Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID

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Abstract

The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited. In a cohort of 280 adults with prior SARS-CoV-2 infection, we observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4 months following initial diagnosis were independently associated with serological evidence of recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen IgG levels, but not with ongoing EBV viremia. Evidence of EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52) and tended to have less severe (>5 symptoms reported) LC (OR 0.44). Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.

SUMMARY

The authors found that Long COVID symptoms in a post-acute cohort were associated with serological evidence of recent EBV reactivation and pre-existing HIV infection when adjusted for participant factors, sample timing, comorbid conditions and prior hospitalization, whereas underlying CMV infection was associated with a decreased risk of Long COVID.

Article activity feed

  1. Paul Farrell

    Review 2: "Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID"

    Reviewers were mixed on the overall reliability of this preprint. There is agreement that the study results are supported by the data, but some concern over the suggested explanation for the results.

  2. Roberto Paganelli

    Review 1: "Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID"

    Reviewers were mixed on the overall reliability of this preprint. There is agreement that the study results are supported by the data, but some concern over the suggested explanation for the results.