SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study.
TL;DR: In this paper, the performance of lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (React 2) was evaluated.
Abstract: Objective To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2—React 2). Design Diagnostic accuracy study. Setting Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London. Research clinics for finger prick sampling were run in two affiliated NHS trusts. Participants Sensitivity analyses were performed on sera stored from 320 previous participants in the React 2 programme with confirmed previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specificity analyses were performed on 1000 prepandemic serum samples. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger prick testing. Interventions Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 serum samples from participants with confirmed SARS-CoV-2 infection and 500 prepandemic serum samples, respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger prick sensitivity of the LFIA currently used in React 2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger prick testing on participants with confirmed previous SARS-CoV-2 infection: two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July 2020 and the third LFIA (AbC-19) in September 2020. A spike protein enzyme linked immunoassay and hybrid double antigen binding assay were used as laboratory reference standards. Main outcome measures The accuracy of LFIAs in detecting immunoglobulin G (IgG) antibodies to SARS-CoV-2 compared with two reference standards. Results The sensitivity and specificity of seven new LFIAs that were analysed using sera varied from 69% to 100%, and from 98.6% to 100%, respectively (compared with the two reference standards). Sensitivity on finger prick testing was 77% (95% confidence interval 61.4% to 88.2%) for Panbio, 86% (72.7% to 94.8%) for Surescreen, and 69% (53.8% to 81.3%) for AbC-19 compared with the reference standards. Sensitivity for sera from matched clinical samples performed on AbC-19 was significantly higher with serum than finger prick at 92% (80.0% to 97.7%, P=0.01). Antibody titres varied considerably among cohorts. The numbers of positive samples identified by finger prick in the lowest antibody titre quarter varied among LFIAs. Conclusions One new LFIA was identified with clinical performance suitable for potential inclusion in seroprevalence studies. However, none of the LFIAs tested had clearly superior performance to the LFIA currently used in React 2 seroprevalence surveys, and none showed sufficient sensitivity and specificity to be considered for routine clinical use.
Citations
More filters
TL;DR: The RECOVERY trial as mentioned in this paper evaluated the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.
224 citations
TL;DR: In this article, the authors compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2.
Abstract: Summary Background By July 14, 2021, 81·3 % of adults (aged ≥18 years) in Chile had received a first SARS-CoV-2 vaccine and 72·3% had received a second SARS-CoV-2 vaccine, with the majority of people given Sinovac's inactivated CoronaVac vaccine (75·3% of vaccines dispensed) or Pfizer–BioNTech's mRNA BNT162b2 vaccine (20·9% of vaccines dispensed). Due to the absence of simultaneous real-world data for these vaccines, we aimed to compare SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy. Methods From March 12, 2021, 28 testing stations for SARS-CoV-2 IgG detection were installed in hotspots based on cellular-phone mobility tracking within the most populated cities in Chile. Individuals voluntarily approaching the testing stations were invited to do a lateral flow test by finger prick and respond to a questionnaire on sociodemographic characteristics, vaccination status (including type of vaccine if one was received), variables associated with SARS-CoV-2 exposure, and comorbidities. We compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2. Unvaccinated participants served as a control population and were matched to vaccinated individuals on the basis of date of presentation to the testing station, gender, and age group. Individuals were excluded from the analysis if they were younger than 18 years, had no declared gender, had an invalid IgG test result, had previously tested positive for SARS-CoV-2 infection on PCR, could not recall their vaccination status, or had been immunised against COVID-19 with vaccines other than CoronaVac or BNT162b2. Here, we report data collected up to July 2, 2021. Findings Of 64 813 individuals enrolled, 56 261 were included in the final analysis, of whom 33 533 (59·6%) had received at least one dose of the CoronaVac vaccine, 8947 (15·9%) had received at least one dose of the BNT162b2 vaccine, and 13 781 (24·5%) had not received a vaccine. SARS-CoV-2 IgG positivity during week 4 after the first dose of CoronaVac was 28·1% (95% CI 25·0–31·2; 220 of 783 individuals), reaching a peak of 77·4% (75·5–79·3; 1473 of 1902 individuals) during week 3 after the second dose. SARS-CoV-2 IgG positivity during week 4 after the first dose of the BNT162b2 vaccine was 79·4% (75·7–83·1; 367 of 462 individuals), increasing to 96·5% (94·9–98·1; 497 of 515 individuals) during week 3 after the second dose and remaining above 92% until the end of the study. For unvaccinated individuals, IgG seropositivity ranged from 6·0% (4·4–7·6; 49 of 810 individuals) to 18·7% (12·5–24·9; 28 of 150 individuals) during the 5 month period. Regression analyses showed that IgG seropositivity was significantly lower in men than women and in people with diabetes or chronic diseases for CoronaVac vaccine recipients (p Interpretation IgG seropositivity was lower after CoronaVac than after BNT162b2 and declined over time since vaccination for CoronaVac recipients but not BNT162b2 recipients. Prolonged IgG monitoring will allow further evaluation of seropositivity overtime, providing data, in conjunction with effectiveness studies, for possible future re-assessment of vaccination strategies. Funding Instituto Sistemas Complejos de Ingenieria and Ministerio de Salud Chile. Translation For the Spanish translation of the abstract see Supplementary Materials section.
