Abstract
Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had non-neutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options. Trial Registration: ClinicalTrials.gov Identifier: NCT04410263 .
【초록키워드】 COVID-19, Treatment, Stratification, SARS-CoV-2, IgG, IgM, intensive care, Hospitalization, Infection, Gender, coronavirus 2, heterogeneity, type I interferon, clinical outcomes, ICU, early diagnosis, Cohort, Critically ill, IgA, autoantibodies, Patient, IFN, CMV, plasma, age, Neutralizing, respiratory, Switzerland, longitudinal, predict, critically ill patients, IFNs, Analysis, Odds ratio, COVID-19 patient, autoantibody, deficiency, 95% confidence interval, healthy donors, tracheobronchial secretions, one patient, antiviral action, predisposition, herpes simplex, COVID-19 cohort, herpesviruses, likelihood, steroid treatment, tested, caused, virus, screened, anatomical, analysis, suffered, exacerbate, herpesvirus disease, IgG level, 【제목키워드】 type I interferon, Neutralizing, COVID-19 patient, autoantibody, increased risk, herpesvirus disease,