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Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the cellular immunity associated with the Omicron variant of SARS-CoV-2 among immunized individuals?

Findings  In this cohort study among 61 individuals who had been vaccinated against COVID-19, cellular responses to the mutated regions of the Omicron spike protein were detected in 80% of participants. The mutations were associated with significantly reduced T-cell recognition compared with the vaccine strain, while reactivity to the whole spike protein was present in 100% of participants, and the proportion of remaining immunity to SARS-CoV-2 was estimated to be 87%.

Meaning  These findings suggest that cellular immunity to the Omicron variant was maintained despite the mutations in its spike protein; thus, immunization may confer protection from severe COVID-19 from the Omicron variant.


Importance  The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from individuals with previous SARS-CoV-2 infection or vaccination highlights the importance of studying cellular immunity to estimate the degree of immune protection to the new SARS-CoV-2 variant.

Objective  To determine T-cell reactivity to the Omicron variant in individuals with established (natural and/or vaccine-induced) immunity to SARS-CoV-2.

Design, Setting, and Participants  This was a cohort study conducted between December 20 and 21, 2021, at the Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy, among health care worker and scientist volunteers. Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the spike protein of SARS-CoV-2.

Main Outcomes and Measures  The main outcomes were the measurement of T-cell reactivity to the mutated regions of the spike protein of the Omicron BA.1 SARS-CoV-2 variant and the assessment of remaining T-cell immunity to the spike protein by stimulation with peptide libraries.

Results  A total of 61 volunteers (mean (range) age, 41.62 (21-62) years; 38 women [62%]) with different vaccination and SARS-CoV-2 infection backgrounds were enrolled. The median (range) frequency of CD4+ T cells reactive to peptides covering the mutated regions in the Omicron variant was 0.039% (0%-2.356%), a decrease of 64% compared with the frequency of CD4+ cells specific for the same regions of the ancestral strain (0.109% [0%-2.376%]). Within CD8+ T cells, a median (range) of 0.02% (0%-0.689%) of cells recognized the mutated spike regions, while 0.039% (0%-3.57%) of cells were reactive to the equivalent unmutated regions, a reduction of 49%. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 87%). No significant differences in loss of immune recognition were identified between groups of participants with different vaccination or infection histories.

Conclusions and Relevance  This cohort study of immunized adults in Italy found that despite the mutations in the spike protein, the SARS-CoV-2 Omicron variant was recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease will be maintained.

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Article Information

Accepted for Publication: March 21, 2022.

Published: April 22, 2022. doi:10.1001/jamanetworkopen.2022.10871

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 De Marco L et al. JAMA Network Open.

Corresponding Authors: Luca Battistini, MD, PhD (l.battistini@hsantalucia.it), and Giovanna Borsellino, MD, PhD (g.borsellino@hsantalucia.it), Neuroimmunology Unit, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano 64, 00143 Rome, Italy.

Author Contributions: Drs Battistini and Borsellino had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs De Marco, D’Orso, Pirronello, and Verdiani contributed equally to this work.

Concept and design: Picozza, Rötzschke, Giardina, Battistini, Borsellino.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Borsellino.

Critical revision of the manuscript for important intellectual content: De Marco, D’Orso, Pirronello, Verdiani, Termine, Fabrizio, Capone, Sabatini, Guerrera, Placido, Sambucci, Angelini, Giannessi, Picozza, Caltagirone, Salvia, Volpe, Balice, Rossini, Rötzschke, Giardina, Battistini.

Statistical analysis: Termine, Fabrizio.

Obtained funding: Battistini.

Administrative, technical, or material support: Caltagirone, Salvia, Rossini.

Supervision: Borsellino.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was partially supported by grant No. COVID-2020-12371735 from the Italian Ministry of Health to Dr Battistini.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Enrico Ghersi, PhD (Cytek Biosciences), provided expert assistance with the Aurora Flow cytometer, and Mirko Lanuti, PhD, and Claudia Maldini, PhD (Miltenyi) provided crucial reagents. They were not compensated for their collaboration.

World Health Organization. WHO coronavirus (COVID-19) dashboard. Accessed October 24, 2021. https://covid19.who.int/
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