ABSTRACT
BackgroundThe kinetics of the neutralizing antibody response against SARS-CoV-2 is crucial for responding to the pandemic as well as developing vaccination strategies. We aimed to fit the antibody curves in symptomatic and asymptomatic individuals. MethodsWe systematically searched PubMed, Embase, Web of Science, and Europe PMC for articles published in English between Jan 1, 2020, and Oct 2, 2022. Studies evaluating neutralizing antibody from people who had a natural SARS-CoV-2 infection history were included. Study quality was assessed using a modified standardized scoring system. We fitted dynamic patterns of neutralizing antibody using a generalized additive model and a generalized additive mixed model. We also used linear regression model to conduct both univariate and multivariable analyses to explore the potential affecting factors on antibody levels. This study is registered with PROSPERO, CRD42022348636. Results7,343 studies were identified in the initial search, 50 were assessed for eligibility after removal of duplicates as well as inappropriate titles, abstracts and full-text review, and 48 studies (2,726 individuals, 5,670 samples) were included in the meta-analysis after quality assessment. The neutralization titer of people who infected with SARS-CoV-2 prototype strain peaked around 27 days (217.4, 95%CI: 187.0-252.9) but remained below the Omicron BA.5 protection threshold all the time after illness onset or confirmation. Furthermore, neither symptomatic infections nor asymptomatic infections could provide over 50% protection against Omicron BA.5 sub-lineage. It also showed that the clinical severity and the type of laboratory assays may significantly correlated with the level of neutralizing antibody. ConclusionsThis study provides a comprehensive mapping of the dynamic of neutralizing antibody against SARS-CoV-2 prototype strain induced by natural infection and compared the dynamic patterns between prototype and variant strains. It suggests that the protection probability provided by natural infection is limited. Therefore, timely vaccination is necessary for both previously infected symptomatic and asymptomatic individuals.
ABSTRACT
Evidence on vaccine-specific protection over time and boosting impact against the Delta variant across different clinical endpoints and age groups is urgently needed. To address this, we used a previously published model, combined with neutralization data for four vaccines - mRNA-1273, BNT162b2, NVX-CoV2373, and CoronaVac - to evaluate long-term dynamics of neutralizing antibody and to predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity. We found that booster vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacies of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95%CI: 51.4-67.3%) and 78.4% (95%CI: 72.2-83.5%), respectively, 14-30 days after the second dose, and that efficacies decreased to 36.0% (95%CI: 24.1-58.0%) and 38.5% (95%CI: 28.7-49.1%) 6-8 months later. After administration of booster doses, efficacies against the Delta variant would be 97.0% (95%CI: 96.4-98.5%) and 97.2% (95.7-98.1%). All four vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and booster vaccination. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants are needed to inform COVID-19 pandemic preparedness.
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BackgroundGenomic surveillance has shaped our understanding of SARS-CoV-2 variants, which have proliferated globally in 2021. Characterizing global genomic surveillance, sequencing coverage, the extent of publicly available genomic data coupled with traditional epidemiologic data can provide evidence to inform SARS-CoV-2 surveillance and control strategies. MethodsWe collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data. We divided countries into three levels of genomic surveillance and sequencing availability based on predefined criteria. We downloaded the merged and deduplicated SARS-CoV-2 sequences from multiple public repositories, and used different proxies to estimate the sequencing coverage and public availability extent of genomic data, in addition to describing the global dissemination of variants. FindingsSince the start of 2021, the COVID-19 global epidemic clearly featured increasing circulation of Alpha, which was rapidly replaced by the Delta variant starting around May 2021 and reaching a global prevalence of 96.6% at the end of July 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 63 countries performing routine genomic surveillance and 79 countries with high availability of SARS-CoV-2 sequencing. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020, with the lowest sequencing coverage in the WHO regions of Eastern Mediterranean, South East Asia, and Africa. Across different variants, 28-52% of countries with explicit reporting on variants shared less than half of their variant sequences in public repositories. More than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. InterpretationOur findings indicated an urgent need to expand sequencing capacity of virus isolates, enhance the sharing of sequences, the standardization of metadata files, and supportive networks for countries with no sequencing capability. Research in context Evidence before this studyOn September 3, 2021, we searched PubMed for articles in any language published after January 1, 2020, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("Global" OR "Region") AND ("genomic surveillance" OR "sequencing" OR "spread"). Among 43 papers identified, few papers discussed the global diversity in genomic surveillance, sequencing, public availability of genomic data, as well as the global spread of SARS-CoV-2 variants. A paper from Furuse employed the publicly GISAID data to evaluate the SARS-CoV-2 sequencing effort by country from the perspectives of "fraction", "timeliness", and "openness". Another viewpoint paper by Case Western Reserve Universitys team discussed the impediments of genomic surveillance in several countries during the COVID-19 pandemic. The paper as reported by Campbell and colleagues used the GISAID data to present the global spread and estimated transmissibility of recently emerged SARS-CoV-2 variants. We also found several studies that reported the country-level genomic surveillance and spread of variants. To our knowledge, no research has quantitatively depicted the global SARS-CoV-2 genomic surveillance, sequencing ability, and public availability extent of genomic data. Added value of this studyThis study collected country-specific data on SARS-CoV-2 genomic surveillance, sequencing capabilities, public genomic data, and aggregated publicly available variant data as of 20 August 2021. We found that genomic surveillance strategies and sequencing availability is globally diverse. Less than 3.5% of confirmed SARS-CoV-2 infections were sequenced globally since September 2020. Our analysis of publicly deposited SARS-CoV-2 sequences and officially reported number of variants implied that the public availability extent of genomic data is low in some countries, and more than 60% of demographic and 95% of clinical data were absent in GISAID metadata accompanying sequences. We also described the pandemic dynamics shaped by VOCs. Implications of all the available evidenceOur study provides a landscape for global sequencing coverage and public availability extent of sequences, as well as the evidence for rapid spread of SRAS-CoV-2 variants. The pervasive spread of Alpha and Delta variants further highlights the threat of SARS-CoV-2 mutations despite the availability of vaccines in many countries. It raised an urgent need to do more work on defining the ideal sampling schemes for different purposes (e.g., identifying new variants) with an additional call to share these data in public repositories to allow for further rapid scientific discovery.
