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

Abstract

Significance Statement 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.

Risk of reinfection and disease after SARS‐CoV‐2 primary infection: Meta‐analysis

“…Of the 3282 papers initially retrieved, we included 91 cohort studies evaluating the onset of reinfection, severe and very severe/lethal COVID‐19 among 15,034,624 previously infected subjects (Figure 1), either among health care workers (27 publications; n = 37,598 2,8,9,15,17,24,36,38,42–59 ) or in the general population (67 publications; n = 14,997,026 3–7,10,12,16–23,25–27,43,49,60–106 ).…”

“…As shown in Table S1, most of the included studies ( n = 43) were carried out in Europe, 2,4–10,12,15,17,18,21,24,26,36,38,44,46–51,58,66,69,71,72,75,81,85–88,91–93,95,99,102 24 in the USA, 20,22,23,25,42,43,57,59,63,67,77,79,82–84,89,90,97,98,103,105–107 18 in Asia 3,16,19,27,45,52–54,56,60,62,64,65,70,73,74,100,101 and the remaining six in South America or South Africa 61,68,80,94,96,104 . The mean age of the participants ranged from 15 to 87 years, and the average follow‐up ranged from 29 to 371 days.…”

“…The mean age of the participants ranged from 15 to 87 years, and the average follow‐up ranged from 29 to 371 days. Overall, 38 publications strictly followed the CDC criteria to identify the reinfections and were classified at low risk of misclassification bias 10,16,19,20,22–24,26,36,44,45,48–50,54,56,58,59,68,71,72,75,84,86,89–91,94,99,100,102 . All but five studies ( n = 3,854,961) 66,71,88,91,96 were completed before the emergence of BA.1/B.1.1.529 (Omicron) variant.…”

“…Overall, a total of 158,478 reinfections were recorded among the 15,034,624 subjects with a previous infection, 2–10,12,13,15–27,36,38,42–107 corresponding to a pooled rate of 0.97% (95% CI: 0.71%–1.27%—Table 1; Figure 2). The summary rate of reinfection rose to 1.07% (95% CI: 0.73%–1.46%) when only the 69 datasets with a more conservative time lag of ≥90 days between the two episodes were considered 3–6,8–10,12,18–23,25,26,36,42–44,46–50,52–56,59,61–65,67–69,72–84,86,87,89,91–96,98,101,103,105–107 and it slightly varied by reinfection definition criteria (0.93% vs 1.01% when considering studies with high vs low risk of misclassification).…”

“…In the 59 available datasets, 2,3,5,6,10,16–22,25–27,36,44,46–59,63–67,69,71–74,79,82,84–87,90,93–95,99–104 a total of 1380 severe COVID‐19 diseases were diagnosed among 5,006,604 subjects with a previous infection, corresponding to a pooled rate of 0.02% (95% CI: 0.00%–0.04%—Table 1). This rate did not substantially vary when only the studies with longer time lag were considered, while it increased—still, however, remaining below 0.1%—when only the studies that used CDC criteria to define reinfections were included (summary rate 0.07%; 0.04%–0.10%).…”