COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+ CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69+ CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

COVID-19 generates SARS-CoV-2-specific antibodies in immunocompetent individuals. However, in immunocompromised patients, the humoral immunity following infection may be impaired or absent. Recently, the assessment of cellular immunity to SARS-CoV-2, both following natural infection and vaccination, has contributed new knowledge regarding patients with low or no antibody responses. As part of a prospective cohort study which included hospitalized patients with COVID-19, we identified immunocompromised patients and compared them with age- and sex-matched immunocompetent patients regarding co-morbidities, biomarkers of COVID-19 and baseline viral load by real-time PCR in nasopharyngeal swabs. Spike and nucleocapsid antibody responses were analyzed at inclusion and after two weeks, six weeks and six months. Plasma immunoglobulin G (IgG) levels were quantified, lymphocyte phenotyping was performed, and SARS-CoV-2 specific CD4 and CD8 T cell responses after in vitro antigen stimulation were assessed at six months post infection. All patients showed IgG levels above or within reference limits. At six months, all patients had detectable SARS-CoV-2 anti-spike antibody levels. SARS-CoV-2 specific T cell responses were detected in 12 of 12 immunocompetent patients and in four of six immunocompromised patients. The magnitude of long-lived SARS-CoV-2 specific T cell responses were significantly correlated with the number of CD4 T cells and NK cells. Determining the durability of the humoral and cellular immune response against SARS-CoV-2 in immunocompromised individuals could be of importance by providing insights into the risk of re-infection and the need for vaccine boosters.