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

Cervia, C.; Nilsson, J.; Zurbuchen, Y.; Valaperti, A.; Schreiner, J.; Wolfensberger, A.; Raeber, M. E.; Adamo, S.; Emmenegger, M.; Hasler, S.; Bosshard, P. P.; De Cecco, E.; Baechli, E.; Rudiger, A.; Stuessi-Helbling, M.; Huber, L. C.; Zinkernagel, A. S.; Schaer, D. J.; Aguzzi, A.; Held, U.; Probst-Mueller, E.; Rampini, S. K.; Boyman, O.

doi:10.1101/2020.05.21.108308

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bioRxiv · 10.1101/2020.05.21.108308

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

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Abstract

BackgroundInfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear. MethodsUsing immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR. FindingsOn average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9-10 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 as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age. InterpretationThese data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

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Cervia, C., Nilsson, J., Zurbuchen, Y., Valaperti, A., Schreiner, J., Wolfensberger, A., Raeber, M. E., Adamo, S., Emmenegger, M., Hasler, S., Bosshard, P. P., De Cecco, E., Baechli, E., Rudiger, A., Stuessi-Helbling, M., Huber, L. C., Zinkernagel, A. S., Schaer, D. J., Aguzzi, A., Held, U., Probst-Mueller, E., Rampini, S. K., Boyman, O.. 2020-05-23. Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19. https://doi.org/10.1101/2020.05.21.108308

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