Gut-brain communication in COVID-19: molecular mechanisms, mediators, biomarkers, and therapeutics

References

• Alimohamadi Y, Sepandi M, Taghdir M, et al. Determine the most common clinical symptoms in COVID-19 patients: a systematic review and meta-analysis. J Prev Med Hyg. 2020;61(3):E304–E12. Epub 2020/11/06. PubMed PMID: 33150219; PubMed Central PMCID: PMCPMC7595075.
   PubMedGoogle Scholar
• Nooti SK, Rai V, and Singh H, et al. Strokes, neurological, and neuropsychiatric disorders in COVID-19. In: Sobti RC, Dhalla NS, Watanabe M, Sobti A, editors. Delineating Health and Health System: Mechanistic Insights into Covid 19 Complications. New York, NY: Springer; 2021. p. 209–231. doi:10.1007/978-981-16-5105-2_12.
   Google Scholar
• Dixon BE, Wools-Kaloustian K, Fadel WF, et al. Symptoms and symptom clusters associated with SARS-CoV-2 infection in community-based populations: results from a statewide epidemiological study. medRxiv. 2020. Epub 2020/10/28. PubMed PMID: 33106813; PubMed Central PMCID: PMCPMC7587833.
   Google Scholar
• Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683–690. Epub 2020/04/11. PubMed PMID: 32275288; PubMed Central PMCID: PMCPMC7149362.
   PubMed Web of Science ®Google Scholar
• Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020;5(3):279–284. Epub 2020/07/04. PubMed PMID: 32616524; PubMed Central PMCID: PMCPMC7371480.
   PubMedGoogle Scholar
• MacDougall M, El-Hajj Sleiman J, Beauchemin P, et al. SARS-CoV-2 and multiple sclerosis: potential for disease exacerbation. Front Immunol. 2022;13:871276. Epub 2022/05/17. PubMed PMID: 35572514; PubMed Central PMCID: PMCPMC9102605.
   PubMed Web of Science ®Google Scholar
• Bellucci G, Rinaldi V, Buscarinu MC, et al. Multiple sclerosis and SARS-CoV-2: has the interplay started?. Front Immunol. 2021;12:755333. Epub 2021/10/15. PubMed PMID: 34646278; PubMed Central PMCID: PMCPMC8503550.
   PubMed Web of Science ®Google Scholar
• Michelena G, Casas M, Eizaguirre MB, et al. inverted question mark Can COVID-19 exacerbate multiple sclerosis symptoms? A case series analysis. Mult Scler Relat Disord. 2022;57:103368. Epub 2022/02/16. PubMed PMID: 35158474.
   PubMed Web of Science ®Google Scholar
• Montalvan V, Lee J, Bueso T, et al. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clin Neurol Neurosurg. 2020;194:105921. Epub 2020/05/19. PubMed PMID: 32422545; PubMed Central PMCID: PMCPMC7227498.
   PubMed Web of Science ®Google Scholar
• Andalib S, Biller J, Di Napoli M, et al. Peripheral Nervous System Manifestations Associated with COVID-19. Curr Neurol Neurosci Rep. 2021;21(3):9. Epub 2021/02/16. PubMed PMID: 33586020; PubMed Central PMCID: PMCPMC7882462.
   PubMed Web of Science ®Google Scholar
• Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997–1001. Epub 2020/04/04. PubMed PMID: 32241899; PubMed Central PMCID: PMCPMC7316116.
   PubMed Web of Science ®Google Scholar
• Villapol S. Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome. Transl Res. 2020;226:57–69. Epub 2020/08/23. PubMed PMID: 32827705; PubMed Central PMCID: PMCPMC7438210.
   PubMed Web of Science ®Google Scholar
• Llorens S, Nava E, Munoz-Lopez M, et al. Neurological symptoms of COVID-19: the zonulin hypothesis. Front Immunol. Epub 2021/05/14. PubMed PMID: 33981312; PubMed Central PMCID: PMCPMC8107207. 2021; 12: 665300.
   PubMed Web of Science ®Google Scholar
• Rezaeitalab F, Jamehdar SA, Sepehrinezhad A, et al. Detection of SARS-coronavirus-2 in the central nervous system of patients with severe acute respiratory syndrome and seizures. J Neurovirol. 2021;27:(2) 348–353. Epub 2021/03/03. PubMed PMID: 33650073; PubMed Central PMCID: PMCPMC7920401.
