This evidence synthesis has been compiled by members of the CITF Secretariat and does not necessarily represent the views of all CITF members.

By Mariana Bego

When our immune system recovers from any given infection, it  often remembers the aggressor long after it is gone. This process is referred to as immunological memory. For instance, after the initial infection is controlled, B cells evolve into memory B cells, which are capable of fighting potential new infections faster and better than their original counterparts. Several independent studies recently evaluated the persistence of this immunological memory in patients that recovered from COVID-19.

Earlier research  hinted that  SARS-CoV-2-specific  memory  B cells  emerge  within a  month after  infection (12). A recent study from the University of Washington published in Cell, demonstrated that not only is this population of memory B cells maintained for the first 1 to 3 months post-infection, but that their numbers increase significantly over time (3). Moreover, in an article published earlier this year in Science, Dan and colleagues noted that SARS-CoV-2 specific memory B cells were more abundant at 6 months than at 1 month post-symptom onset. Their large cohort study sampled cases of COVID-19, from asymptomatic to severe (4). Similarly, research supported by our Task Force and the Canadian Institutes of Health Research (CIHR), led by Drs. Daniel Kaufmann and Andrés Finzi, also confirmed the presence of a functional long- lasting immune response in patients that recovered from COVID-19 in Quebec (5). In their most recent pre- print, they analysed multiple aspects of humoral immunity, including Fc-effector functions and antigen- specific B cells subtypes. In both studies, SARS-CoV-2 antigen-specific memory B cells were detected up to 8 months after infection.

Investigators from Rockefeller University in New York City also noted  that  the  levels  of  SARS-CoV-2  specific memory B cells remained constant, though they took a different  experimental  approach to study  this phenomenon (6). In the recent Nature article by Gaebler and colleagues, antibodies detected were very diverse, had increased neutralizing potency and resistance to viral mutations. Intriguingly, persistent SARS- CoV-2 protein and/or RNA was detected in the intestines of many participants who were negative upon nasopharyngeal swab PCR assays and this lasted up to 4 months after  the initial  infection.  The intestine  was proposed to act as an antigenic ‘reservoir’, potentially providing an extended source of stimulation to the immune system and allowing for continuous evolution of the humoral immune response. Finally, a publication from the latest issue of Cell tracked the source of these SARS-CoV-2 specific B cells (7). Interestingly, Sokal and colleagues found that some of these clones derived from  pre-existing  highly mutated memory B cells specific for seasonal Betacoronaviruses. Nevertheless, the proportion of these cross-reactive clones decreased after the initial activation,  and they were not likely  positively selected in  the SARS-CoV-2 specific memory pool.

Most of these groups also reported a decay in circulating antibodies against SARS-CoV-2 proteins over time, but this does not negate the presence of a persistent protective SARS-CoV-2-specific memory immune response. Many studies looked not only at B cell memory, but also at T cell memory. Indeed, in several cohorts, more than 95% of people who recovered from COVID-19 had durable memories of the virus, up to 8 months after infection. Importantly, these reports cover very different presentations of illness, from asymptomatic, to mild, moderate and severe COVID-19. A functional and long-lasting immune response to SARS-CoV-2 is critical to prevent reinfections, enable herd immunity and predict vaccine effectiveness. These results provide optimism towards achieving long-term protection, either after a natural infection or through vaccination.

For a refreshment or a crash course on immunological memory, particularly on B cell  memory  in  the  context of COVID-19, a very comprehensive Primer was recently released by the journal Immunity.

Find the Primer here.