Longitudinal detection of SARS-CoV-2-specific antibody responses with different serological methods

Serological testing for anti-SARS-CoV-2 antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with PCR-confirmed COVID-19 and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of IgG, IgM and IgA antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using ELISA. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information whether or not the individual has been infected with SARS-CoV-2. ELISAs provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2. ### Competing Interest Statement BM, CM, VBL, KS are employees of EUROIMMUN Medizinische Labordiagnostika AG, a company that commercializes serological assays and co-owns a patent application related to immunoassays for the diagnosis of a SARS-CoV-2 infection. ### Funding Statement PE and CD received funding from the German Federal Ministry of Education and Research (grant number: 01KI20210). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The observational study has been performed in agreement with the Declaration of Helsinki. It has been approved by the Ethics Review Board of the University Medicine Rostock (registration number: A2020-0086) and the Ethics Review Board of the Medical Association Hamburg (registration number: 2020-10162-BO-ff). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are available from the corresponding author, upon reasonable request.