Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches
Abstract
:1. Introduction
2. Main Features of SARS-CoV-2 Infection
3. GM Dysbiosis–Immune Hyperresponse–Inflammation Triad in COVID-19
4. Therapeutic Opportunities for COVID-19 with Impact on the Triad and a Focus on GM
4.1. Immunomodulatory and Anti-Inflammatory Drugs
4.1.1. Chloroquine and Hydroxychloroquine
4.1.2. Interferons
4.1.3. Corticosteroids
4.2. Nutraceutical Approaches
4.2.1. Prebiotics, Probiotics, and Synbiotics
4.2.2. Vitamins
4.2.3. Selenium and Zinc
4.2.4. Flavonoids
4.2.5. Omega-3 Polyunsaturated Fatty Acids
4.2.6. Traditional Chinese Medicine
4.3. Prophylactic Approaches
4.3.1. BCG Vaccination
4.3.2. New Vaccines for SARS-CoV-2
5. Concluding Remarks and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
- Guo, Y.R.; Cao, Q.D.; Hong, Z.S.; Tan, Y.Y.; Chen, S.D.; Jin, H.J.; Tan, K.S.; Wang, D.Y.; Yan, Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak—An update on the status. Mil. Med. Res. 2020, 7, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, H.; Zhou, Y.; Zhang, M.; Wang, H.; Zhao, Q.; Liu, J. Updated Approaches against SARS-CoV-2. Antimicrob. Agents Chemother. 2020, 64. [Google Scholar] [CrossRef] [Green Version]
- Li, J.Y.; You, Z.; Wang, Q.; Zhou, Z.J.; Qiu, Y.; Luo, R.; Ge, X.Y. The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future. Microbes Infect. 2020, 22, 80–85. [Google Scholar] [CrossRef]
- Li, H.; Liu, S.M.; Yu, X.H.; Tang, S.L.; Tang, C.K. Coronavirus disease 2019 (COVID-19): Current status and future perspectives. Int. J. Antimicrob. Agents 2020, 55, 105951. [Google Scholar] [CrossRef] [PubMed]
- Rismanbaf, A. Potential Treatments for COVID-19; a Narrative Literature Review. Arch. Acad. Emerg. Med. 2020, 8, e29. [Google Scholar]
- Siordia, J.A., Jr. Epidemiology and clinical features of COVID-19: A review of current literature. J. Clin. Virol. 2020, 127, 104357. [Google Scholar] [CrossRef] [PubMed]
- Team, C.C.-R. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19)—United States, 12 February–16 March 2020. MMWR Morb. Mortal Wkly Rep. 2020, 69, 343–346. [Google Scholar] [CrossRef]
- Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020, 395, 507–513. [Google Scholar] [CrossRef] [Green Version]
- Du, R.H.; Liang, L.R.; Yang, C.Q.; Wang, W.; Cao, T.Z.; Li, M.; Guo, G.Y.; Du, J.; Zheng, C.L.; Zhu, Q.; et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: A prospective cohort study. Eur. Respir. J. 2020, 55. [Google Scholar] [CrossRef] [Green Version]
- Guan, W.J.; Ni, Z.Y.; Hu, Y.; Liang, W.H.; Ou, C.Q.; He, J.X.; Liu, L.; Shan, H.; Lei, C.L.; Hui, D.S.C.; et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708–1720. [Google Scholar] [CrossRef]
- Li, B.; Yang, J.; Zhao, F.; Zhi, L.; Wang, X.; Liu, L.; Bi, Z.; Zhao, Y. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin. Res. Cardiol. 2020, 109, 531–538. [Google Scholar] [CrossRef] [PubMed]
- Mehra, M.R.; Desai, S.S.; Kuy, S.; Henry, T.D.; Patel, A.N. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N. Engl. J. Med. 2020, 382, e102. [Google Scholar] [CrossRef] [PubMed]
- Roncon, L.; Zuin, M.; Rigatelli, G.; Zuliani, G. Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome. J. Clin. Virol. 2020, 127, 104354. [Google Scholar] [CrossRef] [PubMed]
- Shi, Q.; Zhang, X.; Jiang, F.; Zhang, X.; Hu, N.; Bimu, C.; Feng, J.; Yan, S.; Guan, Y.; Xu, D.; et al. Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. Diabetes Care 2020, 43, 1382–1391. [Google Scholar] [CrossRef]
- Wang, X.; Fang, X.; Cai, Z.; Wu, X.; Gao, X.; Min, J.; Wang, F. Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis. Research (Wash D C) 2020, 2020, 2402961. [Google Scholar] [CrossRef] [Green Version]
- Zhou, F.; Yu, T.; Du, R.; Fan, G.; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020, 395, 1054–1062. [Google Scholar] [CrossRef]
- Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef] [Green Version]
- Channappanavar, R.; Perlman, S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol. 2017, 39, 529–539. [Google Scholar] [CrossRef]
- Fernandes, R.; Viana, S.D.; Nunes, S.; Reis, F. Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy. Biochim. Biophys. Acta Mol. Basis Dis. 2019, 1865, 1876–1897. [Google Scholar] [CrossRef]
- Kumar Singh, A.; Cabral, C.; Kumar, R.; Ganguly, R.; Kumar Rana, H.; Gupta, A.; Rosaria Lauro, M.; Carbone, C.; Reis, F.; Pandey, A.K. Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency. Nutrients 2019, 11, 2216. [Google Scholar] [CrossRef] [Green Version]
- Geuking, M.B.; Koller, Y.; Rupp, S.; McCoy, K.D. The interplay between the gut microbiota and the immune system. Gut Microbes 2014, 5, 411–418. [Google Scholar] [CrossRef] [PubMed]
- Gu, S.; Chen, Y.; Wu, Z.; Chen, Y.; Gao, H.; Lv, L.; Guo, F.; Zhang, X.; Luo, R.; Huang, C.; et al. Alterations of the Gut Microbiota in Patients with COVID-19 or H1N1 Influenza. Clin. Infect. Dis. 2020. [Google Scholar] [CrossRef]
- Zuo, T.; Zhang, F.; Lui, G.C.Y.; Yeoh, Y.K.; Li, A.Y.L.; Zhan, H.; Wan, Y.; Chung, A.; Cheung, C.P.; Chen, N.; et al. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology 2020. [Google Scholar] [CrossRef]
- Yu, F.; Du, L.; Ojcius, D.M.; Pan, C.; Jiang, S. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect 2020, 22, 74–79. [Google Scholar] [CrossRef] [PubMed]
- Tang, X.; Wu, C.; Li, X.; Song, Y.; Yao, X.; Wu, X.; Duan, Y.; Zhang, H.; Wang, Y.; Qian, Z.; et al. On the origin and continuing evolution of SARS-CoV-2. Natl. Sci. Rev. 2020, 7, 1012–1023. [Google Scholar] [CrossRef] [Green Version]
- Bull, J.J.; Sanjuan, R.; Wilke, C.O. Theory of lethal mutagenesis for viruses. J. Virol. 2007, 81, 2930–2939. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Liu, Y. Potential interventions for novel coronavirus in China: A systematic review. J. Med. Virol. 2020, 92, 479–490. [Google Scholar] [CrossRef] [Green Version]
- Almeida, A.; Mitchell, A.L.; Boland, M.; Forster, S.C.; Gloor, G.B.; Tarkowska, A.; Lawley, T.D.; Finn, R.D. A new genomic blueprint of the human gut microbiota. Nature 2019, 568, 499–504. [Google Scholar] [CrossRef] [Green Version]
- Barko, P.C.; McMichael, M.A.; Swanson, K.S.; Williams, D.A. The Gastrointestinal Microbiome: A Review. J. Vet. Intern Med. 2018, 32, 9–25. [Google Scholar] [CrossRef]
