The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the resulting Coronavirus disease 2019 (COVID-19) has massively impacted everyday life. While some risk factors like cardiovascular or pulmonary comorbidity, obesity and male gender are correlated with a higher risk of severe COVID-19 disease, in many cases the cause of severe disease cannot be determined. Even though many efforts have been undertaken to get a better understanding of the pathophysiology of the breadth of disease penetrance, up until now, an extensive explanation for severe COVID-19 disease in previously healthy patients is still missing.
In previous work, we identified a pre-existing infection with the human cytomegalovirus (CMV) as risk factor for developing severe COVID-19 disease, especially in non-geriatric patients. In addition, we could show that CMV seropositivity is associated with a higher prevalence of comorbidities that are known risk factors for severe COVID-19 disease. CMV is a herpesvirus that causes a latently persisting infection that is known to reshape the immune repertoire by creating an inflationary memory T cell response. How the memory CMV-specific T-cell repertoire shapes the immune response against SARS-CoV-2 is subject of our current investigations. A potential mechanism of this might be the cross-reactivity of CMV-primed T-cell responses towards SARS-CoV-2 epitopes. Understanding the underlying causes of severe COVID-19 disease, especially in individuals previously considered healthy, is of high relevance for reducing morbidity and mortality and improving treatment strategies.
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