Skip to content
2000
Volume 26, Issue 10
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

Coronavirus disease 2019 (COVID-19), which led to a global pandemic causing millions of deaths, is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). While previous research on COVID-19 has primarily utilized nasal swabs and blood samples, these do not provide comprehensive insights into all the organ systems affected by the infection. A recent study by Topper addressed this gap by analyzing both nasal samples and autopsy tissues from SARS-CoV-2-infected individuals. Their findings highlight a significant role of mitochondrial damage pathways and RAAS overactivation in contributing to the severity of SARS-CoV-2 infections. Importantly, targeting mitochondrial dysfunction and RAAS overactivation pathways may offer promising and specific druggable targets for treating COVID-19 patients.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdt/10.2174/0113894501387212250525161808
2025-05-27
2025-11-05

  • From This Site

    /content/journals/cdt/10.2174/0113894501387212250525161808
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. JhaP. BrownP.E. AnsumanaR. Counting the global COVID-19 dead.Lancet2022399103391937193810.1016/S0140‑6736(22)00845‑535533709
     [Google Scholar]
  2. NgD.L. GranadosA.C. SantosY.A. ServellitaV. GoldgofG.M. MeydanC. Sotomayor-GonzalezA. LevineA.G. BalcerekJ. HanL.M. AkagiN. TruongK. NeumannN.M. NguyenD.N. BapatS.P. ChengJ. MartinC.S.S. FedermanS. FooxJ. GopezA. LiT. ChanR. ChuC.S. WablC.A. GliwaA.S. ReyesK. PanC.Y. GuevaraH. WadfordD. MillerS. MasonC.E. ChiuC.Y. A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood.Sci. Adv.202176eabe598410.1126/sciadv.abe598433536218
     [Google Scholar]
  3. LamersM.M. HaagmansB.L. SARS-CoV-2 pathogenesis.Nat Rev Microbiol20222027028410.1038/s41579‑022‑00713‑0
     [Google Scholar]
  4. HuB. HuangS. YinL. The cytokine storm and COVID-19.J. Med. Virol.202193125025610.1002/jmv.2623232592501
     [Google Scholar]
  5. ZanzaC. RomenskayaT. ManettiA. FranceschiF. La RussaR. BertozziG. MaieseA. SavioliG. VolonninoG. LonghitanoY. Cytokine storm in COVID-19: Immunopathogenesis and therapy.Medicina202258214410.3390/medicina5802014435208467
     [Google Scholar]
  6. TangL. YinZ. HuY. MeiH. Controlling cytokine storm is vital in COVID-19.Front. Immunol.20201157099310.3389/fimmu.2020.57099333329533
     [Google Scholar]
  7. TopperM.J. GuarnieriJ.W. HaltomJ.A. ChadburnA. CopeH. FrereJ. AnJ. BorczukA. SinhaS. KimJ. ParkJ. ButlerD. MeydanC. FooxJ. BramY. RichardS.A. EpsiN.J. AganB. ChenowethJ.G. SimonsM.P. TribbleD. BurgessT. DalgardC. HeiseM.T. MoormanN.J. BaxterV.K. MaddenE.A. Taft-BenzS.A. AndersonE.J. SandersW.A. DickmanderR.J. BeigelK. WidjajaG.A. JanssenK.A. LieT. MurdockD.G. AngelinA. Soto AlbrechtY.E. OlaliA.Z. CenZ. DybasJ. PriebeW. EmmettM.R. BestS.M. Kelsey JohnsonM. TrovaoN.S. ClarkK.B. ZaksasV. MellerR. GrabhamP. SchislerJ.C. Moraes-VieiraP.M. PollettS. MasonC.E. Syrkin WurteleE. TaylorD. SchwartzR.E. BeheshtiA. WallaceD.C. BaylinS.B. Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.Proc. Natl. Acad. Sci. USA202412149e240196812110.1073/pnas.240196812139602262
     [Google Scholar]
  8. WilczynskiS.A. WenceslauC.F. McCarthyC.G. WebbR.C. A cytokine/bradykinin storm comparison: What is the relationship between hypertension and COVID-19?Am. J. Hypertens.202134430430610.1093/ajh/hpaa21733877321
     [Google Scholar]
  9. de las HerasN. Martín GiménezV.M. FerderL. ManuchaW. LaheraV. Implications of oxidative stress and potential role of mitochondrial dysfunction in COVID-19: Therapeutic effects of vitamin D.Antioxidants20209989710.3390/antiox909089732967329
     [Google Scholar]
  10. BusseP.J. ChristiansenS.C. Hereditary Angioedema.N. Engl. J. Med.2020382121136114810.1056/NEJMra180801232187470
     [Google Scholar]
