The virus is spreading faster than ever before in India despite previous high infection rates in megacities, which should have conferred some protection. The virus is spreading faster than ever before in India despite previous high infection rates in megacities, which should have conferred some protection.

India's massive COVID surge puzzles scientists.

Background Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization’s Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic. Methods and findings We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies—those aligned with the WHO Unity protocol—were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented. Conclusions In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

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Global SARS-CoV-2 seroprevalence from January 2020 to April 2022: A systematic review and meta-analysis of standardized population-based studies

The Delta variant is a major SARS-CoV-2 variant of concern first identified in India. To better understand COVID-19 pandemic dynamics and Delta, we use multiple datasets and model-inference to reconstruct COVID-19 pandemic dynamics in India during March 2020–June 2021. We further use the large discrepancy in one- and two-dose vaccination coverage in India (53% versus 23% by end of October 2021) to examine the impact of vaccination and whether prior non-Delta infection can boost vaccine effectiveness (VE). We estimate that Delta escaped immunity in 34.6% (95% CI: 0–64.2%) of individuals with prior wild-type infection and was 57.0% (95% CI: 37.9–75.6%) more infectious than wild-type SARS-CoV-2. Models assuming higher VE among non-Delta infection recoverees, particularly after the first dose, generated more accurate predictions than those assuming no such increases (best-performing VE setting: 90/95% versus 30/67% baseline for the first/second dose). Counterfactual modelling indicates that high vaccination coverage for first vaccine dose in India combined with the boosting of VE among recoverees averted around 60% of infections during July–mid-October 2021. These findings provide support to prioritizing first-dose vaccination in regions with high underlying infection rates, given continued vaccine shortages and new variant emergence.

COVID-19 pandemic dynamics in India, the SARS-CoV-2 Delta variant and implications for vaccination

The largest burden of COVID-19 is carried by the elderly, and persons living in nursing homes are particularly vulnerable. However, 94% of the global population is younger than 70 years and 86% is younger than 60 years. The objective of this study was to accurately estimate the infection fatality rate (IFR) of COVID-19 among non-elderly people in the absence of vaccination or prior infection. In systematic searches in SeroTracker and PubMed (protocol: https://osf.io/xvupr), we identified 40 eligible national seroprevalence studies covering 38 countries with pre-vaccination seroprevalence data. For 29 countries (24 high-income, 5 others), publicly available age-stratified COVID-19 death data and age-stratified seroprevalence information were available and were included in the primary analysis. The IFRs had a median of 0.034% (interquartile range (IQR) 0.013-0.056%) for the 0-59 years old population, and 0.095% (IQR 0.036-0.119%) for the 0-69 years old. The median IFR was 0.0003% at 0-19 years, 0.002% at 20-29 years, 0.011% at 30-39 years, 0.035% at 40-49 years, 0.123% at 50-59 years, and 0.506% at 60-69 years. IFR increases approximately 4 times every 10 years. Including data from another 9 countries with imputed age distribution of COVID-19 deaths yielded median IFR of 0.025-0.032% for 0-59 years and 0.063-0.082% for 0-69 years. Meta-regression analyses also suggested global IFR of 0.03% and 0.07%, respectively in these age groups. The current analysis suggests a much lower pre-vaccination IFR in non-elderly populations than previously suggested. Large differences did exist between countries and may reflect differences in comorbidities and other factors. These estimates provide a baseline from which to fathom further IFR declines with the widespread use of vaccination, prior infections, and evolution of new variants. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613797

