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ImportanceBoth vaccination and natural infection lead to immunity and may augment mutual immune response against SARS-CoV-2. There is a need for an evidence-driven booster vaccination policy depending on durability of immune response. ObjectiveTo determine the durability of humoral immune response with varying age, vaccine type, duration, and previous natural infection at least six months after complete vaccination with ChAdOx1 nCov-19 or BBV152. DesignCross-sectional observational study conducted between November 2021 and January 2022. SettingParticipants were drawn from a DBT COVID-19 Research Consortium cohort in Delhi National Capital Region, India. ParticipantsWe included 2003 individuals who had completed six months after complete vaccination: (i) vaccination with ChAdOx1 nCoV-19 and aged 18-59 years, (ii) vaccination with ChAdOx1 nCoV-19 and aged [≥]60 years (iii) vaccination with BBV152 and aged 18-59 years (iv) vaccination with BBV152 and aged [≥]60 years (v) vaccination with either vaccine plus SARS-CoV-2 infection referred as those having hybrid immunity. A group of 94 unvaccinated individuals was also included for comparison. ExposureAge, vaccination type, prior SARS-CoV-2 infection and duration from vaccination/infection. Main Outcome(s) and Measure(s)Humoral immune response determined by anti-RBD IgG concentrations and the presence of anti-nucleocapsid IgG. ResultsThe serum anti-RBD IgG antibodies were detected (cut-off 24 BAU/ml) in 85% participants with a median titer of 163 (IQR 73, 403) BAU/ml. In the hybrid immunity group, 97.6% [295 (IQR 128, 687) BAU/mL] tested positive for anti-RBD IgG compared to 81.3% [139 (IQR 62, 326) BAU/ml] of only vaccinated participants [{chi}2 test: p <0.001]. The median anti-RBD IgG titers were higher in the ChAdOx1 nCoV-19 versus BBV152 groups. The median anti-RBD IgG titer in the anti-nucleocapsid positive participants [326 (IQR 132, 739) BAU/ml] was significantly higher than in those without anti-nucleocapsid antibodies [131 (IQR 58, 288) BAU/ml; p <0.001]. The IgG anti-RBD antibodies was present in 85% of participants beyond a median of 8 months after complete vaccination. Conclusions and RelevanceConsidering the wide seropositivity rates due to natural SARS-CoV-2 infection, recommendation for boosters should take into account past infections in the population. Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the extent of waning of humoral immune response in various groups of vaccinated individuals at least six months after complete vaccination with ChAdOx1 nCov-19 or BBV152 with or without prior natural infection? FindingsCross-sectional observational study demonstrates persistence of anti-RBD IgG in 85% of participants even beyond a median of 8 months after complete vaccination. The antibody concentrations were significantly higher in those with hybrid immunity. MeaningHumoral immunity may last longer due to heterologous antigenic exposure following vaccination and natural infection emphasizing the need for contextualizing the booster policy.
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The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) > delta (B.1.617.2) > beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4+ T cells in [~]85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal [~]1.3 fold-reduction was observed in vaccine-induced CD4+ T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4+ T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.
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BackgroundWe report the findings of a large follow-up community-based serosurvey and correlating it with the COVID-19 test-positivity rate and the case load observed during the peak of the second wave of the Covid-19 pandemic in Delhi, India. MethodsIndividuals of age [≥]5 years were recruited from 274 wards of the state (population [~] 19.6 million) during January 11 to January 22 2021. A total of 100 participants each were included from all the wards for a net sample size of [~]28,000. A multi-stage sampling technique was applied for selection of participants for the household serosurvey. Anti SARS CoV-2 IgG antibodies were detected by using the VITROS assay (90% Sn, 100% Sp). ResultsAntibody positivity was observed in 14,298 (50.76%) of the 28,169 samples. The age, sex and district population weighted seroprevalence of the IgG SARS-CoV-2 was 50.52% (95% C.I. 49.94-51.10) and after adjustment for assay characteristics was 56.13% (95% C.I. 55.49-56.77). On adjusted analysis, participants aged [≥]50 years, of female gender, housewives, having ever lived in containment zones, urban slum dwellers, and diabetes or hypertensive patients had significantly higher odds of SARS-CoV-2 antibody positivity. The peak infection rate and the test positivity rate since October 2020 were initially observed in mid-November 2020 with a subsequent steep declining trend, followed by a period of persistently low case burden lasting until the first week of March 2021. This was followed by a steady increase followed by an exponential surge in infections from April 2021 onwards culminating in the second wave of the pandemic. ConclusionsThe presence of infection induced immunity from SARS-CoV-2 even in more than one in two people can be ineffective in protecting the population.
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Clinical and epidemiological characteristics of SARS-CoV-2 infection are now widely available, but there are few data on longitudinal serology in large cohorts, particularly from low-and middle-income countries. We established an ongoing prospective cohort of 3840 SARS-CoV-2 RT-PCR positive individuals in the Delhi-National Capital Region of India, to document clinical and immunological characteristics during illness and convalescence. The IgG responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0-7, 10-28 days and 6-10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates in the post-infection windows of 0-7 days, 10-28 days and 6-10 weeks were 46%, 84.7% and 85.3% respectively (n=782). The proportion with a serological response increased with severity of COVID-19 disease. All participants with severe disease, 89.6% with mild to moderate infection and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values in the nasopharyngeal viral RNA RT-PCR in a subset of asymptomatic and symptomatic seroconverters were comparable (p value: 0.48), with similar results among non-seroconverters (p value: 0.16) (n=169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 infection over a period of ten weeks from South Asia. The low seropositivity in asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys. SummaryWe measured anti-SARS-CoV-2 RBD and NC protein IgG in a multi-hospital-based prospective cohort from northern India up to ten weeks post-infection. The lower seroconversion rate among asymptomatic RT-PCR positive participants has public health significance particularly for interpreting community seroprevalence estimates.
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BackgroundThree rounds of a repeated cross-sectional serosurvey to estimate the seroprevalence and trends of SARS-CoV-2 were conducted from August-October 2020 in the state of Delhi in India in the general population aged [≥]5 years. MethodsThe selection of participants was through a multi-stage sampling design from all the 11 districts and 280 wards of the city-state, with two-stage allocation proportional to population- size. Household selected was via systematic random sampling, and individual participant selection through the age-order procedure. The blood samples were screened using the IgG ELISA COVID-Kawach kit (August Round), and the ERBALISA COVID-19 IgG (September and October) rounds. The seroprevalence was estimated by applying the sampling weights based on age and sex with further adjustment for the assay-kit characteristics. ResultsA total of 4267 (n=15046), 4311 (n=17409), and 3829 (n=15015) positive tests indicative of the presence of IgG antibody to SARS-CoV-2 were observed during the August, September, and October 2020 serosurvey rounds, respectively. The adjusted seroprevalence declined from 28.39% (95% CI 27.65-29.14) (August) to 24.08% (95% CI 23.43-24.74) (September), and 24.71% (95% CI 24.01, 25.42%) (October). The antibody positivity was highest in the [≥]50 and female age-group during all rounds of the serosurvey, while the decline was maximum among the younger age-group (5-17 years). On adjusted analysis, participants with lower per capita income, living in slums or overcrowded households, and those with diabetes comorbidity had significantly higher statistical odds of antibody positivity. ConclusionsDespite high IgG seroprevalence, there was evidence for waning of antibody positivity with the progression of the COVID-19 epidemic, implying a potential reduction in population immunity, especially if also associated with the lack of trained T cell immunity.