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COVID’s Effect on the Brain, Gut, and the Role of the Epstein-Barr Virus

July 21, 2023

A paper recently released in Nature: Molecular Psychiatry presents current thinking on the mechanisms behind potential Long Covid treatments. Some of the most common and debilitating symptoms of Long Covid are neurological or psychiatric. Several studies have shown that the COVID-19 virus can cross the blood-brain barrier and enter the brain (1) (2) (3) (4). Covid infection of the brain has been shown to lead to structural changes and neuroinflammation which could be responsible for the persistent neurological and psychiatric symptoms. One study found that damage to the olfactory cortex of COVID-19 survivors was associated with loss of taste and smell. But viral presence in the brain does not explain all symptoms.

Researchers have found evidence of COVID-19 reactivating Epstein-Barr Virus (EBV) causing more severe illness and persistent symptoms of fatigue and cognitive impairment (5) (6) (7) (8). The drug fluvoxamine is being studied as a potential treatment to block the reactivation of EBV and has shown promise for preventing fatigue in Long Covid.

Another area of ongoing research is disruption in the microbiome caused by COVID-19 infection. Viral particles are known to persist in the gut for up to four months after recovery (9) (10), and persistent gastrointestinal symptoms have been associated with changes in the gut microbiome of COVID-19 patients even after recovery (11) (12) (13) (14). Additional research found a reduction in anti-inflammatory microbes in the guts of such patients. The COVID-19 virus may also be damaging the lining of the intestinal tract leading to intestinal symptoms. Outside the gut, changes in the nasal microbiota have been associated with loss of smell in COVID-19 patients, and research in rodent models suggests that lung microbes may also play a role (15) (16).

Current research on treatment and prevention of both acute infection and Long Covid is underway, including:

  • Implementing plant-based and vegetarian diets was shown to reduce the risk of infection and COVID-19 severity, especially in elderly populations.
  • Supplementation with probiotics showed improved outcomes for patients with acute COVID-19 and was suggested as a treatment for Long Covid (17) (18) (19).
  • Short-chain fatty acid butyrate and the use of fecal microbial transplants have been suggested as means of improving intestinal dysbiosis during and after COVID-19 infection, but more research is needed to determine their efficacy.
  • Vagus nerve stimulation, which has several clinical trials underway. Similarly used to treat refractory epilepsy and depression, vagus nerve stimulation is thought to treat systemic inflammation from Long Covid.

While a comprehensive understanding of COVID-19 and Long Covid is still a long way off, current research suggests that multiple pathways are involved, and many different treatments may be effective.

Citations for report:

Chen, T., Song, J., Liu, H., Zheng, H., & Chen, C. (2021). Positive Epstein-Barr virus detection in coronavirus disease 2019 (COVID-19) patients. Scientific reports, 11(1), 10902. https://doi.org/10.1038/s41598-021-90351-y

Cheng, X., Zhang, Y., Li, Y., Wu, Q., Wu, J., Park, S. K., Guo, C., & Lu, J. (2022). Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases. BMC microbiology, 22(1), 274. https://doi.org/10.1186/s12866-022-02686-9

Douaud, G., Lee, S., Alfaro-Almagro, F., Arthofer, C., Wang, C., McCarthy, P., Lange, F., Andersson, J. L. R., Griffanti, L., Duff, E., Jbabdi, S., Taschler, B., Keating, P., Winkler, A. M., Collins, R., Matthews, P. M., Allen, N., Miller, K. L., Nichols, T. E., & Smith, S. M. (2022). SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, 604(7907), 697–707. https://doi.org/10.1038/s41586-022-04569-5

Farahani, R. H., Ajam, A., & Naeini, A. R. (2023). Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial. BMC infectious diseases, 23(1), 197. https://doi.org/10.1186/s12879-023-08172-5

Gold, J. E., Okyay, R. A., Licht, W. E., & Hurley, D. J. (2021). Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens (Basel, Switzerland), 10(6), 763. https://doi.org/10.3390/pathogens10060763

Gutiérrez-Castrellón, P., Gandara-Martí, T., Abreu Y Abreu, A. T., Nieto-Rufino, C. D., López-Orduña, E., Jiménez-Escobar, I., Jiménez-Gutiérrez, C., López-Velazquez, G., & Espadaler-Mazo, J. (2022). Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gut microbes, 14(1), 2018899. https://doi.org/10.1080/19490976.2021.2018899

