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Article ; Online: Modification of Sympathetic and Hypothalamic Responses to Prevent Complications of COVID-19

Sanjiv K. Hyoju

Stresses, Vol 3, Iss 12, Pp 153-

“Dam and Wall Concept”

2023 Volume 166

Abstract: We are in the midst of the COVID-19 pandemic. Since December 2019, severe acute respiratory coronavirus (SARS-CoV-2) has infected more than half a billion people, killing nearly 7 million people worldwide. Now various variants of SARS-CoV-2 are causing ... ...

Abstract	We are in the midst of the COVID-19 pandemic. Since December 2019, severe acute respiratory coronavirus (SARS-CoV-2) has infected more than half a billion people, killing nearly 7 million people worldwide. Now various variants of SARS-CoV-2 are causing mayhem and driving the global surge. Epidemiologists are aware of the fact that this virus is capable of escaping immunity and likely to infect the same person multiple times despite adequate vaccination status. Elderly people and those with underlying health conditions who are considered high-risk are likely to suffer complications. While it is tempting to frame complications and mortality from COVID-19 as a simple matter of too much of a virulent virus in too weak of a host, much more is at play here. Framing the pathophysiology of COVID-19 in the context of the Chrousos and Gold model of the stress response system can shed insight into its complex pathogenesis. Understanding the mechanisms of pharmacologic modification of the sympathetic and hypothalamic response system via administration of clonidine and/or dexamethasone may offer an explanation as to why a viral pathogen can be well tolerated and cleared by one host while inflaming and killing another.
Keywords	stress response system ; sympathetic activity ; HPA (hypothalamic–pituitary–adrenal) axis ; SARS-CoV-2 ; catecholamine ; corticosteroids ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Central catecholaminergic blockade with clonidine prevent SARS-CoV-2 complication: A case series.

Hyoju, Sanjiv K / Baral, Bidur / Jha, Prabin K

IDCases

2021 Volume 25, Page(s) e01219

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a life-threating viral infection that is highly transmissible and be lethal. Although many patients with mild symptoms recover, an acute form of the infection is characterized by rapidly ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a life-threating viral infection that is highly transmissible and be lethal. Although many patients with mild symptoms recover, an acute form of the infection is characterized by rapidly evolving respiratory failure, an acute inflammatory response, organ failure, and death. Herein, we describe the use of clonidine to modulate the acute inflammatory consequences of this infection in three cases. The patients were three men between 40-50 years from Kathmandu valley, during the peak of COVID-19 (September 2020- January 2021). All three patients presented with typical COVID-19 symptoms (daily fever, loss of smell and taste, excessive fatigue, cough) and had pneumonia with typical finding in CT Scan of chest. Patient 1was able to maintain adequate oxygenation despite having pneumonia, managed at home by regular self-monitoring of vitals and treatment with oral clonidine whereas patient 2 and 3 developed significant pneumonia and had difficult in maintaining oxygenation hence admitted in hospital and treated with clonidine and supplemental oxygen. All three patients recovered completely. In this limited report, we proposed several mechanisms by which clonidine may be useful in managing rapidly evolving SARS-CoV-2 infection based on the rationale that early clonidine administration can intervene in the catecholaminergic response that characterizes rapid clinical deterioration including presumptive cytokine storm that occurs in COVID-19 infection in vulnerable populations.
Language	English
Publishing date	2021-07-06
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	2745454-X
ISSN	2214-2509
ISSN	2214-2509
DOI	10.1016/j.idcr.2021.e01219
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-CoV-2 and the sympathetic immune response: Dampening inflammation with antihypertensive drugs (Clonidine and Propranolol).

Hyoju, Sanjiv K / Zaborina, Olga / van Goor, Harry

Medical hypotheses

2020 Volume 144, Page(s) 110039

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a pandemic with the United States now carrying the highest number of cases and fatalities. Although vaccines and antiviral agents are the main focus of therapy, here we present a ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a pandemic with the United States now carrying the highest number of cases and fatalities. Although vaccines and antiviral agents are the main focus of therapy, here we present a plausible hypothesis to leverage our understanding of neuroimmunomodulation to intervene in the pathophysiology of the disease to prevent death.
MeSH term(s)	Antihypertensive Agents/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19/immunology ; COVID-19/virology ; Clonidine/therapeutic use ; Comorbidity ; Disease Progression ; Humans ; Immune System/virology ; Inflammation/virology ; Interleukin-6/blood ; Models, Theoretical ; Myocardium/pathology ; Propranolol/therapeutic use ; Randomized Controlled Trials as Topic ; Virus Replication
Chemical Substances	Antihypertensive Agents ; Antiviral Agents ; IL6 protein, human ; Interleukin-6 ; Propranolol (9Y8NXQ24VQ) ; Clonidine (MN3L5RMN02)
Keywords	covid19
Language	English
Publishing date	2020-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.110039
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Article ; Online: What Is the Role of the Gut in Wound Infections?

