The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Center for Stem Cell Research College of Medicine King Khalid University Abha Saudi Arabia

Department of Microbiology and Clinical Parasitology College of Medicine King Khalid University Abha Saudi Arabia

Department of Molecular Biology Ekka Diagnostics Chennai Tamil Nadu India

Department of Pharmaceutical Biology Faculty of Pharmaceutical Sciences University College of Sedaya International UCSI University Kuala Lumpur Malaysia

Department of Pharmaceutical Technology Faculty of Pharmaceutical Sciences UCSI University Kuala Lumpur Malaysia

Department of Structural and Cellular Biology Tulane University School of Medicine New Orleans LA United States

Faculty of Science University of South Bohemia České Budějovice Czechia

School of Life Sciences B S Abdur Rahman Crescent Institute of Science and Technology Chennai India

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Abbasi A. F., Marinkovic A., Prakash S., Sanyaolu A., Smith S. (2022). COVID-19 and the human gut microbiome: an under-recognized association. Chonnam. Med. J. 58, 96–101. doi: 10.4068/cmj.2022.58.3.96 PubMed DOI PMC

Abo-Shaban T., Sharna S. S., Hosie S., Lee C. Y. Q., Balasuriya G. K., McKeown S. J., et al. . (2023). Issues for patchy tissues: defining roles for gut-associated lymphoid tissue in neurodevelopment and disease. J. Neural Transm (Vienna). 130, 269–280. doi: 10.1007/s00702-022-02561-x PubMed DOI PMC

Adamo S., Chevrier S., Cervia C., Zurbuchen Y., Raeber M. E., Yang L., et al. . (2021). Profound dysregulation of T cell homeostasis and function in patients with severe covid-19. Allergy. 76, 2866–2881. doi: 10.1111/all.14866 PubMed DOI PMC

Aggarwal N., Kitano S., Puah G. R. Y., Kittelmann S., Hwang I. Y., Chang M. W. (2023). Microbiome and human health: current understanding, engineering, and enabling technologies. Chem. Rev. 123, 31–72. doi: 10.1021/acs.chemrev.2c00431 PubMed DOI PMC

Akter S., Tasnim S., Barua R., Choubey M., Arbee S., Mohib M. M., et al. . (2023). The effect of COVID-19 on gut microbiota: exploring the complex interplay and implications for human health. Gastrointest. Disord. 5, 340–355. doi: 10.3390/gidisord5030028 DOI

Ananya F. N., Ahammed M. R., Fahem M. M., Kafle S., Viswanathan M., Desai D., et al. . (2021). Association of intestinal microbial dysbiosis with chronic obstructive pulmonary disease. Cureus. 13, e19343. doi: 10.7759/cureus.19343 PubMed DOI PMC

Anshory M., Effendi R. M. R. A., Kalim H., Dwiyana R. F., Suwarsa O., Nijsten T. E. C., et al. . (2023). Butyrate properties in immune-related diseases: friend or foe? Fermentation 9, 205. doi: 10.3390/fermentation9030205 DOI

Banerjee A., Somasundaram I., Das D., Jain Manoj S., Banu H., Mitta Suresh P., et al. . (2023). Functional foods: A promising strategy for restoring gut microbiota diversity impacted by SARS-coV-2 variants. Nutrients. 15, 2631. doi: 10.3390/nu15112631 PubMed DOI PMC

Baradaran Ghavami S., Pourhamzeh M., Farmani M., Raftar S. K. A., Shahrokh S., Shpichka A., et al. . (2021). Cross-talk between immune system and microbiota in COVID-19. Expert Rev. Gastroenterol. Hepatol. 15, 1281–1294. doi: 10.1080/17474124.2021.1991311 PubMed DOI PMC

Barnes C. O., Jette C. A., Abernathy M. E., Dam K.-M. A., Esswein S. R., Gristick H. B., et al. . (2020). SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 588, 682–687. doi: 10.1038/s41586-020-2852-1 PubMed DOI PMC