97 citations
TL;DR: The authors in this article compared SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy and found that IgG seropositivity was significantly lower after CoronaVac than after BNT162b2.
Abstract: BackgroundBy July 14, 2021, 81·3 % of adults (aged ≥18 years) in Chile had received a first SARS-CoV-2 vaccine and 72·3% had received a second SARS-CoV-2 vaccine, with the majority of people given Sinovac's inactivated CoronaVac vaccine (75·3% of vaccines dispensed) or Pfizer–BioNTech's mRNA BNT162b2 vaccine (20·9% of vaccines dispensed). Due to the absence of simultaneous real-world data for these vaccines, we aimed to compare SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy.MethodsFrom March 12, 2021, 28 testing stations for SARS-CoV-2 IgG detection were installed in hotspots based on cellular-phone mobility tracking within the most populated cities in Chile. Individuals voluntarily approaching the testing stations were invited to do a lateral flow test by finger prick and respond to a questionnaire on sociodemographic characteristics, vaccination status (including type of vaccine if one was received), variables associated with SARS-CoV-2 exposure, and comorbidities. We compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2. Unvaccinated participants served as a control population and were matched to vaccinated individuals on the basis of date of presentation to the testing station, gender, and age group. Individuals were excluded from the analysis if they were younger than 18 years, had no declared gender, had an invalid IgG test result, had previously tested positive for SARS-CoV-2 infection on PCR, could not recall their vaccination status, or had been immunised against COVID-19 with vaccines other than CoronaVac or BNT162b2. Here, we report data collected up to July 2, 2021.FindingsOf 64 813 individuals enrolled, 56 261 were included in the final analysis, of whom 33 533 (59·6%) had received at least one dose of the CoronaVac vaccine, 8947 (15·9%) had received at least one dose of the BNT162b2 vaccine, and 13 781 (24·5%) had not received a vaccine. SARS-CoV-2 IgG positivity during week 4 after the first dose of CoronaVac was 28·1% (95% CI 25·0–31·2; 220 of 783 individuals), reaching a peak of 77·4% (75·5–79·3; 1473 of 1902 individuals) during week 3 after the second dose. SARS-CoV-2 IgG positivity during week 4 after the first dose of the BNT162b2 vaccine was 79·4% (75·7–83·1; 367 of 462 individuals), increasing to 96·5% (94·9–98·1; 497 of 515 individuals) during week 3 after the second dose and remaining above 92% until the end of the study. For unvaccinated individuals, IgG seropositivity ranged from 6·0% (4·4–7·6; 49 of 810 individuals) to 18·7% (12·5–24·9; 28 of 150 individuals) during the 5 month period. Regression analyses showed that IgG seropositivity was significantly lower in men than women and in people with diabetes or chronic diseases for CoronaVac vaccine recipients (p<0·0001), and for individuals aged 60 years and older compared with people aged 18–39 years for both vaccines (p<0·0001), 3–16 weeks after the second dose.InterpretationIgG seropositivity was lower after CoronaVac than after BNT162b2 and declined over time since vaccination for CoronaVac recipients but not BNT162b2 recipients. Prolonged IgG monitoring will allow further evaluation of seropositivity overtime, providing data, in conjunction with effectiveness studies, for possible future re-assessment of vaccination strategies.FundingInstituto Sistemas Complejos de Ingeniería and Ministerio de Salud Chile.TranslationFor the Spanish translation of the abstract see Supplementary Materials section. By July 14, 2021, 81·3 % of adults (aged ≥18 years) in Chile had received a first SARS-CoV-2 vaccine and 72·3% had received a second SARS-CoV-2 vaccine, with the majority of people given Sinovac's inactivated CoronaVac vaccine (75·3% of vaccines dispensed) or Pfizer–BioNTech's mRNA BNT162b2 vaccine (20·9% of vaccines dispensed). Due to the absence of simultaneous real-world data for these vaccines, we aimed to compare SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy. From March 12, 2021, 28 testing stations for SARS-CoV-2 IgG detection were installed in hotspots based on cellular-phone mobility tracking within the most populated cities in Chile. Individuals voluntarily approaching the testing stations were invited to do a lateral flow test by finger prick and respond to a questionnaire on sociodemographic characteristics, vaccination status (including type of vaccine if one was received), variables associated with SARS-CoV-2 exposure, and comorbidities. We compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2. Unvaccinated participants served as a control population and were matched