Hegazy, M., Ahmed Ashoush, O., Tharwat Hegazy, M., Wahba, M., Lithy, R. M., Abdel-Hamid, H. M., Ahmed Abd Elshafy, S., Abdelfatah, D., El-Din Ibrahim, M. H., & Abdelghani, A. (2022). Beyond probiotic legend: ESSAP gut microbiota health score to delineate SARS-COV-2 infection severity. The British journal of nutrition, 127(8), 1180–1189. https://doi.org/10.1017/S0007114521001926

Hilpert, K., & Mikut, R. (2021). Is There a Connection Between Gut Microbiome Dysbiosis Occurring in COVID-19 Patients and Post-COVID-19 Symptoms?. Frontiers in microbiology, 12, 732838. https://doi.org/10.3389/fmicb.2021.732838

Hashimoto K. (2023). Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein-Barr virus and the gut-brain axis. Molecular psychiatry, 28(12), 4968–4976. https://doi.org/10.1038/s41380-023-02161-5

Hashimoto, Y., Eguchi, A., Wei, Y., Shinno-Hashimoto, H., Fujita, Y., Ishima, T., Chang, L., Mori, C., Suzuki, T., & Hashimoto, K. (2022). Antibiotic-induced microbiome depletion improves LPS-induced acute lung injury via gut-lung axis. Life sciences, 307, 120885. https://doi.org/10.1016/j.lfs.2022.120885

Hosang, L., Canals, R. C., van der Flier, F. J., Hollensteiner, J., Daniel, R., Flügel, A., & Odoardi, F. (2022). The lung microbiome regulates brain autoimmunity. Nature, 603(7899), 138–144. https://doi.org/10.1038/s41586-022-04427-4

Hou, Y. C., Su, W. L., & Chao, Y. C. (2022). COVID-19 Illness Severity in the Elderly in Relation to Vegetarian and Non-vegetarian Diets: A Single-Center Experience. Frontiers in nutrition, 9, 837458. https://doi.org/10.3389/fnut.2022.837458

Liu, F., Ye, S., Zhu, X., He, X., Wang, S., Li, Y., Lin, J., Wang, J., Lin, Y., Ren, X., Li, Y., & Deng, Z. (2021). Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients. Journal of medical case reports, 15(1), 60. https://doi.org/10.1186/s13256-020-02583-7

Merino, J., Joshi, A. D., Nguyen, L. H., Leeming, E. R., Mazidi, M., Drew, D. A., Gibson, R., Graham, M. S., Lo, C. H., Capdevila, J., Murray, B., Hu, C., Selvachandran, S., Hammers, A., Bhupathiraju, S. N., Sharma, S. V., Sudre, C., Astley, C. M., Chavarro, J. E., Kwon, S., … Chan, A. T. (2021). Diet quality and risk and severity of COVID-19: a prospective cohort study. Gut, 70(11), 2096–2104. https://doi.org/10.1136/gutjnl-2021-325353

Nardelli, C., Scaglione, G. L., Testa, D., Setaro, M., Russo, F., Di Domenico, C., Atripaldi, L., Zollo, M., Corrado, F., Salvatore, P., Pinchera, B., Gentile, I., & Capoluongo, E. (2022). Nasal Microbiome in COVID-19: A Potential Role of Corynebacterium in Anosmia. Current microbiology, 80(1), 53. https://doi.org/10.1007/s00284-022-03106-x

Natarajan, A., Zlitni, S., Brooks, E. F., Vance, S. E., Dahlen, A., Hedlin, H., Park, R. M., Han, A., Schmidtke, D. T., Verma, R., Jacobson, K. B., Parsonnet, J., Bonilla, H. F., Singh, U., Pinsky, B. A., Andrews, J. R., Jagannathan, P., & Bhatt, A. S. (2022). Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med (New York, N.Y.), 3(6), 371–387.e9. https://doi.org/10.1016/j.medj.2022.04.001