Bernard-Raichon L., Venzon M., Klein J., Axelrad J. E., Zhang C., Sullivan A. P., et al. . (2022). Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nat. Commun. 13, 5926. doi: 10.1038/s41467-022-33395-6 PubMed DOI PMC

Boechat J. L., Chora I., Morais A., Delgado L. (2021). The immune response to SARS-CoV-2 and COVID-19 immunopathology - Current perspectives. Pulmonology. 27, 423–437. doi: 10.1016/j.pulmoe.2021.03.008 PubMed DOI PMC

Campbell C., Kandalgaonkar M. R., Golonka R. M., Yeoh B. S., Vijay-Kumar M., Saha P. (2023). Crosstalk between gut microbiota and host immunity: impact on inflammation and immunotherapy. Biomedicines 11, 294. doi: 10.3390/biomedicines11020294 PubMed DOI PMC

Cascella M., Rajnik M., Aleem A., Dulebohn S. C., Di Napoli R. (2023). “Features, evaluation, and treatment of coronavirus (COVID-19),” in StatPearls (StatPearls Publishing, Treasure Island (FL: ). PubMed

Chakraborty R. K., Burns B. (2022). Features, evaluation, and treatment of coronavirus (Systemic inflammatory response syndrome. In StatPearls (StatPearls Publishing; ). Available at: http://www.ncbi.nlm.nih.gov/books/NBK547669/. PubMed

Chakraborty C., Sharma A. R., Bhattacharya M., Dhama K., Lee S. S. (2022). Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity. World J. Gastroenterol. 28, 2802–2822. doi: 10.3748/wjg.v28.i25.2802 PubMed DOI PMC

Chia J. K. S., Chia A. Y. (2008). Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J. Clin. Pathol. 61, 43–48. doi: 10.1136/jcp.2007.050054 PubMed DOI

Choto T. A., Makupe I., Cakana A. Z., Sibanda E. N., Mduluza T. (2019). Excessive neutrophil recruitment promotes typical T-helper 17 responses in coronavirus disease 2019 patients. PloS One 17, e0273186. doi: 10.1371/journal.pone.0273186 PubMed DOI PMC

Davis H. E., McCorkell L., Moore Vogel J., Topol E. J. (2023). Long COVID: major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 133–146. doi: 10.1038/s41579-022-00846-2 PubMed DOI PMC

De Biasi S., Meschiari M., Gibellini L., Bellinazzi C., Borella R., Fidanza L., et al. . (2020). Marked T cell activation, senescence, exhaustion and skewing towards Th17 in patients with covid-19 pneumonia. Nat. Commun. 11, 3434. doi: 10.1038/s41467-020-17292-4 PubMed DOI PMC

De Clercq E., Li G. (2016). Approved antiviral drugs over the past 50 years. Clin. Microbiol. Rev. 29, 695–747. doi: 10.1128/CMR.00102-15 PubMed DOI PMC

Del Rio C., Collins L. F., Malani P. (2020). Long-term health consequences of COVID-19. J. Am. Med. Assoc. 324, 1723–1724. doi: 10.1001/jama.2020.19719 PubMed DOI PMC

Deng Y. Q., Zhang N.-N., Zhang Y.-F., Zhong X., Xu S., Qiu H.-Y., et al. . (2022). Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters. Cell Res. 32, 375–382. doi: 10.1038/s41422-022-00630-0 PubMed DOI PMC

Dhar D., Mohanty A. (2020). Gut microbiota and covid-19- possible link and implications. Virus Res. 285, 198018. doi: 10.1016/j.virusres.2020.198018 PubMed DOI PMC

Fakharian F., Thirugnanam S., Welsh D. A., Kim W. K., Rappaport J., Bittinger K., et al. . (2023). The role of gut dysbiosis in the loss of intestinal immune cell functions and viral pathogenesis. Microorganisms 11, 1849. doi: 10.3390/microorganisms11071849 PubMed DOI PMC

Fathi F., Sami R., Mozafarpoor S., Hafezi H., Motedayyen H., Arefnezhad R., et al. . (2020). Immune system changes during covid-19 recovery play key role in determining disease severity. Int. J. Immunopathol. Pharmacol. 34, 1-13. doi: 10.1177/2058738420966497 PubMed DOI PMC

