SARS‐CoV‐2‐reactive interferon‐γ‐producing CD8+ T cells in patients hospitalized with coronavirus disease 2019

Abstract

There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) T‐cell immune responses in patients with coronavirus disease 2019 (COVID‐19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS‐CoV‐2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID‐19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS‐CoV‐2‐reactive CD69+ expressing interferon‐γ (IFN‐γ) producing CD8+ T cells using flow‐cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS‐CoV‐2 Spike glycoprotein N‐terminal 1 to 643 amino acid sequence and the entire sequence of SARS‐CoV‐2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43‐9.98 cells/µL). The detection rate of SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells in patients admitted to intensive care was comparable ( P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS‐CoV‐2‐reactive IFN‐γ CD8+ T‐cell counts and SARS‐CoV‐2 S‐specific antibody levels. Likewise, no correlation was observed between either SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells or S‐specific immunoglobulin G‐antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS‐CoV‐2‐reactive IFN‐γ CD8+ T cells can be detected in a non‐negligible percentage of patients with moderate to severe forms of COVID‐19. Further studies are warranted to determine whether quantitation of these T‐cell subsets may provide prognostic information on the clinical course of COVID‐19.

IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection

“…Previous studies have not reported the association between IFN-γ and death, even evaluating the COVID-19-reactive CD69+ expressing IFN-γ producing CD8 + T in 25 patients with severe and moderate disease [ 22 ]. Most studies have described the evident immunological dysfunction in the moderate and severe disease, with reduced expression of IFN-γ by CD4 + T, CD8 + T, and NK cells [ 23 ].…”

SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 patients

“…Undiluted tracheal aspirate samples obtained from mechanically ventilated patients were also processed when available. Commercially-available RT-PCR kits were used for SARS-CoV-2 RNA testing, as previously detailed [24].…”

Healthy donor T cell responses to common cold coronaviruses and SARS-CoV-2

“…Severe acute respiratory syndrome coronavirus 2-specific (SARS-CoV-2-specific) T cell responses have been detected in patients with coronavirus disease 2019 (COVID-19) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and while T cell responses against SARS-CoV have been shown to be long lasting (8), it is not yet known whether SARS-CoV-2-specific T cells will confer protection against reinfection. Recent studies have suggested that preexisting T cell immunity to SARS-CoV-2 is present in some unexposed, HDs (6)(7)(8)(9)(10)(11).…”