Neris Almeida Viana, S., do Reis Santos Pereira, T., de Carvalho Alves, J., Tianeze de Castro, C., Santana C da Silva, L., Henrique Sousa Pinheiro, L., & Nougalli Roselino, M. (2024). Benefits of probiotic use on COVID-19: A systematic review and meta-analysis. Critical reviews in food science and nutrition, 64(10), 2986–2998. https://doi.org/10.1080/10408398.2022.2128713

Peluso, M. J., Deveau, T. M., Munter, S. E., Ryder, D., Buck, A., Beck-Engeser, G., Chan, F., Lu, S., Goldberg, S. A., Hoh, R., Tai, V., Torres, L., Iyer, N. S., Deswal, M., Ngo, L. H., Buitrago, M., Rodriguez, A., Chen, J. Y., Yee, B. C., Chenna, A., … Henrich, T. J. (2023). Chronic viral coinfections differentially affect the likelihood of developing long COVID. The Journal of clinical investigation, 133(3), e163669. https://doi.org/10.1172/JCI163669

Puelles, V. G., Lütgehetmann, M., Lindenmeyer, M. T., Sperhake, J. P., Wong, M. N., Allweiss, L., Chilla, S., Heinemann, A., Wanner, N., Liu, S., Braun, F., Lu, S., Pfefferle, S., Schröder, A. S., Edler, C., Gross, O., Glatzel, M., Wichmann, D., Wiech, T., Kluge, S., … Huber, T. B. (2020). Multiorgan and Renal Tropism of SARS-CoV-2. The New England journal of medicine, 383(6), 590–592. https://doi.org/10.1056/NEJMc2011400

Ramakrishnan, R. K., Kashour, T., Hamid, Q., Halwani, R., & Tleyjeh, I. M. (2021). Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19. Frontiers in immunology, 12, 686029. https://doi.org/10.3389/fimmu.2021.686029

Sollmann, N., Beer, A. J., & Kirchhoff, F. (2022). SARS-CoV-2 infection and the brain: direct evidence for brain changes in milder cases. Signal transduction and targeted therapy, 7(1), 230. https://doi.org/10.1038/s41392-022-01072-1

Solomon, I. H., Normandin, E., Bhattacharyya, S., Mukerji, S. S., Keller, K., Ali, A. S., Adams, G., Hornick, J. L., Padera, R. F., Jr, & Sabeti, P. (2020). Neuropathological Features of Covid-19. The New England journal of medicine, 383(10), 989–992. https://doi.org/10.1056/NEJMc2019373

Song, E., Zhang, C., Israelow, B., Lu-Culligan, A., Prado, A. V., Skriabine, S., Lu, P., Weizman, O. E., Liu, F., Dai, Y., Szigeti-Buck, K., Yasumoto, Y., Wang, G., Castaldi, C., Heltke, J., Ng, E., Wheeler, J., Alfajaro, M. M., Levavasseur, E., Fontes, B., … Iwasaki, A. (2021). Neuroinvasion of SARS-CoV-2 in human and mouse brain. The Journal of experimental medicine, 218(3), e20202135. https://doi.org/10.1084/jem.20202135

Stein, S. R., Ramelli, S. C., Grazioli, A., Chung, J. Y., Singh, M., Yinda, C. K., Winkler, C. W., Sun, J., Dickey, J. M., Ylaya, K., Ko, S. H., Platt, A. P., Burbelo, P. D., Quezado, M., Pittaluga, S., Purcell, M., Munster, V. J., Belinky, F., Ramos-Benitez, M. J., Boritz, E. A., … Chertow, D. S. (2022). SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature, 612(7941), 758–763. https://doi.org/10.1038/s41586-022-05542-y

Su, Y., Yuan, D., Chen, D. G., Ng, R. H., Wang, K., Choi, J., Li, S., Hong, S., Zhang, R., Xie, J., Kornilov, S. A., Scherler, K., Pavlovitch-Bedzyk, A. J., Dong, S., Lausted, C., Lee, I., Fallen, S., Dai, C. L., Baloni, P., Smith, B., … Heath, J. R. (2022). Multiple early factors anticipate post-acute COVID-19 sequelae. Cell, 185(5), 881–895.e20. https://doi.org/10.1016/j.cell.2022.01.014