Hyoju, Sanjiv / Machutta, Kaylie / Krezalek, Monika A / Alverdy, John C

Advances in surgery

2023 Volume 57, Issue 1, Page(s) 31–46

Abstract: Emerging evidence suggest a major role for the gut microbiome in wound infections. A Trojan Horse mechanism of surgical site infections has been hypothesized to occur when pathogens in the gut, gums, and periodontal areas enter an immune cell and ... ...

Abstract	Emerging evidence suggest a major role for the gut microbiome in wound infections. A Trojan Horse mechanism of surgical site infections has been hypothesized to occur when pathogens in the gut, gums, and periodontal areas enter an immune cell and silently travel to the wound site where they release their infectious payload. Genetic tracking of microbes at the strain level is now possible with genetic sequencing techniques and can clarify the origin of microbes that cause wound infections. An emerging field of dietary prehabilitation to modulate the microbiome before surgery is being described to improve infection-related outcomes from surgery.
MeSH term(s)	Humans ; Surgical Wound Infection/prevention & control ; Gastrointestinal Microbiome
Language	English
Publishing date	2023-06-25
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	411889-3
ISSN	1878-0555 ; 0065-3411
ISSN (online)	1878-0555
ISSN	0065-3411
DOI	10.1016/j.yasu.2023.05.002
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Article ; Online: SARS-CoV-2 and the sympathetic immune response

Hyoju, Sanjiv K / Zaborina, Olga / van Goor, Harry

Medical Hypotheses

Dampening inflammation with antihypertensive drugs (Clonidine and Propranolol)

2020 Volume 144, Page(s) 110039

Keywords	General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2020.110039
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Article ; Online: A Novel Nonantibiotic Gut-directed Strategy to Prevent Surgical Site Infections.

Hyoju, Sanjiv K / Keskey, Robert / Castillo, Gerardo / Machutta, Kaylie / Zaborin, Alexander / Zaborina, Olga / Alverdy, John C

Annals of surgery

2022 Volume 276, Issue 3, Page(s) 472–481

Abstract: Objective: To determine the efficacy of an orally delivered phosphate-rich polymer, Pi-PEG, to prevent surgical site infection (SSI) in a mouse model of spontaneous wound infection involving gut-derived pathogens.: Background: Evidence suggests that ... ...

Abstract	Objective: To determine the efficacy of an orally delivered phosphate-rich polymer, Pi-PEG, to prevent surgical site infection (SSI) in a mouse model of spontaneous wound infection involving gut-derived pathogens. Background: Evidence suggests that pathogens originating from the gut microbiota can cause postoperative infection via a process by which they silently travel inside an immune cell and contaminate a remote operative site (Trojan Horse Hypothesis). Here, we hypothesize that Pi-PEG can prevent SSIs in a novel model of postoperative SSIs in mice. Methods: Mice were fed either a standard chow diet (high fiber/low fat, SD) or a western-type diet (low fiber/high fat, WD), and exposed to antibiotics (oral clindamycin/intraperitoneal cefoxitin). Groups of mice had Pi-PEG added to their drinking water and SSI incidence was determined. Gross clinical infections wound cultures and amplicon sequence variant analysis of the intestinal contents and wound were assessed to determine the incidence and source of the developing SSI. Results: In this model, consumption of a WD and exposure to antibiotics promoted the growth of SSI pathogens in the gut and their subsequent presence in the wound. Mice subjected to this model drinking water spiked with Pi-PEG were protected against SSIs via mechanisms involving modulation of the gut-wound microbiome. Conclusions: A nonantibiotic phosphate-rich polymer, Pi-PEG, added to the drinking water of mice prevents SSIs and may represent a more sustainable approach in lieu of the current trend of greater sterility and the use of more powerful and broader antibiotic coverage.
MeSH term(s)	Animals ; Anti-Bacterial Agents/therapeutic use ; Drinking Water ; Mice ; Phosphates ; Polymers ; Surgical Wound Infection/epidemiology
Chemical Substances	Anti-Bacterial Agents ; Drinking Water ; Phosphates ; Polymers
Language	English
Publishing date	2022-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000005547
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Article: SARS-CoV-2 and the sympathetic immune response: Dampening inflammation with antihypertensive drugs (Clonidine and Propranolol)

