Correlation of interleukin-6 with Epstein–Barr virus levels in COVID-19

Lehner, Georg; Klein, Sebastian; Zoller, Heinz; Peer, Andreas; Bellmann, Romuald; Joannidis, Michael

doi:10.1186/s13054-020-03384-6

Cited by 45 publications

(46 citation statements)

References 6 publications

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“…Latent EBV can be reactivated and become a lytic infection, expressing anti-VCA IgM 16 . In our study, 55.2% COVID-19 patients had positive VCA IgM antibody, indicating a high 17 also observed that 78% of COVID-19 patients in the intensive care unit (ICU) had EBV viremia, and 39% even above 1000 IU/ml. Moreover, the prevalence and levels of EBV viremia in COVID-19 patients were significantly higher than those in non-COVID-19 patients.…”

Section: Discussionsupporting

confidence: 68%

“…In the meantime, 2 COVID-19 patients had PCR Capillary Electrophoresis Fragment Analysis for the MP with negative result. Lehner et al 17 also observed that 78% of COVID-19 patients in the intensive care unit (ICU) had EBV viremia, and 39% even above 1000 IU/ml. Moreover, the prevalence and levels of EBV viremia in COVID-19 patients were significantly higher than those in non-COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

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Positive Epstein–Barr virus detection in coronavirus disease 2019 (COVID-19) patients

Chen

Song

Liu

et al. 2021

Sci Rep

112

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The objective of this study was to detect the Epstein–Barr virus (EBV) coinfection in coronavirus disease 2019 (COVID-19). In this retrospective single-center study, we included 67 COVID-19 patients with onset time within 2 weeks in Renmin Hospital of Wuhan University from January 9 to February 29, 2020. Patients were divided into EBV/SARS-CoV-2 coinfection group and SARS-CoV-2 infection alone group according to the serological results of EBV, and the characteristics differences between the two groups were compared. The median age was 37 years, with 35 (52.2%) females. Among these COVID-19 patients, thirty-seven (55.2%) patients were seropositive for EBV viral capsid antigen (VCA) IgM antibody. EBV/SARS-CoV-2 coinfection patients had a 3.09-fold risk of having a fever symptom than SARS-CoV-2 infection alone patients (95% CI 1.11–8.56; P = 0.03). C-reactive protein (CRP) (P = 0.02) and the aspartate aminotransferase (AST) (P = 0.04) in EBV/SARS-CoV-2 coinfection patients were higher than that in SARS-CoV-2 infection alone patients. EBV/SARS-CoV-2 coinfection patients had a higher portion of corticosteroid use than the SARS-CoV-2 infection alone patients (P = 0.03). We find a high incidence of EBV coinfection in COVID-19 patients. EBV/SARS-CoV-2 coinfection was associated with fever and increased inflammation. EBV reactivation may associated with the severity of COVID-19.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Positive Epstein–Barr virus detection in coronavirus disease 2019 (COVID-19) patients

Chen

Song

Liu

et al. 2021

Sci Rep

112

View full text Add to dashboard Cite

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“…HCMV invasion induces the cellular secretion of IFNs, but this strategy is far less effective than the strategy by which HCMV-encoded miR-US33as-5p targets IFNAR1, which abolishes primary immunomodulatory activity and reduces the release of ISGs. Interestingly, several recent research reported that the association between Covid-19, CMV and inflammageing which potentially leads to higher rates of Covid-19-related mortality ( 54 – 56 ). As miR-US33as-5p would also be active during latent infection, this may become relevant for patients who will experience an IFN response and reactivate CMV.…”

Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus miR-US33as-5p Targets IFNAR1 to Achieve Immune Evasion During Both Lytic and Latent Infection

Zhang

Song

et al. 2021

Front. Immunol.