Focosi D., Franchini M., Pirofski L.-A., Burnouf T., Paneth N., Joyner M. J., et al. . (2022). COVID-19 convalescent plasma and clinical trials: understanding conflicting outcomes. Clin. Microbiol. Rev. 35, e0020021. doi: 10.1128/cmr.00200-21 PubMed DOI PMC

Ghimire S., Roy C., Wongkuna S., Antony L., Maji A., Keena M. C., et al. . (2020). Identification of Clostridioides difficile-inhibiting gut commensals using culturomics, phenotyping, and combinatorial community assembly. mSystems. 5, e00620–e00619. doi: 10.1128/mSystems.00620-19 PubMed DOI PMC

Gibbons S. M., Gurry T., Lampe J. W., Chakrabarti A., Dam V., Everard A., et al. . (2022). Perspective: leveraging the gut microbiota to predict personalized responses to dietary, prebiotic, and probiotic interventions. Adv. Nutr. 2, 13(5):1450–1461. doi: 10.1093/advances/nmac075 PubMed DOI PMC

Gil-Etayo F. J., Suarez-Fernandez P., Cabrera-Marante O., Arroyo D., Garcinuno S., Naranjo. L., et al. . (2021). T-Helper cell subset response is a determining factor in covid-19 progression. Front. Cell Infect. Microbiol. 11. doi: 10.3389/fcimb.2021.624483 PubMed DOI PMC

Giron L. B., Dweep H., Yin X., Wang H., Damra M., Goldman A. R., et al. . (2021). Plasma markers of disrupted gut permeability in severe COVID-19 patients. Front. Immunol. 12, 686240. doi: 10.3389/fimmu.2021.686240 PubMed DOI PMC

Hannoodee S., Nasuruddin D. N. (2022). “Acute inflammatory response,” in StatPearls (StatPearls Publishing, Treasure Island (FL: ).

Harper A., Vijayakumar V., Ouwehand A. C., ter Haar J., Obis D., Espadaler J., et al. . (2021). Viral infections, the microbiome, and probiotics. Front. Cell. Infect. Microbiol. 10. doi: 10.3389/fcimb.2020.596166 PubMed DOI PMC

Hazan S., Stollman N., Bozkurt H. S., Dave S., Papoutsis A. J., Daniels J., et al. . (2022). Lost microbes of covid-19: bifidobacterium, faecalibacterium depletion and decreased microbiome diversity associated with sars-Cov-2 infection severity. BMJ Open Gastroenterol. 9, e000871. doi: 10.1136/bmjgast-2022-000871 PubMed DOI PMC

Hermens J. M., Kesmir C. (2023). Role of T cells in severe COVID-19 disease, protection, and long term immunity. Immunogenetics. 75, 295–307. doi: 10.1007/s00251-023-01294-9 PubMed DOI PMC

Huang C., Huang L., Wang Y., Li X., Ren L., Gu X., et al. . (2021). 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 397, 220–232. doi: 10.1016/S0140-6736(20)32656-8 PubMed DOI PMC

Huang B., Wang J., Li L. (2023). Recent five-year progress in the impact of gut microbiota on vaccination and possible mechanisms. Gut Pathog. 15, 27. doi: 10.1186/s13099-023-00547-y PubMed DOI PMC

Hung Y. P., Lee C. C., Lee J. C., Tsai P. J., Ko W. C. (2021). Gut dysbiosis during COVID-19 and potential effect of probiotics. Microorganisms 9, 1605. doi: 10.3390/microorganisms9081605 PubMed DOI PMC

Hussain I., Cher G. L. Y., Abid M. A., Abid M. B. (2021). Role of gut microbiome in COVID-19: an insight into pathogenesis and therapeutic potential. Front. Immunol. 12. doi: 10.3389/fimmu.2021.765965 PubMed DOI PMC

