Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19

Cervia, Carlo; Nilsson, Jakob; Zurbuchen, Yves; Valaperti, Alan; Schreiner, Jens; Wolfensberger, Aline; Raeber, Miro E.; Adamo, Sarah; Weigang, Sebastian; Emmenegger, Marc; Hasler, Sara; Bosshard, Philipp P.; De Cecco, Elena; Bächli, Esther; Rudiger, Alain; Stüssi-Helbling, Melina; Huber, Lars C.; Zinkernagel, Annelies S.; Schaer, Dominik J.; Aguzzi, Adriano; Kochs, Georg; Held, Ulrike; Probst-Müller, Elsbeth; Rampini, Silvana K.; Boyman, Onur

Background Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. Objectives To evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. Methods Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including SARS-CoV-2 polymerase chain reaction (PCR)+ patients (n = 64) as well as PCR+ and PCR– healthcare workers (n = 109). Results SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases were often transiently positive, whereas serum IgG titers remained negative or became positive 12–14 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 correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some healthcare 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 inversely correlated with age. Conclusions Systemic antibody production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA titers seen in patients with severe ARDS, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion.