July 6, 2021

Study suggests SARS-CoV-2-specific T cell memory sustained in COVID-19 convalescent patients for 10 months

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory T cell responses were maintained in coronavirus disease 2019 (COVID-19) convalescent patients 10 months post-infection regardless of disease severity, according to a study published in Nature Communications

“Notably, we found that SARS-CoV-2-specific stem cell-like memory T (TSCM) cells were successfully developed, indicating that SARS-CoV-2-specific T cell memory may be long-lasting in COVID-19 convalescent patients,” reported Jae Hyung Jung, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea, and colleagues. “These findings were supported by the SARS-CoV-2-specific T cells from peripheral blood mononuclear cells (PBMCs) obtained after 200 days post-symptom onset (DPSO) exhibiting sustained polyfunctionality and proliferation capacity.”

The study involved 101 patients (median age, 39 years) with PCR-confirmed SARS-CoV-2 infection, with varying illness severity: asymptomatic (n = 7), mild (n = 46), moderate (n = 25), severe (n = 14), and critical (n = 9). Whole blood samples were collected from patients 1–317 DPSO and were obtained longitudinally (2–4 time points) from 56 patients or at a single time point from 45 patients. 

When researchers performed direct ex vivo interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assays on the convalescent samples, they observed that spike (S)-, membrane (M)-, and nucleocapsid (N)-specific IFN-γ spot numbers increased during the acute phase (defined as 1–30 DPSO), with a subsequent decreasing tendency until 60-120 DPSO, and the IFN-γ responses were maintained over 10 months. When convalescent samples were divided into three groups based on the DPSO at sample collection: T1 (31–99 DPSO), T2 (100–199 DPSO), and T3 (≥200 DPSO), the researchers found no significant difference in IFN-γ spot numbers among groups, and a maintenance of an even contribution of antigens for the IFN-γ response among groups. Focussing on longitudinally tracked samples from 39 individuals in the convalescent phase, the researchers observed that S-, M-, and N-specific and summed IFN-γ spot numbers were stable during the convalescent phase.

When the SARS-CoV-2-specific CD4+ and CD8+ T cell responses were investigated separately, using activation-induced marker (AIM) assays, it was found that the frequency of S-, M-, and N-specific CD137+OX40+ cells among CD4+ T cells increased during the acute phase, decreased until 60 DPSO, and was maintained over 10 months. Meanwhile, the frequency of CD137+CD69+ cells among CD8+ T cells was relatively low compared to the frequency of CD137+OX40+ cells among CD4+ T cells, but exhibited similar kinetics. 

Further, when the researchers measured the level of SARS-CoV-2 S receptor-binding domain (RBD)-specific immunoglobulin (Ig)G antibodies and SARS-CoV-2 neutralising activity in plasma samples from COVID-19 convalescent patients at T1, T2, and T3, they found that the level of RBD-specific antibodies decreased over time, whereas the level of neutralising activity was maintained. 

“We did not observe a significant correlation between long-term (≥200 DPSO) SARS-CoV-2-specific T cell responses as evaluated by IFN-γ ELISpot and AIM assays and antibody levels. Collectively, these results indicate that SARS-CoV-2-specific T cell responses are long-lasting over 10 months in COVID-19 convalescent patients although SARS-CoV-2-specific antibody response may decrease,” the authors noted.

Additionally, the researchers observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells, whereby no significant difference was noted in the frequency of polyfunctional cells among SARS-CoV-2-specific CD4+ and CD8+ T cells between T1, T2, and T3. On the other hand, CD4+ and CD8+ T cells in PBMCs obtained after 200 DPSO exhibited a significant proliferative response, which, noted the authors, indicates that SARS-CoV-2-specific memory T cells elicit rapid recall responses upon viral re-exposure.

Meanwhile, study data showed that the proportion of TSCM cells was increased, peaking at approximately 120 DPSO, with no significant difference noted in the frequency of TSCM cells among AIM+CD4+ and AIM+CD8+ T cells at T1, T2, and T3. 

In addition, the researchers found no significant difference in long-term SARS-CoV-2-specific T cell responses between the patients in the asymptomatic/mild disease group and those in the moderate/severe/critical disease group. 

“In the current study, we conducted a comprehensive analysis of SARS-CoV-2-specific memory T cell responses over 10 months post-infection. Considering that the current study was based on random sample collection, the conclusion needs to be validated by a study based on a systematic blood collection protocol,” the authors wrote. 

“Despite this limitation, our current analysis provides valuable information regarding the longevity and differentiation of SARS-CoV-2-specific memory T cells elicited by natural infection. These data add to our basic understanding of memory T cell responses in COVID-19, which aids in establishing an effective vaccination programme and epidemiological measurement,” the authors added.

SOURCE: Nature Communications