   PubMed Web of Science ®Google Scholar
• Galanopoulos M, Gkeros F, Doukatas A, et al. COVID-19 pandemic: Pathophysiology and manifestations from the gastrointestinal tract. World J Gastroenterol. 2020;26(31):4579–4588. Epub 2020/09/05. PubMed PMID: 32884218; PubMed Central PMCID: PMCPMC7445869.
   PubMed Web of Science ®Google Scholar
• Ebrahim Nakhli R, Shanker A, Sarosiek I, et al. Gastrointestinal symptoms and the severity of COVID-19: Disorders of gut-brain interaction are an outcome. Epub 2022/04/07. PubMed PMID: 35383423; PubMed Central PMCID: PMCPMC9115309 Neurogastroenterol Motil. 2022;e14368.
   PubMed Web of Science ®Google Scholar
• Troisi J, Venutolo G, Pujolassos Tanya M, et al. COVID-19 and the gastrointestinal tract: source of infection or merely a target of the inflammatory process following SARS-CoV-2 infection?. World J Gastroenterol. 2021;27(14):1406–1418. Epub 2021/04/30. PubMed PMID: 33911464; PubMed Central PMCID: PMCPMC8047540.
   PubMed Web of Science ®Google Scholar
• Premraj L, Kannapadi NV, Briggs J, et al. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: a meta-analysis. J Neurol Sci. 2022;434:120162. Epub 2022/02/06. PubMed PMID: 35121209; PubMed Central PMCID: PMCPMC8798975.
   PubMed Web of Science ®Google Scholar
• Blackett JW, Wainberg M, Elkind MSV, et al. Potential long coronavirus disease 2019 gastrointestinal symptoms 6 months after coronavirus infection are associated with mental health symptoms. Gastroenterology. 2022;162(2):648–50 e2. Epub 2021/11/04. PubMed PMID: 34728186; PubMed Central PMCID: PMCPMC8556689.
   PubMed Web of Science ®Google Scholar
• Douaud G, Lee S, Alfaro-Almagro F, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022;604(7907):697–707. Epub 2022/03/08. PubMed PMID: 35255491; PubMed Central PMCID: PMCPMC9046077.
   PubMed Web of Science ®Google Scholar
• Poloni TE, Medici V, Moretti M, et al. COVID-19-related neuropathology and microglial activation in elderly with and without dementia. Brain Pathol. 2021;31(5):e12997. Epub 2021/06/20. PubMed PMID: 34145669; PubMed Central PMCID: PMCPMC8412067.
   PubMed Web of Science ®Google Scholar
• Generoso JS, Barichello de Quevedo JL, Cattani M, et al. Neurobiology of COVID-19: how can the virus affect the brain?. Braz J Psychiatry. 2021;43(6):650–664. Epub 2021/02/20. PubMed PMID: 33605367; PubMed Central PMCID: PMCPMC8639021.
   PubMedGoogle Scholar
• Radnis C, Qiu S, Jhaveri M, et al. Radiographic and clinical neurologic manifestations of COVID-19 related hypoxemia. J Neurol Sci. 2020;418:117119. Epub 2020/09/2. PubMed PMID: 32957036; PubMed Central PMCID: PMCPMC7474836.
   PubMed Web of Science ®Google Scholar
• Carabotti M, Scirocco A, Maselli MA, et al. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28(2):203–209. Epub 2015/04/02. PubMed PMID: 25830558; PubMed Central PMCID: PMCPMC4367209.
   PubMed Web of Science ®Google Scholar
• Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533. Epub 2016/08/20. PubMed PMID: 27541692; PubMed Central PMCID: PMCPMC4991899.
   PubMed Web of Science ®Google Scholar
• Mayer EA. Gut feelings: the emerging biology of gut-brain communication.Nat Rev Neurosci.2011;12(8):453–466. Epub 2011/07/14. PubMed PMID: 21750565; PubMed Central PMCID: PMCPMC3845678.
   PubMed Web of Science ®Google Scholar
• Barrett E, Ross RP, O’Toole PW, et al. gamma-aminobutyric acid production by culturable bacteria from the human intestine.J Appl Microbiol.2012;113(2):411–417. Epub 2012/05/23. PubMed PMID: 22612585.
