Low IFN-γ Response after Cell Stimulation Predicts Hospitalization in COVID-19 Patients

Background: The SARS-CoV-2 infection has spread rapidly around the world causing millions of deaths. Several treatments can reduce mortality and hospitalization. However, their efficacy depends on the choice of the molecule and the precise timing of its administration to ensure viral clearance and avoid a deleterious inflammatory response.Methods: In 115 subjects at an early stage of SARS-CoV-2 infection (within the first five days) or within one month prior to infection, we studied IFN-γ response, assessed by a functional immunoassay, as a predictive biomarker for the risk of hospitalization.Findings: We found that individuals with IFN-γ levels below 15 IU/mL were 6·57-times more likely to be hospitalized than those with higher values (p<0·001). As confirmed by multivariate analysis, low IFN-γ levels, age >65 years, and no vaccination were independently associated with hospitalization.Interpretation: Early analysis of the IFN-γ response in a contact or recently infected subject with SARS-CoV-2 could predict the individual risk of hospitalization and thus help the clinician to choose the appropriate treatment avoiding severe forms of infection and hospitalization.Funding: French Ministry of Health.Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The participants included in this study were extracted from three prospective monocentric cohorts at Nice University Hospital: (i) patients recruited during an infectious diseases or emergency room consultation following COVID-19 symptoms, or a contact case between March 2020 and January 2022 (CovImmune 1 study, NCT04355351); (ii) patients recruited by partner laboratories during a positive RT-PCR for SARS-CoV-2, performed in the context of suggestive symptomatology, contact case, or health pass, between August 2021 and November 2021 (CovImmune 1 study, NCT04355351); (iii) individuals monitored systematically and periodically since July 2020 as part of an epidemiological study in the context of COVID-19 (CovImmune 2 study, NCT04429594).