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BMC Infect Dis
. 2023 Nov 15;23(1):800.
doi: 10.1186/s12879-023-08820-w. Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course
Alexandra Domnica Hoeggerl # 1 , Verena Nunhofer # 1 , Wanda Lauth 2 3 , Natalie Badstuber 4 , Nina Held 1 , Georg Zimmermann 2 3 , Christoph Grabmer 1 , Lisa Weidner 5 , Christof Jungbauer 5 , Nadja Lindlbauer 1 , Heidrun Neureiter 1 , Tuulia Ortner 4 , Maria Flamm 6 , Jürgen Osterbrink 7 , Eva Rohde 1 8 , Sandra Laner-Plamberger 9
Affiliations
Purpose: 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. Aim 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.
Methods: 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.
Results: 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.
Conclusion: Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.
Keywords: COVID-19; EBV; Long-COVID; Post-COVID-19-syndrome (PCS); SARS-CoV-2.
. 2023 Nov 15;23(1):800.
doi: 10.1186/s12879-023-08820-w. Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course
Alexandra Domnica Hoeggerl # 1 , Verena Nunhofer # 1 , Wanda Lauth 2 3 , Natalie Badstuber 4 , Nina Held 1 , Georg Zimmermann 2 3 , Christoph Grabmer 1 , Lisa Weidner 5 , Christof Jungbauer 5 , Nadja Lindlbauer 1 , Heidrun Neureiter 1 , Tuulia Ortner 4 , Maria Flamm 6 , Jürgen Osterbrink 7 , Eva Rohde 1 8 , Sandra Laner-Plamberger 9
Affiliations
- PMID: 37968601
- DOI: 10.1186/s12879-023-08820-w
Purpose: 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. Aim 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.
Methods: 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.
Results: 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.
Conclusion: Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.
Keywords: COVID-19; EBV; Long-COVID; Post-COVID-19-syndrome (PCS); SARS-CoV-2.