Abstract
Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.
Highlights
It has been reported that about 30% of coronavirus disease 2019 (COVID-19) patients experience long-term symptoms following resolution of acute disease [1]
We found that 66.7% (20/30) of long-term long COVID subjects versus 10% (2/20) of long-term control subjects were positive for Epstein–Barr virus (EBV) reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM
We found that 66.7% (6/9) of short-term long COVID subjects showed evidence of EBV reactivation based on positive titers for EBV EA-D IgG or EBV VCA IgM
Summary
It has been reported that about 30% of coronavirus disease 2019 (COVID-19) patients experience long-term symptoms following resolution of acute disease [1]. These symptoms include fatigue, brain fog, sleep difficulties, arthralgia, pharyngitis, myalgia, headaches, fever, gastrointestinal upset, and skin rashes with a variety of presentations [2,3,4,5]. It is known to have infected and generally become latent in more than 90% of the global population [7], including more than 95% of healthy adults [8] It is found at high rates in every region of the world. EBV can switch between lytic and latent phases of its life cycles in many patients [10]
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