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As the first line of antiviral defense, type I interferon (IFN) binds IFN receptor 1 (IFNAR1) and IFNAR2 to activate the Jak-STAT signal transduction pathway, producing IFN-stimulated genes (ISGs) to control viral infection. The mechanisms by which human cytomegalovirus (HCMV) counteracts the IFN pathway are only partially defined. We show that miR-US33as-5p encoded by HCMV is expressed in both lytic and latent infection. By analysis with RNA hybrid and screening with luciferase reporter assays, we identified IFNAR1 as a target of hcmv-miR-US33as-5p, which was further verified by examining the expression of two IFNAR1 mutants and the binding of IFNAR1 to miR-US33as-5p/miR-US33as-5p-M1/miR-US33as-5p-M2. We found that after the transfection of miR-US33as-5p mimics into different cell lines, the phosphorylation of downstream proteins and ISG expression were downregulated. Immunofluorescence showed that the miR-US33as-5p mimics also inhibited STAT1 translocation into the nucleus. Furthermore, we constructed HCMV with mutant miR-US33as-5p and determined that the mutation did not affect HCMV replication. We found that MRC-5/human foreskin fibroblast (HFF) cells infected with ΔmiRNA HCMV exhibited higher IFNAR1 and ISG expression and a reduced viral load in the presence of exogenous IFN than cells infected with WT HCMV did, confirming that the knockout of miR-US33as-5p impaired viral resistance to IFN. Finally, we tested the effect of ΔmiRNA HCMV on THP-1 and d-THP-1 cells, common in vitro models of latent infection and reactivation, respectively. Again, we found that cells infected with ΔmiRNA HCMV showed a reduced viral load in the presence of IFN than the control cells did, confirming that miR-US33as-5p also affects IFN resistance during both latency and reactivation. These results indicate a new microRNA (miRNA)-based immune evasion mechanism employed by HCMV to achieve lifelong infection.

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“…Since COVID-19 can cause cellular immune dysfunction [8], it can induce reactivation of latent viruses. Several studies have reported a high incidence of reactivated EBV in patients with COVID-19 [5,9]. In addition, these studies reported that COVID-19 was more severe in patients with EBV viremia.…”

Section: Discussionmentioning

confidence: 99%

The effect of Epstein – Barr Virus Viremia on the Progression to Severe COVID-19

Nahm

et al. 2021

Preprint

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BackgroundCoronavirus disease 2019 (COVID-19) can reactivate several latent viruses. Epstein–Barr virus (EBV) is a latent virus that is frequently reactivated in patients with critical illnesses. Recently, a high incidence of viremia has been reported in patients with severe COVID-19. However, it is unclear whether EBV viremia is the result of the severity of COVID-19 or if it affects the severity of COVID-19. Therefore, we conducted a cohort study to evaluate the effects of EBV on the progression of COVID-19.MethodsWe compared the incidence of EBV viremia between the COVID-19 and non-COVID-19 groups. Simplified Acute Physiology Score (SAPS) II and lymphocyte subsets were analyzed in patients with COVID-19. We also observed that patients with COVID-19 with EBV viremia progressed to severe pneumonia more often than those without EBV viremia.ResultsTwo hundred and nine patients with COVID-19 were compared with the control (non-COVID-19) group. The incidence of EBV viremia was lower in the COVID-19 group than in the non-COVID-19 group (17.1% vs. 26.8%, P=0.034). In the subgroup analysis of the COVID-19 group, the EBV-positive group patients had more severe COVID-19 infection than the EBV-negative group (SAPS II, 22.3 vs. 17.4%; P=0.002). However, progression to moderate or severe pneumonia in patients with mild COVID-19 was rather high in the EBV-negative group (not statistically significant), contrary to our expectations.ConclusionsAlthough the severity of COVID-19 may affect EBV viremia, there is no evidence that EBV viremia is a factor that exacerbates pneumonia in patients with early COVID-19. The effect of EBV viremia on prolonged organizing pneumonia should be further studied.

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Correlation of interleukin-6 with Epstein–Barr virus levels in COVID-19

Cited by 45 publications

References 6 publications

Positive Epstein–Barr virus detection in coronavirus disease 2019 (COVID-19) patients

Positive Epstein–Barr virus detection in coronavirus disease 2019 (COVID-19) patients

Human Cytomegalovirus miR-US33as-5p Targets IFNAR1 to Achieve Immune Evasion During Both Lytic and Latent Infection

The effect of Epstein – Barr Virus Viremia on the Progression to Severe COVID-19

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