ABSTRACT
Background There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the 18 to 45-year age-group began in April 2021 when seropositivity rates in the general population were rising due to the Delta wave in April-May 2021. Methods Between 30 June 2021 and 28 January 2022, we enrolled 691 participants in the 18-45 age group across 4 clinical sites in India. In this non-randomized and laboratory blinded study, participants received either two doses of Covaxin(R) 4 weeks apart or two doses of Covishield 12 weeks apart per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titer (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield elicited higher antibody responses than Covaxin(R) as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 BAU/ml, p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). Not all sites recruited at the same time, therefore site-specific immunogenicity was impacted by the timing of vaccination relative to the Delta and Omicron waves. Surrogate neutralizing antibody responses against variants-of-concern were higher in Covishield recipients than in Covaxin(R) recipients and in seropositive than in seronegative individuals after both vaccination and asymptomatic Omicron infection. T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the Omicron wave. In seronegative individuals, Covishield elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin(R) elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Interpretation Covishield elicited immune responses of higher magnitude and breadth than Covaxin(R) in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population.
Subject(s)
COVID-19ABSTRACT
: COVID-19 vaccination certificates (CVCs) have played a key role in safe reopening of borders for international travel and trade, so understanding key stakeholder perceptions of enablers and barriers for their effective use is critical. The COVID-19 Vaccination Policy Research and Deci-sion-Support Initiative in Asia (CORESIA) was established to address policy questions related to CVCs. We conducted two online surveys, i.e., one for the public and one for health and non-health sector experts, from June to October 2021 in nine Asian countries. Descriptive analysis identified participants, enablers, and barriers. Most participants (78% public, 89% experts) accepted the use of CVCs, primarily to resume international travel (76%). Most respondents in both surveys wanted the minimum vaccination coverage to be 60% before CVCs were implemented nation-wide. Most of the public (82%) agreed to maintain existing non-pharmaceutical interventions, while most experts wanted risk-based testing and quarantine policy for incoming travellers (51%) and both digital and paper format CVCs (64%). Support for CVCs for international travel remains high in Asia. Recognising key enablers and barriers for effective use of CVCs from COVID-19 pandemic may help policymakers draft effective border policies for future epidemics.
Subject(s)
COVID-19ABSTRACT
India reported over 10 million COVID-19 cases and 149,000 deaths in 2020. To estimate exposure and the potential for further spread, we used a SARS-CoV-2 transmission model fit to seroprevalence data from three serosurveys in Delhi and the time-series of reported deaths to reconstruct the epidemic. The cumulative proportion of the population estimated infected was 48.7% (95% CrI 22.1% - 76.8%) by end-September 2020. Using an age-adjusted overall infection fatality ratio (IFR) based on age-specific estimates from mostly high-income countries (HICs), we estimate that 15.0% (95% CrI 9.3% - 34.0%) of COVID-19 deaths were reported. This indicates either under-reporting of COVID-19 deaths and/or a lower age-specific IFR in India compared with HICs. Despite the high attack rate of SARS-CoV-2, a third wave occurred in late 2020, suggesting that herd immunity was not yet reached. Future dynamics will strongly depend on the duration of immunity and protection against new variants.
Subject(s)
COVID-19 , DeathABSTRACT
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.