- Koppel, N.; Maini Rekdal, V.; Balskus, E.P. Chemical transformation of xenobiotics by the human gut microbiota. Science 2017, 356. [Google Scholar] [CrossRef]
- Weiss, G.A.; Hennet, T. Mechanisms and consequences of intestinal dysbiosis. Cell. Mol. Life Sci. 2017, 74, 2959–2977. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hugon, P.; Dufour, J.C.; Colson, P.; Fournier, P.E.; Sallah, K.; Raoult, D. A comprehensive repertoire of prokaryotic species identified in human beings. Lancet Infect. Dis. 2015, 15, 1211–1219. [Google Scholar] [CrossRef]
- Li, J.; Jia, H.; Cai, X.; Zhong, H.; Feng, Q.; Sunagawa, S.; Arumugam, M.; Kultima, J.R.; Prifti, E.; Nielsen, T.; et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 2014, 32, 834–841. [Google Scholar] [CrossRef] [PubMed]
- Scarpellini, E.; Ianiro, G.; Attili, F.; Bassanelli, C.; De Santis, A.; Gasbarrini, A. The human gut microbiota and virome: Potential therapeutic implications. Dig. Liver Dis. 2015, 47, 1007–1012. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cani, P.D. Human gut microbiome: Hopes, threats and promises. Gut 2018, 67, 1716–1725. [Google Scholar] [CrossRef] [PubMed]
- Garmaeva, S.; Sinha, T.; Kurilshikov, A.; Fu, J.; Wijmenga, C.; Zhernakova, A. Studying the gut virome in the metagenomic era: Challenges and perspectives. BMC Biol. 2019, 17, 84. [Google Scholar] [CrossRef]
- Reyes, A.; Semenkovich, N.P.; Whiteson, K.; Rohwer, F.; Gordon, J.I. Going viral: Next-generation sequencing applied to phage populations in the human gut. Nat. Rev. Microbiol. 2012, 10, 607–617. [Google Scholar] [CrossRef]
- Milani, C.; Duranti, S.; Bottacini, F.; Casey, E.; Turroni, F.; Mahony, J.; Belzer, C.; Delgado Palacio, S.; Arboleya Montes, S.; Mancabelli, L.; et al. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol. Mol. Biol. Rev. 2017, 81. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lim, E.S.; Zhou, Y.; Zhao, G.; Bauer, I.K.; Droit, L.; Ndao, I.M.; Warner, B.B.; Tarr, P.I.; Wang, D.; Holtz, L.R. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat. Med. 2015, 21, 1228–1234. [Google Scholar] [CrossRef]
- Zang, R.; Gomez Castro, M.F.; McCune, B.T.; Zeng, Q.; Rothlauf, P.W.; Sonnek, N.M.; Liu, Z.; Brulois, K.F.; Wang, X.; Greenberg, H.B.; et al. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci. Immunol. 2020, 5. [Google Scholar] [CrossRef]
- Cheng, P.K.; Wong, D.A.; Tong, L.K.; Ip, S.M.; Lo, A.C.; Lau, C.S.; Yeung, E.Y.; Lim, W.W. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet 2004, 363, 1699–1700. [Google Scholar] [CrossRef] [Green Version]
- Wu, Y.; Guo, C.; Tang, L.; Hong, Z.; Zhou, J.; Dong, X.; Yin, H.; Xiao, Q.; Tang, Y.; Qu, X.; et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol. Hepatol. 2020, 5, 434–435. [Google Scholar] [CrossRef]
- Zhang, H.; Li, H.B.; Lyu, J.R.; Lei, X.M.; Li, W.; Wu, G.; Lyu, J.; Dai, Z.M. Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection. Int. J. Infect. Dis. 2020, 96, 19–24. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Chu, M.; Zhong, F.; Tan, X.; Tang, G.; Mai, J.; Lai, N.; Guan, C.; Liang, Y.; Liao, G. Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs. Cell Death Discov. 2020, 6, 76. [Google Scholar] [CrossRef] [PubMed]
- Fu, B.; Qian, K.; Fu, X. SARS-CoV-2-Induced Vomiting as Onset Symptom in a Patient with COVID-19. Dig. Dis. Sci. 2020, 65, 1568–1570. [Google Scholar] [CrossRef] [PubMed]
- Song, Y.; Liu, P.; Shi, X.L.; Chu, Y.L.; Zhang, J.; Xia, J.; Gao, X.Z.; Qu, T.; Wang, M.Y. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut 2020, 69, 1143–1144. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Villapol, S. Gastrointestinal symptoms associated with COVID-19: Impact on the gut microbiome. Transl. Res. 2020. [Google Scholar] [CrossRef]
- Trottein, F.; Sokol, H. Potential Causes and Consequences of Gastrointestinal Disorders during a SARS-CoV-2 Infection. Cell Rep. 2020, 32, 107915. [Google Scholar] [CrossRef]
- Dhar, D.; Mohanty, A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020, 285, 198018. [Google Scholar] [CrossRef]
- Viana, S.D.; Nunes, S.; Reis, F. ACE2 imbalance as a key player for the poor outcomes in COVID-19 patients with age-related comorbidities—Role of gut microbiota dysbiosis. Ageing Res. Rev. 2020, 62, 101123. [Google Scholar] [CrossRef]
- Kalantar-Zadeh, K.; Ward, S.A.; Kalantar-Zadeh, K.; El-Omar, E.M. Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles. ACS Nano 2020, 14, 5179–5182. [Google Scholar] [CrossRef] [PubMed]
- Chiu, L.; Bazin, T.; Truchetet, M.E.; Schaeverbeke, T.; Delhaes, L.; Pradeu, T. Protective Microbiota: From Localized to Long-Reaching Co-Immunity. Front. Immunol. 2017, 8, 1678. [Google Scholar] [CrossRef] [PubMed]
- Chu, H.; Mazmanian, S.K. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat. Immunol. 2013, 14, 668–675. [Google Scholar] [CrossRef]
- Kamada, N.; Seo, S.U.; Chen, G.Y.; Nunez, G. Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol. 2013, 13, 321–335. [Google Scholar] [CrossRef] [PubMed]
- Wrzosek, L.; Miquel, S.; Noordine, M.L.; Bouet, S.; Joncquel Chevalier-Curt, M.; Robert, V.; Philippe, C.; Bridonneau, C.; Cherbuy, C.; Robbe-Masselot, C.; et al. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 2013, 11, 61. [Google Scholar] [CrossRef] [Green Version]
- Hepworth, M.R.; Monticelli, L.A.; Fung, T.C.; Ziegler, C.G.; Grunberg, S.; Sinha, R.; Mantegazza, A.R.; Ma, H.L.; Crawford, A.; Angelosanto, J.M.; et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 2013, 498, 113–117. [Google Scholar] [CrossRef] [Green Version]
- Noh, K.; Kang, Y.R.; Nepal, M.R.; Shakya, R.; Kang, M.J.; Kang, W.; Lee, S.; Jeong, H.G.; Jeong, T.C. Impact of gut microbiota on drug metabolism: An update for safe and effective use of drugs. Arch. Pharm. Res. 2017, 40, 1345–1355. [Google Scholar] [CrossRef]
- Zhang, J.; Zhang, J.; Wang, R. Gut microbiota modulates drug pharmacokinetics. Drug Metab. Rev. 2018, 50, 357–368. [Google Scholar] [CrossRef]
- Zimmermann, M.; Zimmermann-Kogadeeva, M.; Wegmann, R.; Goodman, A.L. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 2019, 363. [Google Scholar] [CrossRef]
- Megarbane, B. Chloroquine and hydroxychloroquine to treat COVID-19: Between hope and caution. Clin. Toxicol. (Phila) 2020. [Google Scholar] [CrossRef] [Green Version]
