Background Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. Methods In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18–59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 μg dose or 6 μg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 μg, 3 μg, or 6 μg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 μg groups, since 3 μg is the licensed formulation. The trials are registered with ClinicalTrials.gov , NCT04352608 and NCT04383574 . Findings 540 (90%) of 600 participants aged 18–59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 μg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1–5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2–8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9–190·4) for cohort 1b-14d-8m and 143·1 (110·8–184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3–27·6) on day 28 after the second dose to 45·8 (35·7–58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4–51·1) to 49·7 (39·9–61·9) in cohor...

Background A rapidly increasing number of serological surveys for antibodies to SARS-CoV-2 have been reported worldwide. We aimed to synthesise, combine, and assess this large corpus of data.Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and five preprint servers for articles published in English between Dec 1, 2019, and Dec 22, 2020. Studies evaluating SARS-CoV-2 seroprevalence in humans after the first identified case in the area were included. Studies that only reported serological responses among patients with COVID-19, those using known infection status samples, or any animal experiments were all excluded. All data used for analysis were extracted from included papers. Study quality was assessed using a standardised scale. We estimated age-specific, sex-specific, and race-specific seroprevalence by WHO regions and subpopulations with different levels of exposures, and the ratio of serology-identified infections to virologically confirmed cases. This study is registered with PROSPERO, CRD42020198253.Findings 16 506 studies were identified in the initial search, 2523 were assessed for eligibility after removal of duplicates and inappropriate titles and abstracts, and 404 serological studies (representing tests in 5 168 360 individuals) were included in the meta-analysis. In the 82 studies of higher quality, close contacts (18•0%, 95% CI 15•7-20•3) and highrisk health-care workers (17•1%, 9•9-24•4) had higher seroprevalence than did low-risk health-care workers (4•2%, 1•5-6•9) and the general population (8•0%, 6•8-9•2). The heterogeneity between included studies was high, with an overall I² of 99•9% (p<0•0001). Seroprevalence varied greatly across WHO regions, with the lowest seroprevalence of general populations in the Western Pacific region (1•7%, 95% CI 0•0-5•0). The pooled infection-to-case ratio was similar between the region of the Americas (6•9, 95% CI 2•7-17•3) and the European region (8•4, 6•5-10•7), but higher in India (56•5, 28•5-112•0), the only country in the South-East Asia region with data.Interpretation Antibody-mediated herd immunity is far from being reached in most settings. Estimates of the ratio of serologically detected infections per virologically confirmed cases across WHO regions can help provide insights into the true proportion of the population infected from routine confirmation data.

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

Background: A rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed. Purpose: To evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys. Data sources: PubMed, Embase, Web of Science, medRxiv, bioRxiv, SSRN and Wellcome were searched for English-language papers published from December 1, 2019 to August 28, 2020. Study selection: Serological studies that evaluated seroprevalence of SARS-CoV-2 infections in humans. Data extraction: Two investigators independently extracted data from included studies. Data Synthesis: Most of 178 serological studies, representing tests in >800,000 individuals, identified were of low quality. Close contacts and high-risk healthcare workers had higher seroprevalence of 22.9% (95% CI: 11.1-34.7%) and 14.9% (4.8-25.0%), compared to low-risk healthcare workers and general population of 5.5% (4.6-6.4%) and 6.3% (5.5-7.1%). Generally, young people (0-20 yrs) were less likely to be seropositive compared to the middle-aged (21-55 yrs) populations (RR, 0.8, 95% CI: 0.7-0.8). Seroprevalence correlated with clinical COVID-19 reports with 10 (range: 2 to 34) infections per confirmed COVID-19 case. Limitations: Some heterogeneity cannot be well explained quantitatively. Conclusions: The overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given that ratio of infections to confirmed cases is on the same order of magnitude across different locales, reported case numbers may help provide insights into the proportion of the population infected. Primary Funding source: National Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).

Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.