Magnitude of Venous or Capillary Blood-derived SARS-CoV-2-specific T Cell Response Determines COVID-19 Immunity

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 21

PMID 36130936

Authors

Martin J Scurr

George Lippiatt

Lorenzo Capitani

Kirsten Bentley

Sarah N Lauder

Kathryn Smart

Michelle S Somerville

Tara Rees

Richard J Stanton

Awen Gallimore

James P Hindley

Andrew Godkin

Affiliations

Soon will be listed here.

Abstract

T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence for this is lacking. Here, we associated whole-blood-based measurement of SARS-CoV-2-specific interferon-γ-positive T cell responses with positive COVID-19 diagnostic (PCR and/or lateral flow) test results up to 6 months post-blood sampling. Amongst 148 participants donating venous blood samples, SARS-CoV-2-specific T cell response magnitude is significantly greater in those who remain protected versus those who become infected (P < 0.0001); relatively low magnitude T cell response results in a 43.2% risk of infection, whereas high magnitude reduces this risk to 5.4%. These findings are recapitulated in a further 299 participants testing a scalable capillary blood-based assay that could facilitate the acquisition of population-scale T cell immunity data (14.9% and 4.4%, respectively). Hence, measurement of SARS-CoV-2-specific T cells can prognosticate infection risk and should be assessed when monitoring individual and population immunity status.

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References

Swadling L, Diniz M, Schmidt N, Amin O, Chandran A, Shaw E . Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. 2021; 601(7891):110-117. PMC: 8732273. DOI: 10.1038/s41586-021-04186-8. View

Wilkinson T, Li C, Chui C, Huang A, Perkins M, Liebner J . Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012; 18(2):274-80. DOI: 10.1038/nm.2612. View

Ward H, Atchison C, Whitaker M, Ainslie K, Elliott J, Okell L . SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic. Nat Commun. 2021; 12(1):905. PMC: 7876103. DOI: 10.1038/s41467-021-21237-w. View

Stuart A, Shaw R, Liu X, Greenland M, Aley P, Andrews N . Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial. Lancet. 2021; 399(10319):36-49. PMC: 8648333. DOI: 10.1016/S0140-6736(21)02718-5. View

Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W . Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013; 19(10):1305-12. DOI: 10.1038/nm.3350. View

Peng Y, Felce S, Dong D, Penkava F, Mentzer A, Yao X . An immunodominant NP-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease. Nat Immunol. 2021; 23(1):50-61. PMC: 8709787. DOI: 10.1038/s41590-021-01084-z. View

Lee A, Wong S, Chai L, Lee S, Lee M, Muthiah M . Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis. BMJ. 2022; 376:e068632. PMC: 8889026. DOI: 10.1136/bmj-2021-068632. View

Scurr M, Lippiatt G, Capitani L, Bentley K, Lauder S, Smart K . Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity. Nat Commun. 2022; 13(1):5422. PMC: 9492763. DOI: 10.1038/s41467-022-32985-8. View

Gao Y, Cai C, Grifoni A, Muller T, Niessl J, Olofsson A . Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant. Nat Med. 2022; 28(3):472-476. PMC: 8938268. DOI: 10.1038/s41591-022-01700-x. View

10.

Munro A, Janani L, Cornelius V, Aley P, Babbage G, Baxter D . Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet. 2021; 398(10318):2258-2276. PMC: 8639161. DOI: 10.1016/S0140-6736(21)02717-3. View

11.

Bradley R, Ponsford M, Scurr M, Godkin A, Jolles S . Persistent COVID-19 Infection in Wiskott-Aldrich Syndrome Cleared Following Therapeutic Vaccination: a Case Report. J Clin Immunol. 2021; 42(1):32-35. PMC: 8554737. DOI: 10.1007/s10875-021-01158-5. View

12.

Hollis V, Holloway J, Harris S, Spencer D, van Berkel C, Morgan H . Comparison of venous and capillary differential leukocyte counts using a standard hematology analyzer and a novel microfluidic impedance cytometer. PLoS One. 2012; 7(9):e43702. PMC: 3447872. DOI: 10.1371/journal.pone.0043702. View

13.

Riou C, Schafer G, du Bruyn E, Goliath R, Stek C, Mou H . Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2-specific T-cells. Eur Respir J. 2021; 59(1). PMC: 8215505. DOI: 10.1183/13993003.00285-2021. View

14.

Carreno J, Alshammary H, Tcheou J, Singh G, Raskin A, Kawabata H . Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature. 2022; 602(7898):682-688. DOI: 10.1038/s41586-022-04399-5. View

15.

Moss P . The T cell immune response against SARS-CoV-2. Nat Immunol. 2022; 23(2):186-193. DOI: 10.1038/s41590-021-01122-w. View

16.

Lipsitch M, Krammer F, Regev-Yochay G, Lustig Y, Balicer R . SARS-CoV-2 breakthrough infections in vaccinated individuals: measurement, causes and impact. Nat Rev Immunol. 2021; 22(1):57-65. PMC: 8649989. DOI: 10.1038/s41577-021-00662-4. View

17.

GeurtsvanKessel C, Geers D, Schmitz K, Mykytyn A, Lamers M, Bogers S . Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients. Sci Immunol. 2022; 7(69):eabo2202. PMC: 8939771. DOI: 10.1126/sciimmunol.abo2202. View

18.

Levin E, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S . Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months. N Engl J Med. 2021; 385(24):e84. PMC: 8522797. DOI: 10.1056/NEJMoa2114583. View

19.

Dejnirattisai W, Shaw R, Supasa P, Liu C, Stuart A, Pollard A . Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum. Lancet. 2021; 399(10321):234-236. PMC: 8687667. DOI: 10.1016/S0140-6736(21)02844-0. View

20.

Tallantyre E, Vickaryous N, Anderson V, Asardag A, Baker D, Bestwick J . COVID-19 Vaccine Response in People with Multiple Sclerosis. Ann Neurol. 2021; 91(1):89-100. PMC: 8652739. DOI: 10.1002/ana.26251. View