Age-stratified infection fatality rate of COVID-19 in the non-elderly population

Lebanon, a small country in the Middle East, remains severely affected by the COVID-19 pandemic. Seroprevalence surveys of anti-SARS-CoV-2 antibodies provide accurate estimates of SARS-CoV-2 infection and hence evaluate the extent of the pandemic. The present study aimed to evaluate the prevalence of SARS-CoV-2 antibodies in Lebanon and to compare the estimated cumulative number of COVID-19 cases with the officially registered number of laboratory-confirmed cases up to January 15, 2021.A nationwide population-based serosurvey study was conducted in Lebanon between December 7, 2020, and January 15, 2021, before the initiation of the national vaccination program. The nCOVID-19 IgG & IgM point-of-care (POCT) rapid test was used to detect the presence of anti-SARS-COV-2 immunoglobulin G (IgG) in the blood. Seroprevalence was estimated after weighting for sex, age, and area of residence and adjusting for the test performance.Of the 2058 participants, 329 were positive for IgG SARS-COV-2, resulting in a crude seroprevalence of 16.0% (95% CI 14.4-17.6). The weighed seroprevalence was 15.9% (95% CI of 14.4 and 17.4). After adjusting for test performance, the population weight-adjusted seroprevalence was 18.5% (95% CI 16.8-20.2). This estimate implies that 895,770 individuals of the general population were previously infected by COVID-19 up to January 15, 2021 in Lebanon. The overall estimated number of subjects with previous SARS-CoV-2 infection was three times higher than the officially reported cumulative number of confirmed cases. Seroprevalence was similar across age groups and sexes (p-value > 0.05). However, significant differences were revealed across governorates.Our results suggest that the Lebanese population is still susceptible to SARS-CoV-2 infection and far from achieving herd immunity. These findings represent an important contribution to the surveillance of the COVID-19 pandemic in Lebanon and to the understanding of how this virus spreads. Continued surveillance for COVID-19 cases and maintaining effective preventive measures are recommended to control the epidemic spread in conjunction with a national vaccination campaign to achieve the desired level of herd immunity against COVID-19. 

/pdf/sars-cov-2-antibody-seroprevalence-in-lebanon-findings-from-fi9cvi8b.pdf

SARS-CoV-2 antibody seroprevalence in Lebanon: findings from the first nationwide serosurvey

Background: Repeated cross-sectional serosurveys in the same geographic area establish the trend of the evolving pandemic. We present the findings of the third round of a national serosurvey to estimate the seroprevalence of SARS-CoV-2 infection among the general population and health care workers of India. 

Methods: We conducted the third population-based serosurvey between Dec 18, 2020 and Jan 6, 2021 in the same 700 villages or wards from 70 districts in 21 states across India, which were selected for the first and second serosurveys. We enrolled from each district, at least 400 individuals aged ≥ 10 years from general population and 100 HCWs from sub-district level public health facilities. Serum samples from general population were tested for the presence of IgG antibodies against nucleocapsid (N) and spike protein (S1-RBD) of SARS-CoV-2 using the Abbott and Siemens assays respectively, whereas sera from HCWs were tested for anti-S1-RBD. For general population, sera positive for either of the antibodies were considered positive, while sera positive for anti-S1-RBD were considered as positive for HCW. Weighted seroprevalence estimates were adjusted for sensitivity and specificity of respective assays. 

Findings: Of the 28,598 sera from general population, 4585 (16%) had IgG antibodies against N, 6647 (23.2%) against S1-RBD and 7436 (26%) against either. The weighted and assay characteristic adjusted seroprevalence against either of the antibodies was 24.1 (95%CI: 23.0% to 25.3%). Seroprevalence was lower in rural areas (21.4%, 95% CI: 20.3% to 22.6%) compared to urban non-slum (29.4%, 95% CI: 26.9% - 32.1%) and slum areas (34.6%, 95% CI: 31.0% to 38.3%). Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI: 23.5% to 27.8%). 

Interpretation: Nearly one in four individuals aged 10 years or older from general population as well as HCWs were exposed to SARS-CoV-2 by December 2020 amounting to 271 million infections in India.

Funding Statement: Indian Council of Medical Research

Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no competing interests

Ethics Approval Statement: The project was approved by Institutional Human Ethics Committee at ICMR-National Institute of Epidemiology.

Nandan Kumar Mishra

Papers

SARS-CoV-2 Sero-Prevalence Among General Population and Healthcare Workers in India, December 2020 - January 2021