Wu, X., Jing, H., Wang, C., Wang, Y., Zuo, N., Jiang, T., Novakovic, V. A., & Shi, J. (2022). Intestinal Damage in COVID-19: SARS-CoV-2 Infection and Intestinal Thrombosis. Frontiers in microbiology, 13, 860931. https://doi.org/10.3389/fmicb.2022.860931

Zhang, F., Wan, Y., Zuo, T., Yeoh, Y. K., Liu, Q., Zhang, L., Zhan, H., Lu, W., Xu, W., Lui, G. C. Y., Li, A. Y. L., Cheung, C. P., Wong, C. K., Chan, P. K. S., Chan, F. K. L., & Ng, S. C. (2022). Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19. Gastroenterology, 162(2), 548–561.e4. https://doi.org/10.1053/j.gastro.2021.10.013

Zuo, T., Liu, Q., Zhang, F., Lui, G. C., Tso, E. Y., Yeoh, Y. K., Chen, Z., Boon, S. S., Chan, F. K., Chan, P. K., & Ng, S. C. (2021). Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut, 70(2), 276–284. https://doi.org/10.1136/gutjnl-2020-322294

Zuo, T., Wu, X., Wen, W., & Lan, P. (2021). Gut Microbiome Alterations in COVID-19. Genomics, proteomics & bioinformatics, 19(5), 679–688. https://doi.org/10.1016/j.gpb.2021.09.004





Sources

  1. Article Sources and Footnotes

    1. Chen, T., Song, J., Liu, H., Zheng, H., & Chen, C. (2021). Positive Epstein-Barr virus detection in coronavirus disease 2019 (COVID-19) patients. Scientific reports, 11(1), 10902. https://doi.org/10.1038/s41598-021-90351-y

    2. Cheng, X., Zhang, Y., Li, Y., Wu, Q., Wu, J., Park, S. K., Guo, C., & Lu, J. (2022). Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases. BMC microbiology, 22(1), 274. https://doi.org/10.1186/s12866-022-02686-9

    3. Douaud, G., Lee, S., Alfaro-Almagro, F., Arthofer, C., Wang, C., McCarthy, P., Lange, F., Andersson, J. L. R., Griffanti, L., Duff, E., Jbabdi, S., Taschler, B., Keating, P., Winkler, A. M., Collins, R., Matthews, P. M., Allen, N., Miller, K. L., Nichols, T. E., & Smith, S. M. (2022). SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, 604(7907), 697–707. https://doi.org/10.1038/s41586-022-04569-5

    4. Farahani, R. H., Ajam, A., & Naeini, A. R. (2023). Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial. BMC infectious diseases, 23(1), 197. https://doi.org/10.1186/s12879-023-08172-5

    5. Gold, J. E., Okyay, R. A., Licht, W. E., & Hurley, D. J. (2021). Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens (Basel, Switzerland), 10(6), 763. https://doi.org/10.3390/pathogens10060763

    6. Gutiérrez-Castrellón, P., Gandara-Martí, T., Abreu Y Abreu, A. T., Nieto-Rufino, C. D., López-Orduña, E., Jiménez-Escobar, I., Jiménez-Gutiérrez, C., López-Velazquez, G., & Espadaler-Mazo, J. (2022). Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gut microbes, 14(1), 2018899. https://doi.org/10.1080/19490976.2021.2018899

    7. Hegazy, M., Ahmed Ashoush, O., Tharwat Hegazy, M., Wahba, M., Lithy, R. M., Abdel-Hamid, H. M., Ahmed Abd Elshafy, S., Abdelfatah, D., El-Din Ibrahim, M. H., & Abdelghani, A. (2022). Beyond probiotic legend: ESSAP gut microbiota health score to delineate SARS-COV-2 infection severity. The British journal of nutrition, 127(8), 1180–1189. https://doi.org/10.1017/S0007114521001926

    8. Hilpert, K., & Mikut, R. (2021). Is There a Connection Between Gut Microbiome Dysbiosis Occurring in COVID-19 Patients and Post-COVID-19 Symptoms?. Frontiers in microbiology, 12, 732838. https://doi.org/10.3389/fmicb.2021.732838

    9. Hashimoto K. (2023). Detrimental effects of COVID-19 in the brain and therapeutic options for long COVID: The role of Epstein-Barr virus and the gut-brain axis. Molecular psychiatry, 28(12), 4968–4976. https://doi.org/10.1038/s41380-023-02161-5