   PubMed Web of Science ®Google Scholar
• Effenberger M, Grabherr F, Mayr L, et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut. 2020;69(8):1543–1544. Epub 2020/04/22. PubMed PMID: 32312790; PubMed Central PMCID: PMCPMC7211078.
   PubMed Web of Science ®Google Scholar
• Fajnzylber J, Regan J, Coxen K, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun. 2020;11(1):5493. Epub 2020/11/01. PubMed PMID: 33127906; PubMed Central PMCID: PMCPMC7603483.
   PubMed Web of Science ®Google Scholar
• Kim HS. Do an altered gut microbiota and an associated leaky gut affect COVID-19 severity?. mBio. 2021;12(1). Epub 2021/01/14. PubMed PMID: 33436436; PubMed Central PMCID: PMCPMC7845625.
   Web of Science ®Google Scholar
• Berer K, Mues M, Koutrolos M, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479(7374):538–541. Epub 2011/10/28. PubMed PMID: 22031325.
   PubMed Web of Science ®Google Scholar
• Mohle L, Mattei D, Heimesaat MM, et al. Ly6C(hi) monocytes provide a link between antibiotic-induced changes in gut microbiota and adult hippocampal neurogenesis. Cell Rep. 2016;15(9):1945–1956. Epub 2016/05/24. PubMed PMID: 27210745.
   PubMed Web of Science ®Google Scholar
• Ivanov AK II, Manel N, Brodie EL, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485–498. Epub 2009/10/20. PubMed PMID: 19836068; PubMed Central PMCID: PMCPMC2796826.
   PubMed Web of Science ®Google Scholar
• Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31(4):677–689. Epub 2009/10/17. PubMed PMID: 19833089.
   PubMed Web of Science ®Google Scholar
• Erny D, Hrabe de Angelis AL, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965–977. Epub 2015/06/02. PubMed PMID: 26030851; PubMed Central PMCID: PMCPMC5528863.
   PubMed Web of Science ®Google Scholar
• Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of parkinson’s disease. Cell. 2016;167:(6) 1469–80 e12. Epub 2016/12/03. PubMed PMID: 27912057; PubMed Central PMCID: PMCPMC5718049.
   PubMed Web of Science ®Google Scholar
• Thomas T, Stefanoni D, Reisz JA, et al. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI Insight. Epub 2020/06/20. PubMed PMID: 32559180; PubMed Central PMCID: PMCPMC7453907. 2020;5(14).
   Web of Science ®Google Scholar
• Johnson ME, Stecher B, Labrie V, et al. Facilitators, and aggravators: redefining parkinson’s disease pathogenesis.Trends Neurosci.2019;42(1):4–13. Epub 2018/10/22. PubMed PMID: 30342839; PubMed Central PMCID: PMCPMC6623978;
   PubMed Web of Science ®Google Scholar
• Proal AD, VanElzakker MB. Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms. Front Microbiol. 2021;12:698169. Epub 2021/07/13. PubMed PMID: 34248921; PubMed Central PMCID: PMCPMC8260991.
   PubMed Web of Science ®Google Scholar
• Petra AI, Panagiotidou S, Hatziagelaki E, et al. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015;37(5):984–995. Epub 2015/06/06. PubMed PMID: 26046241; PubMed Central PMCID: PMCPMC4458706;
   PubMed Web of Science ®Google Scholar
• Sajdel-Sulkowska EM. Neuropsychiatric ramifications of COVID-19: short-chain fatty acid deficiency and disturbance of microbiota-gut-brain axis signaling. Biomed Res Int. 2021;2021:7880448. Epub 2021/10/16. PubMed PMID: 34651049; PubMed Central PMCID: PMCPMC8510788 interest.
   PubMed Web of Science ®Google Scholar
• Barrantes FJ. The unfolding palette of COVID-19 multisystemic syndrome and its neurological manifestations. Brain Behav Immun Health. 2021;14:100251. Epub 2021/04/13. PubMed PMID: 33842898; PubMed Central PMCID: PMCPMC8019247.
   PubMedGoogle Scholar
• Lei HY, Ding YH, Nie K, et al. Potential effects of SARS-CoV-2 on the gastrointestinal tract and liver. Biomed Pharmacother. 2021;133:111064. Epub 2021/01/01. PubMed PMID: 33378966; PubMed Central PMCID: PMCPMC7700011.