to vaccinated individuals on the basis of date of presentation to the testing station, gender, and age group. Individuals were excluded from the analysis if they were younger than 18 years, had no declared gender, had an invalid IgG test result, had previously tested positive for SARS-CoV-2 infection on PCR, could not recall their vaccination status, or had been immunised against COVID-19 with vaccines other than CoronaVac or BNT162b2. Here, we report data collected up to July 2, 2021. Of 64 813 individuals enrolled, 56 261 were included in the final analysis, of whom 33 533 (59·6%) had received at least one dose of the CoronaVac vaccine, 8947 (15·9%) had received at least one dose of the BNT162b2 vaccine, and 13 781 (24·5%) had not received a vaccine. SARS-CoV-2 IgG positivity during week 4 after the first dose of CoronaVac was 28·1% (95% CI 25·0–31·2; 220 of 783 individuals), reaching a peak of 77·4% (75·5–79·3; 1473 of 1902 individuals) during week 3 after the second dose. SARS-CoV-2 IgG positivity during week 4 after the first dose of the BNT162b2 vaccine was 79·4% (75·7–83·1; 367 of 462 individuals), increasing to 96·5% (94·9–98·1; 497 of 515 individuals) during week 3 after the second dose and remaining above 92% until the end of the study. For unvaccinated individuals, IgG seropositivity ranged from 6·0% (4·4–7·6; 49 of 810 individuals) to 18·7% (12·5–24·9; 28 of 150 individuals) during the 5 month period. Regression analyses showed that IgG seropositivity was significantly lower in men than women and in people with diabetes or chronic diseases for CoronaVac vaccine recipients (p<0·0001), and for individuals aged 60 years and older compared with people aged 18–39 years for both vaccines (p<0·0001), 3–16 weeks after the second dose. IgG seropositivity was lower after CoronaVac than after BNT162b2 and declined over time since vaccination for CoronaVac recipients but not BNT162b2 recipients. Prolonged IgG monitoring will allow further evaluation of seropositivity overtime, providing data, in conjunction with effectiveness studies, for possible future re-assessment of vaccination strategies.
89 citations
TL;DR: In this article , the authors analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1.
Abstract: Abstract Population antibody surveillance helps track immune responses to COVID-19 vaccinations at scale, and identify host factors that may affect antibody production. We analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1. For both vaccines, antibody positivity peaks 4-5 weeks after first dose and then declines. At least 21 days after second dose of BNT162b2, close to 100% of respondents test positive, while for ChAdOx1, this is significantly reduced, particularly in the oldest age groups (72.7% [70.9–74.4] at ages 75 years and above). For both vaccines, antibody positivity decreases with age, and is higher in females and those with previous infection. Antibody positivity is lower in transplant recipients, obese individuals, smokers and those with specific comorbidities. These groups will benefit from additional vaccine doses.
84 citations
TL;DR: In this article, the seroconversion of IgM and IgG occurs at around 12 days post onset of symptoms and most patients have neutralizing titers on days 14-20, with great titer variability.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic. Although its seroprevalence is highly variable among territories, it has been reported at around 10%, but higher in health workers. Evidence regarding cross-neutralizing response between SARS-CoV and SARS-CoV-2 is still controversial. However, other previous coronaviruses may interfere with SARS-CoV-2 infection, since they are phylogenetically related and share the same target receptor. Further, the seroconversion of IgM and IgG occurs at around 12 days post onset of symptoms and most patients have neutralizing titers on days 14-20, with great titer variability. Neutralizing antibodies correlate positively with age, male sex, and severity of the disease. Moreover, the use of convalescent plasma has shown controversial results in terms of safety and efficacy, and due to the variable immune response among individuals, measuring antibody titers before transfusion is mostly required. Similarly, cellular immunity seems to be crucial in the resolution of the infection, as SARS-CoV-2-specific CD4+ and CD8+ T cells circulate to some extent in recovered patients. Of note, the duration of the antibody response has not been well established yet.
83 citations
References
More filters
TL;DR: A general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies is presented and tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interob server agreement are developed as generalized kappa-type statistics.
