ABSTRACT
STUDY OBJECTIVE: SARS-CoV-2, which causes coronavirus disease (COVID-19), continues to cause significant morbidity and mortality. The diagnosis of acute infection relies on reverse transcription-polymerase chain reaction (RT-PCR)-based viral detection. The objective of this study was to evaluate the optimal serological testing strategy for anti-SARS-CoV-2 antibodies which provides an important indicator of prior infection and potential short-term immunity. METHODS: The sensitivity and specificity of four different ELISA assays (Euroimmun IgG, Euroimmun NCP-IgG, Fortress and DIAsource) and one CLIA assay (Roche ELECSYS) were evaluated in 423 samples; 137 patients with confirmed RT-PCR COVID-19 infection (true positives), and 100 pre-pandemic samples collected prior to October 2019 (true negatives). A further 186 samples were collected from health-care staff and analysed by all five assays. RESULTS: The Fortress ELISA assay demonstrated the highest sensitivity and specificity followed by the Roche ECLIA assay. The highest overall sensitivity came from the assays that measured total antibody (IgM-IgG combined) and the three assays that performed the best (Fortress, Roche, Euroimmun IgG) all have different antigens as their target proteins which suggests that antigen target does not affect assay performance. In mildly symptomatic participants with either a negative RT-PCR or no RT-PCR performed, 16.76% had detectable antibodies suggesting previous infection. CONCLUSIONS: We recommend a combined testing strategy utilizing assays with different antigenic targets using the fully automated Roche ECLIA assay and confirming discordant samples with the Fortress Total Antibody ELISA assay. This study provides an important indicator of prior infection in symptomatic and asymptomatic individuals.
Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , COVID-19/immunology , Pandemics , SARS-CoV-2 , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing/statistics & numerical data , Electrochemical Techniques/methods , Electrochemical Techniques/statistics & numerical data , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , Female , Health Personnel , Humans , Immunoglobulin G/blood , Ireland/epidemiology , Luminescent Measurements/methods , Luminescent Measurements/statistics & numerical data , Male , Pregnancy , Sensitivity and SpecificityABSTRACT
BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity. TRIAL REGISTRATION NUMBER: NCT0434740.