- Farzana, R.; Jones, L.S.; Barratt, A.; Rahman, M.A.; Sands, K.; Portal, E.; Boostrom, I.; Espina, L.; Pervin, M.; Uddin, A.; et al. Emergence of Mobile Colistin Resistance (mcr-8) in a Highly Successful Klebsiella pneumoniae Sequence Type 15 Clone from Clinical Infections in Bangladesh. mSphere 2020, 5. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vincent, M.J.; Bergeron, E.; Benjannet, S.; Erickson, B.R.; Rollin, P.E.; Ksiazek, T.G.; Seidah, N.G.; Nichol, S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J. 2005, 2, 69. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fantini, J.; Di Scala, C.; Chahinian, H.; Yahi, N. Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection. Int. J. Antimicrob. Agents 2020, 55, 105960. [Google Scholar] [CrossRef] [PubMed]
- Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA 2020. [Google Scholar] [CrossRef]
- Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020, 30, 269–271. [Google Scholar] [CrossRef]
- Cortegiani, A.; Ingoglia, G.; Ippolito, M.; Giarratano, A.; Einav, S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J. Crit. Care 2020, 57, 279–283. [Google Scholar] [CrossRef]
- Gao, J.; Tian, Z.; Yang, X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci. Trends 2020, 14, 72–73. [Google Scholar] [CrossRef] [Green Version]
- Hashem, A.M.; Alghamdi, B.S.; Algaissi, A.A.; Alshehri, F.S.; Bukhari, A.; Alfaleh, M.A.; Memish, Z.A. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel. Med. Infect. Dis. 2020, 35, 101735. [Google Scholar] [CrossRef]
- Flanagan, P.K.; Chiewchengchol, D.; Wright, H.L.; Edwards, S.W.; Alswied, A.; Satsangi, J.; Subramanian, S.; Rhodes, J.M.; Campbell, B.J. Killing of Escherichia coli by Crohn’s Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D. Inflamm. Bowel. Dis. 2015, 21, 1499–1510. [Google Scholar] [CrossRef] [Green Version]
- Shi, N.; Zhang, S.; Silverman, G.; Li, M.; Cai, J.; Niu, H. Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis. Animal. Model. Exp. Med. 2019, 2, 98–106. [Google Scholar] [CrossRef]
- Angelakis, E.; Million, M.; Kankoe, S.; Lagier, J.C.; Armougom, F.; Giorgi, R.; Raoult, D. Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment. Antimicrob. Agents Chemother. 2014, 58, 3342–3347. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pott, J.; Stockinger, S. Type I and III Interferon in the Gut: Tight Balance between Host Protection and Immunopathology. Front. Immunol. 2017, 8, 258. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, A.J.; Ashkar, A.A. The Dual Nature of Type I and Type II Interferons. Front. Immunol. 2018, 9, 2061. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sallard, E.; Lescure, F.X.; Yazdanpanah, Y.; Mentre, F.; Peiffer-Smadja, N. Type 1 interferons as a potential treatment against COVID-19. Antivir. Res. 2020, 178, 104791. [Google Scholar] [CrossRef] [PubMed]
- Chan, J.F.; Chan, K.H.; Kao, R.Y.; To, K.K.; Zheng, B.J.; Li, C.P.; Li, P.T.; Dai, J.; Mok, F.K.; Chen, H.; et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J. Infect. 2013, 67, 606–616. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Falzarano, D.; de Wit, E.; Martellaro, C.; Callison, J.; Munster, V.J.; Feldmann, H. Inhibition of novel beta coronavirus replication by a combination of interferon-alpha2b and ribavirin. Sci. Rep. 2013, 3, 1686. [Google Scholar] [CrossRef] [Green Version]
- Hart, B.J.; Dyall, J.; Postnikova, E.; Zhou, H.; Kindrachuk, J.; Johnson, R.F.; Olinger, G.G.; Frieman, M.B.; Holbrook, M.R.; Jahrling, P.B.; et al. Interferon-beta and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J. Gen. Virol. 2014, 95, 571–577. [Google Scholar] [CrossRef]
- Hensley, L.E.; Fritz, L.E.; Jahrling, P.B.; Karp, C.L.; Huggins, J.W.; Geisbert, T.W. Interferon-beta 1a and SARS coronavirus replication. Emerg. Infect. Dis. 2004, 10, 317–319. [Google Scholar] [CrossRef]
- Cinatl, J.; Morgenstern, B.; Bauer, G.; Chandra, P.; Rabenau, H.; Doerr, H.W. Treatment of SARS with human interferons. Lancet 2003, 362, 293–294. [Google Scholar] [CrossRef]
- Morgenstern, B.; Michaelis, M.; Baer, P.C.; Doerr, H.W.; Cinatl, J., Jr. Ribavirin and interferon-beta synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem. Biophys. Res. Commun. 2005, 326, 905–908. [Google Scholar] [CrossRef]
- Chen, F.; Chan, K.H.; Jiang, Y.; Kao, R.Y.; Lu, H.T.; Fan, K.W.; Cheng, V.C.; Tsui, W.H.; Hung, I.F.; Lee, T.S.; et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J. Clin. Virol. 2004, 31, 69–75. [Google Scholar] [CrossRef] [PubMed]
- Lokugamage, K.G.; Hage, A.; Schindewolf, C.; Rajsbaum, R.; Menachery, V.D. SARS-CoV-2 is sensitive to type I interferon pretreatment. bioRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
- Shen, K.L.; Yang, Y.H. Diagnosis and treatment of 2019 novel coronavirus infection in children: A pressing issue. World J. Pediatr. 2020, 16, 219–221. [Google Scholar] [CrossRef] [Green Version]
- Meng, Z.; Wang, T.; Li, C.; Chen, X.; Li, L.; Qin, X.; Li, H.; Luo, J. An experimental trial of recombinant human interferon alpha nasal drops to prevent coronavirus disease 2019 in medical staff in an epidemic area. medRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
- Ren, W.; Chen, S.; Zhang, L.; Liu, G.; Hussain, T.; Hao, X.; Yin, J.; Duan, J.; Tan, B.; Wu, G.; et al. Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17. Mediat. Inflamm. 2016, 2016, 2839232. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tschurtschenthaler, M.; Wang, J.; Fricke, C.; Fritz, T.M.; Niederreiter, L.; Adolph, T.E.; Sarcevic, E.; Kunzel, S.; Offner, F.A.; Kalinke, U.; et al. Type I interferon signalling in the intestinal epithelium affects Paneth cells, microbial ecology and epithelial regeneration. Gut 2014, 63, 1921–1931. [Google Scholar] [CrossRef]
- Carrero, J.A.; Calderon, B.; Unanue, E.R. Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection. J. Exp. Med. 2004, 200, 535–540. [Google Scholar] [CrossRef]
- Castillo-Alvarez, F.; Perez-Matute, P.; Oteo, J.A.; Marzo-Sola, M.E. The influence of interferon beta-1b on gut microbiota composition in patients with multiple sclerosis. Neurologia 2018. [Google Scholar] [CrossRef]
- Cain, D.W.; Cidlowski, J.A. Immune regulation by glucocorticoids. Nat. Rev. Immunol. 2017, 17, 233–247. [Google Scholar] [CrossRef]
