“…While a limitation of our study is that we were not able to pinpoint the exact timing of EBV reactivation in the subjects we studied, given that we found similar reactivation frequencies in both long-term and short-term long COVID subjects, this indicates a likelihood that EBV reactivation occurs early in SARS-CoV-2 infection. Early EBV reactivation has been previously documented in several studies of COVID-19 ICU patients [ 20 , 21 , 22 , 23 ].…”
Section: Discussionmentioning
confidence: 96%
“…Paolucci et al (2020) tested 104 COVID-19 patients, 42 in an intensive care unit (ICU) and 62 in a sub-intensive care unit (SICU) in Italy and observed EBV reactivation in 95.2% (40/42) of the ICU patients and in 83.6% (51/61) of the SICU patients. They further determined that the median EBV DNA level in ICU patients was significantly higher than that of SICU patients [ 20 ]. A similar study in France found evidence of EBV reactivation in 82% (28/34) of COVID-19 ICU patients.…”
Section: Discussionmentioning
confidence: 99%
“…EBV can be serially reactivated as the result of a variety of stressor events [16]. Stress levels have been linked to the duration and intensity of reactivated EBV infections and variations of the steady-state expression of latent EBV [17,18] They further determined that the median EBV DNA level in ICU patients was significantly higher than that of SICU patients [20]. A similar study in France found evidence of EBV reactivation in 82% (28/34) of COVID-19 ICU patients.…”
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.
“…While a limitation of our study is that we were not able to pinpoint the exact timing of EBV reactivation in the subjects we studied, given that we found similar reactivation frequencies in both long-term and short-term long COVID subjects, this indicates a likelihood that EBV reactivation occurs early in SARS-CoV-2 infection. Early EBV reactivation has been previously documented in several studies of COVID-19 ICU patients [ 20 , 21 , 22 , 23 ].…”
Section: Discussionmentioning
confidence: 96%
“…Paolucci et al (2020) tested 104 COVID-19 patients, 42 in an intensive care unit (ICU) and 62 in a sub-intensive care unit (SICU) in Italy and observed EBV reactivation in 95.2% (40/42) of the ICU patients and in 83.6% (51/61) of the SICU patients. They further determined that the median EBV DNA level in ICU patients was significantly higher than that of SICU patients [ 20 ]. A similar study in France found evidence of EBV reactivation in 82% (28/34) of COVID-19 ICU patients.…”
Section: Discussionmentioning
confidence: 99%
“…EBV can be serially reactivated as the result of a variety of stressor events [16]. Stress levels have been linked to the duration and intensity of reactivated EBV infections and variations of the steady-state expression of latent EBV [17,18] They further determined that the median EBV DNA level in ICU patients was significantly higher than that of SICU patients [20]. A similar study in France found evidence of EBV reactivation in 82% (28/34) of COVID-19 ICU patients.…”
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.
“…Liu et al found a decrease in CD8 count in the laboratory examination of 12 COVID-19 patients 22 . Paolucci et al 23 found a correlation between reduced CD8 + T cells and EBV DNA levels and COVID-19 severity. In our study, we also noted that CD8 count was lower in our EBV/SARS-CoV-2 coinfection patients, which neared statistical significance (P = 0.07).…”
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.
“…4 c, Supplementary Table 4 ), including an EBV specific virus infection protein network. Remarkably, EBV reactivation and increased EBV DNA load have recently been reported in severe SARS-CoV2 patients with impaired lymphocyte subpopulation counts [ 73 ]. Fig.…”
Background
Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.
Methods
Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes.
Results
Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections.
Conclusions
Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.
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