When researchers conducted a longitudinal assessment of humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 32 convalescent individuals up to 8 months post-symptom onset, they observed that immunoglobulin (Ig)M levels and the neutralising capacity of plasma in these individuals decreases rapidly, whereas IgG level and Fc-effector activity were more sustained. Meanwhile, SARS-CoV-2-specific B cell immunity persisted despite overall antibody decline.

These findings were published in Cell Reports Medicine.

“Our findings aid in the understanding of durability of coronavirus disease 2019 (COVID-19) immunity, which is important in the context of secondary infections, vaccine efficacy and herd immunity,” wrote Sai Priya Anand, McGill University, Montreal, Canada, and colleagues. 

The average age of the individuals was 47 years (range 20-65 years) and the cohort included 17 males and 15 females. All individuals, enrolled following two negative RT-PCR tests and a complete resolution of symptoms for at least 14 days before blood sampling, previously had mild to moderate disease symptoms but none of them were hospitalised. 

Plasma samples were collected at four longitudinal time points between 16 and 233 days post-symptom onset, at 6 weeks (median 43 days), 11 weeks (median 77 days), 21 weeks (median 145 days), and 31 weeks (median 218 days).

The researchers observed that total receptor-binding domain (RBD)-specific Ig levels, comprising IgG, IgM, and IgA, gradually decreased between 6 and 31 weeks after the onset of symptoms. Nonetheless, all individuals were found to have detectable IgG at the last time point, while IgM and IgA were found to have diminished more rapidly, with 85% and 69% of the individuals having undetectable IgM and IgA levels, respectively, at 31 weeks post-symptom onset. On the other hand, while all individuals still had detectable spike (S)-specific total Ig and IgG in their plasma at 31 weeks post-symptom onset, only 38% and 54% of the plasma samples tested positive for the presence of S-specific IgM and IgA, respectively.

Meanwhile, neutralising antibody titres (ID50) were detected in 63% of the individuals at 6 weeks post-symptom onset. Titres declined from 155.6 at 6 weeks to 60.0 at 31 weeks post-symptom onset, with 77% of individuals having undetectable neutralisation activity in their plasma at the last time point. The researchers also found that plasma from individuals that had undetectable neutralisation activity at later time points started with lower peak titres at earlier time points. 

“Since the depletion of IgM from plasma has been associated with loss of viral neutralisation capacity and IgA has also been shown to dominate the early neutralising response, the sharp decline in neutralisation activity seen in this study is corroborated by the striking decrease in anti-S and anti-RBD IgM and IgA levels,” the researchers noted.

Further, when the researchers assessed the ability of plasma from convalescent individuals to trigger antibody-dependent cellular cytotoxicity (ADCC) responses over time, they observed a modest decline in the ADCC activity of convalescent plasma compared to the decrease in neutralisation activity of plasma, whereby 85% of the convalescent individuals’ plasma still elicited substantial ADCC activity at the latest study time point. Additionally, the presence of Fc-mediated antibody effector functions up to 8 months post-symptom onset was corroborated with the presence of significant IgG levels. 

Meanwhile, total RBD-specific memory B cells were detected in all convalescent individuals and the mean frequency remained stable between 6 and 31 weeks post-symptom onset (0.020% to 0.026%), while RBD-specific naive B cells were observed in lower proportions and modestly decreased over time.

“We show that COVID-19 patients generate RBD-specific memory B cells and IgG+ B memory cells that persist for over 8 months. This is similar to recent studies on the durability of SARS-CoV-2 immune responses showing that despite decreases in antibody levels, S-specific IgG+ memory B cells are generated and maintained likely due to antigen persistence in convalescent individuals,” the authors noted. “Thus, the decline of antibody levels does not negate the protective potential because of the importance of cellular responses against SARS-CoV-2 infection.”

“The presence and persistence of antigen-specific memory B cells in all individuals is encouraging with regards to long-term immunity” the authors added. 

Reference: https://www.cell.com/action/showPdf?pii=S2666-3791%2821%2900118-X

SOURCE: Cell Reports Medicine