Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood

Abstract

T cell immunity to natural SARS-CoV-2 infection may be more robust and longer lived than Ab responses. Accurate assessment of T cell responses is critical for understanding the magnitude and longevity of immunity across patient cohorts, and against emerging variants. By establishing a simple, accurate, and rapid whole blood test, natural and vaccine-induced SARS-CoV-2 immunity was determined. Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with previous PCR-confirmed infection, suspected infection, or with no exposure history (n 5 128), as well as in donors before and after vaccination (n 5 32). Longitudinal assessment of T cell responses following initial vaccination and booster vaccination was also conducted (n 5 50 and n 5 62, respectively). Cytokines were measured by ELISA and multiplex array. IL-2 and IFN-g were highly elevated in PCRconfirmed donors compared with history-negative controls, with median levels ~33-fold and ~48-fold higher, respectively. Receiver operating curves showed IL-2 as the superior biomarker (area under the curve 5 0.9950). Following vaccination, all donors demonstrated a positive IL-2 response. Median IL-2 levels increased ~32-fold from prevaccination to postvaccination in uninfected individuals. Longitudinal assessment revealed that T cell responses were stable up to 6 mo postvaccination. No significant differences in cytokine production were observed between stimulations with Wuhan, Delta, or Omicron peptides. This rapid, whole blood-based test can be used to make comparable longitudinal assessments of vaccine-induced T cell immunity across multiple cohorts and against variants of concern, thus aiding decisions on public health policies. ImmunoHorizons, 2022, 6: 398-407.

Nationwide analysis of COVID-19 death rate throughout the pandemic in Italy

“…Yet, such variation is not comparable to the magnitude of clinical benefits probably generated by the primary COVID-19 vaccination, which contributed to lower the mortality rate by over 4 folds between December 2020 and September 2021 (i.e., from 3.53% to 0.81%). This is in keeping with recent evidence showing that booster doses of COVID-19 vaccines may be effective to reduce the likelihood of developing acute SARS-CoV-2 infection by boosting humoral immunity, whilst both immunological memory (20) and cellular immunity (21,22) developed after primary vaccination remain almost unvaried (23), thus preserving part of their original potential to produce a marked anti-viral response that will ultimately prevent an unfavorable disease progression, including death (24).…”