   PubMed Web of Science ®Google Scholar
• Faraco G, Brea D, Garcia-Bonilla L, et al. Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 2018;21(2):240–249. Epub 2018/01/18. PubMed PMID: 29335605; PubMed Central PMCID: PMCPMC6207376.
   PubMed Web of Science ®Google Scholar
• Benakis C, Brea D, Caballero S, et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. Nat Med. 2016;22(5):516–523. Epub 2016/03/29. PubMed PMID: 27019327; PubMed Central PMCID: PMCPMC4860105.
   PubMed Web of Science ®Google Scholar
• Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337–341. Epub 2015/06/02. PubMed PMID: 26030524; PubMed Central PMCID: PMCPMC4506234.
   PubMed Web of Science ®Google Scholar
• Rahman MT, Ghosh C, Hossain M, et al. IFN-gamma, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: relevance for neuro-inflammatory diseases. Biochem Biophys Res Commun. 2018;507:(1–4) 274–279. Epub 2018/11/20. PubMed PMID: 30449598.
   PubMed Web of Science ®Google Scholar
• Xu J, Wu Z, Zhang M, et al. The role of the gastrointestinal system in neuroinvasion by SARS-CoV-2. Front Neurosci. 2021;15:694446. Epub 2021/07/20. PubMed PMID: 34276298; PubMed Central PMCID: PMCPMC8283125.
   PubMed Web of Science ®Google Scholar
• Shinu P, Morsy MA, Deb PK, et al. SARS CoV-2 organotropism associated pathogenic relationship of gut-brain axis and illness. Front Mol Biosci. 2020;7:606779. Epub 2021/01/09. PubMed PMID: 33415126; PubMed Central PMCID: PMCPMC7783391.
   PubMed Web of Science ®Google Scholar
• Wan D, Du T, Hong W, et al. Neurological complications and infection mechanism of SARS-COV-2. Signal Transduct Target Ther. 2021;6(1):406. Epub 2021/11/25. PubMed PMID: 34815399; PubMed Central PMCID: PMCPMC8609271.
   PubMed Web of Science ®Google Scholar
• Beach TG, Corbille AG, Letournel F, et al. Multicenter assessment of immunohistochemical methods for pathological alpha-synuclein in sigmoid colon of autopsied parkinson’s disease and control subjects. J Parkinsons Dis. 2016;6(4):761–770. Epub 2016/10/22. PubMed PMID: 27589538; PubMed Central PMCID: PMCPMC5501392.
   PubMedGoogle Scholar
• Chaumette T, Lebouvier T, Aubert P, et al. Neurochemical plasticity in the enteric nervous system of a primate animal model of experimental parkinsonism. Neurogastroenterol Motil. 2009;21(2):215–222. Epub 2008/12/17. PubMed PMID: 19077145.
   PubMed Web of Science ®Google Scholar
• Zhang X, Li Y, Liu C, et al. Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine-induced Parkinson’s disease rats. Transl Res. 2015;166(2):152–162. Epub 2015/03/15. PubMed PMID: 25766133.
   PubMed Web of Science ®Google Scholar
• Cevik M, Kuppalli K, Kindrachuk J, et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. 2020;371:m3862. Epub 2020/10/25. PubMed PMID: 33097561.
   PubMedGoogle Scholar
• Parasher A. COVID-19: current understanding of its pathophysiology, clinical presentation and treatment.Postgrad Med J.2021;97(1147):312–320. Epub 2020/09/27. PubMed PMID: 32978337.
   PubMed Web of Science ®Google Scholar
• Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:(2) 271–80 e8. Epub 2020/03/07. PubMed PMID: 32142651; PubMed Central PMCID: PMCPMC7102627.
   PubMed Web of Science ®Google Scholar
• Kumar A, Faiq MA, Pareek V, et al. Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients. Med Hypotheses. 2020;144:110271. Epub 2020/12/02. PubMed PMID: 33254575; PubMed Central PMCID: PMCPMC7487155.
   PubMed Web of Science ®Google Scholar
• Lee DJ, Lockwood J, Das P, et al. Self-reported anosmia and dysgeusia as key symptoms of coronavirus disease 2019. Cjem. 2020;22(5):595–602. Epub 2020/06/09. PubMed PMID: 32507123; PubMed Central PMCID: PMCPMC7308595.
