RESUMO
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.
RESUMO
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.
RESUMO
Seroprevalence studies have been used throughout the COVID-19 pandemic to monitor infection and immunity. These studies are often reported in peer-reviewed journals, but the academic writing and publishing process can delay reporting and thereby public health action. Seroprevalence estimates have been reported faster in preprints and media, but with concerns about data quality. We aimed to (i) describe the timeliness of SARS-CoV-2 serosurveillance reporting by publication venue and study characteristics and (ii) identify relationships between timeliness, data validity, and representativeness to guide recommendations for serosurveillance efforts. We included seroprevalence studies published between January 1, 2020 and December 31, 2021 from the ongoing SeroTracker living systematic review. For each study, we calculated timeliness as the time elapsed between the end of sampling and the first public report. We evaluated data validity based on serological test performance and correction for sampling error, and representativeness based on use of a representative sample frame and adequate sample coverages. We examined how timeliness varied with study characteristics, representativeness, and data validity using univariate and multivariate Cox regression. We analyzed 1,844 studies. Median time to publication was 154 days (IQR 64-255), varying by publication venue (journal articles: 212 days, preprints: 101 days, institutional reports: 18 days, and media: 12 days). Multivariate analysis confirmed the relationship between timeliness and publication venue and showed that general population studies were published faster than special population or health care worker studies; there was no relationship between timeliness and study geographic scope, geographic region, representativeness, or serological test performance. Seroprevalence studies in peer-reviewed articles and preprints are published slowly, highlighting the limitations of using the academic literature to report seroprevalence during a health crisis. More timely reporting of seroprevalence estimates can improve their usefulness for surveillance, enabling more effective responses during health emergencies.
RESUMO
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.
RESUMO
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.
RESUMO
BackgroundRisk of bias (RoB) assessments are a core element of evidence synthesis but can be time consuming and subjective. We aimed to develop a decision rule-based algorithm for RoB assessment of seroprevalence studies. MethodsWe developed the SeroTracker-RoB algorithm. The algorithm derives seven objective and two subjective critical appraisal items from the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence studies and implements decision rules that determine study risk of bias based on the items. Decision rules were validated using the SeroTracker seroprevalence study database, which included non-algorithmic RoB judgements from two reviewers. We quantified efficiency as the mean difference in time for the algorithmic and non-algorithmic assessments of 80 randomly selected articles, coverage as the proportion of studies where the decision rules yielded an assessment, and reliability using intraclass correlations comparing algorithmic and non-algorithmic assessments for 2,070 articles. ResultsA set of decision rules with 61 branches was developed using responses to the nine critical appraisal items. The algorithmic approach was faster than non-algorithmic assessment (mean reduction 2.32 minutes [SD 1.09] per article), classified 100% (n=2,070) of studies, and had good reliability compared to non-algorithmic assessment (ICC 0.77, 95% CI 0.74-0.80). We built the SeroTracker-RoB Excel Tool which embeds this algorithm for use by other researchers. ConclusionsThe SeroTracker-RoB decision-rule based algorithm was faster than non-algorithmic assessment with complete coverage and good reliability. This algorithm enabled rapid, transparent, and reproducible RoB evaluations of seroprevalence studies and may support evidence synthesis efforts during future disease outbreaks. This decision rule-based approach could be applied to other types of prevalence studies.
RESUMO
BackgroundSARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) remain unclear. ObjectiveTo analyze SARS-CoV-2 shedding dynamics across COVID-19 severity, the respiratory tract, sex and age cohorts (aged 0 to 17 years, 18 to 59 years, and 60 years or older). DesignSystematic review and pooled analyses. SettingMEDLINE, EMBASE, CENTRAL, Web of Science Core Collection, medRxiv and bioRxiv were searched up to 20 November 2020. ParticipantsThe systematic dataset included 1,266 adults and 136 children with COVID-19. MeasurementsCase characteristics (COVID-19 severity, age and sex) and quantitative respiratory viral loads (rVLs). ResultsIn the URT, adults with severe COVID-19 had higher rVLs at 1 DFSO than adults (P = 0.005) or children (P = 0.017) with nonsevere illness. Between 1-10 DFSO, severe adults had comparable rates of SARS-CoV-2 clearance from the URT as nonsevere adults (P = 0.479) and nonsevere children (P = 0.863). In the LRT, severe adults showed higher post-symptom-onset rVLs than nonsevere adults (P = 0.006). In the analyzed period (4-10 DFSO), severely affected adults had no significant trend in SARS-CoV-2 clearance from LRT (P = 0.105), whereas nonsevere adults showed a clear trend (P < 0.001). After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of the duration of respiratory shedding. LimitationLimited data on case comorbidities and few samples in some cohorts. ConclusionHigh, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. After symptom onset, severe cases tended to have higher URT shedding than their nonsevere counterparts. Disease severity, rather than age or sex, predicted SARS-CoV-2 kinetics. LRT specimens should more accurately prognosticate COVID-19 severity than URT specimens. Primary Funding SourceNatural Sciences and Engineering Research Council.
