Immune memory may strengthen over at least 6 months

Following an infection, mature B lymphocytes produce antibodies that target the pathogenic agent but have a limited life span. However, some of them remain in germinal centres (lymph nodes, spleen) where they multiply and continue to refine their antibody qualities. Their life span is longer: these are the memory B lymphocytes that are called upon in the case of re-infection.

Infection by SARS-CoV-2 triggers production of neutralizing antibodies to different levels, depending on the patient. They block the entry of the virus into the cell by binding to the viral spike protein. Studies have shown than they can prevent re-infection in animals, but the situation is less clear in humans. In addition, we don’t know enough about the nature or the quality of the memory-antibodies’ response.

In order to investigate these issues, American researchers (at Rockefeller University) studied the responses of the antibodies of 87 COVID-19 patients. Analyses were carried out 40, then 191, days after infection. In this small cohort, volunteers were aged from 18 to 76 and their symptoms had lasted an average of 12 days. Amongst these patients, 10 had been hospitalized and 38 had had long-term symptoms.

The conclusions initially seemed somewhat pessimistic. Using ELISA tests, the researchers observed that the levels of anti-Receptor Binding Domain antibodies (where the spike interacts with the receptor) and nucleoprotein antibodies (organization of the viral protein) tend to decrease. The anti-RBD IgMs, antibodies characteristic of a primary infection, decrease by 53%, and anti-RBD IgGs (which represent 80% of blood antibodies) decrease by 32%. With in vitro infection testing, the authors also concluded that blood neutralization activity had decreased 5-fold.

But is this really problematic? No, since it should be noted that even if levels of antibodies decrease over time, they can be detected in the majority of individuals 6 months after infection.

So, in a sub-group of 41 people selected at random, the team showed that the blood B lymphocytes had been under-represented during the whole of the study. However, the B memory cells maintained stable levels during the study and underwent a turnover within their populations, which indicates that they had evolved and that the germinal centers remained very active.

The authors showed that these cells produce antibodies and that their neutralizing potential and their specificity increased over the period of the study. In vitro tests showed that certain mutations were recognised by these antibodies 6 months after infection, whereas they had not been recognised after 1 month. In a supplementary cohort of 14 patients, researchers detected the presence of N viral proteins (in 5 patients) and viral RNA (in 7 patients) in intestinal biopsies taken 4 months after infection.

Contrary to what other research has suggested, this study shows that B-memory immunity is functional and evolves over the 6 months following SARS-CoV-2 infection so as to be able to produce more efficient antibodies. It is in part supported by the presence of persistent viral antigens in certain tissues, probably in the form of immune complexes. These results strongly suggest that individuals infected by SARS-CoV-2  will be protected in the case of a second infection.