- Harvey, H.B.; Wu, C.C.; Gilman, M.D.; Vartanians, V.; Halpern, E.F.; Pandharipande, P.V.; Shepard, J.O.; Alkasab, T.K. Correlation of the Strength of Recommendations for Additional Imaging to Adherence Rate and Diagnostic Yield. J. Am. Coll. Radiol. 2015, 12, 1016–1022. [Google Scholar] [CrossRef]
- Barnes, P.J. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br. J. Pharmacol. 2006, 148, 245–254. [Google Scholar] [CrossRef] [PubMed]
- Zha, L.; Li, S.; Pan, L.; Tefsen, B.; Li, Y.; French, N.; Chen, L.; Yang, G.; Villanueva, E.V. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19). Med. J. Aust. 2020, 212, 416–420. [Google Scholar] [CrossRef] [PubMed]
- Tang, C.; Wang, Y.; Lv, H.; Guan, Z.; Gu, J. Caution against corticosteroid-based COVID-19 treatment. Lancet 2020, 395, 1759–1760. [Google Scholar] [CrossRef]
- Veronese, N.; Demurtas, J.; Yang, L.; Tonelli, R.; Barbagallo, M.; Lopalco, P.; Lagolio, E.; Celotto, S.; Pizzol, D.; Zou, L.; et al. Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature. Front. Med. (Lausanne) 2020, 7, 170. [Google Scholar] [CrossRef]
- Ye, Z.; Rochwerg, B.; Wang, Y.; Adhikari, N.K.; Murthy, S.; Lamontagne, F.; Fowler, R.A.; Qiu, H.; Wei, L.; Sang, L.; et al. Treatment of patients with nonsevere and severe coronavirus disease 2019: An evidence-based guideline. CMAJ 2020, 192, E536–E545. [Google Scholar] [CrossRef] [PubMed]
- Russell, C.D.; Millar, J.E.; Baillie, J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020, 395, 473–475. [Google Scholar] [CrossRef] [Green Version]
- Shang, L.; Zhao, J.; Hu, Y.; Du, R.; Cao, B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020, 395, 683–684. [Google Scholar] [CrossRef] [Green Version]
- da Silva Chaves, S.N.; Dutra Costa, B.P.; Vidal Gomes, G.C.; Lima-Maximino, M.; Pacheco Rico, E.; Maximino, C. NOS-2 participates in the behavioral effects of ethanol withdrawal in zebrafish. Neurosci Lett. 2020, 728, 134952. [Google Scholar] [CrossRef]
- Wu, C.; Chen, X.; Cai, Y.; Xia, J.; Zhou, X.; Xu, S.; Huang, H.; Zhang, L.; Zhou, X.; Du, C.; et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020. [Google Scholar] [CrossRef] [Green Version]
- Ling, Y.; Xu, S.B.; Lin, Y.X.; Tian, D.; Zhu, Z.Q.; Dai, F.H.; Wu, F.; Song, Z.G.; Huang, W.; Chen, J.; et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin. Med. J. (Engl.) 2020, 133, 1039–1043. [Google Scholar] [CrossRef]
- Barlow, A.; Landolf, K.M.; Barlow, B.; Yeung, S.Y.A.; Heavner, J.J.; Claassen, C.W.; Heavner, M.S. Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019. Pharmacotherapy 2020, 40, 416–437. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tisoncik, J.R.; Korth, M.J.; Simmons, C.P.; Farrar, J.; Martin, T.R.; Katze, M.G. Into the eye of the cytokine storm. Microbiol. Mol. Biol. Rev. 2012, 76, 16–32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, E.Y.; Inoue, T.; Leone, V.A.; Dalal, S.; Touw, K.; Wang, Y.; Musch, M.W.; Theriault, B.; Higuchi, K.; Donovan, S.; et al. Using corticosteroids to reshape the gut microbiome: Implications for inflammatory bowel diseases. Inflamm. Bowel Dis. 2015, 21, 963–972. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ünsal, H.B.M. Glucocorticoids—New Recognition of Our Familiar Friend: Glucocorticoids and the Intestinal Environment; InTech: Rijeka, Croatia, 2012. [Google Scholar] [CrossRef]
- Wu, T.; Yang, L.; Jiang, J.; Ni, Y.; Zhu, J.; Zheng, X.; Wang, Q.; Lu, X.; Fu, Z. Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats. Life Sci. 2018, 192, 173–182. [Google Scholar] [CrossRef] [PubMed]
- Zhao, H.; Jiang, X.; Chu, W. Shifts in the gut microbiota of mice in response to dexamethasone administration. Int. Microbiol. 2020. [Google Scholar] [CrossRef] [PubMed]
- Hua, C.; Geng, Y.; Chen, Q.; Niu, L.; Cai, L.; Tao, S.; Ni, Y.; Zhao, R. Chronic dexamethasone exposure retards growth without altering the digestive tract microbiota composition in goats. BMC Microbiol. 2018, 18, 112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pandey, K.R.; Naik, S.R.; Vakil, B.V. Probiotics, prebiotics and synbiotics- a review. J. Food Sci. Technol. 2015, 52, 7577–7587. [Google Scholar] [CrossRef]
- Akour, A. Probiotics and COVID-19: Is there any link? Lett. Appl. Microbiol. 2020. [Google Scholar] [CrossRef]
- Markowiak, P.; Slizewska, K. Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients 2017, 9, 1021. [Google Scholar] [CrossRef]
- Vyas, U.; Ranganathan, N. Probiotics, prebiotics, and synbiotics: Gut and beyond. Gastroenterol. Res. Pract. 2012, 2012, 872716. [Google Scholar] [CrossRef] [Green Version]
- Hemarajata, P.; Versalovic, J. Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Therap. Adv. Gastroenterol. 2013, 6, 39–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shinde, T.; Hansbro, P.M.; Sohal, S.S.; Dingle, P.; Eri, R.; Stanley, R. Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives. Microorganisms 2020, 8, 921. [Google Scholar] [CrossRef] [PubMed]
- Vanderpool, C.; Yan, F.; Polk, D.B. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflamm. Bowel Dis. 2008, 14, 1585–1596. [Google Scholar] [CrossRef]
- Antunes, A.E.C.; Vinderola, G.; Xavier-Santos, D.; Sivieri, K. Potential contribution of beneficial microbes to face the COVID-19 pandemic. Food Res. Int. 2020, 136, 109577. [Google Scholar] [CrossRef] [PubMed]
- Baud, D.; Dimopoulou Agri, V.; Gibson, G.R.; Reid, G.; Giannoni, E. Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. Front. Public Health 2020, 8, 186. [Google Scholar] [CrossRef]
- Morrow, L.E.; Kollef, M.H.; Casale, T.B. Probiotic prophylaxis of ventilator-associated pneumonia: A blinded, randomized, controlled trial. Am. J. Respir. Crit. Care Med. 2010, 182, 1058–1064. [Google Scholar] [CrossRef] [Green Version]
- Mahmoodpoor, A.; Hamishehkar, H.; Asghari, R.; Abri, R.; Shadvar, K.; Sanaie, S. Effect of a Probiotic Preparation on Ventilator-Associated Pneumonia in Critically Ill Patients Admitted to the Intensive Care Unit: A Prospective Double-Blind Randomized Controlled Trial. Nutr. Clin. Pract. 2019, 34, 156–162. [Google Scholar] [CrossRef] [Green Version]
- Li, J.; Zhao, J.; Wang, X.; Qayum, A.; Hussain, M.A.; Liang, G.; Hou, J.; Jiang, Z.; Li, A. Novel Angiotensin-Converting Enzyme-Inhibitory Peptides From Fermented Bovine Milk Started by Lactobacillus helveticus KLDS.31 and Lactobacillus casei KLDS.105: Purification, Identification, and Interaction Mechanisms. Front. Microbiol. 2019, 10, 2643. [Google Scholar] [CrossRef]
