Interferon Gamma Injection and Its Effect on the Respiratory Anelloviridae Population in ICU Ventilated Patients

ABSTRACT Immune dysfunctions induced by critical illness are associated with an increased risk of hospital‐acquired pneumonia (HAP) in intensive care unit (ICU) patients. The use of immunomodulatory molecules in this setting is under evaluation. The presence of persistent viruses, such as anelloviruses (AVs) or herpesviruses, which are frequently detected in respiratory samples, may indicate immune dysfunction. Herpesvirus infections are associated with increased morbidity in ICU patients, and variations in AV DNA loads are associated with rejection events in immunocompromised patients. We investigated the respiratory viral landscape of 94 patients during the first week under invasive mechanical ventilation using quantitative PCR and targeted metagenomics after capture probe enrichment. The patients were included in a placebo‐controlled randomized clinical trial testing IFNγ for the prevention of HAP. We measured AV and herpes simplex virus‐1 (HSV‐1) DNA loads over time in respiratory samples collected at admission ( n = 54), and on Days 3 ( n = 73) and 7 ( n = 57) after admission. There were no significant differences in mortality, HAP, the development of acute respiratory distress syndrome (ARDS), HSV, or AV DNA detection between patients treated with IFNg and those who received a placebo. Patients who developed HAP had a significantly higher AV DNA load in tracheal aspirates over time ( p = 0.011) than those who did not. Target enrichment analysis revealed AV presence in all respiratory samples, with no differences observed in AV composition between IFNg‐treated and placebo patients, or between HAP and noHAP patients. Trial Registration: CPP Ouest II 17/02/2021 (avis N°2021/03); ClinicalTrial.gov number: NCT04793568.