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Félix P, Melo AA, Costa JP, Colaço M, Pereira D, Núñez J, de Almeida LP, Borges O. Exploring TLR agonists as adjuvants for COVID-19 oral vaccines. Vaccine 2025; 53:127078. [PMID: 40184639 DOI: 10.1016/j.vaccine.2025.127078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/18/2025] [Accepted: 03/27/2025] [Indexed: 04/07/2025]
Abstract
The COVID-19 pandemic underscored the importance of advancing technologies that enable the rapid development and distribution of more effective vaccines when required. Since SARS-CoV-2 enters the body through the nasal mucosa, optimising the induction of secretory IgA (sIgA) production, a key component of the mucosal immune response, is essential. It has long been known that the induction of sIgA occurs when a vaccine is administered through mucosal surfaces and the immune responses initiated at one mucosal site can influence immune activity at other mucosal surfaces. Consequently, we propose an oral vaccine formulation (Vacform) comprising the immunomodulator CL097, a TLR7/8 agonist, and the SARS-CoV-2 spike protein, both encapsulated within glucan particles (GPs). The studies demonstrated that Vacform induced ROS production in RAW 264.7 cells but not in human neutrophils. The concentrations of Vacform tested did not induce NO production in RAW 264.7 cells. While Vacform stimulated the production of TNF-α and IL-6 in mouse spleen cells, this effect was not observed in RAW 264.7 cells. Finally, Vacform stimulated the proliferation of human PBMCs. Thus, its immunomodulatory properties were evident in specific cells under certain in vitro conditions. The Vacform was subsequently tested in vaccination studies. C57BL/6 mice were initially immunized subcutaneously, followed by two oral boosts with Vacform every two weeks. The Vacform elicited both, humoral (serum IgG and mucosal sIgA) and cellular immune responses. A balanced Th1/Th2/Th17 immune profile was observed. In conclusion, the GPs:CL097 adjuvant system shows promise for eliciting robust immune responses against SARS-CoV-2 and provides a foundation for future studies on dose-response optimization and challenge models.
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Affiliation(s)
- Paulo Félix
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - Alexandra A Melo
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - João Panão Costa
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - Mariana Colaço
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - Dina Pereira
- Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal; Gene Therapy Center of Excellence (GeneT), Coimbra 3004-504, Portugal; IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal
| | - Jisette Núñez
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal; Gene Therapy Center of Excellence (GeneT), Coimbra 3004-504, Portugal
| | - Luís Pereira de Almeida
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal; Gene Therapy Center of Excellence (GeneT), Coimbra 3004-504, Portugal
| | - Olga Borges
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal.
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Cherne MD, Snyder D, Sidar B, Blackwell K, Jenkins B, Huang S, Sebrell TA, Hedges JF, Spence JR, Chang CB, Wilking JN, Walk ST, Jutila MA, Loveday EK, Bimczok D. Strain- and vaccine-specific effects of serum antibodies in the protection of intestinal SARS-CoV-2 infection. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.03.24.25324570. [PMID: 40196264 PMCID: PMC11974977 DOI: 10.1101/2025.03.24.25324570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a public health challenge worldwide. The gastrointestinal tract has emerged as an important site of infection and has been implicated as a reservoir for long-term infection, particularly for post-acute COVID-19 syndrome. However, whether vaccine-induced systemic antibodies can prevent intestinal infection with SARS-CoV-2 is unclear. Compared to Vero cells commonly used to assess SARS-CoV-2 neutralization, the intestinal epithelium has a functional interferon response and expresses higher levels of ACE2, enzymes, and antibody-binding Fc receptors that may impact SARS-CoV-2 immune elimination. Methods We evaluated the potential of antibodies from both naturally infected and vaccinated human subjects to inhibit SARS-CoV-2 infection of the intestinal epithelium. Serum samples were collected from human volunteers who had undergone natural infection with SARS-CoV-2 in 2020 (n=5) or who had received the Pfizer BNT162b2 COVID-19 vaccine (n=13). Banked sera collected in 2016 served as negative controls (n=2). SARS-CoV-2 (WA01, Delta or Omicron) was pre-treated with sera and then used to infect iPSC-derived human intestinal organoids (HIO) or Caco-2 colonic epithelial cells, and SARS-CoV-2 infection was quantified by plaque assay, PCR, or immunofluorescence (IF) after 48-96 h. Results Both HIOs and Caco-2 cells supported robust infection with SARS-CoV-2. In HIOs, pretreatment of SARS-CoV-2 with a high titer post-vaccine serum completely blocked replication of WA01. Similarly, sera from both naturally infected donors collected in 2020 and sera from individuals who had received a BNT162b2 vaccine significantly inhibited replication of the WA01 strain in Caco-2 cells. In contrast, none of the sera significantly inhibited infection with the Delta variant of SARS-CoV-2. For Omicron, only sera from individuals who had received an Omicron-based vaccine significantly inhibited infection with SARS-CoV-2 in the plaque assay. Across all virus types, sera from individuals who had received Omicron-based BNT162b2 boosters were the most effective at reducing infection in Caco-2 cells. Conclusion Our results suggest that vaccine-induced antibody responses to SARS-CoV-2 are protective in the gut. Our study also supports previous reports indicating that SARS-CoV-2 vaccines need to be adapted to circulating virus strains to convey full protection from infection.