Iyer A. S., Jones F. K., Nodoushani A., Kelly M., Becker M., Slater D., et al. . (2020). Persistence and decay of human antibody responses to the receptor binding domain of sars-Cov-2 spike protein in covid-19 patients. Sci. Immunol. 5, eabe0367. doi: 10.1126/sciimmunol.abe0367 PubMed DOI PMC

Katz-Agranov N., Zandman-Goddard G. (2021). Autoimmunity and covid-19 – the microbiotal connection. Autoimmun Rev. 20, 102865. doi: 10.1016/j.autrev.2021.102865 PubMed DOI PMC

Kedor C., Freitag H., Meyer-Arndt L.-A., Wittke K., Zoller T., Steinbeis F., et al. . (2021). Chronic COVID-19 syndrome and chronic fatigue syndrome (ME/CFS) following the first pandemic wave in Germany: a first analysis of a prospective observational study. Med. Rxiv, 1-23. doi: 10.1101/2021.02.06.21249256v1 DOI

Kenny G., Townsend L., Savinelli S., Mallon P. W. G. (2023). Long COVID: Clinical characteristics, proposed pathogenesis and potential therapeutic targets. Front. Mol. Biosci. 10. doi: 10.3389/fmolb.2023.1157651 PubMed DOI PMC

Khan M., Mathew B. J., Gupta P., Garg G., Khadanga S., Vyas A. K., et al. . (2021). Gut dysbiosis and il-21 response in patients with severe covid-19. Microorganisms. 9, 1292. doi: 10.3390/microorganisms9061292 PubMed DOI PMC

Komaroff A. L., Bateman L. (2021). Will COVID-19 lead to myalgicencephalomyelitis/chronic fatigue syndrome? Front. Med. 7, 606824. doi: 10.3389/fmed.2020.606824 PubMed DOI PMC

Kruglikov I. L., Shah M., Scherer P. E. (2020). Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral-bacterial interactions. Elife. 9, e61330. doi: 10.7554/eLife.61330 PubMed DOI PMC

Lamers M. M., Beumer J., van der Vaart J., Knoops K., Puschhof J., Breugem T. I., et al. . (2020). SARS-CoV-2 productively infects human gut enterocytes. Science. 369, 50–54. doi: 10.1126/science.abc1669 PubMed DOI PMC

Lee W. S., Wheatley A. K., Kent S. J., DeKosky B. J. (2020). Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat. Microbiol. 5, 1185–1191. doi: 10.1038/s41564-020-00789-5 PubMed DOI

Li C., Chen W., Lin F., Li W., Wang P., Liao G., et al. . (2023). Functional two-way crosstalk between brain and lung: the brain-lung axis. Cell Mol. Neurobiol. 43, 991–1003. doi: 10.1007/s10571-022-01238-z PubMed DOI PMC

Liang B., Xing D. (2023). The current and future perspectives of postbiotics. Probiotics Antimicro. Prot 15 (6), 1626-1643. doi: 10.1007/s12602-023-10045-x PubMed DOI PMC

Lionakis M. S., Drummond R. A., Hohl. T. M. (2023). Immune responses to human fungal pathogens and therapeutic prospects. Nat. Rev. Immunol. 23, 433–452. doi: 10.1038/s41577-022-00826-w PubMed DOI PMC

Liu X., Cheng Y., Zang D., Zhang M., Li X., Liu D., et al. . (2021). The role of gut microbiota in lung cancer: from carcinogenesis to immunotherapy. Front. Oncol. 11. doi: 10.3389/fonc.2021.720842 PubMed DOI PMC

Low R. N., Low R. J., Akrami A. (2023). A review of cytokine-based pathophysiology of Long COVID symptoms. Front. Med. (Lausanne). 10. doi: 10.3389/fmed.2023.1011936 PubMed DOI PMC

Mańkowska-Wierzbicka D., Zuraszek J., Wierzbicka A., Gabryel M., Mahadea D., Baturo A., et al. . (2023). Alterations in gut microbiota composition in patients with COVID-19: A pilot study of whole hypervariable 16S rRNA gene sequencing. Biomedicines 11, 367. doi: 10.3390/biomedicines11020367 PubMed DOI PMC