- Minato, T.; Nirasawa, S.; Sato, T.; Yamaguchi, T.; Hoshizaki, M.; Inagaki, T.; Nakahara, K.; Yoshihashi, T.; Ozawa, R.; Yokota, S.; et al. B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction. Nat. Commun. 2020, 11, 1058. [Google Scholar] [CrossRef] [Green Version]
- Chan, C.K.Y.; Tao, J.; Chan, O.S.; Li, H.B.; Pang, H. Preventing Respiratory Tract Infections by Synbiotic Interventions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv. Nutr. 2020, 11, 979–988. [Google Scholar] [CrossRef]
- Kumar, R.; Seo, B.J.; Mun, M.R.; Kim, C.J.; Lee, I.; Kim, H.; Park, Y.H. Putative probiotic Lactobacillus spp. from porcine gastrointestinal tract inhibit transmissible gastroenteritis coronavirus and enteric bacterial pathogens. Trop. Anim. Health Prod. 2010, 42, 1855–1860. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Turner, R.B.; Woodfolk, J.A.; Borish, L.; Steinke, J.W.; Patrie, J.T.; Muehling, L.M.; Lahtinen, S.; Lehtinen, M.J. Effect of probiotic on innate inflammatory response and viral shedding in experimental rhinovirus infection—A randomised controlled trial. Benef. Microbes 2017, 8, 207–215. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chai, W.; Burwinkel, M.; Wang, Z.; Palissa, C.; Esch, B.; Twardziok, S.; Rieger, J.; Wrede, P.; Schmidt, M.F. Antiviral effects of a probiotic Enterococcus faecium strain against transmissible gastroenteritis coronavirus. Arch. Virol. 2013, 158, 799–807. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mak, J.W.Y.; Chan, F.K.L.; Ng, S.C. Probiotics and COVID-19: One size does not fit all. Lancet Gastroenterol. Hepatol. 2020, 5, 644–645. [Google Scholar] [CrossRef]
- Garcia, O.P.; Ronquillo, D.; del Carmen Caamano, M.; Martinez, G.; Camacho, M.; Lopez, V.; Rosado, J.L. Zinc, iron and vitamins A, C and e are associated with obesity, inflammation, lipid profile and insulin resistance in Mexican school-aged children. Nutrients 2013, 5, 5012–5030. [Google Scholar] [CrossRef] [Green Version]
- Lee, C.H.; Chan, R.S.M.; Wan, H.Y.L.; Woo, Y.C.; Cheung, C.Y.Y.; Fong, C.H.Y.; Cheung, B.M.Y.; Lam, T.H.; Janus, E.; Woo, J.; et al. Dietary Intake of Anti-Oxidant Vitamins A, C, and E Is Inversely Associated with Adverse Cardiovascular Outcomes in Chinese-A 22-Years Population-Based Prospective Study. Nutrients 2018, 10, 1664. [Google Scholar] [CrossRef] [Green Version]
- Qiang, Y.; Li, Q.; Xin, Y.; Fang, X.; Tian, Y.; Ma, J.; Wang, J.; Wang, Q.; Zhang, R.; Wang, J.; et al. Intake of Dietary One-Carbon Metabolism-Related B Vitamins and the Risk of Esophageal Cancer: A Dose-Response Meta-Analysis. Nutrients 2018, 10, 835. [Google Scholar] [CrossRef] [Green Version]
- Tardy, A.L.; Pouteau, E.; Marquez, D.; Yilmaz, C.; Scholey, A. Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients 2020, 12, 228. [Google Scholar] [CrossRef] [Green Version]
- Calder, P.C.; Carr, A.C.; Gombart, A.F.; Eggersdorfer, M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181. [Google Scholar] [CrossRef] [Green Version]
- Stephensen, C.B. Vitamin A, infection, and immune function. Annu. Rev. Nutr. 2001, 21, 167–192. [Google Scholar] [CrossRef]
- Huang, Z.; Liu, Y.; Qi, G.; Brand, D.; Zheng, S.G. Role of Vitamin A in the Immune System. J. Clin. Med. 2018, 7, 258. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pinto, J.T.; Zempleni, J. Riboflavin. Adv. Nutr. 2016, 7, 973–975. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rowland, I.; Gibson, G.; Heinken, A.; Scott, K.; Swann, J.; Thiele, I.; Tuohy, K. Gut microbiota functions: Metabolism of nutrients and other food components. Eur. J. Nutr. 2018, 57, 1–24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Steinert, R.E.; Lee, Y.K.; Sybesma, W. Vitamins for the Gut Microbiome. Trends Mol. Med. 2020, 26, 137–140. [Google Scholar] [CrossRef] [PubMed]
- Jin, D.; Wu, S.; Zhang, Y.G.; Lu, R.; Xia, Y.; Dong, H.; Sun, J. Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome. Clin. Ther. 2015, 37, 996–1009 e1007. [Google Scholar] [CrossRef]
- Riccio, P.; Rossano, R. Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis. Neurotherapeutics 2018, 15, 75–91. [Google Scholar] [CrossRef] [Green Version]
- Sun, J. Dietary vitamin D, vitamin D receptor, and microbiome. Curr. Opin. Clin. Nutr. Metab. Care 2018, 21, 471–474. [Google Scholar] [CrossRef]
- Waterhouse, M.; Hope, B.; Krause, L.; Morrison, M.; Protani, M.M.; Zakrzewski, M.; Neale, R.E. Vitamin D and the gut microbiome: A systematic review of in vivo studies. Eur. J. Nutr. 2019, 58, 2895–2910. [Google Scholar] [CrossRef]
- Yang, Q.; Liang, Q.; Balakrishnan, B.; Belobrajdic, D.P.; Feng, Q.J.; Zhang, W. Role of Dietary Nutrients in the Modulation of Gut Microbiota: A Narrative Review. Nutrients 2020, 12, 381. [Google Scholar] [CrossRef] [Green Version]
- Pierre, J.F.; Hinterleitner, R.; Bouziat, R.; Hubert, N.A.; Leone, V.; Miyoshi, J.; Jabri, B.; Chang, E.B. Dietary antioxidant micronutrients alter mucosal inflammatory risk in a murine model of genetic and microbial susceptibility. J. Nutr. Biochem. 2018, 54, 95–104. [Google Scholar] [CrossRef]
- Lee, H.; Ko, G. Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome. Sci. Rep. 2016, 6, 25835. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, H.; Ko, G. New perspectives regarding the antiviral effect of vitamin A on norovirus using modulation of gut microbiota. Gut. Microbes 2017, 8, 616–620. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stoffaneller, R.; Morse, N.L. A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients 2015, 7, 1494–1537. [Google Scholar] [CrossRef] [PubMed]
- Hoffmann, P.R.; Berry, M.J. The influence of selenium on immune responses. Mol. Nutr. Food Res. 2008, 52, 1273–1280. [Google Scholar] [CrossRef] [PubMed]
- Rayman, M.P. Selenium intake, status, and health: A complex relationship. Hormones (Athens) 2020, 19, 9–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beck, M.A.; Nelson, H.K.; Shi, Q.; Van Dael, P.; Schiffrin, E.J.; Blum, S.; Barclay, D.; Levander, O.A. Selenium deficiency increases the pathology of an influenza virus infection. FASEB J. 2001, 15, 1481–1483. [Google Scholar] [CrossRef] [PubMed]
- Gangadoo, S.; Dinev, I.; Chapman, J.; Hughes, R.J.; Van, T.T.H.; Moore, R.J.; Stanley, D. Selenium nanoparticles in poultry feed modify gut microbiota and increase abundance of Faecalibacterium prausnitzii. Appl. Microbiol. Biotechnol. 2018, 102, 1455–1466. [Google Scholar] [CrossRef]