    10. Hashimoto, Y., Eguchi, A., Wei, Y., Shinno-Hashimoto, H., Fujita, Y., Ishima, T., Chang, L., Mori, C., Suzuki, T., & Hashimoto, K. (2022). Antibiotic-induced microbiome depletion improves LPS-induced acute lung injury via gut-lung axis. Life sciences, 307, 120885. https://doi.org/10.1016/j.lfs.2022.120885

    11. Hosang, L., Canals, R. C., van der Flier, F. J., Hollensteiner, J., Daniel, R., Flügel, A., & Odoardi, F. (2022). The lung microbiome regulates brain autoimmunity. Nature, 603(7899), 138–144. https://doi.org/10.1038/s41586-022-04427-4

    12. Hou, Y. C., Su, W. L., & Chao, Y. C. (2022). COVID-19 Illness Severity in the Elderly in Relation to Vegetarian and Non-vegetarian Diets: A Single-Center Experience. Frontiers in nutrition, 9, 837458. https://doi.org/10.3389/fnut.2022.837458

    13. Liu, F., Ye, S., Zhu, X., He, X., Wang, S., Li, Y., Lin, J., Wang, J., Lin, Y., Ren, X., Li, Y., & Deng, Z. (2021). Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients. Journal of medical case reports, 15(1), 60. https://doi.org/10.1186/s13256-020-02583-7

    14. Merino, J., Joshi, A. D., Nguyen, L. H., Leeming, E. R., Mazidi, M., Drew, D. A., Gibson, R., Graham, M. S., Lo, C. H., Capdevila, J., Murray, B., Hu, C., Selvachandran, S., Hammers, A., Bhupathiraju, S. N., Sharma, S. V., Sudre, C., Astley, C. M., Chavarro, J. E., Kwon, S., … Chan, A. T. (2021). Diet quality and risk and severity of COVID-19: a prospective cohort study. Gut, 70(11), 2096–2104. https://doi.org/10.1136/gutjnl-2021-325353

    15. Nardelli, C., Scaglione, G. L., Testa, D., Setaro, M., Russo, F., Di Domenico, C., Atripaldi, L., Zollo, M., Corrado, F., Salvatore, P., Pinchera, B., Gentile, I., & Capoluongo, E. (2022). Nasal Microbiome in COVID-19: A Potential Role of Corynebacterium in Anosmia. Current microbiology, 80(1), 53. https://doi.org/10.1007/s00284-022-03106-x

    16. Natarajan, A., Zlitni, S., Brooks, E. F., Vance, S. E., Dahlen, A., Hedlin, H., Park, R. M., Han, A., Schmidtke, D. T., Verma, R., Jacobson, K. B., Parsonnet, J., Bonilla, H. F., Singh, U., Pinsky, B. A., Andrews, J. R., Jagannathan, P., & Bhatt, A. S. (2022). Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med (New York, N.Y.), 3(6), 371–387.e9. https://doi.org/10.1016/j.medj.2022.04.001

    17. Neris Almeida Viana, S., do Reis Santos Pereira, T., de Carvalho Alves, J., Tianeze de Castro, C., Santana C da Silva, L., Henrique Sousa Pinheiro, L., & Nougalli Roselino, M. (2024). Benefits of probiotic use on COVID-19: A systematic review and meta-analysis. Critical reviews in food science and nutrition, 64(10), 2986–2998. https://doi.org/10.1080/10408398.2022.2128713

    18. Peluso, M. J., Deveau, T. M., Munter, S. E., Ryder, D., Buck, A., Beck-Engeser, G., Chan, F., Lu, S., Goldberg, S. A., Hoh, R., Tai, V., Torres, L., Iyer, N. S., Deswal, M., Ngo, L. H., Buitrago, M., Rodriguez, A., Chen, J. Y., Yee, B. C., Chenna, A., … Henrich, T. J. (2023). Chronic viral coinfections differentially affect the likelihood of developing long COVID. The Journal of clinical investigation, 133(3), e163669. https://doi.org/10.1172/JCI163669

