Background Many 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. Methods In 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. Results We 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. Discussion Most 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.
Background. As 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.Methods. This 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.Results. Seventy 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. Discussion.Study 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.
BackgroundStudies reporting estimates of the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have rapidly emerged. We aimed to synthesize seroprevalence data to better estimate the burden 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 August 28, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. Estimates were corrected for imperfect test accuracy with Bayesian measurement error models. We 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.FindingsWe identified 338 seroprevalence studies including 2.3 million participants in 50 countries. Seroprevalence was low in the general population (median 3.2%, IQR 1.0-6.4%) and slightly higher in at-risk populations (median 5.4%, IQR 1.5-18.4%). Median seroprevalence varied by WHO Global Burden of Disease region (p < 0.01), from 1.0% in Southeast Asia, East Asia and Oceania to 18.8% in South Asia. National studies had lower seroprevalence estimates than local (p = 0.02) studies. Compared to White persons, Black persons (prevalence ratio [RR] 2.34, 95% CI 1.60-3.43) and Asian persons (RR 1.56, 95% CI 1.22-2.01) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.26, 95% CI 1.04-1.52). Health care workers had a 1.74x (95% CI: 1.18-2.58) higher risk compared to the general population. There was no difference in seroprevalence between sexes. There were 123 studies (36%) at low or moderate risk of bias. Seroprevalence estimates from national studies were median 11.9 (IQR 8.0 - 16.6) times higher than the corresponding SARS-CoV-2 cumulative incidence.InterpretationMost of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including non-White people and adults. Measures taken in SE Asia, E Asia and Oceania, and Latin America and Caribbean may have been more effective in controlling virus transmission than measures taken in other regions.FundingPublic Health Agency of Canada through the COVID-19 Immunity Task Force.
Neospora caninum is a coccidian intracellular protozoan capable of infecting a wide range of mammals, although severe disease is mostly reported in dogs and cattle. Innate defences triggered by monocytes/macrophages are key in the pathogenesis of neosporosis, as these cells are first-line defenders against intracellular infections. The aim of this study was to characterize infection and innate responses in macrophages infected with N. caninum using a well-known cell model to study macrophage functions (human monocyte THP-1 cells). Intracellular invasion of live tachyzoites occurred as fast as 4 h (confirmed with immunofluorescence microscopy using N. caninum-specific antibodies). Macrophages infected by N. caninum had increased expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-8, IFNγ). Interestingly, N. caninum induced expression of host-defence peptides (cathelicidins), a mechanism of defence never reported for N. caninum infection in macrophages. The expression of cytokines and cathelicidins in macrophages invaded by N. caninum was mediated by mitogen-activated protein kinase (MEK 1/2). Secretion of such innate factors from N. caninum-infected macrophages reduced parasite internalization and promoted the secretion of pro-inflammatory cytokines in naïve macrophages. We concluded that rapid invasion of macrophages by N. caninum triggered protective innate defence mechanisms against intracellular pathogens.
Background Guidelines recommend screening for frailty in all hospitalised older adults to inform care, based mainly on studies in outpatient and speciality-specific settings. However, most hospital bed-days in older people are for acute, non-elective admissions to general medicine, for which the prevalence and prognostic value of frailty might differ. Therefore, we undertook a systematic review of frailty prevalence and outcomes in older people with unplanned hospital admissions. Methods We searched MEDLINE, EMBASE and CINAHL up to 30/04/2021 for observational studies using validated frailty measures in unplanned adult hospital-wide or general medicine admissions. We related frailty prevalence to measurement tool, setting and risk of bias (RoB). Relative risks (RR) for mortality, length of stay (LOS), discharge destination and readmission were pooled using random-effects models where appropriate, and area-under-the-ROC-curves calculated. Heterogeneity was explored with meta-regression. Dose-response effects were assessed with the Cochran-Armitage test. Results Among 38 cohorts (median/SD age=80/5 years; n=37,733,147 admissions), the median prevalence of moderate-severe frailty was 40.5% (IQR=33.2-53.2; low-moderate RoB=23/38), with considerable heterogeneity (PQ<0.001) apparently unrelated to measure, setting or RoB. Nevertheless, frailty still predicted mortality (RR range=1.08-16.06), long LOS (range=1.35-3.04) and discharge destination (range=1.97-3.45) in all studies with more severe frailty associated with worse outcomes, although associations with 30-day readmission were conflicting (range=0.52-1.64). Studies reporting lower frailty prevalence showed stronger associations between frailty and mortality (beta=-0.009, P=0.03, R=49.6%), with the most consistent (PQ=0.11) associations found in studies using prospective measures (pooled RR=2.57, 95%CI=2.30-2.88) and little attenuation after adjustment for age, sex and comorbidity. Ordinal cut-points appeared to provide superior discrimination to dichotomous thresholds. Conclusions Frailty is common in older patients with acute, non-elective hospital admissions and remains an independent predictor of mortality, LOS and discharge home in the acute setting, justifying more widespread implementation of screening using prospective tools and consideration of the degree of frailty in guidance.
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