- Kudva, A.K.; Shay, A.E.; Prabhu, K.S. Selenium and inflammatory bowel disease. Am. J. Physiol. Gastrointest. Liver Physiol. 2015, 309, G71–G77. [Google Scholar] [CrossRef] [Green Version]
- Speckmann, B.; Steinbrenner, H. Selenium and selenoproteins in inflammatory bowel diseases and experimental colitis. Inflamm. Bowel. Dis. 2014, 20, 1110–1119. [Google Scholar] [CrossRef]
- Haase, H.; Rink, L. Multiple impacts of zinc on immune function. Metallomics 2014, 6, 1175–1180. [Google Scholar] [CrossRef]
- Prasad, A.S. Zinc in human health: Effect of zinc on immune cells. Mol. Med. 2008, 14, 353–357. [Google Scholar] [CrossRef] [PubMed]
- Gammoh, N.Z.; Rink, L. Zinc in Infection and Inflammation. Nutrients 2017, 9, 624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- te Velthuis, A.J.; van den Worm, S.H.; Sims, A.C.; Baric, R.S.; Snijder, E.J.; van Hemert, M.J. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010, 6, e1001176. [Google Scholar] [CrossRef] [PubMed]
- Reed, S.; Neuman, H.; Moscovich, S.; Glahn, R.P.; Koren, O.; Tako, E. Chronic Zinc Deficiency Alters Chick Gut Microbiota Composition and Function. Nutrients 2015, 7, 9768–9784. [Google Scholar] [CrossRef]
- Zackular, J.P.; Moore, J.L.; Jordan, A.T.; Juttukonda, L.J.; Noto, M.J.; Nicholson, M.R.; Crews, J.D.; Semler, M.W.; Zhang, Y.; Ware, L.B.; et al. Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection. Nat. Med. 2016, 22, 1330–1334. [Google Scholar] [CrossRef]
- Perez-Cano, F.J.; Castell, M. Flavonoids, Inflammation and Immune System. Nutrients 2016, 8, 659. [Google Scholar] [CrossRef]
- Alkhalidy, H.; Wang, Y.; Liu, D. Dietary Flavonoids in the Prevention of T2D: An Overview. Nutrients 2018, 10, 438. [Google Scholar] [CrossRef] [Green Version]
- Grassi, D.; Desideri, G.; Ferri, C. Flavonoids: Antioxidants against atherosclerosis. Nutrients 2010, 2, 889–902. [Google Scholar] [CrossRef] [Green Version]
- Monteiro, A.F.M.; Viana, J.O.; Nayarisseri, A.; Zondegoumba, E.N.; Mendonca Junior, F.J.B.; Scotti, M.T.; Scotti, L. Computational Studies Applied to Flavonoids against Alzheimer’s and Parkinson’s Diseases. Oxid. Med. Cell. Longev. 2018, 2018, 7912765. [Google Scholar] [CrossRef]
- Zakaryan, H.; Arabyan, E.; Oo, A.; Zandi, K. Flavonoids: Promising natural compounds against viral infections. Arch. Virol. 2017, 162, 2539–2551. [Google Scholar] [CrossRef]
- Yu, M.S.; Lee, J.; Lee, J.M.; Kim, Y.; Chin, Y.W.; Jee, J.G.; Keum, Y.S.; Jeong, Y.J. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13. Bioorg. Med. Chem. Lett. 2012, 22, 4049–4054. [Google Scholar] [CrossRef] [PubMed]
- Jo, S.; Kim, H.; Kim, S.; Shin, D.H.; Kim, M.S. Characteristics of flavonoids as potent MERS-CoV 3C-like protease inhibitors. Chem. Biol. Drug Des. 2019, 94, 2023–2030. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carrera-Quintanar, L.; Lopez Roa, R.I.; Quintero-Fabian, S.; Sanchez-Sanchez, M.A.; Vizmanos, B.; Ortuno-Sahagun, D. Phytochemicals That Influence Gut Microbiota as Prophylactics and for the Treatment of Obesity and Inflammatory Diseases. Mediators Inflamm. 2018, 2018, 9734845. [Google Scholar] [CrossRef] [PubMed]
- Pei, R.; Liu, X.; Bolling, B. Flavonoids and gut health. Curr. Opin. Biotechnol. 2020, 61, 153–159. [Google Scholar] [CrossRef]
- Oteiza, P.I.; Fraga, C.G.; Mills, D.A.; Taft, D.H. Flavonoids and the gastrointestinal tract: Local and systemic effects. Mol. Aspects Med. 2018, 61, 41–49. [Google Scholar] [CrossRef]
- Steed, A.L.; Christophi, G.P.; Kaiko, G.E.; Sun, L.; Goodwin, V.M.; Jain, U.; Esaulova, E.; Artyomov, M.N.; Morales, D.J.; Holtzman, M.J.; et al. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science 2017, 357, 498–502. [Google Scholar] [CrossRef] [Green Version]
- Xu, G.; Dou, J.; Zhang, L.; Guo, Q.; Zhou, C. Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the serum. Biol. Pharm. Bull. 2010, 33, 238–243. [Google Scholar] [CrossRef] [Green Version]
- Gutierrez, S.; Svahn, S.L.; Johansson, M.E. Effects of Omega-3 Fatty Acids on Immune Cells. Int. J. Mol. Sci. 2019, 20, 5028. [Google Scholar] [CrossRef] [Green Version]
- Calder, P.C. n-3 fatty acids, inflammation and immunity: New mechanisms to explain old actions. Proc. Nutr. Soc. 2013, 72, 326–336. [Google Scholar] [CrossRef] [Green Version]
- Gottrand, F. Long-chain polyunsaturated fatty acids influence the immune system of infants. J. Nutr. 2008, 138, 1807S–1812S. [Google Scholar] [CrossRef]
- Parolini, C. Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System. Mar. Drugs 2019, 17, 374. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morita, M.; Kuba, K.; Ichikawa, A.; Nakayama, M.; Katahira, J.; Iwamoto, R.; Watanebe, T.; Sakabe, S.; Daidoji, T.; Nakamura, S.; et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell 2013, 153, 112–125. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fenton, J.I.; Hord, N.G.; Ghosh, S.; Gurzell, E.A. Immunomodulation by dietary long chain omega-3 fatty acids and the potential for adverse health outcomes. Prostaglandins Leukot Essent Fatty Acids 2013, 89, 379–390. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Costantini, L.; Molinari, R.; Farinon, B.; Merendino, N. Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int. J. Mol. Sci. 2017, 18, 2645. [Google Scholar] [CrossRef] [Green Version]
- Patterson, E.; RM, O.D.; Murphy, E.F.; Wall, R.; O’Sullivan, O.; Nilaweera, K.; Fitzgerald, G.F.; Cotter, P.D.; Ross, R.P.; Stanton, C. Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice. Br. J. Nutr. 2014, 111, 1905–1917. [Google Scholar] [CrossRef] [Green Version]
- Watson, H.; Mitra, S.; Croden, F.C.; Taylor, M.; Wood, H.M.; Perry, S.L.; Spencer, J.A.; Quirke, P.; Toogood, G.J.; Lawton, C.L.; et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut 2018, 67, 1974–1983. [Google Scholar] [CrossRef]
- Yang, Y.; Islam, M.S.; Wang, J.; Li, Y.; Chen, X. Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Int. J. Biol. Sci. 2020, 16, 1708–1717. [Google Scholar] [CrossRef]
- Lau, T.F.; Leung, P.C.; Wong, E.L.; Fong, C.; Cheng, K.F.; Zhang, S.C.; Lam, C.W.; Wong, V.; Choy, K.M.; Ko, W.M. Using herbal medicine as a means of prevention experience during the SARS crisis. Am. J. Chin. Med. 2005, 33, 345–356. [Google Scholar] [CrossRef]
