BackgroundInfection with the severe acute respiratory syndrome coronavirus 2 MESHD
(SARS-CoV-2) causes an acute illness termed coronavirus disease MESHD
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 SERO
responses are unclear.
MethodsUsing immunoassays SERO
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 TRANS
61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age TRANS
36 years) with or without symptoms and tested negative or positive by RT-qPCR.
FindingsOn average, SARS-CoV-2-specific serum SERO
IgA titers in mild COVID-19 cases became positive eight days after symptom onset TRANS
and were often transient, whereas serum SERO
IgG levels remained negative or reached positive values 9-10 days after symptom onset TRANS
. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum SERO
IgA and IgG titers as a function of duration since symptom onset TRANS
, independent of patient age TRANS
and comorbidities. Very high levels of SARS-CoV-2-specific serum SERO
IgA correlated with severe acute respiratory distress HP
syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum SERO
titers had detectable SARS-CoV-2-specific IgA antibodies SERO
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 TRANS
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 SERO
titers of SARS-CoV-2-specific antibodies SERO
but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody SERO
responses dependent on COVID-19 severity.