A study conducted by researchers in the United States has found that most patients who recovered from coronavirus disease 2019 (COVID-19) showed signs of long-lasting immunity against the causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The longitudinal analysis of 254 COVID-19 patients found that most convalescent individuals mounted durable SARS-CoV-2-specific antibody, B cell and T cell responses that are likely to confer long-lived immunity.
“Because the cohort will be followed for 2 to 3 more years, we can build on these results to define the progression to long-lived immunity against this novel human coronavirus, which can guide rational responses when future outbreaks occur,” writes Kristen Cohen from the Fred Hutchinson Cancer Research Center in Seattle, Washington and colleagues.
A pre-print version of the research article is available on the medRxiv* server, while the article undergoes peer review.
Long-lived immunity is needed to end the COVID-19 pandemic
To finally bring an end to the COVID-19 pandemic, long-lived population immunity against the causative agent SARS-CoV-2 will need to be achieved.
Multiple cross-sectional and longitudinal studies have shown that natural infection with SARS-CoV-2 induces humoral (antibody) and cellular responses that target multiple viral proteins.
However, “more comprehensive, quantitative analyses with extensive serial sampling in larger numbers of COVID-19 patients are limited, and could resolve some conflicting views about the durability of immunity,” says Cohen and the team.
Importantly, determining the frequency, immune function, specificity and duration of antibodies and memory B and T cell responses among COVID-19 patients could help researchers understand the integral components required for long-lived immunity.
What did the current study involve?
The researchers conducted a longitudinal prospective study of 254 COVID-19 patients who became infected with SARS-CoV-2 during the first surge of the pandemic.
The team evaluated participants from the point of early infection and for eight months thereafter using highly standardized or validated assays.
A sharp rise in immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies against the viral spike protein was observed during the first month of infection, after which levels of these antibodies quickly declined.
The spike protein mediates the initial stage of the SARS-CoV-2 infection process by attaching to host cells via its receptor-binding domain (RBD).
The researchers say the fast decline in IgG and IgA after one month of infection can likely be explained by the disappearance of the short-lived plasmablasts that secrete these antibodies once B cells first encounter the viral spike protein.
However, samples taken after 250 days revealed a slowing of this antibody decay towards a plateau level, indicating the generation of longer-lived plasma cells and more durable antibody responses.
“The importance of these observations is that following recovery, neutralizing antibodies may persist, albeit at low levels, and may act as the first line of defense against future encounters of SARS-CoV-2 and possibly related human coronaviruses,” writes the team.
There was an ongoing rise in both spike and RBD memory B cell responses
The potential durability of these antibody responses was further substantiated by an ongoing rise in both spike and RBD memory B cell responses after more than 3 to 5 months and a plateauing of these responses after 6 to 8 months.
The researchers say this persistence of memory B cells may be explained by their sustained production in the germinal centers of lymph nodes that drain the respiratory tract during the early months of infection. The memory B cells are then redistributed into the circulation once the germinal centers begin to recede.
“Thus, the induction and maintenance of memory B cells and, over time, long-lived plasma cells will continue to furnish higher affinity antibodies if re-exposures occur,” they write.
Polyfunctional CD4+ and CD8+ T cells were also generated and maintained
Polyfunctional SARS-CoV-2-specific CD4+ and CD8+ T cells were also generated and maintained, with an estimated half-life of 200 days.
Interestingly, the CD4+ T cells mounted a broader antigen-specific response and targeted several structural and accessory proteins, while CD8+ T cells preferentially targeted the nucleoprotein, which binds and packages viral RNA for virion assembly.
Cohen and colleagues say this finding highlights the importance of including the nucleoprotein as a potential vaccine antigen.
What are the study implications?
The team says that taken together, the findings suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.
“Thus, recovered COVID-19 patients are likely to better defend against the variants than persons who have not been infected but have been immunized with spike-containing vaccines only,” writes Cohen and colleagues.
“Nevertheless, vaccine induction of CD8+ T cells to more conserved antigens such as the nucleocapsid, rather than just to SARS-CoV-2 spike antigens, may add benefit to more rapid containment of infection as SARS-CoV-2 variants overtake the prevailing strains,” they conclude.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.