Abstract: This paper presents a general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies. The procedure essentially involves the construction of functions of the observed proportions which are directed at the extent to which the observers agree among themselves and the construction of test statistics for hypotheses involving these functions. Tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interobserver agreement are developed as generalized kappa-type statistics. These procedures are illustrated with a clinical diagnosis example from the epidemiological literature.
64,109 citations
TL;DR: In this paper, a nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.
1,435 citations
TL;DR: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed, as available evidence does not support the continued use of existing point-of-care serological Tests for coronavirus disease-2019.
Abstract: Objective To determine the diagnostic accuracy of
serological tests for coronavirus disease-2019
(covid-19). Design Systematic review and meta-analysis. Data sources Medline, bioRxiv, and medRxiv from 1 January to
30 April 2020, using subject headings or
subheadings combined with text words for the
concepts of covid-19 and serological tests for
covid-19. Eligibility criteria and data
analysis Eligible studies measured sensitivity or
specificity, or both of a covid-19 serological
test compared with a reference standard of viral
culture or reverse transcriptase polymerase chain
reaction. Studies were excluded with fewer than
five participants or samples. Risk of bias was
assessed using quality assessment of diagnostic
accuracy studies 2 (QUADAS-2). Pooled sensitivity
and specificity were estimated using random
effects bivariate meta-analyses. Main outcome measures The primary outcome was overall sensitivity and
specificity, stratified by method of serological
testing (enzyme linked immunosorbent assays
(ELISAs), lateral flow immunoassays (LFIAs), or
chemiluminescent immunoassays (CLIAs)) and
immunoglobulin class (IgG, IgM, or both).
Secondary outcomes were stratum specific
sensitivity and specificity within subgroups
defined by study or participant characteristics,
including time since symptom onset. Results 5016 references were identified and 40 studies
included. 49 risk of bias assessments were carried
out (one for each population and method
evaluated). High risk of patient selection bias
was found in 98% (48/49) of assessments and high
or unclear risk of bias from performance or
interpretation of the serological test in 73%
(36/49). Only 10% (4/40) of studies included
outpatients. Only two studies evaluated tests at
the point of care. For each method of testing,
pooled sensitivity and specificity were not
associated with the immunoglobulin class measured.
The pooled sensitivity of ELISAs measuring IgG or
IgM was 84.3% (95% confidence interval 75.6% to
90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and
of CLIAs was 97.8% (46.2% to 100%). In all
analyses, pooled sensitivity was lower for LFIAs,
the potential point-of-care method. Pooled
specificities ranged from 96.6% to 99.7%. Of the
samples used for estimating specificity, 83%
(10 465/12 547) were from populations tested
before the epidemic or not suspected of having
covid-19. Among LFIAs, pooled sensitivity of
commercial kits (65.0%, 49.0% to 78.2%) was lower
than that of non-commercial tests (88.2%, 83.6% to
91.3%). Heterogeneity was seen in all analyses.
Sensitivity was higher at least three weeks after
symptom onset (ranging from 69.9% to 98.9%)
compared with within the first week (from 13.4% to
50.3%). Conclusion Higher quality clinical studies assessing the
diagnostic accuracy of serological tests for
covid-19 are urgently needed. Currently, available
evidence does not support the continued use of
existing point-of-care serological tests. Study registration PROSPERO CRD42020179452.
703 citations
TL;DR: To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS, and the accuracy of antibodies for use in seroprevalence surveys is assessed.
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS-CoV-2 aim to identify previous SARS-CoV-2 infection, and may help to confirm the presence of current infection. Objectives To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection, and the accuracy of antibody tests for use in seroprevalence surveys. Search methods We undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020. Selection criteria We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS-CoV-2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR) and clinical diagnostic criteria). Data collection and analysis We assessed possible bias and applicability of the studies using the QUADAS-2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random-effects logistic regression where appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs). Main results We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints. We had concerns about risk of bias and applicability. Common issues were use of multi-group designs (n = 29), inclusion of only COVID-19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n = 33) defined COVID-19 cases based on RT-PCR results alone, ignoring the potential for false-negative RT-PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5). We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post-symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands. Authors' conclusions The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.
651 citations
TL;DR: This population epidemiology study investigates the prevalence of IgG and IgM antibodies to SARS-CoV-2 in Los Angeles County, California, as a marker of both active and past infections.
Abstract: This population epidemiology study investigates the prevalence of IgG and IgM antibodies to SARS-CoV-2 in Los Angeles County, California, as a marker of both active and past infections.
386 citations