Next Article in Journal
The Evolution of Hypovolemic and Euvolemic Hyponatremia Coincides with an Inflammatory Status in Patients with COVID-19: An Observational Cohort Study
Previous Article in Journal
Interactions between 14-3-3 Proteins and Actin Cytoskeleton and Its Regulation by microRNAs and Long Non-Coding RNAs in Cancer
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

by
Adonis Sfera
1,2,*,
Carolina Osorio
3,
Sabine Hazan
4,
Zisis Kozlakidis
5,
Jose Campo Maldonado
6,
Carlos Manuel Zapata-Martín del Campo
7,
Jonathan J. Anton
8,
Leah Rahman
9,
Christina V. Andronescu
10 and
Garth L. Nicolson
11
1
Patton State Hospital, San Bernardino, CA 92407, USA
2
Department of Psychiatry, University of California, Riverside, CA 92521, USA
3
Department of Psychiatry, Loma Linda University, Loma Linda, CA 92354, USA
4
ProgenomaBiome, Ventura, CA 93003, USA
5
International Agency for Research on Cancer World Health Organization, 69372 Lyon, France
6
Department of Medicine, The University of Texas Rio Grande Valley, Edinburg, TX 78539, USA
7
Instituto Nacional de Cardiología and in Ignacio Chávez, Mexico City 14080, Mexico
8
Department of Biology, California Baptist University, Riverside, CA 92521, USA
9
Department of Neuroscience, University of Oregon, Eugene, OR 97402, USA
10
Medical Anthropology Department, Stanford University, Stanford, CA 94305, USA
11
Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA 92647, USA
*
Author to whom correspondence should be addressed.
Endocrines 2022, 3(4), 703-725; https://doi.org/10.3390/endocrines3040058
Submission received: 30 September 2022 / Revised: 14 October 2022 / Accepted: 25 October 2022 / Published: 7 November 2022
(This article belongs to the Special Issue COVID-19 and Endocrinology)

Abstract

Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood–brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement.
Keywords: cortisol; HMGB1; microbial translocation; SARS-CoV-2 cortisol; HMGB1; microbial translocation; SARS-CoV-2

Share and Cite

MDPI and ACS Style

Sfera, A.; Osorio, C.; Hazan, S.; Kozlakidis, Z.; Maldonado, J.C.; Zapata-Martín del Campo, C.M.; Anton, J.J.; Rahman, L.; Andronescu, C.V.; Nicolson, G.L. Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies. Endocrines 2022, 3, 703-725. https://doi.org/10.3390/endocrines3040058

AMA Style

Sfera A, Osorio C, Hazan S, Kozlakidis Z, Maldonado JC, Zapata-Martín del Campo CM, Anton JJ, Rahman L, Andronescu CV, Nicolson GL. Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies. Endocrines. 2022; 3(4):703-725. https://doi.org/10.3390/endocrines3040058

Chicago/Turabian Style

Sfera, Adonis, Carolina Osorio, Sabine Hazan, Zisis Kozlakidis, Jose Campo Maldonado, Carlos Manuel Zapata-Martín del Campo, Jonathan J. Anton, Leah Rahman, Christina V. Andronescu, and Garth L. Nicolson. 2022. "Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies" Endocrines 3, no. 4: 703-725. https://doi.org/10.3390/endocrines3040058

APA Style

Sfera, A., Osorio, C., Hazan, S., Kozlakidis, Z., Maldonado, J. C., Zapata-Martín del Campo, C. M., Anton, J. J., Rahman, L., Andronescu, C. V., & Nicolson, G. L. (2022). Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies. Endocrines, 3(4), 703-725. https://doi.org/10.3390/endocrines3040058

Article Metrics

Back to TopTop