   PubMedGoogle Scholar
• Netland J, Meyerholz DK, Moore S, et al. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264–7275. Epub 2008/05/23. PubMed PMID: 18495771; PubMed Central PMCID: PMCPMC2493326.
   PubMed Web of Science ®Google Scholar
• Esposito G, Pesce M, Seguella L, et al. Can the enteric nervous system be an alternative entrance door in SARS-CoV2 neuroinvasion?. Brain Behav Immun. 2020;87:93–94. Epub 2020/04/27. PubMed PMID: 32335192; PubMed Central PMCID: PMCPMC7179488.
   PubMed Web of Science ®Google Scholar
• Esposito G, Capoccia E, Gigli S, et al. HIV-1 Tat-induced diarrhea evokes an enteric glia-dependent neuroinflammatory response in the central nervous system. Sci Rep. 2017;7(1):7735. Epub 2017/08/12. PubMed PMID: 28798420; PubMed Central PMCID: PMCPMC5552820.
   PubMedGoogle Scholar
• Matsuda K, Park CH, Sunden Y, et al. The vagus nerve is one route of transneural invasion for intranasally inoculated influenza a virus in mice. Vet Pathol. 2004;41(2):101–107. Epub 2004/03/16. PubMed PMID: 15017022.
   PubMed Web of Science ®Google Scholar
• Dube M, Le Coupanec A, Wong AHM, et al. Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43. J Virol. 2018;92(17). Epub 2018/06/22. PubMed PMID: 29925652; PubMed Central PMCID: PMCPMC6096804.
   PubMed Web of Science ®Google Scholar
• Cole-Jeffrey CT, Liu M, Katovich MJ, et al. ACE2 and microbiota: emerging targets for cardiopulmonary disease therapy. J Cardiovasc Pharmacol. 2015;66(6):540–550. Epub 2015/09/01. PubMed PMID: 26322922; PubMed Central PMCID: PMCPMC4807023.
   PubMed Web of Science ®Google Scholar
• Nisoli E, Cinti S, Valerio A. COVID-19 and Hartnup disease: an affair of intestinal amino acid malabsorption. Eat Weight Disord. 2021;26(5):1647–1651. Epub 2020/07/22. PubMed PMID: 32691334; PubMed Central PMCID: PMCPMC7369504.
   PubMed Web of Science ®Google Scholar
• Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012;487(7408):477–481. Epub 2012/07/28. PubMed PMID: 22837003; PubMed Central PMCID: PMCPMC7095315
   PubMed Web of Science ®Google Scholar
• Belladonna ML, Orabona C. Potential benefits of tryptophan metabolism to the efficacy of tocilizumab in COVID-19. Front Pharmacol. 2020;11:959. Epub 2020/07/09. PubMed PMID: 32636755; PubMed Central PMCID: PMCPMC7319082.
   PubMed Web of Science ®Google Scholar
• Devaux CA, Lagier JC, Raoult D. New insights into the physiopathology of COVID-19: SARS-CoV-2-associated gastrointestinal illness. Front Med (Lausanne). 2021;8:640073. Epub 2021/03/09. PubMed PMID: 33681266; PubMed Central PMCID: PMCPMC7930624.
   PubMed Web of Science ®Google Scholar
• George AK, Behera J, Homme RP, et al. Rebuilding microbiome for mitigating traumatic brain injury: importance of restructuring the gut-microbiome-brain axis. Mol Neurobiol. 2021;58(8):3614–3627. Epub 2021/03/29. PubMed PMID: 33774742; PubMed Central PMCID: PMCPMC8003896.
   PubMed Web of Science ®Google Scholar
• Rothhammer V, Borucki DM, Tjon EC, et al. Microglial control of astrocytes in response to microbial metabolites. Nature. 2018;557(7707):724–728. Epub 2018/05/18. PubMed PMID: 29769726; PubMed Central PMCID: PMCPMC6422159.
   PubMed Web of Science ®Google Scholar
• Anderson G. Melatonin: roles in influenza, Covid-19, and other viral infections. Rev Med Virol. 2020;30(3):e2109. Epub 2020/04/22. PubMed PMID: 32314850; PubMed Central PMCID: PMCPMC7235470.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Sharma R, Simko F, et al. Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection. Cell Mol Life Sci. 2022;79(3):143. Epub 2022/02/22. PubMed PMID: 35187603; PubMed Central PMCID: PMCPMC8858600.
