Does reactivation of cytomegalovirus contribute to severe COVID-19 disease?

Abstract

The majority of people infected with SARS-CoV-2 are asymptomatic or have mild to moderate symptoms. However, for unknown reasons, about 15 % have severe pneumonia requiring hospital care and oxygen support, and about 5 % develop acute respiratory distress syndrome, septic shock, and multiorgan failure that result in a high mortality rate. The risk of severe COVID-19 is highest among those who are over 70 years of age. Why severe COVID-19 develops in some people but not others is not understood. Could some cases involve reactivation of latent cytomegalovirus (CMV)?

Cytomegalovirus infection in critically ill patients with COVID-19

“…CMV reactivation and virus-induced immune dysfunction may be overlooked as a cause of immunomodulation in patients with severe COVID-19. 9 Considering that the lung is a major reservoir for CMV and patients with COVID-19 are at risk for CMV disease, 10 CMV pneumonia may be underestimated in critically ill patients with COVID-19 pneumonia. 11 Untreated infection can lead to rapid deterioration and fatal outcomes.…”

Immune Landscape of CMV Infection in Cancer Patients: From “Canonical” Diseases Toward Virus-Elicited Oncomodulation

“…The severe and mortal complications resulting from HCMV reactivation mainly occur in immunosuppressed and seriously ill immunocompetent individuals in whom the HCMV infection is accompanied by prolonged hospitalization and/or mortality. Furthermore, the manipulation of the host immunity can result in superinfections with other herpesviruses or bacteria, and exacerbate SARS-CoV-2 infections that are benefiting from the weakened immune system ( 18 , 19 , 103 , 104 ). Since HCMV infection is known as a prevalent congenital viral infection, it might generate viral hepatitis with jaundice in addition to long-lasting disabilities, including hearing and visual damage, neurological impairments, and mental retardation ( 103 ).…”

“…Years later, persistent HCMV infection might be considered a potential risk factor exacerbating age-associated diseases and immunosenescence which is defined as the age-associated deterioration in overall immune condition (12)(13)(14) although some studies have indicated that the link between HCMV and immune aging is obscure (3,15). Further, various stimuli can induce HCMV reactivation; it might be triggered in SARS-CoV-2 infected patients (16,17) thus exacerbating the risk of coronavirus disease 2019 (COVID-19) (18,19). Even if this interaction is still elusive and additional large scale studies are recommended (16), CMV testing and treatment should be taken into consideration in such critical conditions (18).…”

“…Further, various stimuli can induce HCMV reactivation; it might be triggered in SARS-CoV-2 infected patients (16,17) thus exacerbating the risk of coronavirus disease 2019 (COVID-19) (18,19). Even if this interaction is still elusive and additional large scale studies are recommended (16), CMV testing and treatment should be taken into consideration in such critical conditions (18). CMV status must be taken into account for several vaccine responses, especially cancer despite the use of HCMV-based therapeutic cancer vaccines (20), since it has been suggested that with advanced age and due to CMV-associated altered immunity in both healthy and immunocompromised hosts, vaccine immunogenicity was modulated (21)(22)(23).…”

Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

“…In human studies, CMV-induced memory inflation was associated with a decreased memory response to EBV [ 62 ] and to influenza [ 63 ] in older people. Although not extensively studied yet, its role in the clinical course and severity of coronavirus disease 2019 (COVID-19) has also been proposed, due to the probable role of immunosenescence in the increased vulnerability of older patients [ 64 , 65 ].…”