  11. DuarteM. PelorossoF. NicolosiL.N. Victoria SalgadoM. VetulliH. AquieriA. AzzatoF. CastroM. CoyleJ. DavolosI. CriadoI.F. GregoriR. MastrodonatoP. RubioM.C. SarquisS. WahlmannF. RothlinR.P. Telmisartan for treatment of Covid-19 patients: An open multicenter randomized clinical trial.EClinicalMedicine20213710096210.1016/j.eclinm.2021.10096234189447
     [Google Scholar]
  12. NiW. YangX. YangD. BaoJ. LiR. XiaoY. HouC. WangH. LiuJ. YangD. XuY. CaoZ. GaoZ. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19.Crit Care202024142210.1186/s13054‑020‑03120‑032660650
     [Google Scholar]
  13. BourgonjeA.R. AbdulleA.E. TimensW. HillebrandsJ.L. NavisG.J. GordijnS.J. BollingM.C. DijkstraG. VoorsA.A. OsterhausA.D.M.E. van der VoortP.H.J. MulderD.J. van GoorH. Angiotensin-converting enzyme 2 ( ACE2 ), SARS-CoV -2 and the pathophysiology of coronavirus disease 2019 ( COVID -19).J. Pathol.2020251322824810.1002/path.547132418199
     [Google Scholar]
  14. QudusM.S. TianM. SirajuddinS. LiuS. AfaqU. WaliM. LiuJ. PanP. LuoZ. ZhangQ. YangG. WanP. LiY. WuJ. The roles of critical pro-inflammatory cytokines in the drive of cytokine storm during SARS-CoV-2 infection.J. Med. Virol.2023954e2875110.1002/jmv.2875137185833
     [Google Scholar]
  15. RamosS.G. RattisB.A.C. OttavianiG. CelesM.R.N. DiasE.P. ACE2 down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among COVID-19 patients.Am. J. Pathol.202119171154116410.1016/j.ajpath.2021.04.01033964216
     [Google Scholar]
  16. WilkersonR.G. MoellmanJ.J. Hereditary angioedema.Emerg Med Clin North Am20224019911810.1016/j.emc.2021.09.00234782094
     [Google Scholar]
  17. ShouS. LiuM. YangY. KangN. SongY. TanD. LiuN. WangF. LiuJ. XieY. Animal models for COVID-19: Hamsters, mouse, ferret, mink, tree shrew, and non-human primates.Front. Microbiol.20211262655310.3389/fmicb.2021.62655334531831
     [Google Scholar]
  18. WangX. ChenZ. NieD. ZengX. ZhongM. LiuX. ZhongS. WangL. LiaoZ. ChenC. LiY. ZengC. CASP1 is a target for combination therapy in pancreatic cancer.Eur. J. Pharmacol.202396117617510.1016/j.ejphar.2023.17617537949157
     [Google Scholar]
  19. LiuX. YangN. TangJ. LiuS. LuoD. DuanQ. WangX. Downregulation of angiotensin-converting enzyme 2 by the neuraminidase protein of influenza A (H1N1) virus.Virus Res.2014185647110.1016/j.virusres.2014.03.01024662240
     [Google Scholar]
  20. YangP. GuH. ZhaoZ. WangW. CaoB. LaiC. YangX. ZhangL. DuanY. ZhangS. ChenW. ZhenW. CaiM. PenningerJ.M. JiangC. WangX. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury.Sci. Rep.201441702710.1038/srep0702725391767
     [Google Scholar]
  21. BanuN. PanikarS.S. LealL.R. LealA.R. Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to macrophage activation syndrome: Therapeutic implications.Life Sci.202025611790510.1016/j.lfs.2020.11790532504757
     [Google Scholar]
  22. HampshireA. AzorA. AtchisonC. TrenderW. HellyerP.J. GiunchigliaV. HusainM. CookeG.S. CooperE. LoundA. DonnellyC.A. Chadeau-HyamM. WardH. ElliottP. Cognition and memory after Covid-19 in a large community sample.N. Engl. J. Med.2024390980681810.1056/NEJMoa231133038416429
     [Google Scholar]
  23. NoonongK. ChatatikunM. SurinkaewS. KotepuiM. HossainR. BunluepuechK. NoothongC. TedasenA. KlangbudW.K. ImaiM. KawakamiF. KuboM. KitagawaY. IchikawaH. KanekuraT. SukatiS. SomsakV. UdomwechL. IchikawaT. NissapatornV. TangpongJ. IndoH.P. MajimaH.J. Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis.Front. Immunol.202314127500110.3389/fimmu.2023.127500138187378
     [Google Scholar]
/content/journals/cdt/10.2174/0113894501387212250525161808
Loading
RAAS Overactivation and Mitochondrial Damage Signaling as Key Players in Lethal COVID-19
Curr Drug Targets 26, 722 (2025); https://doi.org/10.2174/0113894501387212250525161808
/content/journals/cdt/10.2174/0113894501387212250525161808
/content/journals/cdt/10.2174/0113894501387212250525161808
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Aldosterone, COVID-19; mitochondrial damage; mitochondrial dysfunction; RAAS overactivation; SARS-CoV-2

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test