Persistent and robust T-cell reactivity to the SARS-CoV-2 Omicron variant among immunized adults

1. Among adults vaccinated against SARS-CoV-2, there was a persistent and robust T-cell response despite mutations in the Omicron variant.

2. These findings suggest that cellular immunity against the Omicron BA.1 variant of SARS-CoV-2 from vaccination and/or previous infection was not compromised and will continue to protect against severe disease.

Evidence Rating Level: 2 (Good)

Study Rundown: With the emergence of highly contagious variants of SARS-CoV-2 such as Omicron, it is uncertain whether the cross-reactivity of the spike-specific T-cells among individuals who have had previous SARSCoV-2 infection or vaccinated against SARSCoV-2 will confer a broad enough adaptive immune response to respond. This study assessed the T-cell response to the mutated regions of the spike protein from the Omicron BA.1 variant among individuals vaccinated against COVID-19 and/or with immunity from previous COVID-19 infection. The main outcomes included the measurement of T-cell response to the mutated regions of the spike protein of the Omicron BA.1 variant and the assessment of residual T-cell immunity to the spike protein. Despite mutations in the Omicron variant of SARS-CoV-2, 80% of participants demonstrated adequate cellular immunity responses to the mutated regions of the spike protein. Furthermore, mutations as a result of the Omicron variant were associated with significantly reduced T-cell recognition compared to the vaccine strain. Lastly, the response to the entire spike protein was present in 100% of participants, while the proportion of remaining immunity to SARS-CoV-2 was approximately 87%. A limitation of this study was the reduced sample size in each cohort resulting in low statistical power for the identification of differences in T-cell responses between cohorts.

Click to read the study in JAMA Network Open

Relevant Reading: Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals

In-Depth [prospective cohort]: This cohort study included 61 individuals (mean [range] age, 42 [21-62] years; 38 [62%] women) vaccinated from or infected with SARS-CoV-2 from a tertiary center in Rome, Italy during December 2021. Lymphocytes from blood samples were isolated and tested for reactivity to the SARS-CoV-2 spike protein. Overall, the median (range) frequency of CD4+ T cells reactivity to the mutated regions in the Omicron variant was 0.039% (0%-2.356%). Compared to the frequency of CD4+ cells reactive to the same regions of the ancestral strain (0.109% [0%-2.376%]), this was a 64% decrease. For CD8+ T cells, 0.02% (0%-0.689%) reacted to the mutated spike regions, compared to 0.039% (0%-3.57%) specific to the equivalent unmutated regions (49% reduction). Overall reactivity to the the full-length protein was maintained at approximately 87%.

Image: PD

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