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Singh S, Srivastava NK, Yadav R, Paul S, Gupta S, Sankalp, Dixit P. Acute gastrointestinal and post-acute COVID-19 gastrointestinal syndrome assessment on the Gastrointestinal Symptom Rating Scale scoring system: A questionnaire-based survey. J Family Med Prim Care 2024; 13:5787-5798. [PMID: 39790770 PMCID: PMC11709014 DOI: 10.4103/jfmpc.jfmpc_707_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 08/04/2024] [Accepted: 08/08/2024] [Indexed: 01/12/2025] Open
Abstract
Background Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is the persistence of sequel of acute SARS-COV-2 infection. Persistent/acquired gastrointestinal symptoms (GI-PACS) include loss of appetite, nausea, weight loss, abdominal pain, heartburn, dysphagia, altered bowel motility, dyspepsia, and irritable bowel syndrome. The study aimed to assess the short- and long-term GI-PACS syndrome on the GSRS scale. Methods A cross-sectional, retrospective record analysis and telephonic questionnaire-based survey were conducted at a tertiary referral center in northern India. The data incorporated patients treated from April 2021 to March 2023. Exclusion criteria were neurological disorders, dementia, inability to understand Hindi/English languages, and psychiatric problems. All patients who met the inclusion criteria were telephonically called from November 2023 to January 2024. Results The study population was 350 recovered patients from SARS-COVID-19 illness. Forty-three responses were removed during data cleaning and removal of duplication. The data analysis of 307 participants (ICU admissions=92, non-ICU admissions=123, and outdoor treatment =92) was done. The proportion of patients not having any GI symptoms, having at least one GI symptom, and having more than one GI symptom before SARS-COV-2 illness was 3%(3/307), 4.9% (15/307), and 3.6% (11/307), respectively. The four major GI symptoms analyzed in the study were vomiting, pain in the abdomen, diarrhea, and constipation. Overall, 13% (40/307) of the study population did not have any major GI symptoms before SARS-COV-2 diseases. During acute SARS-COV-2 illness, 86.97% (267/307) of patients develop new GI symptoms. Post SARS-COV-2 illness, the overall mean GSRS score for 15 items was 2.14 ± 0.829. The acquired GI-PACS was abdominal pain syndrome (mean score 2.5190 ± SD 0.86650), constipation syndrome (mean score 2.3844 ± 0.83840), reflux syndrome (mean score 2.2866 ± 1.31889), indigestion syndrome (mean score 1.8591 ± 0.93076), and diarrhea syndrome (mean score 1.8122 ± 0.90899). Overall, fever (95.1%, P = 0.007), anosmia (45.0%, P = 0.042), cough (80.1%, P = 0.032), and hospitalization (30.0%, P = 0.003) had a more significant association with one of the major four GI symptoms during the acute phase of SARS-COV-2 illness. Home-isolated patients having loss of appetite (95.4%, P = 0.0001) had a significant association with one of the major four GI symptoms during the acute phase of SARS-COV-2 illness. Hospitalized patients having fever (80.7%, P = 0.031), breathlessness (83.8%, P = 0.003), loss of smell (97.0%, P = 0.001), and cough (82.7%, P = 0.048) had a more significant association with one of the major four GI symptoms during the acute SARS-COV-2 illness. Abdominal pain, reflux, and constipation were considered severe GI symptoms (symptom GSRS score greater than total mean GSRS score). Diarrhea and indigestion were considered mild symptoms (symptom GSRS score was less than the total mean GSRS score). The GI symptoms during acute SARS-COV-2 illness recovered in 66.1% (203/307) patients within 3 months. The respondents taking medicines for more than 1 year following SARS-COV-2 illness were 19.2%. 12.0% (37/307) of respondents suffered from persistent GI symptoms on a mean follow-up of 20.1 ± 0.82 months. Conclusion Long-term COVID-19 syndrome frequently manifested as GI symptoms, whereas most symptoms subsided with time.
