SARS-CoV-2-Specific T Cell Responses Are Not Associated with Protection against Reinfection in Hemodialysis Patients

Abstract

Patients on hemodialysis (HD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mount poor neutralizing antibody responses after two-dose vaccination. Although serological responses have been associated with reduced rates of reinfection, the relationship between cellular immunogenicity and protection has not been established. We report, for the first time, high incidence of reinfection in patients on HD who are vaccine naive (25%), which identifies that T cell responses do not predict protection against reinfection. Instead, patients on HD who went on to become reinfected had mounted highly variable and sometimes robust proliferative T cell responses to a broad array of SARS-CoV-2 peptide pools during the primary infection. The understanding that SARS-CoV-2–specific T cell responses are not predictive of protection against future infection will be a critical issue when measuring clinical efficacy of vaccination in these vulnerable cohorts, particularly when facing rapidly emerging variants of concern.

Keywords: COVID-19; SARS-CoV-2; T cells; hemodialysis; protection; reinfection.

Figure 1.

SARS-CoV-2–specific T cell responses are not associated with protection against RI in patients on HD. (A and B) T cell proliferative responses were compared between HCs (two time points after initial primary infection: day 28 [d28] and d182) versus patients on HD with a single infection (33–153 days after infection; median [IQR], 67 [58–92] days). Each dot is an individual response and bar shows median with IQR; y axes are log transformed so 0% is not represented. (C and D) T cell responses were compared between patients on HD who become reinfected with SARS-CoV-2 (RI) with those with a single infection (SI). T cell responses after first infection (37–188 days after first infection; median [IQR], 108 [62–182] days) and after second infection (17–72 days after second infection; median [IQR], 30 [23–51] days) within the RI cohort were also compared. Each dot is an individual response and bar shows median with IQR; y axes are log transformed so 0% is not represented. (E and F) No correlation between T cell proliferative responses to S1 peptide pool and S1 IgG titers after primary infection. Each dot is an individual response. Red dots are RI patients (n=6), gray dots are SI patients (n=15). R and P values in black are for the whole HD cohort; R and P values in gray are for the SI cohort; R and P values in red are for the RI cohort. (A and B) Statistical analyses to perform unpaired comparisons across multiple groups were performed using the Kruskal–Wallis test with Dunn post-test for multiple comparisons (adjusted P values displayed). (C and D) Statistical analysis done using Mann–Whitney two-tailed t test. (E and F) Statistical analysis done using Spearman rank correlation, two-tailed test. ID, patients’ study identification number; M, membrane; NP, nucleocapsid; ORF3, open reading frame 3; ORF8, open reading frame 8; post 1st inf, after first infection in an RI patient; post 2nd inf, after second infection in an RI patient; Pt, patient; S1, spike 1; S2, spike 2.