Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa

Hannestad, Ulf; Apostolou, Eirini; Sjögren, Per; Bragée, Björn; Polo, Olli; Bertilson, Bo Christer; Rosén, Anders

doi:10.3389/fmed.2023.1208181

Cited by 4 publications

(2 citation statements)

References 27 publications

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“…An exhausted dysfunctional antiviral immune response from SARS-CoV-2 infection could trigger reactivation of human adenovirus with a sequelae effect of ME/CFS in PASC patients 270 . Immuno-compromised individuals susceptible to HHV infection are at higher risk for SARS-CoV-2 infection, PASC, are vulnerable to develop virus‐associated cancers.…”

Section: Lon-covid/pasc: Virus-induced Human Metabolic Reprogramming ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

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Section: Lon-covid/pasc: Virus-induced Human Metabolic Reprogramming ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

View full text Add to dashboard Cite

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“…Multiple viral infections have long been implicated in the onset and chronicity of ME/CFS pathology, but no single pathogen has been identified. Viruses predominantly linked to ME/CFS belong to the family of herpesviruses that include large double-stranded DNA viruses, notably Epstein-Barr virus (EBV) [51][52][53][54][55][56][57], human herpesvirus-6 (HHV-6) [58][59][60], HHV-7 [58,59], herpes simplex virus-1 (HSV-1), and HSV-2 [3,7,61]. Herpesviruses are common infectious agents within the general population that establish life-long latency in humans.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses

Apostolou,

Rosén

2024

J Intern Med

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post‐exertional malaise, and cognitive disturbances—among a spectrum of symptoms—that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent–lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses—particularly Epstein–Barr virus—may employ in long‐term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.

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The Mouth as a Site of SARS-CoV-2 Infection

Atyeo,

Perez,

Matuck

et al. 2024

Curr Oral Health Rep

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Purpose of Review During the height of the coronavirus pandemic, the oral cavity was recognized as a critically important site for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The purpose of this review is to analyze the literature surrounding SARS-CoV-2 entry, replication, and transmission and the resulting impact on host tissues in the oral cavity. Recent Findings The detection of viral genetic material in saliva allows for widespread surveillance testing and emphasizes the importance of viral transmission through shed in saliva. As the cohort of patients who have recovered from acute SARS-CoV-2 infection grows, several questions remain about the long-term impacts of viral infection on the oral tissues, including whether the oral cavity may serve as a persistent viral reservoir. Therefore, a thorough understanding of the viral life cycle in the diverse tissues of the oral cavity is warranted. We conclude with a broad outlook on the long-term effects of SARS-CoV-2 infection in the oral cavity and how these effects may relate to the post-acute coronavirus syndrome sequelae experienced by recovered patients. Summary SARS-CoV-2 can enter and replicate in the oral cavity and be spread between individuals via shed in saliva. Several acute oral manifestations of infection have been reported, and the lingering effects of infection on oral tissues are an area of ongoing investigation.

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Post-COVID sequelae effect in chronic fatigue syndrome: SARS-CoV-2 triggers latent adenovirus in the oral mucosa

Cited by 4 publications

References 27 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses

The Mouth as a Site of SARS-CoV-2 Infection

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