   PubMed Web of Science ®Google Scholar
• Lan SH, Lee HZ, Chao CM, et al. Efficacy of melatonin in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials. J Med Virol. 2022;94(5):2102–2107. Epub 2022/01/16. PubMed PMID: 35032042; PubMed Central PMCID: PMCPMC9015545.
   PubMed Web of Science ®Google Scholar
• Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384. Epub 2017/01/27. PubMed PMID: 28123927; PubMed Central PMCID: PMCPMC5214347.
   PubMed Web of Science ®Google Scholar
• Sharma L, Riva A. Intestinal barrier function in health and disease-any role of SARS-CoV-2?. Microorganisms. 2020;8(11). Epub 2020/11/12. PubMed PMID: 33172188; PubMed Central PMCID: PMCPMC7694956.
   Web of Science ®Google Scholar
• Oliva A, Cammisotto V, Cangemi R, et al. Low-grade endotoxemia and thrombosis in COVID-19. Clin Transl Gastroenterol. 2021;12(6):e00348. Epub 2021/06/08. PubMed PMID: 34092777; PubMed Central PMCID: PMCPMC8183715.
   PubMed Web of Science ®Google Scholar
• Li Z, Liu T, Yang N, et al. Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain. Front Med. 2020;14(5):533–541. Epub 2020/05/06. PubMed PMID: 32367431; PubMed Central PMCID: PMCPMC7197033.
   PubMed Web of Science ®Google Scholar
• Meinhardt J, Radke J, Dittmayer C, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021;24(2):168–175. Epub 2020/12/02. PubMed PMID: 33257876.
   PubMed Web of Science ®Google Scholar
• Ojetti V, Saviano A, Covino M, et al. COVID-19 and intestinal inflammation: Role of fecal calprotectin. Dig Liver Dis. 2020;52(11):1231–1233. Epub 2020/10/17. PubMed PMID: 33060042; PubMed Central PMCID: PMCPMC7508507 grant support.
   PubMedGoogle Scholar
• Skarlis C, Nezos A, and Mavragani CP, et al. The role of insulin growth factors in autoimmune diseases. Ann Res Hosp. 2019;3:10.
   Google Scholar
• Li G, Zhou L, Zhang C, et al. Insulin-like growth factor 1 regulates acute inflammatory lung injury mediated by influenza virus infection. Front Microbiol. 2019;10:2541. Epub 2019/12/19. PubMed PMID: 31849847; PubMed Central PMCID: PMCPMC6887893.
   PubMed Web of Science ®Google Scholar
• Fan X, Yin C, Wang J, et al. Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank. Eur J Epidemiol. 2021;36(3):311–318. Epub 2021/01/10. PubMed PMID: 33420872; PubMed Central PMCID: PMCPMC7794621.
   PubMed Web of Science ®Google Scholar
• Chen BH, Ahn JH, Park JH, et al. Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB. Chem Biol Interact. 2018;286:71–77. Epub 2018/03/20. PubMed PMID: 29548728.
   PubMed Web of Science ®Google Scholar
• Ge RT, Mo LH, Wu R, et al. Insulin-like growth factor-1 endues monocytes with immune suppressive ability to inhibit inflammation in the intestine. Sci Rep. 2015;5:7735. Epub 2015/01/16. PubMed PMID: 25588622; PubMed Central PMCID: PMCPMC4295102.
   PubMed Web of Science ®Google Scholar
• Orlov M, Wander PL, Morrell ED, et al. A case for targeting Th17 cells and IL-17A in SARS-CoV-2 infections. J Immunol. 2020;205(4):892–898. Epub 2020/07/12. PubMed PMID: 32651218; PubMed Central PMCID: PMCPMC7486691.
   PubMed Web of Science ®Google Scholar
• Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. Epub 2020/01/28. PubMed PMID: 31986264; PubMed Central PMCID: PMCPMC7159299.
   PubMed Web of Science ®Google Scholar
• Lee PH, Tay WC, Sutjipto S, et al. Associations of viral ribonucleic acid (RNA) shedding patterns with clinical illness and immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clin Transl Immunology. 2020;9(7):e1160. Epub 2020/08/04. PubMed PMID: 32742654; PubMed Central PMCID: PMCPMC7385430.
