Kinetics and isotype assessment of antibodies targeting the spike protein receptor‐binding domain of severe acute respiratory syndrome‐coronavirus‐2 in COVID‐19 patients as a function of age, biological sex and disease severity

Abstract

Objectives. There is an incomplete understanding of the host humoral immune response to severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which underlies COVID-19, during acute infection. Host factors such as age and sex as well as the kinetics and functionality of antibody responses are important factors to consider as vaccine development proceeds. The receptorbinding domain of the CoV spike (RBD-S) protein mediates host cell binding and infection and is a major target for vaccine design to elicit neutralising antibodies. Methods. We assessed serum anti-SARS-CoV-2 RBD-S IgG, IgM and IgA antibodies by a two-step ELISA and neutralising antibodies in a cross-sectional study of hospitalised COVID-19 patients of varying disease severities. Anti-RBD-S IgG levels were also determined in asymptomatic seropositives. Results. We found equivalent levels of anti-RBD-S antibodies in male and female patients and no age-related deficiencies even out to 93 years of age. The anti-RBD-S response was evident as little as 6 days after onset of symptoms and for at least 5 weeks after symptom onset. Anti-RBD-S IgG, IgM and IgA responses were simultaneously induced within 10 days after onset, with anti-RBD-S IgG sustained over a 5-week period. Anti-RBD-S antibodies strongly correlated with neutralising activity. Lastly,

Longitudinal analysis of SARS‐CoV‐2 antibodies in 8000 U.S. first‐time convalescent plasma donations

“…After the cohort (n = 8697) had been corrected for underrepresentation of the greater than 65 years age group, the marked increase in SARS‐CoV‐2 IgG levels that was observed with advancing donor age was similar for both sexes, except for the 50–55 years age group, where a trend for higher index S/C values was seen for plasma from male versus female donors (Figure 3(A)). Although higher fatality rates and severe COVID‐19 are consistently reported for men, 24 there was no significant difference in serum IgG levels across sex in mild COVID‐19, 25,26 fully consistent with the results obtained here. In a previous study, we reported significantly higher neutralization titer for CP units from male donors 17 .…”

IgA2 Antibodies against SARS-CoV-2 Correlate with NET Formation and Fatal Outcome in Severely Diseased COVID-19 Patients

“…In contrast, SARS-CoV-2-specific IgG was detected in a wide range of SARS-CoV-2-infected subjects, including those with mild, moderate and severe disease manifestations. Contrary to other studies [ 23 , 24 ], we did not see a significant difference between patients with mild or moderate and severe disease. The fact that OD values from a single dilution do not have a linear correlation with titers might contribute to the underestimation of the IgG response in patients with high levels.…”

“…Of note, in severely diseased patients, we found a correlation of SARS-CoV-2-specific IgA1 and IgA2 levels with age. This observation is in accordance with other studies showing that increased age is associated with stronger disease [ 24 , 34 , 35 ].…”

SARS-CoV-2 Infection Is Asymptomatic in Nearly Half of Adults with Robust Anti-Spike Protein Receptor-Binding Domain Antibody Response

“…Among 1847 participants working in three sites at an institution in Paris conurbation, of those detected immunoglobulin G (IgG)-positive for SARS-CoV-2 nucleocapsid (N)- and spike (S)-proteins, 21% had been asymptomatic [ 8 ]. Further evidence suggests that there is a positive correlation between the severity of clinical symptoms and serum levels of anti-SARS-CoV-2 antibodies, being less prominent in oligosymptomatic patients [ 9 , 10 ]. According to other reports, asymptomatic infection may not even induce a detectable humoral response, suggesting that high viral load is possibly associated with the levels of humoral immunity.…”