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. 2021 Nov 2;73(9):e3130-e3132.
doi: 10.1093/cid/ciaa1537.

Interferon-γ Release Assay for Accurate Detection of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Response

Kanagavel Murugesan  1 , Prasanna Jagannathan  2 , Tho D Pham  1   3 , Suchitra Pandey  1   3 , Hector F Bonilla  2 , Karen Jacobson  2 , Julie Parsonnet  2 , Jason R Andrews  2 , Daniela Weiskopf  4 , Alessandro Sette  4   5 , Benjamin A Pinsky  1   2   6 , Upinder Singh  2 , Niaz Banaei  1   2   7
Affiliations

Interferon-γ Release Assay for Accurate Detection of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Response

Kanagavel Murugesan et al. Clin Infect Dis. .

Abstract

We investigated feasibility and accuracy of an interferon-γ release assay (IGRA) for detection of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whole blood IGRA accurately distinguished between convalescent and uninfected healthy blood donors with a predominantly CD4+ T-cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the coronavirus disease 2019 pandemic.

Keywords: IGRA; SARS-CoV-2; T cells; immune response; interferon-γ release assay.

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Figures

Figure 1.
Figure 1.
Performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interferon gamma (IFN-γ) release assay (IGRA). A, Schematic showing methodology of whole blood IGRA for detection of cellular immune response to SARS-CoV-2. B, IFN-γ response of whole blood stimulated with CD4+ T-cell peptide pool in healthy blood donors with negative SARS-CoV-2 immunoglobulin G (controls) and convalescent cases with mild coronavirus disease 2019 (COVID-19) (convalescent plasma donors [CPDs] and participants of an interferon lambda [IFN-λ] therapy trial [IλT] on day 17 post–reverse-transcription polymerase chain reaction [RT-PCR] positivity). Median IFN-γ response was 0.36 (interquartile range {IQR}, 0.14–0.74) IU/mL in cases vs 0.01 (IQR, 0–0.01) IU/mL in controls. SARS-CoV-2 IGRA showed sensitivity of 90% (95% confidence interval [CI], 82%–95%) and specificity of 96% (95% CI, 86%–99%) at a cutoff of 0.08 IU/mL (dotted line). C, IFN-γ responses for peptide pools stimulating CD4+ and CD8+ (pools A and B) T cells. Median IFN-γ response was 0.31 (IQR, 0.14–0.75) IU/mL to CD4+ T-cell peptide pool vs 0.05 (IQR, 0.02–0.30) IU/mL to CD8+ T-cell peptide pool A and 0.01 (IQR, 0–0.04) IU/mL to CD8+ T-cell peptide pool B. D, IFN-γ response to CD4+ T-cell peptide pool on days 17 and 31 post–RT-PCR positivity in convalescent IλT participants. Median IFN-γ response was 0.35 (IQR, 0.14–1.06) IU/mL on day 14 vs 0.11 (IQR, 0.04–0.32) IU/mL on day 28. E, IFN-γ response in 20 controls and 24 IλT convalescents (16 on day 17 and 8 on day 31) using a commercial peptide pool consisting of spike, S1, nucleocapsid, and membrane proteins from Miltenyi Biotec (Bergisch Gladbach, Germany). Median IFN-γ response was 0.02 (IQR, 0.01–0.05) IU/mL in controls and 3.59 (IQR, 1.31–6.58) IU/mL in convalescents. Bars show median IFN-γ response and whiskers show IQR. Abbreviations: APC, antigen presenting cell; CPD, convalescent plasma donor; ELISA, enzyme-linked immunosorbent assay; IFN-γ, interferon gamma; MHC, major histocompatibility complex; RT-PCR, reverse-transcription polymerase chain reaction; TCR, T-cell receptor.
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