Mazhar M., Zhu Y., Qin L. (2023). The interplay of dietary fibers and intestinal microbiota affects type 2 diabetes by generating short-chain fatty acids. Foods 12, 1023. doi: 10.3390/foods12051023 PubMed DOI PMC

Mazziotta C., Tognon M., Martini F., Torreggiani E., Rotondo J. C. (2023). Probiotics mechanism of action on immune cells and beneficial effects on human health. Cells. 12, 184. doi: 10.3390/cells12010184 PubMed DOI PMC

Mazzoni A., Salvati L., Maggi L., Capone M., Vanni A., Spinicci M., et al. . (2020). Impaired immune cell cytotoxicity in severe covid-19 is il-6 dependent. J. Clin. Invest. 130, 4694–4703. doi: 10.1172/JCI138554 PubMed DOI PMC

McMahan K., Yu J., Mercado N. B., Loos C., Tostanoski L. H., Chandrashekar A., et al. . (2021). Correlates of protection against sars-Cov-2 in rhesus macaques. Nature. 590, 630–634. doi: 10.1038/s41586-020-03041-6 PubMed DOI PMC

Mohandas S., Jagannathan P., Henrich T. J., Sherif Z. A., Bime C., Quinlan E., et al. . (2023). RECOVER Mechanistic Pathways Task Force. Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 12, e86014. doi: 10.7554/eLife.86014 PubMed DOI PMC

Montazersaheb S., Hosseiniyan Khatibi S. M., Hejazi M. S., Tarhriz V., Farjami A., Ghasemian Sorbeni F., et al. . (2022). COVID-19 infection: an overview on cytokine storm and related interventions. Virol. J. 19, 92. doi: 10.1186/s12985-022-01814-1 PubMed DOI PMC

Müller L., Di Benedetto S. (2023). Aged brain and neuroimmune responses to COVID-19: post-acute sequelae and modulatory effects of behavioral and nutritional interventions. Immun. Ageing 20, 17. doi: 10.1186/s12979-023-00341-z PubMed DOI PMC

Nejadghaderi S. A., Nazemalhosseini-Mojarad E., Asadzadeh Aghdaei H. (2021). Fecal microbiota transplantation for covid-19; a potential emerging treatment strategy. Med. Hypotheses. 147, 110476. doi: 10.1016/j.mehy.2020.110476 PubMed DOI PMC

Newberry F., Hsieh S. Y., Wileman T., Carding S. R. (2018). Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome? Clin. Sci. 132, 523–542. doi: 10.1042/cs20171330 PubMed DOI PMC

Opsteen S., Files J. K., Fram T., Erdmann N. (2023). The role of immune activation and antigen persistence in acute and long COVID. J. Investig. Med. 71, 545–562. doi: 10.1177/10815589231158041 PubMed DOI PMC

Pantazi A. C., Balasa A. L., Mihai C. M., Chisnoiu T., Lupu V. V., Kassim M. A. K., et al. . (2023). Development of gut microbiota in the first 1000 days after birth and potential interventions. Nutrients 15, 3647. doi: 10.3390/nu15163647 PubMed DOI PMC

Parackova Z., Bloomfield M., Klocperk A., Sediva A. (2021). Neutrophils mediate Th17 promotion in covid-19 patients. J. Leukocyte Biol. 109, 73–76. doi: 10.1002/JLB.4COVCRA0820-481RRR PubMed DOI PMC

Park J. I., Cho S. W., Kang J. H., Park T. E. (2023). Intestinal peyer's patches: structure, function, and in vitro modeling. Tissue Eng. Regener. Med. 20, 341–353. doi: 10.1007/s13770-023-00543-y PubMed DOI PMC

Pheeha S. M., Tamuzi J. L., Chale-Matsau B., Manda S., Nyasulu P. S. A. (2023). Scoping review evaluating the current state of gut microbiota research in Africa. Microorganisms 11, 2118. doi: 10.3390/microorganisms11082118 PubMed DOI PMC

