Are herpesviruses reactivated more often in acute COVID-19?

Systematic review and meta-analysis found strong evidence for EBV in the seriously ill; only 6 of 36 studies included HHV-6 testing.

Although there have been multiple reports of reactivated latent herpesvirus infection in people with acute COVID-19, the reports have defined reactivation using different criteria and have not always had adequate non-COVID comparison groups.

A new systematic review and meta-analysis of 36 publications included only studies in which herpesvirus reactivation was defined by positive IgM antibodies or PCR result, and in which there was a non-COVID comparison group. The publications selected included cross-sectional studies (18/37), case-control studies (8/37), cohort studies (5/37), and case series (4/37).

The prevalence of active infection was:  EBV 41% (95% CI 27%-57%), HHV6 34% (95% CI 17%-54%), HSV 28% (95% CI 1%-85%), CMV 25% (95% CI 1%-63%), HSV1 22% (95% CI 10%-35%), and VZV 18% (95% CI 4%-34%).

When the prevalence of active infection in COVID-19 vs. non-COVID-19 cases was compared, the authors state that only active EBV infection was associated with COVID-19, and only then in the most severely ill cases (OR=6.45, 95% CI = 1.09-38.13, p=0.04).

Inexplicably, the authors do not report the results of this comparison for HHV-6, despite the fact that in the six studies that included HHV-6, the reactivation rate (34%) was higher than any other herpesvirus except EBV.  The reactivation rate in healthy controls is near zero.

Thus, this review finds that EBV is frequently reactivated in the most severely ill people with acute COVID-19. The review did not shed light on the question of whether acute COVID-19 might also prompt reactivation of latent HHV-6 infection, and what the clinical consequences of this might be.

One clue suggesting HHV-6 and HHV-7 may be reactivated by COVID-19 is that there have been many case reports of pityriasis rosea concurrent with either COVID-19 infection or vaccination (Wong 2023). Pityriasis rosea is an acute exanthematous disease thought to be associated with reactivation of HHV-6 &7.

Read the full text: Banko 2023