ABSTRACT
The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.
ABSTRACT
ImportanceWhether herd immunity through mass vaccination is sufficient to curb SARS-CoV-2 transmission requires an understanding of the duration of vaccine-induced immunity, and the necessity and timing of booster doses. Objective: To evaluate immune persistence of two priming doses of CoronaVac, and immunogenicity and safety of a third dose in healthy adults [≥]60 years. Design, setting, and participants: We conducted a vaccine booster study built on a single-center, randomized, double-blind phase 1/2 trial of the two-dose schedule of CoronaVac among healthy adults[≥]60 years in Hebei, China. We examined neutralizing antibody titres six months or more after the second dose in all participants. We provided a third dose to 303 participants recruited in phase 2 trial to assess their immune responses. InterventionsTwo formulations (3 g, and 6 g) were used in phase 1 trial, and an additional formulation of 1.5 g was used in phase 2 trial. All participants were given two doses 28 days apart and followed up 6 months after the second dose. Participants in phase 2 received a third dose 8 months after the second dose. Main outcomes and measuresGeometric mean titres (GMT) of neutralizing antibodies to live SARS-CoV-2 and adverse events were assessed at multiple time points following vaccination. ResultsNeutralizing antibody titres dropped below the seropositive cutoff of 8 at 6 months after the primary vaccination in all vaccine groups in the phase 1/2 trial. A third dose given 8 months or more after the second dose significantly increased neutralizing antibody levels. In the 3 g group (the licensed formulation), GMT increased to 305 [95%CI 215.3-432.0] on day 7 following the third dose, an approximately 7-fold increase compared with the GMT 28 days after the second dose. All solicited adverse reactions reported within 28 days after a booster dose were of grade 1 or 2 severity. Conclusion and relevanceNeutralizing antibody titres declined substantially six months after two doses of CoronaVac among older adults. A booster dose rapidly induces robust immune responses. This evidence could help policymakers determine the necessity and the timing of a booster dose for older adults. Trial registrationClinicalTrials.gov (NCT04383574).
ABSTRACT
BackgroundImmunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. MethodsWe systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. FindingsWe identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non-replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). InterpretationOur findings indicate that the antibody response established by natural infection or vaccination might be able to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. FundingChinese National Science Fund for Distinguished Young Scholars Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSeveral newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants. Added value of this studyIn this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural-infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Implications of all the available evidenceOur findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies.
ABSTRACT
BackgroundA 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. PurposeTo 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 sourcesWe searched PubMed, Embase, Web of Science, and 4 pre-print servers for English-language papers published from December 1, 2019 to September 25, 2020. Study selectionSerological studies evaluating SARS-CoV-2 seroprevalence in humans. Data extractionTwo investigators independently extracted data from studies. Data SynthesisMost of 230 serological studies, representing tests in >1,400,000 individuals, identified were of low quality based on a standardized study quality scale. In the 51 studies of higher quality, high-risk healthcare workers had higher seroprevalence of 17.1% (95% CI: 9.9-24.4%), compared to low-risk healthcare workers and general population of 5.4% (0.7-10.1%) and 5.3% (4.2-6.4%). Seroprevalence varied hugely across WHO regions, with lowest seroprevalence of general population in Western Pacific region (1.7%, 0.0-5.0%). Generally, the young (<20 years) and the old ([≥]65 years) were less likely to be seropositive compared to middle-aged (20-64 years) populations. Seroprevalence correlated with clinical COVID-19 reports, with pooled average of 7.7 (range: 2.0 to 23.1) serologically-detected-infections per confirmed COVID-19 case. LimitationsSome heterogeneity cannot be well explained quantitatively. ConclusionsThe 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 the relatively narrow range of estimates of the ratio of serologically-detected infections to confirmed cases across different locales, reported case counts may help provide insights into the true proportion of the population infected. Primary Funding sourceNational Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).