Piccioni A., Covino M., Candelli M., Ojetti V., Capacci A., Gasbarrini A., et al. . (2023). How do diet patterns, single foods, prebiotics and probiotics impact gut microbiota? Microbiol. Res. 14, 390–408. doi: 10.3390/microbiolres14010030 DOI

Pircalabioru G. G., Savu O., Mihaescu G., Vrancianu C. O., Chifiriuc M.-C. (2022). Dysbiosis, tolerance, and development of autoimmune diseases. Immunology of the GI tract - recent advances. IntechOpen. doi: 10.5772/intechopen.101293 DOI

Portincasa P., Bonfrate L., Vacca M., De Angelis M., Farella I., Lanza E., et al. . (2022). Gut microbiota and short chain fatty acids: implications in glucose homeostasis. Int. J. Mol. Sci. 23, 1105. doi: 10.3390/ijms23031105 PubMed DOI PMC

Proal A. D., VanElzakker M. B. (2021). Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms. Front. Microbiol. 12, 312. doi: 10.3389/fmicb.2021.698169 PubMed DOI PMC

Quaranta G., Guarnaccia A., Fancello G., Agrillo C., Iannarelli F., Sanguinetti M., et al. . (2022). Fecal microbiota transplantation and other gut microbiota manipulation strategies. Microorganisms 10, 2424. doi: 10.3390/microorganisms10122424 PubMed DOI PMC

Ralli T., Saifi Z., Rathee A., Aeri V., Kohli K. (2023). Decoding the bidirectional relationship between gut microbiota and COVID-19. Heliyon. 9, e13801. doi: 10.1016/j.heliyon.2023.e13801 PubMed DOI PMC

Rasa S., Nora-Krukle Z., Henning N., Eliassen E., Shikova E., Harrer T., et al. . (2018). Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J. Transl. Med. 16, 268. doi: 10.1186/s12967-018-1644-y PubMed DOI PMC

Ray M., Manjunath A., Halami P. M. (2023). Effect of probiotics as an immune modulator for the management of COVID-19. Arch. Microbiol. 205, 182. doi: 10.1007/s00203-023-03504-0 PubMed DOI PMC

Rodda L. B., Netland J., Shehata L., Pruner K. B., Morawski P. A., Thouvenel C. D., et al. . (2021). Functional sars-Cov-2-Specific immune memory persists after mild covid-19. Cell. 184, 169–83.e17. doi: 10.1016/j.cell.2020.11.029 PubMed DOI PMC

Samavati L., Uhal B. D. (2020). ACE2, much more than just a receptor for SARS-COV-2. Front. Cell. Infect. Microbiol. 10. doi: 10.3389/fcimb.2020.00317 PubMed DOI PMC

Sanekommu H., Taj S., Mah Noor R., Umair Akmal M., Akhtar R., Hossain M., et al. . (2023). Probiotics and fecal transplant: an intervention in delaying chronic kidney disease progression? Clin. Pract. 13, 881–888. doi: 10.3390/clinpract13040080 PubMed DOI PMC

Sekine T., Perez-Potti A., Rivera-Ballesteros O., Stralin K., Gorin J. B., Olsson A., et al. . (2020). Robust T cell immunity in convalescent individuals with asymptomatic or mild covid-19. Cell. 183, 158–68.e14. doi: 10.1016/j.cell.2020.08.017 PubMed DOI PMC

Senefeld J. W., Casadevall A., Joyner M. J. (2022). Convalescent plasma to deliver therapeutic antibodies against COVID-19. Trends Mol. Med. 28, 435–436. doi: 10.1016/j.molmed.2022.02.005 PubMed DOI PMC

SeyedAlinaghi S., Afzalian A., Pashaei Z., Varshochi S., Karimi A., Mojdeganlou H., et al. . (2023). Gut microbiota and COVID-19: A systematic review. Health Sci. Rep. 6, e1080. doi: 10.1002/hsr2.1080 PubMed DOI PMC

