Background SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination. Methods We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-tosevere disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine. Findings Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3•6%) were fully vaccinated compared with 168 (8•5%) of 1981 controls (adjusted OR [aOR] 0•37 [95% CI 0•28-0•48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63•1% (95% CI 51•5-72•1). 157 (6•4%) of 2451 of cases and 181 (9•1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0•54 [95% CI 0•42-0•68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46•2% (95% CI 31•6-57•7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0•19 [95% CI 0•01-0•90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81•5% (95% CI 9•9-99•0). The effectiveness of a single dose against moderate-to-severe disease was 79•2% (95% CI 46•1-94•0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0•20 [95% CI 0•06-0•54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244•7 [95% CI 151•8-394•4]), beta (B.1.351; 97•6 [61•2-155•8]), kappa (B.1.617.1; 112•8 [72•7-175•0]), and delta (88•4 [61•2-127•8]) variants than against wild-type SARS-CoV-2 (599•4 [376•9-953•2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2. Interpretation The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune p...
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)
Approximately forty-four percent of the global population lives in villages, including 59% in Africa (
https://unhabitat.org/World%20Cities%20Report%202020
). The fast-evolving nature of SARS-CoV-2 and its extremely contagious nature warrant early and accurate COVID-19 diagnostics across rural and urban population as a key to prevent viral transmission. Unfortunately, lack of adequate infrastructure, including the availability of biosafety-compliant facilities and an end-to-end cold chain availability for COVID-19 molecular diagnosis, limits the accessibility of testing in these countries.
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