Longitudinal analysis of virus load, serum antibody levels and virus neutralizing activity in vitro in cases with less severe COVID-19

Abstract

Background: Patients infected with SARS-CoV-2 exhibit a highly variable clinical course, varying from barely discernible signs of disease, to moderate flu-like symptoms and, occasionally, with life-threatening pneumonia and/or cytokine storm. The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein as well the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients has not been investigated longitudinally so far. Methods: Several new serological methods to examine these parameters were developed and validated for the longitudinal investigation in three patients of a family which underwent a mild course of COVID-19. Findings: We observed that the virus load had almost completely disappeared after about four weeks, whereas serum antibodies showed a contrasting course. IgA levels to S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau approximately six weeks after disease onset. NAbs in serum reached a peak about four weeks after disease onset but dropped to a lower level about six weeks later. Interpretation: Our data establishes associations of virus neutralization and a serological immune response foremost against Sars-CoV-2 S1-RDB-protein in a longitudinal manner.

Viral infection neutralization tests: A focus on severe acute respiratory syndrome‐coronavirus‐2 with implications for convalescent plasma therapy

“…21 In less severe cases, nAb in serum reached a peak about 4 weeks after disease onset but dropped to a lower level about 6 weeks later. 78 An earlier IgG antibody response against the S2 domain of the S protein could better mediate virus neutralization, as previously suggested for SARS-CoV-1 nAb targeting the S2 domain. 26,[79][80][81] Analyses at a 1-month interval on 31 convalescent individuals showed that RBDspecific IgG slightly decreased between 6 and 10 weeks after symptoms onset but RBD-specific IgM decreased much more abruptly.…”

“…In most of Covid‐19 inpatients, nAb reached a plateau 2 weeks post‐symptom onset and then declined, reaching a low or undetectable level ≥40 days post‐symptom onset 21 . In less severe cases, nAb in serum reached a peak about 4 weeks after disease onset but dropped to a lower level about 6 weeks later 78 . An earlier IgG antibody response against the S2 domain of the S protein could better mediate virus neutralization, as previously suggested for SARS‐CoV‐1 nAb targeting the S2 domain 26 ,.…”