Severe SARS‐CoV‐2 patients develop a higher specific T‐cell response

Abstract

Objectives Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot). Methods Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak. Results Specific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies. Conclusion IFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response.

Passive Immunity Should and Will Work for COVID-19 for Some Patients

“…Others have found no consistent IgG/IgA correlation for intensity of production [34]. Quantitation by most methods increase with the severity of infection [33,34,36,41,50,52,56,60,[70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87]. Severe disease may be associated with a delay of the humoral response [88].…”

“…Affinity maturation is time accrued [50,78]. A small proportion do not seroconvert after infection, and thus not all post-infectious sera may be useful, even though other aspects of post-infection immunity via cell-mediated immunity may have arisen in these patients [33,34,68,[72][73][74]77,[92][93][94].…”

“…T cell immunity arises, as anticipated, during infection, and the quality and quantity of the same varies according to the intensity of disease. [31,48,51,63,65,67,68,70,74,89,91,93,94,98,102,[109][110][111].…”

How to interpret and use COVID-19 serology and immunology tests

“…Enzyme-linked immunospot (ELISpot) is an antigen-specific T-cell functional assay that can measure the proportion of T-cells producing a specific cytokine [ 55 ] ( Table 1 ). It is a highly sensitive approach and has been used to assess SARS-CoV-2-specific T-cell responses [ 36 , 43 , 51 , 56 , 57 ]. IFNγ-secreting T cells were reactive against M, N and S peptides in 70% to 100% of convalescent COVID-19 patients depending on the specific antigens and techniques used in the test [ 47 , 51 , [57] , [58] , [59] ].…”

“…IFNγ-secreting T cells were reactive against M, N and S peptides in 70% to 100% of convalescent COVID-19 patients depending on the specific antigens and techniques used in the test [ 47 , 51 , [57] , [58] , [59] ]. Illness severity is correlated with anti-M and anti-S T-cell responses [ 56 , 57 ]. IFNγ-ELISpot assays have also been used for the assessment of cellular responses after SARS-CoV-2 vaccination, with vaccine candidates reporting robust S-specific T-cell responses after vaccination [ 60 ].…”