Rare potent neutralizing antibodies in patients recovered from Covid-19.

In spite of the growing understanding of the molecular aspects of SARS-CoV2, knowledge of the human antibody response to the virus is still limited. As an example, questions are still open about the persistence of antibodies in recovered individuals and about the actual capacity of the antibodies generated to neutralize the virus and protect against subsequent infections.

Main finding. In a recent paper published in Nature, authors show that the plasma (component of the blood containing proteins, metabolites, electrolytes) of the majority of recovered patients have overall poor neutralizing ability against the virus. However, importantly, even in those with very low neutralizing activity, rare potent antibodies may be found, able to neutralize SARS-CoV2.

Experimental details. The authors analysed plasma of convalescent patients (148 patients recruited at the Rockefeller University Hospital in New York); within the patient cohort analysed, 7% were hospitalized.

Analyses showed that patients’ plasma contained IgG which reacted against the Spike protein of SARS CoV2, more specifically, the receptor binding domain (RBD, upper part of the Spike proteins present on the virus lipid envelope –which confer their typical crown-like appearance to the virus–, essential for virus binding and entry into the host cell; namely, crucial for virus infection). The levels of anti-RBD IgG in the plasma modestly correlated with age and severity of symptoms; furthermore, women had lower IgG levels than men.

Then, the authors measured the neutralizing activity of patients’ plasma (which would reflect the ability of the patients’ plasma to prevent a future virus infection). Overall, patients’ plasma showed a rather low neutralizing activity. A correlation was observed between neutralizing activity and i. levels of anti-IgG, ii. age, iii. duration of symptoms, iv. severity of symptoms; for instance, plasma of hospitalized patients with longer symptom duration had higher neutralizing activity, and women plasma, having lower IgG levels, had lower neutralizing activity.

The vast majority (95%) of the anti-SARS-CoV2 antibodies bound SARS-CoV2 RBD and was able to neutralize the virus; a fraction of them cross-reacted with RBD of SARS-CoV (virus causing the SARS epidemic), while no cross-reactivity was observed with MERS-CoV (virus causing the MERS epidemic).

Importantly, potent neutralizing antibodies were found in plasma of patients with low neutralizing activity.

Conclusions. This study shows that even though the overall neutralizing activity of the plasma of patients who recovered from Covid-19 is low, they still may have rare, potent anti-SARS-CoV2 antibodies, demonstrating that humans are able to produce antibodies potently neutralizing the virus, and vaccines against the SARS-CoV2 RBD may be widely efficient.