- Cinatl, J.; Morgenstern, B.; Bauer, G.; Chandra, P.; Rabenau, H.; Doerr, H.W. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003, 361, 2045–2046. [Google Scholar] [CrossRef] [Green Version]
- Chen, L.; Li, J.; Luo, C.; Liu, H.; Xu, W.; Chen, G.; Liew, O.W.; Zhu, W.; Puah, C.M.; Shen, X.; et al. Binding interaction of quercetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): Structure-activity relationship studies reveal salient pharmacophore features. Bioorg. Med. Chem. 2006, 14, 8295–8306. [Google Scholar] [CrossRef]
- Yi, L.; Li, Z.; Yuan, K.; Qu, X.; Chen, J.; Wang, G.; Zhang, H.; Luo, H.; Zhu, L.; Jiang, P.; et al. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J. Virol. 2004, 78, 11334–11339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jian-ya, G. Clinical characteristics of 51 patients discharged from hospital with COVID-19 in Chongqing, China. medRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
- Feng, W.; Ao, H.; Peng, C.; Yan, D. Gut microbiota, a new frontier to understand traditional Chinese medicines. Pharmacol. Res. 2019, 142, 176–191. [Google Scholar] [CrossRef] [PubMed]
- Zhang, R.; Gao, X.; Bai, H.; Ning, K. Traditional Chinese Medicine and Gut Microbiome: Their Respective and Concert Effects on Healthcare. Front. Pharmacol. 2020, 11, 538. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, B.; Yue, R.; Chen, Y.; Yang, M.; Huang, X.; Shui, J.; Peng, Y.; Chin, J. Gut Microbiota, a Potential New Target for Chinese Herbal Medicines in Treating Diabetes Mellitus. Evid. Based Complement. Alternat. Med. 2019, 2019, 2634898. [Google Scholar] [CrossRef]
- Xu, J.; Lian, F.; Zhao, L.; Zhao, Y.; Chen, X.; Zhang, X.; Guo, Y.; Zhang, C.; Zhou, Q.; Xue, Z.; et al. Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula. ISME J. 2015, 9, 552–562. [Google Scholar] [CrossRef]
- Chang, C.J.; Lin, C.S.; Lu, C.C.; Martel, J.; Ko, Y.F.; Ojcius, D.M.; Tseng, S.F.; Wu, T.R.; Chen, Y.Y.; Young, J.D.; et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat. Commun. 2015, 6, 7489. [Google Scholar] [CrossRef] [Green Version]
- Yue, S.J.; Wang, W.X.; Yu, J.G.; Chen, Y.Y.; Shi, X.Q.; Yan, D.; Zhou, G.S.; Zhang, L.; Wang, C.Y.; Duan, J.A.; et al. Gut microbiota modulation with traditional Chinese medicine: A system biology-driven approach. Pharmacol. Res. 2019, 148, 104453. [Google Scholar] [CrossRef]
- Miyasaka, M. Is BCG vaccination causally related to reduced COVID-19 mortality? EMBO Mol. Med. 2020, 12, e12661. [Google Scholar] [CrossRef]
- O’Neill, L.A.J.; Netea, M.G. BCG-induced trained immunity: Can it offer protection against COVID-19? Nat. Rev. Immunol. 2020, 20, 335–337. [Google Scholar] [CrossRef]
- Arts, R.J.W.; Moorlag, S.; Novakovic, B.; Li, Y.; Wang, S.Y.; Oosting, M.; Kumar, V.; Xavier, R.J.; Wijmenga, C.; Joosten, L.A.B.; et al. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe 2018, 23, 89–100.e105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Curtis, N.; Sparrow, A.; Ghebreyesus, T.A.; Netea, M.G. Considering BCG vaccination to reduce the impact of COVID-19. Lancet 2020, 395, 1545–1546. [Google Scholar] [CrossRef]
- Floc’h, F.; Werner, G.H. Increased resistance to virus infections of mice inoculated with BCG (Bacillus calmette-guerin). Ann. Immunol. (Paris) 1976, 127, 173–186. [Google Scholar]
- Ohrui, T.; Nakayama, K.; Fukushima, T.; Chiba, H.; Sasaki, H. [Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations]. Nihon. Ronen Igakkai Zasshi 2005, 42, 34–36. [Google Scholar] [CrossRef] [Green Version]
- Old, L.J.; Benacerraf, B.; Clarke, D.A.; Carswell, E.A.; Stockert, E. The role of the reticuloendothelial system in the host reaction to neoplasia. Cancer Res. 1961, 21, 1281–1300. [Google Scholar] [PubMed]
- Wardhana, D.E.; Sultana, A.; Mandang, V.V.; Jim, E. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med. Indones 2011, 43, 185–190. [Google Scholar] [PubMed]
- Escobar, L.E.; Molina-Cruz, A.; Barillas-Mury, C. BCG vaccine-induced protection from COVID-19 infection, wishful thinking or a game changer? medRxiv 2020. [Google Scholar] [CrossRef]
- Kumar, J.; Meena, J. Demystifying BCG Vaccine and COVID-19 Relationship. Indian Pediatr. 2020, 57, 588–589. [Google Scholar] [CrossRef]
- Escobar, L.E.; Molina-Cruz, A.; Barillas-Mury, C. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Proc. Natl. Acad. Sci. USA 2020, 117, 17720–17726. [Google Scholar] [CrossRef]
- Ciabattini, A.; Olivieri, R.; Lazzeri, E.; Medaglini, D. Role of the Microbiota in the Modulation of Vaccine Immune Responses. Front. Microbiol. 2019, 10, 1305. [Google Scholar] [CrossRef] [Green Version]
- Nadeem, S.; Maurya, S.K.; Das, D.K.; Khan, N.; Agrewala, J.N. Gut Dysbiosis Thwarts the Efficacy of Vaccine Against Mycobacterium tuberculosis. Front. Immunol. 2020, 11, 726. [Google Scholar] [CrossRef] [PubMed]
- Lex, J.R.; Azizi, A. Microbiota, a forgotten relic of vaccination. Expert Rev. Vaccines 2017, 16, 1171–1173. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oh, J.Z.; Ravindran, R.; Chassaing, B.; Carvalho, F.A.; Maddur, M.S.; Bower, M.; Hakimpour, P.; Gill, K.P.; Nakaya, H.I.; Yarovinsky, F.; et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 2014, 41, 478–492. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lynn, M.A.; Tumes, D.J.; Choo, J.M.; Sribnaia, A.; Blake, S.J.; Leong, L.E.X.; Young, G.P.; Marshall, H.S.; Wesselingh, S.L.; Rogers, G.B.; et al. Early-Life Antibiotic-Driven Dysbiosis Leads to Dysregulated Vaccine Immune Responses in Mice. Cell Host Microbe 2018, 23, 653–660.e655. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huda, M.N.; Lewis, Z.; Kalanetra, K.M.; Rashid, M.; Ahmad, S.M.; Raqib, R.; Qadri, F.; Underwood, M.A.; Mills, D.A.; Stephensen, C.B. Stool microbiota and vaccine responses of infants. Pediatrics 2014, 134, e362–e372. [Google Scholar] [CrossRef] [Green Version]
- Funk, C.D.; Laferriere, C.; Ardakani, A. A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic. Front. Pharmacol. 2020, 11, 937. [Google Scholar] [CrossRef]
- Kaur, S.P.; Gupta, V. COVID-19 Vaccine: A comprehensive status report. Virus Res. 2020, 288, 198114. [Google Scholar] [CrossRef]
- Mullard, A. COVID-19 vaccine development pipeline gears up. Lancet 2020, 395, 1751–1752. [Google Scholar] [CrossRef]
