Combining SARS‐CoV‐2 interferon‐gamma release assay with humoral response assessment to define immune memory profiles
2 BIOMERIEUX [Lyon, France]
3 CIRI - Centre International de Recherche en Infectiologie
4 CIRI-VirPath - Virology and human respiratory Pathologies - Virology and human respiratory Pathologies [CIRI]
5 PI3 - Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression
6 HCL - Hospices Civils de Lyon
7 CSMime - Commission Spécialisée Maladies infectieuses et maladies émergentes
8 Service des Agents Infectieux et Hygiène [CHU Saint-Etienne]
9 UMRESTTE UMR_T9405 - Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement
10 EFS - Établissement Français du Sang [La Plaine Saint-Denis]
11 CIRI-ICL - Immunité et lymphocytes T CD8 cytotoxiques - Immunity and cytotoxic CD8 T-lymphocytes [CIRI]
12 SFR Biosciences
13 I2V - Immunité infection vaccination
14 INSERM U851
15 CIRI-LYACTS - Activation et transduction du signal dans les lymphocytes - Lymphocyte activation and signaling [CIRI]
16 CNR - laboratoire coordonnateur - Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) [Lyon]
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Résumé
Abstract Objectives In the post‐SARS‐CoV‐2 pandemic era, “breakthrough infections” are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti‐Spike (S) immunoglobulin‐G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T‐cell response assessment to enhance the definition of immune memory profile. Methods SARS‐CoV‐2 interferon‐gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti‐receptor‐binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated. Results Close to 40% of our samples were exclusively IGRA‐positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long‐lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti‐receptor‐binding domain IgG and IGRA levels tended to reduce it. Conclusion The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level.