    19. Puelles, V. G., Lütgehetmann, M., Lindenmeyer, M. T., Sperhake, J. P., Wong, M. N., Allweiss, L., Chilla, S., Heinemann, A., Wanner, N., Liu, S., Braun, F., Lu, S., Pfefferle, S., Schröder, A. S., Edler, C., Gross, O., Glatzel, M., Wichmann, D., Wiech, T., Kluge, S., … Huber, T. B. (2020). Multiorgan and Renal Tropism of SARS-CoV-2. The New England journal of medicine, 383(6), 590–592. https://doi.org/10.1056/NEJMc2011400

    20. Ramakrishnan, R. K., Kashour, T., Hamid, Q., Halwani, R., & Tleyjeh, I. M. (2021). Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19. Frontiers in immunology, 12, 686029. https://doi.org/10.3389/fimmu.2021.686029

    21. Sollmann, N., Beer, A. J., & Kirchhoff, F. (2022). SARS-CoV-2 infection and the brain: direct evidence for brain changes in milder cases. Signal transduction and targeted therapy, 7(1), 230. https://doi.org/10.1038/s41392-022-01072-1

    22. Solomon, I. H., Normandin, E., Bhattacharyya, S., Mukerji, S. S., Keller, K., Ali, A. S., Adams, G., Hornick, J. L., Padera, R. F., Jr, & Sabeti, P. (2020). Neuropathological Features of Covid-19. The New England journal of medicine, 383(10), 989–992. https://doi.org/10.1056/NEJMc2019373

    23. Song, E., Zhang, C., Israelow, B., Lu-Culligan, A., Prado, A. V., Skriabine, S., Lu, P., Weizman, O. E., Liu, F., Dai, Y., Szigeti-Buck, K., Yasumoto, Y., Wang, G., Castaldi, C., Heltke, J., Ng, E., Wheeler, J., Alfajaro, M. M., Levavasseur, E., Fontes, B., … Iwasaki, A. (2021). Neuroinvasion of SARS-CoV-2 in human and mouse brain. The Journal of experimental medicine, 218(3), e20202135. https://doi.org/10.1084/jem.20202135

    24. Stein, S. R., Ramelli, S. C., Grazioli, A., Chung, J. Y., Singh, M., Yinda, C. K., Winkler, C. W., Sun, J., Dickey, J. M., Ylaya, K., Ko, S. H., Platt, A. P., Burbelo, P. D., Quezado, M., Pittaluga, S., Purcell, M., Munster, V. J., Belinky, F., Ramos-Benitez, M. J., Boritz, E. A., … Chertow, D. S. (2022). SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature, 612(7941), 758–763. https://doi.org/10.1038/s41586-022-05542-y

    25. Su, Y., Yuan, D., Chen, D. G., Ng, R. H., Wang, K., Choi, J., Li, S., Hong, S., Zhang, R., Xie, J., Kornilov, S. A., Scherler, K., Pavlovitch-Bedzyk, A. J., Dong, S., Lausted, C., Lee, I., Fallen, S., Dai, C. L., Baloni, P., Smith, B., … Heath, J. R. (2022). Multiple early factors anticipate post-acute COVID-19 sequelae. Cell, 185(5), 881–895.e20. https://doi.org/10.1016/j.cell.2022.01.014

    26. Wu, X., Jing, H., Wang, C., Wang, Y., Zuo, N., Jiang, T., Novakovic, V. A., & Shi, J. (2022). Intestinal Damage in COVID-19: SARS-CoV-2 Infection and Intestinal Thrombosis. Frontiers in microbiology, 13, 860931. https://doi.org/10.3389/fmicb.2022.860931

    27. Zhang, F., Wan, Y., Zuo, T., Yeoh, Y. K., Liu, Q., Zhang, L., Zhan, H., Lu, W., Xu, W., Lui, G. C. Y., Li, A. Y. L., Cheung, C. P., Wong, C. K., Chan, P. K. S., Chan, F. K. L., & Ng, S. C. (2022). Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19. Gastroenterology, 162(2), 548–561.e4. https://doi.org/10.1053/j.gastro.2021.10.013

    28. Zuo, T., Liu, Q., Zhang, F., Lui, G. C., Tso, E. Y., Yeoh, Y. K., Chen, Z., Boon, S. S., Chan, F. K., Chan, P. K., & Ng, S. C. (2021). Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut, 70(2), 276–284. https://doi.org/10.1136/gutjnl-2020-322294

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