Hyoju, Sanjiv K / Zaborina, Olga / van Goor, Harry

Med Hypotheses

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a pandemic with the United States now carrying the highest number of cases and fatalities. Although vaccines and antiviral agents are the main focus of therapy, here we present a plausible hypothesis to leverage our understanding of neuroimmunomodulation to intervene in the pathophysiology of the disease to prevent death.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #695861
Database	COVID19

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Article ; Online: Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate.

van den Berg, Fons F / van Dalen, Demi / Hyoju, Sanjiv K / van Santvoort, Hjalmar C / Besselink, Marc G / Wiersinga, Willem Joost / Zaborina, Olga / Boermeester, Marja A / Alverdy, John

Gut

2020 Volume 70, Issue 5, Page(s) 915–927

Abstract: Objective: The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising ... ...

Abstract	Objective: The gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation. Design: C57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed. Results: Mortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom of Conclusion: Butyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.
MeSH term(s)	Animals ; Butyrates/pharmacology ; Diet, Western ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Mice ; Mice, Inbred C57BL ; Pancreatitis, Acute Necrotizing/diet therapy ; Pancreatitis, Acute Necrotizing/microbiology ; Pancreatitis, Acute Necrotizing/mortality ; Phenotype
Chemical Substances	Butyrates
Language	English
Publishing date	2020-09-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2019-320430
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Article: Sustained Release of Phosphates From Hydrogel Nanoparticles Suppresses Bacterial Collagenase and Biofilm Formation

Nichols, Dylan / Pimentel, Marja B / Borges, Fernando T P / Hyoju, Sanjiv K / Teymour, Fouad / Hong, Seok Hoon / Zaborina, Olga Y / Alverdy, John C / Papavasiliou, Georgia

Frontiers in bioengineering and biotechnology

2019 Volume 7, Page(s) 153

Abstract: Intestinal disease or surgical intervention results in local changes in tissue and host-derived factors triggering bacterial virulence. A key phenotype involved in impaired tissue healing is increased bacterial collagenase expression which degrades ... ...

Abstract	Intestinal disease or surgical intervention results in local changes in tissue and host-derived factors triggering bacterial virulence. A key phenotype involved in impaired tissue healing is increased bacterial collagenase expression which degrades intestinal collagen. Antibiotic administration is ineffective in addressing this issue as it inadvertently eliminates normal flora while allowing pathogenic bacteria to "bloom" and acquire antibiotic resistance. Compounds that could attenuate collagenase production while allowing commensal bacteria to proliferate normally would offer major advantages without the risk of the emergence of resistance. We have previously shown that intestinal phosphate depletion in the surgically stressed host is a major cue that triggers
Language	English
Publishing date	2019-06-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2019.00153
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Article ; Online: Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts.

Hyoju, Sanjiv K / Zaborin, Alexander / Keskey, Robert / Sharma, Anukriti / Arnold, Wyatt / van den Berg, Fons / Kim, Sangman M / Gottel, Neil / Bethel, Cindy / Charnot-Katsikas, Angella / Jianxin, Peng / Adriaansens, Carleen / Papazian, Emily / Gilbert, Jack A / Zaborina, Olga / Alverdy, John C

mBio

2019 Volume 10, Issue 4

Abstract: Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard ... ...

Abstract	Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of
MeSH term(s)	Animals ; Anti-Bacterial Agents/therapeutic use ; C-Reactive Protein/metabolism ; Diet, Western/adverse effects ; Drug Resistance, Bacterial/genetics ; Gastrointestinal Microbiome/drug effects ; In Situ Nick-End Labeling ; Interleukin-6/blood ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Sepsis/blood ; Sepsis/drug therapy ; Sepsis/microbiology ; Sepsis/surgery
Chemical Substances	Anti-Bacterial Agents ; Interleukin-6 ; RNA, Ribosomal, 16S ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2019-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00903-19
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