• Carlo Cervia, Jakob Nilsson, Yves Zurbuchen, Alan Valaperti, Jens Schreiner, Aline Wolfensberger, Miro E Raeber, Sarah Adamo, Sebastian Weigang, Marc Emmenegger, Sara Hasler, Philipp P Bosshard, Elena De Cecco, Esther Bächli, Alain Rudiger, Melina Stüssi-Helbling, Lars C Huber, Annelies S Zinkernagel, Dominik J Schaer, Adriano Aguzzi, Georg Kochs, Ulrike Held, Elsbeth Probst-Müller, Silvana K Rampini, and Onur Boyman.
• Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
• J. Allergy Clin. Immunol. 2021 Feb 1; 147 (2): 545-557.e9.

BackgroundWhereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear.ObjectivesOur aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases.MethodsUsing immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109).ResultsSARS-CoV-2-specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids were inversely correlated with age.ConclusionsSystemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but may stimulate mucosal SARS-CoV-2-specific IgA secretion.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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