- de Jong, S.E.; Olin, A.; Pulendran, B. The Impact of the Microbiome on Immunity to Vaccination in Humans. Cell Host Microbe 2020, 28, 169–179. [Google Scholar] [CrossRef]
ID, Country, and Status † | Study Type and Participants | Trial Title (Main Hypothesis/Aims) |
---|---|---|
NCT04325919 Hong Kong Recruiting | Obs./Prosp. Hospitalized COVID-19 patients (170 *) | Comprehensive Clinical, Virological, Microbiological, Immunological and Laboratory Monitoring of Patients Hospitalized With COVID-19 |
NCT04359706 France Recruiting | Obs./Prosp. COVID-19 patients at ICU (30 *) | Bacterial and Fungal Microbiota of Patients with Severe Viral Pneumonia With SARS-CoV2 (determine the respiratory and fecal microbiota—microbial and fungal—of critically ill patients) |
NCT04410263 Switzerland Recruiting | Obs./Prosp. COVID-positive patients at ICU (300 *) | Microbiota in COVID-19 Patients for Future Therapeutic and Preventive Approaches |
NCT04486482 USA Recruiting | Interv./Par. Ass. Mild-to-moderate COVID-19 patients (50 *) | An Exploratory, Open Label, Clinical Study to Evaluate the Physiologic Effects of KB109 in Adult Patients with Mild-to-Moderate COVID-19 on Gut Microbiota Structure and Function in the Outpatient Setting |
NCT04399252 USA Recruiting | Interv./Par. Ass. Exposed household contacts of COVID-19 (1000 *) | A Randomized Trial of the Effect of Lactobacillus on the Microbiome of Household Contacts Exposed to COVID-19 |
NCT04355741 Portugal Recruiting | Obs./Prosp. COVID-19 patients (60 *) | Gut Microbiota, “Spark and Flame” of COVID-19 Disease (fecal gut microbiota composition could affect vulnerability and disease outcomes of COVID-19) |
NCT04366089 Italy Recruiting | Interv./Par. Ass. Hospitalized COVID-19 patients (152 *) | Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated with Modulation of the Gut Microbial Flora (Phase 2) |
NCT04332016 France Recruiting | Obs./Prosp. Hospitalized COVID-19 patients (2000 *) | COVID-19 Biological Samples Collection (COLCOV19-BX) |
NCT04458519 Canada Not yet Recruiting | Interv./Par. Ass. COVID-19 patients not requiring hospitaliz. (40 *) | Randomised Single Blinded Clinical Study of Efficacy of Intranasal Probiotic Treatment to Reduce Severity of Symptoms in COVID19 Infection |
NCT04327570 Belgium Recruiting | Obs./Prosp. Hospitalized COVID-19 patients (100 *) | In-depth Characterisation of the Dynamic Host Immune Response to Coronavirus SARS-CoV-2 (Correlation of immune profiling with microbiome analysis) |
NCT04390477 Spain Recruiting | Interv./Par. Ass. Hospitalized COVID-19 patients (40 *) | The Intestinal Microbiota as a Therapeutic Target in Hospitalized Patients With COVID-19 Infection (a positive effect of probiotic on the GM that could produce a less severe clinical evolution of the disease) |
NCT04368351 Italy Active, not recruiting | Obs./Retros. Hospitalized COVID-19 patients (70 *) | Evaluation of the Impact of Bacteriotherapy in the Treatment of COVID-19 (probiotic supplementation (SivoMixx) + Azithromycin) |
NCT04373148 USA Recruiting | Obs./Prosp. Adults and children with COVID-19 (1000 *) | Understanding Immunity to SARS-CoV-2, the Coronavirus Causing COVID-19 |
NCT04451577 Italy Recruiting | Obs./Case-Control Hospital employees with or without COVID-19 (5000 *) | Epidemiologic, Clinical, Molecular Characteristics of Hospital Employees With or Without Covid-19 Infection: a Retrospective-prospective Cohort Study |
NCT04497402 Italy Not yet Recruiting | Obs./Prosp. Covid-19 patients (88 *) | Sex-Informed Data in the COVID-19 Pandemic (determine whether there are sex differences in biomarkers, including in gut microbiome) |
NCT04359459 The Netherlands Not yet recruiting | Obs./Prosp. COVID-19 patients (150 *) | Nasal CIliated EPithelial Genetic and Single Cell RNA prOfiLes of miLd, Severe and Very Severe COVID-Nineteen patIents (CIPOLLINI) Study (correlation of feces microbiome and clinical outcome for COVID-19) |
NCT04403646 Argentina Not Yet Recruiting | Interv./Par. Ass. Hospitalized COVID-19 patients (140 *) | Efficacy of Tannin Specific Natural Extract for Coronavirus Disease (COVID-19): Randomized Controlled Trial |
NCT04517422 Mexico Not Yet Recruiting | Interv./Par. Ass COVID-19 patients with mild symptoms (300 *) | Efficacy and Safety of Lactobacillus Plantarum and P. Acidilactici as Co-adjuvant Therapy for Reducing the Risk of Severe Disease in Adults With SARS-CoV-2 and Its Modulation of the Fecal Microbiota: A RCT |
NCT04447144 Egypt Recruiting | Obs./Prosp.; COVID-19 patients with mild and moderate severity (200 *) | Nutritional Habits, Does it Affect Coronavirus Disease 2019 (COVID-19) Infection Outcome? An Egyptian Experience |
NCT04420676 Austria Not yet recruiting | Interv./Par. Ass. COVID-19 patients (108 *) | Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection: A Randomized, Double-blind, Placebo Controlled, Telemedicine Study (SynCov Study) (probiotic supplementation: Omnibiotic® AAD) |
NCT04345510 Germany Not yet recruiting | Obs./Prosp. Asymptomatic Carriers (500 *) | Testing for COVID-19 Infection in Asymptomatic Persons (analyze for a possible correlation between oral microbiome and COVID-19 infection status) |
NCT04444609 United Kingdom Recruiting | Obs./Prosp. COVID-19 patients with lung disease (230 *) | PROSAIC-19 - Prospective Longitudinal Assessment in a COVID-19 Infected Cohort |
NCT04359836 USA Recruiting | Obs. COVID-19 patients (250 *) | A Non-Interventional Pilot Study to Explore the Role of Gut Flora in COVID-19 Infection |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ferreira, C.; Viana, S.D.; Reis, F. Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches. Microorganisms 2020, 8, 1514. https://doi.org/10.3390/microorganisms8101514
Ferreira C, Viana SD, Reis F. Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches. Microorganisms. 2020; 8(10):1514. https://doi.org/10.3390/microorganisms8101514
Chicago/Turabian StyleFerreira, Carolina, Sofia D. Viana, and Flávio Reis. 2020. "Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches" Microorganisms 8, no. 10: 1514. https://doi.org/10.3390/microorganisms8101514
APA StyleFerreira, C., Viana, S. D., & Reis, F. (2020). Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches. Microorganisms, 8(10), 1514. https://doi.org/10.3390/microorganisms8101514