RESUMO
BackgroundMany studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. MethodsIn this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. ResultsWe identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6 % in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64-4.29), Asian persons (RR 2.47, 95% CI 1.96-3.11), Indigenous persons (RR 5.47, 95% CI 1.01-32.6), and multi-racial persons (RR 1.89, 95% CI 1.60-2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.27, 95% CI 1.11-1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28-3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9-38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. DiscussionMost of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response. FundingPublic Health Agency of Canada through the COVID-19 Immunity Task Force.
RESUMO
Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a longstanding question in infectious disease epidemiology. Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols. Our analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1-5 days post-symptom onset. Our findings show how individual case variations influence virus transmissibility and present considerations for disease control in the COVID-19 pandemic. Significance StatementFor some emerging infectious diseases, including COVID-19, few cases cause most secondary infections. Others, like influenza A(H1N1)pdm09, spread more homogenously. The virological factors that mediate such distinctions in transmissibility remain unelucidated, prohibiting the development of specific disease control measures. We find that intrinsic case variation in respiratory viral load (rVL) facilitates overdispersion, and superspreading, for COVID-19 but more homogeneous transmission for A(H1N1)pdm09. We interpret the influence of heterogeneity in rVL on individual infectiousness by modelling likelihoods of shedding viable virus via respiratory droplets and aerosols. We analyze the distribution and kinetics of SARS-CoV-2 rVL, including across age and symptomatology subgroups. Our findings compare individual infectiousness across COVID-19 and A(H1N1)pdm09 cases and present quantitative guidance on triaging COVID-19 contact tracing.
RESUMO
BackgroundAs the world grapples with the COVID-19 pandemic, there is increasing global interest in the role of serological testing for population monitoring and to inform public policy. However, limitations in serological study designs and test standards raise concerns about the validity of seroprevalence estimates and their utility in decision-making. There is now a critical window of opportunity to learn from early SARS-CoV-2 serology studies. We aimed to synthesize the results of SARS-CoV-2 serosurveillance projects from around the world and provide recommendations to improve the coordination, strategy, and methodology of future serosurveillance efforts. MethodsThis was a rapid systematic review of cross-sectional and cohort studies reporting seroprevalence outcomes for SARS-CoV 2. We included completed, ongoing, and proposed serosurveys. The search included electronic databases (PubMed, MedRXIV, BioRXIV, and WHO ICTPR); five medical journals (NEJM, BMJ, JAMA, The Lancet, Annals of Internal Medicine); reports by governments, NGOs, and health systems; and media reports (Google News) from December 1, 2019 to May 1, 2020. We extracted data on study characteristics and critically appraised prevalence estimates using Joanna Briggs Institute criteria. ResultsSeventy records met inclusion criteria, describing 73 studies. Of these, 23 reported prevalence estimates: eight preprints, 14 news articles, and one government report. These studies had a total sample size of 35,784 and reported 42 prevalence estimates. Seroprevalence estimates ranged from 0.4% to 59.3%. No estimates were found to have a low risk of bias (43% high risk, 21% moderate risk, 36% unclear). Fifty records reported characteristics of ongoing or proposed serosurveys. Overall, twenty countries have completed, ongoing, or proposed serosurveys. DiscussionStudy design, quality, and prevalence estimates of early SARS-CoV2 serosurveys are heterogeneous, suggesting that the urgency to examine seroprevalence may have compromised methodological rigour. Based on the limitations of included studies, future serosurvey investigators and stakeholders should ensure that: i) serological tests used undergo high-quality independent evaluations that include cross-reactivity; ii) all reports of serosurvey results, including media, describe the test used, sample size, and sampling method; and iii) initiatives are coordinated to prevent test fatigue, minimize redundant efforts, and encourage better study methodology. OtherPROSPERO: CRD42020183634. No third-party funding.
