CMV seropositivity is a potential novel risk factor for severe COVID-19 in non-geriatric patients

• Published in: PloS one Vol. 17; no. 5; p. e0268530
• Main Authors: Weber, Simone, Kehl, Victoria, Erber, Johanna, Wagner, Karolin I, Jetzlsperger, Ana-Marija, Burrell, Teresa, Schober, Kilian, Schommers, Philipp, Augustin, Max, Crowell, Claudia S, Gerhard, Markus, Winter, Christof, Moosmann, Andreas, Spinner, Christoph D, Protzer, Ulrike, Hoffmann, Dieter, D'Ippolito, Elvira, Busch, Dirk H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.05.2022; Public Library of Science (PLoS)
• Subjects: Age; Aged; Aged patients; Antibodies, Viral; Antigens; Biology and Life Sciences; Biomarkers; Comorbidity; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 vaccines; Cross-reactivity; Cytomegalovirus; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - epidemiology; Cytomegaloviruses; Diagnosis; Disease transmission; Epstein-Barr virus; Health aspects; Health risks; Herpes Simplex; Hospitalization; Humans; Immunoglobulin G; Infections; Lymphocytes; Lymphocytes T; Mathematical models; Medicine and Health Sciences; Older people; Patients; People and Places; Peptides; Prediction models; Research and Analysis Methods; Retrospective Studies; Risk analysis; Risk Factors; SARS-CoV-2; Serology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Statistical models; T cell receptors; Viral diseases; Viruses; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0268530

COVID-19 has so far affected more than 250 million individuals worldwide, causing more than 5 million deaths. Several risk factors for severe disease have been identified, most of which coincide with advanced age. In younger individuals, severe COVID-19 often occurs in the absence of obvious comorbidities. Guided by the finding of cytomegalovirus (CMV)-specific T cells with some cross-reactivity to SARS-CoV-2 in a COVID-19 intensive care unit (ICU) patient, we decided to investigate whether CMV seropositivity is associated with severe or critical COVID-19. Herpes simplex virus (HSV) serostatus was investigated as control. National German COVID-19 bio-sample and data banks were used to retrospectively analyze the CMV and HSV serostatus of patients who experienced mild (n = 101), moderate (n = 130) or severe to critical (n = 80) disease by IgG serology. We then investigated the relationship between disease severity and herpesvirus serostatus via statistical models. Non-geriatric patients (< 60 years) with severe COVID-19 were found to have a very high prevalence of CMV-seropositivity, while CMV status distribution in individuals with mild disease was similar to the prevalence in the German population; interestingly, this was not detectable in older patients. Prediction models support the hypothesis that the CMV serostatus, unlike HSV, might be a strong biomarker in identifying younger individuals with a higher risk of developing severe COVID-19, in particular in absence of other co-morbidities. We identified 'CMV-seropositivity' as a potential novel risk factor for severe COVID-19 in non-geriatric individuals in the studied cohorts. More mechanistic analyses as well as confirmation of similar findings in cohorts representing the currently most relevant SARS-CoV-2 variants should be performed shortly.