Whole blood‐based measurement of SARS‐CoV‐2‐specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid‐organ cancers

Abstract

Accurate assessment of SARS‐CoV‐2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS‐CoV‐2‐specific T‐cell responses are a critical feature that will likely form a key correlate of protection against COVID‐19. Here, we developed and optimized a high‐throughput whole blood‐based assay to determine the T‐cell response associated with prior SARS‐CoV‐2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS‐CoV‐2‐specific peptides, blood plasma samples were analysed for T H 1‐type cytokines. Highly significant differential IFN‐γ + /IL‐2 + SARS‐CoV‐2‐specific T‐cell responses were seen amongst previously infected COVID‐19‐positive healthy donors in comparison with unknown / naïve individuals ( p < 0·0001). IFN‐γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL‐2. A single COVID‐19 vaccine dose induced IFN‐γ and/or IL‐2 SARS‐CoV‐2‐specific T‐cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients ( p < 0·0001). A second dose was sufficient to boost T‐cell responses in the majority (90·6%) of cancer patients, albeit IFN‐γ + responses were still significantly lower overall than those induced in healthy donors ( p = 0·034). Three‐month post‐vaccination T‐cell responses also declined at a faster rate in cancer patients. Overall, this cost‐effective standardizable test ensures accurate and comparable assessments of SARS‐CoV‐2‐specific T‐cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.

Response to COVID-19 booster vaccinations in seronegative people with MS

“…Higher incidence and/or worse outcomes in the context of in vivo COVID-19 infection in people receiving anti-CD20, [5,6] and fingolimod,[7] have been observed in some large population-based studies performed prior to the widespread availability of booster vaccines. These observations require further study to fully understand the clinical implications of booster vaccination and their underlying mechanisms.…”

“…Whole blood samples were incubated at 37°C for 20-24 hours before harvesting plasma from each sample to quantify IFN-g by ELISA (BioLegend). SARS-CoV-2-specific T-cell responses were identified as positive using previously defined criteria for differentiating naïve controls from prior COVID-19 vaccinated and/or infected individuals (sensitivity 96.0% and specificity 84.4%) [5].…”

“…Further explanations could be that the relevant T-cells are trapped in secondary lymphoid organs due to the mode of action of fingolimod, or that circulating fingolimod in whole blood samples blocks in vitro responses. Higher incidence and/or worse outcomes in the context of in vivo COVID-19 infection in people receiving anti-CD20, [5,6] and fingolimod, [7] have been observed in some large population-based studies performed prior to the widespread availability of booster vaccines. These observations require further study to fully understand the clinical implications of booster vaccination and their underlying mechanisms.…”

“…The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.12.22272083 doi: medRxiv preprint 96.0% and specificity 84.4%) [5].…”

Healthy Immunity on Preventive Medicine for Combating COVID-19

“…Studies of viral infections such as influenza have reported that physical distancing is effective at limiting disease spread, a scenario certainly influential for the protection of COVID-19 infections. The most effective preventive measure for deadly contagious diseases, including COVID-19, is vaccination, which fundamentally boosts the immune system, especially in susceptible populations [ 145 , 146 ]. Vaccines allow for preemptive development of memory B- and T-cells to neutralize pathogens; however, the efficacy of vaccines depends on age, existing immunity, underlying medical conditions, and/or and immunological disorders.…”