune and THSTI.Randomization Five subwards were randomly selected from among the 13 subwards (∼400,000 population) classified as high incidence settings for a sero-epidemiological survey. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources We assumed that the IgG antibodies are detectable 14 to 21 days post-infection and that these antibodies persist, following infection, for four months4,16,17. IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources SARS-CoV-2 (isolate USA-WA1/2020) virus expanded in Vero E6 cells was used with heat-inactivated sera for Plaque Reduction Neutralization Tests ( Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources The reproduction numbers at different time points were estimated for each sub ward using EpiEstim package18. EpiEstimsuggested: (EpiEstim, RRID:SCR_018538)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study had several limitations. We focussed on the seroprevalence in settings reporting the highest incidence, in part due to concerns about the impact of imperfect diagnostic accuracy on seroprevalence in low prevalence settings. This along with the limited sample size made it challenging to extrapolate seroprevalence more broadly. For operational reasons, we excluded active containment zones, those with an acute illness and restricted sampling to one individual per household; these could have biased the seroprevalence estimates. Our study did not include children who may have an important role in transmission. Nonetheless, this study, demonstrates the heterogenous, but widespread transmission of SARS-CoV-2 in a dense urban population. The high seroprevalence combined with evidence of neutralizing antibodies and of declining incidence in settings of high seroprevalence raises the possibility of population immunity, at least in the short term. That indoor crowding, living in a slum and sharing a common toilet were significant predictors of seropositivity highlights the challenges India faced in controlling the pandemic despite stringent lockdown measures. Despite this, the relative protection of the elderly, and low infection fatality ratios and evidence of population immunity provide hope that if control measures continue, urban India may well have passed the peak of the pandemic. High seroprevalence in the dense urban localities of the study site, despite a protracted an...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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