Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder

Chen, Tsung‐Hsien; Chang, Chia-Jung; Hung, Peir-Haur

doi:10.3390/ijms24098034

Cited by 35 publications

(18 citation statements)

References 205 publications

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“…The m -Dys-induced exercise intolerance with elevated arterial blood lactate levels and reduced fatty acid β-oxidation rates is a major health issue in PASC 173 . These patients complain about chronic fatigue during exercise, despite no obvious heart or lung abnormalities 174 .…”

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

show abstract

“…ATP5F1A (ATP Synthase F1 Subunit Alpha) is a subunit of the mitochondrial ATP Synthase protein complex, which is crucial in the process of oxidative phosphorylation (Guarnieri et al, 2022). Chen et al (2023) previously discussed how the lack of components of the ATP Synthase protein complex may cause defects in the complex, jeopardizing its functionality. While the overall expression of ATP5F1A across all naive B-cells is equal between healthy donors and moderately ill patients, the lower average detection in the individual cells of the latter indicates a lower proportion of individual cells in which ATP5F1A is present.…”

Section: Resultsmentioning

confidence: 99%

Differential detection workflows for multi-sample single-cell RNA-seq data

Gilis,

Perin,

Malfait

et al. 2023

Preprint

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In single-cell transcriptomics, differential gene expression (DE) analyses typically focus on testing differences in the average expression of genes between cell types or conditions of interest. Single-cell transcriptomics, however, also has the promise to prioritise genes for which the expression differ in other aspects of the distribution. Here we develop a workflow for assessing differential detection (DD), which tests for differences in the average fraction of samples or cells in which a gene is detected. After benchmarking eight different DD data analysis strategies, we provide a unified workflow for jointly assessing DE and DD. Using simulations and two case studies, we show that DE and DD analysis provide complementary information, both in terms of the individual genes they report and in the functional interpretation of those genes.

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“…Dysfunctional mitochondria can lead to reactive oxygen species accumulation, exacerbating cell death, inflammation and subsequent tissue damage. 32 This downregulation could also impact the intensity of apoptosis and autophagy — the key regulators of cell survival and immune responses. Investigating the virus’s direct or immune response-mediated effect on mitochondria is crucial.…”

Section: Discussionmentioning

confidence: 99%

Systems-wide view of host-pathogen interactions across COVID-19 severities using integrated omics analysis

Singh,

Pyati,

Rubi

et al. 2024

iScience

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Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder

Cited by 35 publications

References 205 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

Differential detection workflows for multi-sample single-cell RNA-seq data

Systems-wide view of host-pathogen interactions across COVID-19 severities using integrated omics analysis

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