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BackgroundMany serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. MethodsWe conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between January 1, 2020, and November 19, 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. ResultsAmong 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [-0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. ConclusionsThe Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.
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BackgroundWe aimed to systematically review the magnitude and duration of the protective effectiveness of prior infection (PE) and hybrid immunity (HE) against Omicron infection and severe disease. MethodsWe searched pre-print and peer-reviewed electronic databases for controlled studies from January 1, 2020, to June 1, 2022. Risk of bias (RoB) was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I)-Tool. We used random-effects meta-regression to estimate the magnitude of protection at 1-month intervals and the average change in protection since the last vaccine dose or infection from 3 months to 6 or 12 months. We compared our estimates of PE and HE to previously published estimates of the magnitude and durability of vaccine effectiveness (VE) against Omicron. FindingsEleven studies of prior infection and 15 studies of hybrid immunity were included. For prior infection, there were 97 estimates (27 at moderate RoB and 70 at serious RoB), with the longest follow up at 15 months. PE against hospitalization or severe disease was 82{middle dot}5% [71{middle dot}8-89{middle dot}7%] at 3 months, and 74{middle dot}6% [63{middle dot}1-83{middle dot}5%] at 12 months. PE against reinfection was 65{middle dot}2% [52{middle dot}9-75{middle dot}9%] at 3 months, and 24{middle dot}7% [16{middle dot}4-35{middle dot}5%] at 12 months. For HE, there were 153 estimates (78 at moderate RoB and 75 at serious RoB), with the longest follow up at 11 months for primary series vaccination and 4 months for first booster vaccination. Against hospitalization or severe disease, HE involving either primary series vaccination or first booster vaccination was consistently >95% for the available follow up. Against reinfection, HE involving primary series vaccination was 69{middle dot}0% [58{middle dot}9-77{middle dot}5%] at 3 months after the most recent infection or vaccination, and 41{middle dot}8% [31{middle dot}5-52{middle dot}8%] at 12 months, while HE involving first booster vaccination was 68{middle dot}6% [58{middle dot}8-76{middle dot}9%] at 3 months, and 46{middle dot}5% [36{middle dot}0-57{middle dot}3%] at 6 months. Against hospitalization or severe disease at 6 months, hybrid immunity with first booster vaccination (effectiveness 95{middle dot}3% [81{middle dot}9-98{middle dot}9%]) or with primary series alone (96{middle dot}5% [90{middle dot}2-98{middle dot}8%]) provided significantly greater protection than prior infection alone (80{middle dot}1% [70{middle dot}3-87{middle dot}2%]), first booster vaccination alone (76{middle dot}7% [72{middle dot}5-80{middle dot}4%]), or primary series alone (64{middle dot}6% [54{middle dot}5-73{middle dot}6%]). Results for protection against reinfection were similar. InterpretationPrior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. All protection estimates waned quickly against infection but remained high for hospitalisation or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection against all outcomes, reinforcing the global imperative for vaccination. FundingWHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe global emergence and rapid spread of Omicron (B.1.1.529) variant of concern, characterized by their ability to escape immunity, has required scientists and policymakers to reassess the population protection against Omicron infection and severe disease. So far, few systematic reviews have incorporated data on Omicron, and none have examined the protection against Omicron conferred by hybrid immunity (i.e. the immunity gained from the combination of vaccination and prior infection) which is now widespread globally. While one preprint has recently reported protection from prior infection over time, no systematic review has systematically compared the magnitude and duration of vaccination, prior infection, and hybrid immunity. A large single-country study has reported that protection from either infection or hybrid immunity against Omicron infection wanes to low levels at 15 months, but is relatively stable against severe disease. Added value of this studyPrior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. Individuals with hybrid immunity had the highest magnitude and durability of protection against all outcomes; protection against severe disease remained above 95% until the end of available follow-up at 11 months after hybrid immunity with primary series and 4 months after hybrid immunity with booster vaccination, and was sustained at these high levels of protection in projections to 12 months and 6 months, respectively. Implications of all the available evidenceThese results may serve to tailor guidance on the optimal number and timing of vaccinations. At the public health level, these findings can be combined with data on local infection prevalence, vaccination rates, and their timing. In settings with high seroprevalence, limited resources, and competing health priorities, it may be reasonable to focus on achieving high coverage rates with primary series among individuals who are at higher risk of poor outcome, as this will provide a high level of protection against severe disease for at least one year among those with prior infection. Furthermore, given the waning protection for both infection-and vaccine induced immunity against infection or reinfection, mass vaccination could be timed for roll-out prior to periods of expected increased incidence, such as the winter season. At the individual level, these results can be combined with knowledge of a persons infection and vaccination history. A six-month delay in booster may be justified after the last infection or vaccination for individuals with a known prior infection and full primary series vaccination. Further follow-up of the protective effectiveness of hybrid immunity against hospitalization or severe disease for all vaccines is needed to clarify how much waning of protection might occur with longer duration since the last infection or vaccination. Producing estimates of protection for new variant-containing vaccines will be crucial for COVID-19 vaccine policy and decision-making bodies. Policy makers considering the use and timing of vaccinations should include the local extent of past infection, the protection conferred by prior infection or hybrid immunity, and the duration of this protection as key considerations to inform their decision-making.
