Dynamics and significance of the antibody response to SARS-CoV-2 infection

Key Words:Immunology, Antibodies 

Research Highlights

1. IgA and IgM antibodies against the receptor-binding domain (RBD) peak at week 3 and decline rapidly below detection limit around week 6.  

2. Anti-RBD IgG antibodies persisted through 75 days post-symptoms and concentrations were highly correlated with neutralizing antibodies targeting the Spike (S) protein with limited cross-reactivity to RBD of CoV-1 Spike and none to other coronaviruses. 

3. Individuals with more severe disease seroconverted earlier than individuals not requiring ICU-level support, suggesting an association between disease severity and antibody response kinetics. 

Summary

Kinetics of early Ab responses to the RBD of the S protein of SARS-CoV-2 were measured in a cohort of 259 symptomatic COVID-19 infected patients up to 75 days after symptom onset and compared to antibody levels in 1548 healthy samples (obtained prior to the pandemic). Most infected cases showed elevated anti-SARS-CoV-2 Ab levels and a sharp rise in those levels were observed from day 5-14. While Ag-specific IgA and IgM levels declined towards pre-pandemic levels, IgG titres were shown to wane at much slower rtes. Combining multiple Ab isotype measurements was also shown to improve the predictive accuracy of serological tests. All patients tested (15) developed neutralizing antibodies (NAb) and anti-RBD IgG concentrations were shown to correlate with NAb titres.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Study Type 

• In vitro study 

• Patient case study 

Strengths and limitations of the paper 

Novelty: One of many recent papers longitudinally analyzing antibody levels following SARS-CoV-2 infection (e.g. Long et al. Nat Med 2020, Wajnberg et al. 2020; Seow et al. 2020; Wu et al. 2020) 

Standing in the field:How long-lasting antibody levels are post infection is currently a matter of scientific debate. 

Main limitations:  

• Majority of their infected patients had a severe disease progression (with 95% requiring hospitalization and 31% requiring ICU level care). They did not look at asymptomatic or mildly infected individuals as some other studies did (e.g. Wajnberg et al. 2020). Significantly higher IgG responses to Spike protein were observed in patients with non-severe symptoms (J. Wu et al 2020), so the results here are highly skewed towards a particular patient subset and associated response. 

• As shown in Figure 1, while anti-S IgG levels remain clearly above pre-pandemic control levels up to 75 days post-disease onset, levels do not necessarily appear to be really stabilizing, just to decline to a nearly insignificant level. However, also taken together with the findings of another recent preprint looking even further, up to 26 weeks post disease onset (Wu et al. 2020), it is probably fair to conclude that IgG levels post infection do remain stable following an intermediate contraction period 

• As pointed out by the authors, optimal immunological correlations of protection for SARS-CoV-2 remain unknown, so it is not known if those sustained Ab levels provide protection from subsequent infection 

• They used a pseudo-lentivirus neutralization model (Chandrashekar et al. Science 2020) to measure neutralizing activity. It would have been good to compare the results to other, more widely used assays, such as a Plaque Neutralization Assays or use clinical isolate of SARS-CoV-2.