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Prognostic potential of circulating cell free mitochondrial DNA levels in COVID-19 patients

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Abstract

Background

In viral infections, mitochondria act as one of the main hubs of the pathogenesis. Recent findings present new insights into the potential role of circulating cell-free mitochondrial DNA (ccf-mtDNA) in COVID-19 pathogenesis by the induction of immune response and aggressive cytokine storm in SARS-CoV-2 infection.

Methods and results

The levels of ccf-mtDNA were investigated in 102 hospitalized patients with COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong association between the levels of ccf-mtDNA and and mortality, ICU admission, and intubation. Also, our findings highlighted the pivotal role of comorbidities as a risk factor for COVID-19 mortality and severity.

Conclusion

Higher levels of ccf-mtDNA can serve as a potential early indicator for progress and poor prognosis of COVID-19.

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Data Availability

Data and materials are available upon request.

Abbreviations

COVID-19:

Coronavirus disease 2019

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus-2

DAMP:

Damage-associated molecular pattern

mt-DAMP:

Mitochondrial damage-associated molecular pattern

ccf-mtDNA:

Circulating cell-free mitochondrial DNA

ICU:

Intensive care unit

RT-PCR:

Reverse transcription polymerase chain reaction

CYB:

Cytochrome b

COX3:

Cytochrome c oxidase subunit III

SD:

Standard deviation

CVD:

Cardiovascular diseases

HTN:

Hypertension

DM type2:

Diabetes mellitus type 2

ROC:

Receiver operating characteristic

TLR9:

Toll-like receptors 9

cGAS-STING:

Cyclic guanosine monophosphate -adenosine monophosphate synthase stimulator of interferon genes

OS:

Oxidative stress

References

  1. Wang C, Horby PW, Hayden FG, Gao GF (2020) A novel coronavirus outbreak of global health concern. The Lancet 395(10223):470–473

    Article  CAS  Google Scholar 

  2. Lynch SM, Guo G, Gibson DS, Bjourson AJ, Rai TS (2021) Role of senescence and aging in SARS-CoV-2 infection and COVID-19 disease. Cells 10(12):3367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mahmoodpoor A, Sanaie S, Ostadi Z et al (2022) Roles of mitochondrial DNA in dynamics of the immune response to COVID-19. Gene 836:146681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mahmoodpoor A, Sanaie S, Roudbari F, Sabzevari T, Sohrabifar N, Kazeminasab S (2022) Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity. Gene 811:146069

    Article  CAS  PubMed  Google Scholar 

  5. Bhowal C, Ghosh S, Ghatak D, De R (2023) Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight. Mol Cell Biochem 478(6):1325–1343

    Article  CAS  PubMed  Google Scholar 

  6. West AP, Shadel GS, Ghosh S (2011) Mitochondria in innate immune responses. Nat Rev Immunol 11(6):389–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Piantadosi CA (2020) Mitochondrial DNA, oxidants, and innate immunity. Free Radic Biol Med 152:455–461

    Article  CAS  PubMed  Google Scholar 

  8. Scozzi D, Cano M, Ma L et al (2021) Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19. JCI Insight. ;6(4)

  9. Herst PM, Rowe MR, Carson GM, Berridge MV (2017) Functional mitochondria in health and disease. Front Endocrinol 8:296

    Article  Google Scholar 

  10. Moro L (2020) Mitochondria at the Crossroads of Physiology and Pathology. MDPI, p 1971

  11. Gallucci S, Maffei ME (2017) DNA sensing across the tree of life. Trends Immunol 38(10):719–732

    Article  CAS  PubMed  Google Scholar 

  12. Valdes-Aguayo JJ, Garza-Veloz I, Badillo-Almaraz JI et al (2021) Mitochondria and mitochondrial DNA: key elements in the pathogenesis and exacerbation of the inflammatory state caused by COVID-19. Medicina 57(9):928

    Article  PubMed  PubMed Central  Google Scholar 

  13. Itagaki K, Kaczmarek E, Lee YT et al (2015) Mitochondrial DNA released by trauma induces neutrophil extracellular traps. PLoS ONE 10(3):e0120549

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hepokoski ML, Odish M, Lam MT et al (2022) Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions. Am J Physiology-Lung Cell Mol Physiol 323(1):L84–L92

    Article  CAS  Google Scholar 

  15. Leonard A, Rolfsen M, Ix J et al (2022) Circulating, cell-free mitochondrial DNA Marks Disease Severity in COVID-19. B45 PREDICTING COVID SEVERITY AND OUTCOMES. American Thoracic Society, pp A2927–A