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We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for Unity-aligned First Few X cases (FFX) and HHTIs published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%-90% (95% prediction interval: 3%-71%; I2=99.7%); I2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.
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IntroductionEstimating COVID-19 cumulative incidence in Africa remains problematic due to challenges in contact tracing, routine surveillance systems and laboratory testing capacities and strategies. We undertook a meta-analysis of population-based seroprevalence studies to estimate SARS-CoV-2 seroprevalence in Africa to inform evidence-based decision making on Public Health and Social Measures (PHSM) and vaccine strategy. MethodsWe searched for seroprevalence studies conducted in Africa published 01-01-2020 to 30-12-2021 in Medline, Embase, Web of Science, and Europe PMC (preprints), grey literature, media releases and early results from WHO Unity studies. All studies were screened, extracted, assessed for risk of bias and evaluated for alignment with the WHO Unity protocol for seroepidemiological investigations. We conducted descriptive analyses of seroprevalence and meta-analysed seroprevalence differences by demographic groups, place and time. We estimated the extent of undetected infections by comparing seroprevalence and cumulative incidence of confirmed cases reported to WHO. PROSPERO: CRD42020183634. ResultsWe identified 54 full texts or early results, reporting 151 distinct seroprevalence studies in Africa Of these, 95 (63%) were low/moderate risk of bias studies. SARS-CoV-2 seroprevalence rose from 3.0% [95% CI: 1.0-9.2%] in Q2 2020 to 65.1% [95% CI: 56.3-73.0%] in Q3 2021. The ratios of seroprevalence from infection to cumulative incidence of confirmed cases was large (overall: 97:1, ranging from 10:1 to 958:1) and steady over time. Seroprevalence was highly heterogeneous both within countries - urban vs. rural (lower seroprevalence for rural geographic areas), children vs. adults (children aged 0-9 years had the lowest seroprevalence) - and between countries and African sub-regions (Middle, Western and Eastern Africa associated with higher seroprevalence). ConclusionWe report high seroprevalence in Africa suggesting greater population exposure to SARS-CoV-2 and protection against COVID-19 disease than indicated by surveillance data. As seroprevalence was heterogeneous, targeted PHSM and vaccination strategies need to be tailored to local epidemiological situations.
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BackgroundOur understanding of the global scale of SARS-CoV-2 infection remains incomplete: routine surveillance data underestimates 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 WHOs Unity protocol for general population seroepidemiological studies, two years into the pandemic, to estimate the extent of population infection and remaining susceptibility. Methods and FindingsWe conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between 2020-01-01 and 2022-05-20. 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 under-ascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. The main limitations of our methodology include that some estimates were driven by certain countries or populations being over-represented. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% LMIC) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/sub-national scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1-62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6-28.8] to 86.7% [84.6-88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3-11.0%] to 95.9% [92.6-97.8%] in Europe high-income countries in December 2021). After the emergence of Omicron, infection-induced seroprevalence rose to 47.9% [41.0-54.9%] in EUR HIC and 33.7% [31.6-36.0%] in AMR HIC in March 2022. 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 0-9 years and adults 60+ were at lower risk of seropositivity than adults 20-29 (p<0.0001 and p=0.005, respectively). In a multivariable model using pre-vaccination data, stringent public health and social measures were associated with lower seroprevalence (p=0.02). ConclusionsIn this study, we observed that global seroprevalence has risen considerably over time and with regional variation, however around 40 % of the global population remains susceptible to SARS-CoV-2 infection. Our estimates of infections based on seroprevalence far exceed reported COVID-19 cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.
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BackgroundSeroprevalence surveys are essential to assess the age-specific prevalence of pre-existing cross-reactive antibodies in the population with the emergence of a novel pathogen; to measure population cumulative seroincidence of infection, and to contribute to estimating infection severity. With the emergence of SARS-CoV-2, ECDC and WHO Regional Office for Europe have supported Member States in undertaking standardized population-based SARS-CoV-2 seroprevalence surveys across the WHO European Region. ObjectivesThe objective of this study was to undertake a systematic literature review of SARS-CoV-2 population seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes. MethodsWe systematically searched MEDLINE, ELSEVIER and the pre-print servers medRxiv and bioRxiv within the "COVID-19 Global literature on coronavirus disease" database using a predefined search strategy. We included seroepidemiology studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and ECDC. ResultsIn total, 111 studies from 26 countries published or conducted between 01/01/2020 and 31/12/2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Eighty-one (73%) studies were assessed to be of low to medium risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7-5.2%); n=124), while sub-national estimates ranged from 0% to 52% (median 5.8% (IQR 2.3-12%); n=101), with the highest estimates in areas following widespread local transmission. ConclusionsThe review found evidence of low national SARS-CoV-2 seroprevalence (<10%) across the WHO European Region in 2020. The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes highlights the critical importance of vaccinating priority groups at risk of severe disease while maintaining reduced levels of transmission to minimize population morbidity and mortality.
