Viral Reactivation in COVID-19 Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection not only provokes a primary viral pneumonia but can also disturb the equilibrium of latent viruses harboured in human cells. Members of the Herpesviridae family, notably Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1) and Kaposi’s sarcoma-associated herpesvirus (KSHV), persist in a state of latency following primary infection. In the context of COVID-19, factors such as lymphopenia, dysregulated cytokine release, high-dose corticosteroid therapy and other immunomodulatory treatments may precipitate viral reactivation. Clinically, reactivation events have been linked to heightened inflammation, prolonged hospital stay, secondary respiratory complications and increased mortality. Recognition of viral reactivation is therefore essential for risk stratification and may inform timely antiviral interventions. Strategies that combine vigilant laboratory monitoring with tailored antiviral therapy have the potential to mitigate the burden of co-reactivation in individuals with moderate to critical COVID-19 and may influence long-term outcomes in survivors.

Research from Nature Portfolio

Recent studies have shown a notably high prevalence of EBV serological reactivation in patients with acute COVID-19, with fresh onset of EBV-specific IgM responses correlating with elevated C-reactive protein levels and a greater incidence of febrile symptoms. This work highlights the interplay between SARS-CoV-2-induced immune perturbation and latent herpesvirus activation during the early phase of infection. In parallel, mechanistic investigations have revealed that certain SARS-CoV-2 structural proteins, as well as repurposed anti-COVID-19 drugs, can trigger lytic reactivation of KSHV by modulating key intracellular signalling cascades. Such findings raise considerations about the long-term oncogenic risk in populations with endemic KSHV and underscore the need to balance antiviral therapies against unintended effects on latent viral genomes.

Viral Reactivation in COVID-19 Patients publication trend

The graph below shows the total number of articles in viral reactivation in covid-19 patients across all publications each year (not limited to Nature Index journals).

Technical terms

Viral latency: Dormant state of a virus within host cells with minimal gene expression and no production of infectious particles.

Reactivation: Process by which a latent virus resumes active replication, leading to renewed infection.

Cytokine storm: Excessive and uncontrolled release of pro-inflammatory cytokines contributing to tissue damage.

Seropositivity: Presence of specific antibodies in the blood, indicating past or current infection.

Immunosuppression: Reduction of the efficacy of the immune system, often due to disease or therapeutics.

References

1. Positive Epstein–Barr virus detection in coronavirus disease 2019 (COVID-19) patients. Scientific Reports (2021).
2. SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus. Communications Biology (2021).
3. Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients. International Journal of Molecular Sciences (2023).
4. HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients. Critical Care (2021).
5. Case report: Enhancing prognosis in severe COVID-19 through human herpes virus coinfection treatment strategies. Frontiers in Cellular and Infection Microbiology (2024).