   PubMed Web of Science ®Google Scholar
• A randomized, blinded, controlled, multicenter clinical trial to evaluate the efficacy and safety of Ixekizumab combined with conventional antiviral drugs in patients with novel coronavirus pneumonia (COVID-19). [cited 2022 Apr 20]. Available from http://www.chictr.org.cn/showprojen.aspx?proj=50251.
   Google Scholar
• Gutierrez-Castrellon P, Gandara-Marti T, Abreu YAAT, et al. Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gut Microbes. 2022;14(1):2018899. Epub 2022/01/12. PubMed PMID: 35014600; PubMed Central PMCID: PMCPMC8757475.
   PubMed Web of Science ®Google Scholar
• Johnson SD, Olwenyi OA, Bhyravbhatla N, et al. Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis. World J Gastroenterol. 2021;27:(29) 4763–4783. Epub 2021/08/28. PubMed PMID: 34447225; PubMed Central PMCID: PMCPMC8371510.
   PubMed Web of Science ®Google Scholar
• Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020;159(3):944–55 e8. Epub 2020/05/23. PubMed PMID: 32442562; PubMed Central PMCID: PMCPMC7237927.
   PubMed Web of Science ®Google Scholar
• Parker A, Fonseca S, Carding SR. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health.Gut Microbes.2020;11(2):135–157. Epub 2019/08/02. PubMed PMID: 31368397; PubMed Central PMCID: PMCPMC7053956.
   PubMed Web of Science ®Google Scholar
• Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.Nat Rev Neurosci.2012;13(10):701–712. Epub 2012/09/13. PubMed PMID: 22968153.
   PubMed Web of Science ®Google Scholar
• Fadlallah S, Sham Eddin MS, Rahal EA. IL-17A in COVID-19 cases: a meta-analysis.J Infect Dev Ctries.2021;15(11):1630–1639. Epub 2021/12/14. PubMed PMID: 34898490.
   PubMed Web of Science ®Google Scholar
• Carugno A, Gambini DM, Raponi F, et al. COVID-19 and biologics for psoriasis: A high-epidemic area experience-Bergamo, Lombardy, Italy. J Am Acad Dermatol. 2020;83(1):292–294. Epub 2020/05/11. PubMed PMID: 32387660; PubMed Central PMCID: PMCPMC7202829.
   PubMed Web of Science ®Google Scholar
• Krueger JG, Murrell DF, Garcet S, et al. Secukinumab lowers expression of ACE2 in affected skin of patients with psoriasis. J Allergy Clin Immunol. 2021;147(3):1107–9 e2. Epub 2020/10/02. PubMed PMID: 33002515; PubMed Central PMCID: PMCPMC7834246.
   PubMed Web of Science ®Google Scholar
• Mahoney M, Damalanka VC, Tartell MA, et al. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. Proc Natl Acad Sci U S A. 2021;118(43). Epub 2021/10/13. PubMed PMID: 34635581; PubMed Central PMCID: PMCPMC8694051.
   Web of Science ®Google Scholar
• Ragia G, Manolopoulos VG. Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies.Eur J Clin Pharmacol.2020;76(12):1623–1630. Epub 2020/07/23. PubMed PMID: 32696234; PubMed Central PMCID: PMCPMC7372205.
   PubMed Web of Science ®Google Scholar
• Hoffmann M, Hofmann-Winkler H, Smith JC, et al. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. EBioMedicine. 2021;65:103255. Epub 2021/03/08. PubMed PMID: 33676899; PubMed Central PMCID: PMCPMC7930809.
   PubMed Web of Science ®Google Scholar
• Li K, Meyerholz DK, Bartlett JA, et al. The TMPRSS2 inhibitor nafamostat reduces SARS-CoV-2 pulmonary infection in mouse models of COVID-19. mBio. 2021;12(4):e0097021. Epub 2021/08/04. PubMed PMID: 34340553; PubMed Central PMCID: PMCPMC8406266.
   PubMed Web of Science ®Google Scholar
• National Library of Medicine (U.S.). (2020). The impact of camostat mesilate on COVID-19 infection (CamoCO-19). Identifier NCT04321096. [cited 2022 Feb 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT04321096
   Google Scholar
• National Library of Medicine (U.S.). (2021). Efficacy of Nafamostat in Covid-19 Patients (RACONA Study) (RACONA). Identifier NCT04352400. [cited 2022 Mar 28]. Available from: https://clinicaltrials.gov/ct2/show/NCT04352400
   Google Scholar
• Ungerstedt JS, Blomback M, Soderstrom T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin Exp Immunol. 2003;131(1):48–52. Epub 2003/01/10. PubMed PMID: 12519385; PubMed Central PMCID: PMCPMC1808598.
