Sepsis and cytomegalovirus: foes or conspirators?

Abstract

Cytomegalovirus (CMV) reactivation in non-immune suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune suppressed hosts during critical illness, however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis, and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature, and highlight areas for future investigation.

Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study

“…Failure of these defense mechanisms impairs the ability of the immune system to mount an appropriate response against invading pathogens and latent viruses such as CMV. The 23% incidence of CMV reactivation in our patients with septic shock is similar to other reports [4, 6]. The CMV reactivation observed in our patients was presumably due to impaired lymphocyte function because these patients did not show progression from group A to group D. Previous studies have demonstrated that chronic HIV infection can lead to defects of virus-specific CD8 T cell effector functions (e.g., cytokine production and/or cytotoxicity) [35].…”

Spatiotemporal Virus Surveillance for Severe Acute Respiratory Infections in Resource-limited Settings: How Deep Need We Go?

“…Cytomegalovirus (CMV) was identified in 26.9% of the SARI clusters, and may either reflect reactivation as a bystander of significant inflammatory states including infections with other including viral pathogens [17][18][19], or may in fact reflect the manifestation of CMV primary infections as SARI, a hypothesis viable in view of the high seroprevalence in developing countries [20] and the very young age of 80% of the SARI cluster patients described here. Similarly, the discovery modus of deep sequencing identified more somewhat expected pathogens in that age group, such as human herpesvirus 6 and parvovirus B19, for which similar arguments could be made.…”

Cytomegalovirus Retinitis in HIV and Non-HIV Individuals

“…In immunocompetent individuals, CMV remains asymptomatic but has the potential to reactivate when the immune system is compromised [19]. In immunocompromised patients, primary CMV infection causes severe complications such as pyrexia, viremic-septicemia, pneumonitis and in rare cases CMV induced immunosuppression [23,24]. CMV may also disseminate to the gastrointestinal tract and cause ulcerations.…”

“…The most common non-HIV form of immunosuppression associated with CMVR occurs in the setting of organ transplantation [11,12,23,40,[60][61][62]. CMVR following solid organ transplantation is rare but has been documented in kidney, heart, and liver recipients.…”