Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19
Authors: 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, Onur Boyman
Journal: Journal of Allergy and Clinical Immunology (2020)

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. Whereas 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. Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. Using 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). SARS-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. Systemic 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.