   PubMed Web of Science ®Google Scholar
• Altay O, Arif M, Li X, et al. Combined metabolic activators accelerates recovery in mild-to-moderate COVID-19. Adv Sci (Weinh). 2021;8(17):e2101222. Epub 2021/06/29. PubMed PMID: 34180141; PubMed Central PMCID: PMCPMC8420376.
   PubMedGoogle Scholar
• Hermel M, Sweeney M, Ni YM, et al. Natural Supplements for COVID19-Background, Rationale, and Clinical Trials. J Evid Based Integr Med. 2021;26:2515690X211036875. Epub 2021/08/14. PubMed PMID: 34384258; PubMed Central PMCID: PMCPMC8369961.
   PubMed Web of Science ®Google Scholar
• Biagioli M, Marchiano S, Roselli R, et al. Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction.Biochem Pharmacol. Epub 2021/04/20. PubMed PMID: 33872570; PubMed Central PMCID: PMCPMC8052506 2021;188 114564.
   PubMed Web of Science ®Google Scholar
• Tanimoto K, Hirota K, Fukazawa T, et al. Inhibiting SARS-CoV-2 infection in vitro by suppressing its receptor, angiotensin-converting enzyme 2, via aryl-hydrocarbon receptor signal. Sci Rep. 2021;11(1):16629. Epub 2021/08/19. PubMed PMID: 34404832; PubMed Central PMCID: PMCPMC8371152.
   PubMed Web of Science ®Google Scholar
• Di Micco S, Musella S, Sala M, et al. Peptide derivatives of the zonulin inhibitor larazotide (AT1001) as potential anti SARS-CoV-2: molecular modelling, synthesis and bioactivity evaluation. Int J Mol Sci. Epub 2021/09/11. PubMed PMID: 34502335; PubMed Central PMCID: PMCPMC8431481. 2021;22(17).
   PubMed Web of Science ®Google Scholar
• Giron LB, Dweep H, Yin X, et al. Plasma markers of disrupted gut permeability in severe COVID-19 patients. Front Immunol. Epub 2021/06/29. PubMed PMID: 34177935; PubMed Central PMCID: PMCPMC8219958 2021;12 686240.
   PubMed Web of Science ®Google Scholar
• Rossi AD, de Araujo JLF, de Almeida TB, et al. Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress. Sci Rep. 2021;11(1):9658. Epub 2021/05/08. PubMed PMID: 33958627; PubMed Central PMCID: PMCPMC8102547.
   PubMed Web of Science ®Google Scholar
• Di Micco S, Musella S, Scala MC, et al. In silico analysis revealed potential anti-SARS-CoV-2 main protease activity by the zonulin inhibitor larazotide acetate. Front Chem. 2020;8:628609. Epub 2021/02/02. PubMed PMID: 33520943; PubMed Central PMCID: PMCPMC7843458.
   PubMed Web of Science ®Google Scholar
• Yonker LM, Gilboa T, Ogata AF, et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J Clin Invest. Epub 2021/05/26. PubMed PMID: 34032635; PubMed Central PMCID: PMCPMC8279585. 2021;131(14).
   Web of Science ®Google Scholar
• Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021;384(9):795–807. Epub 2020/12/12. PubMed PMID: 33306283; PubMed Central PMCID: PMCPMC7745180.
   PubMed Web of Science ®Google Scholar
• Davis G, Li K, Thankam FG, et al. Ocular transmissibility of COVID-19: possibilities and perspectives.Mol Cell Biochem.2022;477(3):849–864. Epub 2022/01/24. PubMed PMID: 35066705; PubMed Central PMCID: PMCPMC8783769
   PubMed Web of Science ®Google Scholar
• Thankam FG, Agrawal DK. Molecular chronicles of cytokine burst in patients with coronavirus disease 2019 (COVID-19) with cardiovascular diseases.J Thorac Cardiovasc Surg.2021;161(2):e217–e26. Epub 2020/07/08. PubMed PMID: 32631657; PubMed Central PMCID: PMCPMC7834736
   PubMed Web of Science ®Google Scholar