Immune memory persistent but exhausted 1 year after COVID-19

In convalescent patients with the coronavirus disease 2019 (COVID-19), humoral and cellular responses against the SARS-CoV-2 virus remain robust at 1 year after infection, according to a recent study. However, a notable dysfunction in CD4+ T cells emphasizes the need for vaccination to prevent reinfection.

“For the first time, our study provided evidence that although robust SARS-CoV-2–specific humoral and cellular responses were maintained in convalescent patients for as long as 1 year, the low titres of neutralizing antibodies (nAbs) and exhausted function of SARS-CoV-2-specific CD4+ T cells indicated that vaccination was needed in convalescent patients for preventing reinfection,” the researchers said.

Seventy-eight convalescent COVID-19 patients were enrolled after 1 year of recovery. Of these, 43 had severe disease and nine were critical, while the remaining 26 had moderate infections. Blood samples were subjected to appropriate assays for antibody quantification. Peripheral blood mononuclear cells were isolated from the blood samples for the assessment of CD4+ T cell activity.

All convalescent patients were positive for antibodies against the receptor binding domain and N proteins of SARS-CoV-2. Levels of such antibodies did not differ according to infection severity. [J Allerg Clin Immunol 2021;148:1481-1492.e2]

Moreover, nAbs were present in 93.59 percent of convalescent patients 1 year after infection. However, convalescent nAb titres were significantly lower than when measured in patients with mild infections at the time of diagnosis.

Convalescent patients also showed robust immune memory to COVID-19. After stimulation with a SARS-CoV-2 peptide pool, virus-specific T cells were detected in 100 percent of convalescent patients 1 year after recovery. T cell counts were higher in patients who had had moderate infections.

However, further focus on CD4+ T cells revealed notable gaps in immune memory. After peptide stimulation, most CD4+ T cells produce only a single cytokine: interferon-γ, tumour necrosis factor-α, or interleukin-2. Meanwhile, the proportion of multifunctional CD4+ T cells, which could produce a combination of two or more cytokines, was notably lower.

According to the researchers “these data suggested that SARS-CoV-2-specific CD4+ T cells were gradually losing their functional potential in convalescent patients with COVID-19 after 1 year of recovery.”

Moreover, CD4+ T cells from convalescent patients showed heightened expression of exhaustion markers such as CD39, CTLA-4, TIGIT, Tim-3, and PD-1.

“We observed that the expressions of inhibitory receptors including PD-1, Tim-3, TIGIT, CTLA-4, and CD39 were all remarkably increased on SARS-CoV-2-specific CD4+ T cells,” the researchers said. “These findings indicated that although the number of SARS-CoV-2–specific CD4+ T cells was maintained in convalescent patients with COVID-19 after 1 year of recovery, their function may be exhausted.”

“Our study not only extends our understanding of the durability of immune memory in convalescent patients with COVID-19 but also may have implications that vaccination is needed in convalescent patients for preventing reinfection,” they added.