Sherif Z. A., Gomez C. R., Connors T. J., Henrich T. J., Reeves W. B. (2023). Recover Mechanistic Pathway Task Force. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 12, e86002. doi: 10.7554/eLife.86002 PubMed DOI PMC

Sun Z., Song Z. G., Liu C., Tan S., Lin S., Zhu J., et al. . (2022). Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in covid-19 patients. BMC Med. 20, 24. doi: 10.1186/s12916-021-02212-0 PubMed DOI PMC

Tao W., Zhang G., Wang X., Guo M., Zeng W., Xu Z., et al. . (2020). Analysis of the intestinal microbiota in covid-19 patients and its correlation with the inflammatory factor il-18. Med. Microecology. 5, 100023. doi: 10.1016/j.medmic.2020.100023 PubMed DOI PMC

Tavakol Z., Ghannadi S., Tabesh M. R., Halabchi F., Noormohammadpour P., Akbarpour S., et al. . (2023). Relationship between physical activity, healthy lifestyle and COVID-19 disease severity; a cross-sectional study. Z Gesundh Wiss 31, 267–275. doi: 10.1007/s10389-020-01468-9 PubMed DOI PMC

Tieu V., Tibi S., Ling J. (2023). Regulation of SARS-CoV-2 infection by diet-modulated gut microbiota. Front. Cell. Infect. Microbiol. 13. doi: 10.3389/fcimb.2023.1167827 PubMed DOI PMC

Tirelli C., De Amici M., Albrici C., Mira S., Nalesso G., Re B., et al. . (2023). Exploring the role of immune system and inflammatory cytokines in SARS-coV-2 induced lung disease. A Narrative Review. Biol. 12, 177. doi: 10.3390/biology12020177 PubMed DOI PMC

Tomkinson S., Triscott C., Schenk E., Foey A. (2023). The potential of probiotics as ingestible adjuvants and immune modulators for antiviral immunity and management of SARS-coV-2 infection and COVID-19. Pathogens 12, 928. doi: 10.3390/pathogens12070928 PubMed DOI PMC

Toor D., Wsson M. K., Kumar P., Karthikeyan G., Kaushik N. K., Goel C., et al. . (2019). Dysbiosis disrupts gut immune homeostasis and promotes gastric diseases. Int. J. Mol. Sci. 20, 2432. doi: 10.3390/ijms20102432 PubMed DOI PMC

Troisi A. (2023). Mental health challenges during the COVID-19 pandemic. J. Clin. Med. 12 (3), 1213. doi: 10.3390/jcm12031213 PubMed DOI PMC

Troisi J., Venutolo G., Pujolassos, Tanyà M., Delli Carri M., Landolfi A., Fasano A. (2021). 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. 27, 1406–1418. doi: 10.3748/wjg.v27.i14.1406 PubMed DOI PMC

Uzzan M., Corcos O., Martin J. C., Treton X., Bouhnik Y. (2020). Why is sars-Cov-2 infection more severe in obese men? the gut lymphatics - lung axis hypothesis. Med. Hypotheses. 144, 110023. doi: 10.1016/j.mehy.2020.110023 PubMed DOI PMC

Vibholm L. K., Nielsen S. S., Pahus M. H., Frattari G. S., Olesen R., Andersen R., et al. . (2021). SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses. EBioMedicine. 64, 103230. doi: 10.1016/j.ebiom.2021.103230 PubMed DOI PMC

Vojdani A., Vojdani E., Saidara E., Maes M. (2023). Persistent SARS-coV-2 infection, EBV, HHV-6 and other factors may contribute to inflammation and autoimmunity in long COVID. Viruses 15, 400. doi: 10.3390/v15020400 PubMed DOI PMC

Wang L., Cai Y., Garssen J., Henricks P. A. J., Folkerts G., Braber S. (2023). The bidirectional gut-lung axis in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 207, 1145–1160. doi: 10.1164/rccm.202206-1066TR PubMed DOI PMC

Wang J., Jiang M., Chen X., Montaner L. J. (2020). Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J. Leukoc. Biol. 108, 17–41. doi: 10.1002/JLB.3COVR0520-272R PubMed DOI PMC