Subject(s)
COVID-19ABSTRACT
BackgroundCurrent testing guidelines for COVID-19 substantially underestimates the spread of SARS-CoV-2 in dense urban populations. Granular estimates of infection are important for understanding population-level immunity. We examined seroprevalence of anti-SARS-CoV-2 antibodies in Pune city in India and its implication for protective immunity. MethodsSeroprevalence was estimated during July 20-August 5, 2020 from 1659 randomly selected individuals recruited from five administrative Pune sub-wards (combined population 366,984). Prevalence of anti-SARS-CoV-2 spike protein antibodies were estimated and along with correlates of virus neutralisation. FindingsSeropositivity was extensive (51{middle dot}3%; 95%CI 39{middle dot}9-62{middle dot}4) but varied widely in the five localities tested, ranging from 35{middle dot}8% to 66{middle dot}4%. Seropositivity was higher in crowded living conditions in the slums (OR 1{middle dot}91), and was lower in those 65 years or older (OR 0{middle dot}59). The infection-fatality ratio was estimated at 0.28%. 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. InterpretationDespite 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 and is supported by substantial neutralising activity in asymptomatically infected individuals. The heterogeneity in antibody levels and neutralisation capacity indicates the existence of immunological sub-groups of functional interest. FundingPersistent Foundation, Pune, India RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched the literature (upto 2 Nov 2020), using the terms "seroprevalence", "serosurveillance", "seroepidemiology", "immune response", "seroconversion" and "SARS-CoV-2," without any article type restrictions, and selected only population- or community-level seroprevalence studies for collecting background information. The survey of literature indicated that community serosurveys for SARS-CoV-2 in LICs and LMICs have been limited and have largely reported correlations of seroprevalence with demographic factors. There are no reports of protective immunity-associated characteristics in community surveillance settings from LMIC/LICs. In fact, such studies from the global North are also limited. The existing evidence thus lacks granular details critical to understand community-level heterogeneities, and provides limited epidemiological data without meaningful immunobiological correlates. Added value of this studyThis is the first systematic study (at the time of submission) from a LMIC reporting community SARS-CoV-2 sero-surveillance of high granularity alongside estimation of correlates of immune protection. We estimated seroprevalence as well as serological correlates of protection in a cross-sectional cohort of 1659 asymptomatic participants from five small urban localities in the metropolitan city of Pune, India. IgG seroprevalence was determined against the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, to aid correlation with immune protection since RBD is the predominant target for neutralising antibodies. Large subsets of the sera were also tested for surrogate neutralisation as well as live SARS-CoV-2 virus neutralisation, data not so far reported in community sero-surveillance studies. We identified substantial locality-specific variations in seropositivity levels and infection fatality rates (IFRs), highlighting heterogeneities of infection behaviour even in dense, urban populations often lost in more global analyses. Notably, the incidence of new infections after the sero-sampling period revealed a strong negative association with seropositivity, indicating potential modification of transmission by community immunity. While RBD-specific antibody levels expectedly showed broad correlation with neutralisation capacities, 30% of individuals showed significant departures from this correlation, again underlining significant immune response heterogeneities. Implications of all the available evidenceHigh seroprevalence in the dense urban localities of the study site, despite a protracted and stringent lockdown, provides a realistic account on transmission dynamics crucial for public health policies in LMICs. Micro-geographic variability within locales, dominated by sub-optimal living conditions, needs to be acknowledged and used to develop measures designed for people in such socio-economic contexts. The heterogeneity of correlation between RBD seropositivity and neutralising capacity, as well as the complex association with age encountered in this study open up a plethora of research questions into epitope dominance and affinity variations in anti-viral antibodies in asymptomatic infection.
Subject(s)
COVID-19ABSTRACT
Objective: Estimate seroprevalence in representative samples from slum and non-slum communities in Mumbai, India, a mega-city in a low or middle-income country and test if prevalence is different in slums. Design: After geographically-spaced community sampling of households, one individual per household was tested for IgG antibodies to SARS-CoV-2 N-protein in a two-week interval. Setting: Slum and non-slum communities in three wards, one each from the three main zones of Mumbai. Participants: Individuals over age 12 who consent to and have no contraindications to venipuncture were eligible. 6,904 participants (4,202 from slums and 2,702 from non-slums) were tested. Main outcome measures: The primary outcomes were the positive test rate for IgG antibodies to the SARS-CoV-2 N-protein by demographic group (age and gender) and location (slums and non-slums). The secondary outcome is seroprevalence at slum and non-slum levels. Sera was tested via chemiluminescence (CLIA) using Abbott Diagnostics ArchitectTM N-protein based test. Seroprevalence was calculated using weights to match the population distribution by age and gender and accounting for imperfect sensitivity and specificity of the test. Results: The positive test rate was 54.1% (95% CI: 52.7 to 55.6) and 16.1% (95% CI: 14.9 to 17.4) in slums and non-slums, respectively, a difference of 38 percentage points (P < 0.001). Accounting for imperfect accuracy of tests (e.g., sensitivity, 0.90; specificity 1.00), seroprevalence was as high as 58.4% (95% CI: 56.8 to 59.9) and 17.3% (95% CI: 16 to 18.7) in slums and non-slums, respectively. Conclusions: The high seroprevalence in slums implies a moderate infection fatality rate. The stark difference in seroprevalence across slums and non-slums has implications for the efficacy of social distancing, the level of herd immunity, and equity. It underlines the importance of geographic specificity and urban structure in modeling SARS-CoV-2.