  16. Aswani A, Manson J, Itagaki K et al (2018) Scavenging circulating mitochondrial DNA as a potential therapeutic option for multiple organ dysfunction in trauma hemorrhage. Front Immunol 9:891

    Article  PubMed  PubMed Central  Google Scholar 

  17. Alyammahi SK, Abdin SM, Alhamad DW, Elgendy SM, Altell AT, Omar HA (2021) The dynamic association between COVID-19 and chronic disorders: an updated insight into prevalence, mechanisms and therapeutic modalities. Infect Genet Evol 87:104647

    Article  CAS  PubMed  Google Scholar 

  18. Chatterjee S, Nalla LV, Sharma M et al (2023) Association of COVID-19 with Comorbidities: an update. ACS Pharmacol Translational Sci 6(3):334–354

    Article  CAS  Google Scholar 

  19. Reyna-Villasmil E, Caponcello MG, Maldonado N et al (2022) Association of Patients’ epidemiological characteristics and comorbidities with severity and related mortality risk of SARS-CoV-2 infection: results of an umbrella systematic review and Meta-analysis. Biomedicines 10(10):2437

    Article  PubMed  PubMed Central  Google Scholar 

  20. Saleh J, Peyssonnaux C, Singh KK, Edeas M (2020) Mitochondria and microbiota dysfunction in COVID-19 pathogenesis. Mitochondrion 54:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Valdés-Aguayo JJ, Garza-Veloz I, Vargas-Rodríguez JR et al (2021) Peripheral blood mitochondrial DNA levels were modulated by SARS-CoV-2 infection severity and its lessening was associated with mortality among hospitalized patients with COVID-19. Front Cell Infect Microbiol 11:1285

    Article  Google Scholar 

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Acknowledgements

Not applicable.

Funding

This work was supported by Tabriz University of Medical Sciences [grant code 68454].

Author information

Author notes

  1. Nasim Sohrabifar and Somayeh Kazeminasab contributed equally as the corresponding author.

Authors and Affiliations

  1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ata Mahmoodpoor

  2. Department of Anesthesiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Mojtaba Mohammadzadeh, Rogayyeh Asghari, Majid Tagizadeh & Mansour Rezayi

  3. Anesthesiology Departments, Al Zahra Hospital, Dubai, UAE

    Afshin Iranpour

  4. Department of Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran

    Aynour Jalali Pahnvar

  5. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Babak Emamalizadeh & Somayeh Kazeminasab

  6. Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nasim Sohrabifar

  7. Sadr Laboratories Group, Medical Genetics Laboratory, Tabriz, Iran

    Somayeh Kazeminasab

Authors
  1. Ata Mahmoodpoor
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  2. Mojtaba Mohammadzadeh
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  8. Babak Emamalizadeh
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Contributions

A.M. administered the project and provided final approval of the manuscript, M.M. and R.A. helped with sample collection,M.T. and A.I. revised the manuscript, M.R. and A.J.P. reviewed and edited the draft, B.E. performed methodology and validated data, N.S. and S.K. conceived the study, performed the statistical analysis and wrote the original draft.

Corresponding authors

Correspondence to Nasim Sohrabifar or Somayeh Kazeminasab.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Tabriz University of medical sciences (IR.TBZMED.REC.1399.542). All participants signed the informed consent.

Consent for publication

Consent to publish had been obtained from all participants, and all authors agreed to publish this paper.

Competing interests

The authors declare no competing interests.

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Figure S1

: A) Association of ccf-mtDNA copy number with mortality in patients with COVID-19. B) Receiver operating characteristic (ROC) curves and predictive value of ccf-mtDNA copy number in predicting mortality

Figure S2: A) Association of ccf-mtDNA copy number with ICU admission in patients with COVID-19. B) Receiver operating characteristic (ROC) curves and predictive value of ccf-mtDNA copy number in predicting ICU admission

Figure S3: A) Association of ccf-mtDNA copy number with intubation in patients with COVID-19. B) Receiver operating characteristic (ROC) curves and predictive value of ccf-mtDNA copy number in predicting intubation.

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Mahmoodpoor, A., Mohammadzadeh, M., Asghari, R. et al. Prognostic potential of circulating cell free mitochondrial DNA levels in COVID-19 patients. Mol Biol Rep 50, 10249–10255 (2023). https://doi.org/10.1007/s11033-023-08841-3

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  • DOI: https://doi.org/10.1007/s11033-023-08841-3

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