Wang M., Zhang Y., Li C., Chang W., Zhang L. (2023). The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment. Front. Immunol. 14. doi: 10.3389/fimmu.2023.1180336 PubMed DOI PMC

Wu Y., Cheng X., Jiang G., Tang H., Ming S., Tang L., et al. . (2021. b). Altered oral and gut microbiota and its association with sars-Cov-2 viral load in covid-19 patients during hospitalization. NPJ Biofilms Microbiomes. 7, 61. doi: 10.1038/s41522-021-00232-5 PubMed DOI PMC

Wu C., Xu Q., Cao Z., Pan D., Zhu Y., Wang S., et al. . (2021. a). The volatile and heterogeneous gut microbiota shifts of covid-19 patients over the course of a probiotics-assisted therapy. Clin. Trans. Med. 11, e643. doi: 10.1002/ctm2.643 PubMed DOI PMC

Wylie K. M., Mihindukulasuriya K. A., Zhou Y., Sodergren E., Storch G. A., Weinstock G. M. (2014). Metagenomic analysis of double-stranded DNA viruses in healthy adults. BMC Med. 12, 71. doi: 10.1186/s12915-014-0071-7 PubMed DOI PMC

Xiang H., Liu Q. P. (2022). Alterations of the gut microbiota in coronavirus disease 2019 and its therapeutic potential. World J. Gastroenterol. 28, 6689–6701. doi: 10.3748/wjg.v28.i47.6689 PubMed DOI PMC

Xiong R. G., Li J., Cheng J., Zhou D. D., Wu S. X., Huang S. Y., et al. . (2023). The role of gut microbiota in anxiety, depression, and other mental disorders as well as the protective effects of dietary components. Nutrients 15, 3258. doi: 10.3390/nu15143258 PubMed DOI PMC

Xu X., Zhang W., Guo M., Xiao C., Fu Z., Yu S., et al. . (2022). Integrated analysis of gut microbiome and host immune responses in covid-19. Front. Med. 16, 263–275. doi: 10.1007/s11684-022-0921-6 PubMed DOI PMC

Yamamoto S., Saito M., Tamura A., Prawisuda D., Mizutani T., Yotsuyanagi H. (2021). The human microbiome and COVID-19: A systematic review. PloS One 16, e0253293. doi: 10.1371/journal.pone.0253293 PubMed DOI PMC

Yeoh Y. K., Zuo T., Lui G. C., Zhang F., Liu Q., Li A. Y., et al. . (2021). Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with covid-19. Gut. 70, 698–706. doi: 10.1136/gutjnl-2020-323020 PubMed DOI PMC

Yuksel N., Gelmez B., Yildiz-Pekoz A. (2023). Lung microbiota: its relationship to respiratory system diseases and approaches for lung-targeted probiotic bacteria delivery. Mol. Pharmaceutics 20, 3320–3337. doi: 10.1021/acs.molpharmaceut.3c00323 PubMed DOI PMC

Zhang F., Lau R. I., Liu Q., Su Q., Chan F. K. L., Ng S. C. (2023). Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications. Nat. Rev. Gastroenterol. Hepatol. 20, 323–337. doi: 10.1038/s41575-022-00698-4 PubMed DOI PMC

Zhao S., Feng P., Meng W., Jin W., Li X., Li X. (2022). Modulated gut microbiota for potential COVID-19 prevention and treatment. Front. Med. 9. doi: 10.3389/fmed.2022.811176 PubMed DOI PMC

Zheng D., Liwinski T., Elinav E. (2020). Interaction between microbiota and immunity in health and disease. Cell Res. 30, 492–506. doi: 10.1038/s41422-020-0332-7 PubMed DOI PMC

Zhou Y., Shi X., Fu W., Xiang F., He X., Yang B., et al. . (2021). Gut microbiota dysbiosis correlates with abnormal immune response in moderate covid-19 patients with fever. J. Inflammation Res. 14, 2619–2631. doi: 10.2147/JIR.S311518 PubMed DOI PMC