Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild disease course, 2023, Hoeggerl+

SNT Gatchaman

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Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course
Hoeggerl, Alexandra Domnica; Nunhofer, Verena; Lauth, Wanda; Badstuber, Natalie; Held, Nina; Zimmermann, Georg; Grabmer, Christoph; Weidner, Lisa; Jungbauer, Christof; Lindlbauer, Nadja; Neureiter, Heidrun; Ortner, Tuulia; Flamm, Maria; Osterbrink, Jürgen; Rohde, Eva; Laner-Plamberger, Sandra

Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aims of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS.

The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed.

Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups.

Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.

Link | PDF (BMC Infectious Diseases)
 
In total, 400 seropositive blood donors willing to participate in this longitudinal study were included after signing informed consent between December 2020 and September 2022. As depicted in Fig. 1, several serum and plasma samples of each individual were analysed at different points in time. Besides the samples from the initial SARS-CoV-2 seropositive blood donation (0 months), which induced the participation in our study, we examined further samples collected 3, 6 and 9 months after the initial blood donation. In addition, we also used serum and plasma samples of the participants collected in the course of a voluntary blood donation in the pre-pandemic time between January and September 2019.
 
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