Abstract
Background
An immunodiagnostic assay that sensitively detects a cell-mediated immune response to SARS-CoV-2 is needed for epidemiological investigation and for clinical assessment of T cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses.
Methods
The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in COVID-19 convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen.
Results
The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI] 79.0-89.0) and 86.6% (123/142; 95% CI;80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI 64.4-89.2) at 10 months post-infection (P<0.01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs. 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of +50% (95% CI +25.4-+74.6) and +21.7% (95% CI, +9.23-+42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts.
Conclusions
The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.
Keywords: IGRA, COVID-19, T-cell response, Immunocompromised patients, whole blood assay
Contributor Information
Kanagavel Murugesan, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Prasanna Jagannathan, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Jonathan Altamirano, Division of Infectious Diseases, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Yvonne A Maldonado, Division of Infectious Diseases, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Hector F Bonilla, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Karen B Jacobson, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Julie Parsonnet, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Jason R Andrews, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Run-Zhang Shi, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Scott Boyd, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Benjamin A Pinsky, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Clinical Virology Laboratory, Stanford Health Care, Stanford, CA, USA.
Upinder Singh, Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Microbiology and Immunology.
Niaz Banaei, Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Clinical Microbiology Laboratory, Stanford Health Care, Stanford, CA, USA.
Supplementary Material
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.