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SARS-CoV-2 antibody tests are available in various formats, detecting different viral target proteins and antibody subclasses. The specificity and sensitivity of SARS-CoV-2 antibody tests are known to vary and very few studies have addressed the performance of these tests in COVID-19 patient groups at different time points. We here compared the sensitivity and specificity of seven commercial (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor) and two in-house LIPS assays (LIPS N and LIPS S-RBD) IgG/total Ab tests in serum samples from 97 COVID-19 patients and 100 controls, and correlated the results with the patients' clinical data and the time-point the test was performed. We found a remarkable variation in the sensitivity of antibody tests with the following performance: LIPS N (91.8%), Epitope (85.6%), Abbott and in-house LIPS S-RBD (both 84.5%), Roche (83.5%), Euroimmun (82.5%), DiaSorin (81.4%), SNIBE (70.1%), and Biosensor (64.9%). The overall agreement between the tests was between 71-95%, whereas the specificity of all tests was within 98-100%. The correlation with patients' clinical symptoms score ranged from strongest in LIPS N (ρ = 0.41; p<0.001) to nonsignificant in LIPS S-RBD. Furthermore, the time of testing since symptom onset had an impact on the sensitivity of some tests. Our study highlights the importance to consider clinical symptoms, time of testing, and using more than one viral antigen in SARS-CoV-2 antibody testing. Our results suggest that some antibody tests are more sensitive for the detection of antibodies in early stage and asymptomatic patients, which may explain the contradictory results of previous studies and should be taken into consideration in clinical practice and epidemiological studies., Competing Interests: The authors have read the journal's policy and have the following competing interests: PN, KH, JH, IE are employees of SYNLAB Estonia. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.

Profiling antibodies to SARS-CoV-2 can help to assess potential immune response after COVID-19 disease. Luciferase IP system (LIPS) assay is a sensitive method for quantitative detection of antibodies to antigens in their native conformation. We here describe LIPS to detect antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in COVID-19 patients. The antibodies targeted both S and N fragments and gave a high assay sensitivity by identifying 26 out of 26 COVID-19 patients with N antigen or with three protein fragments when combined into a single reaction. The assay correlated well with ELISA method and was specific to COVID-19 as we saw no reactivity among uninfected healthy controls. Our results show that LIPS is a rapid and measurable method to screen antibody responses against SARS-CoV-2 antigens., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)