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Affiliation(s)
- Sunita Singh
- Department of Paediatric Surgery, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Niraj K. Srivastava
- Department of General Surgery, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Rahul Yadav
- Department of General Surgery, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Saurabh Paul
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Shefali Gupta
- Department of Microbiology, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Sankalp
- Department of Cardiothoracic Surgery, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India
| | - Priyanshi Dixit
- Nursing Tutor, Vardhman Mahaveer Nursing Medical College, New Delhi, India
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Tandon A, Baral B, Saini V, Kandpal M, Dixit AK, Parmar HS, Meena AK, Chandra Jha H. The role of Helicobacter pylori in augmenting the severity of SARS-CoV-2 related gastrointestinal symptoms: An insight from molecular mechanism of co-infection. Heliyon 2024; 10:e37585. [PMID: 39364240 PMCID: PMC11447314 DOI: 10.1016/j.heliyon.2024.e37585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 08/24/2024] [Accepted: 09/05/2024] [Indexed: 10/05/2024] Open
Abstract
Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 -Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre-H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre-H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre-H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes.
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Affiliation(s)
- Akrati Tandon
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Budhadev Baral
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Vaishali Saini
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Meenakshi Kandpal
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
| | - Amit Kumar Dixit
- Central Ayurveda Research Institute, Kolkata, 4-CN Block, Sector –V, Bidhannagar, Kolkata, 700 091, India
| | - Hamendra Singh Parmar
- School of Biotechnology, Devi Ahilya Vishwavidyalaya, Takshashila Campus, Indore, Madhya Pradesh, 452001, India
| | - Ajay Kumar Meena
- Regional Ayurveda Research Institute, Amkhoh, Gwalior, Madhya Pradesh, 474001, India
| | - Hem Chandra Jha
- Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
- Centre for Rural Development and Technology, Indian Institute of Technology Indore, Simrol, Indore, Madhya Pradesh, 453552, India
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Eisenreich W, Leberfing J, Rudel T, Heesemann J, Goebel W. Interactions of SARS-CoV-2 with Human Target Cells-A Metabolic View. Int J Mol Sci 2024; 25:9977. [PMID: 39337465 PMCID: PMC11432161 DOI: 10.3390/ijms25189977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/13/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Viruses are obligate intracellular parasites, and they exploit the cellular pathways and resources of their respective host cells to survive and successfully multiply. The strategies of viruses concerning how to take advantage of the metabolic capabilities of host cells for their own replication can vary considerably. The most common metabolic alterations triggered by viruses affect the central carbon metabolism of infected host cells, in particular glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. The upregulation of these processes is aimed to increase the supply of nucleotides, amino acids, and lipids since these metabolic products are crucial for efficient viral proliferation. In detail, however, this manipulation may affect multiple sites and regulatory mechanisms of host-cell metabolism, depending not only on the specific viruses but also on the type of infected host cells. In this review, we report metabolic situations and reprogramming in different human host cells, tissues, and organs that are favorable for acute and persistent SARS-CoV-2 infection. This knowledge may be fundamental for the development of host-directed therapies.
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Affiliation(s)
- Wolfgang Eisenreich
- Structural Membrane Biochemistry, Bavarian NMR Center (BNMRZ), Department of Bioscience, TUM School of Natural Sciences, Technical University of Munich, Lichtenbergstr. 4, 85747 Garching, Germany;
| | - Julian Leberfing
- Structural Membrane Biochemistry, Bavarian NMR Center (BNMRZ), Department of Bioscience, TUM School of Natural Sciences, Technical University of Munich, Lichtenbergstr. 4, 85747 Garching, Germany;
| | - Thomas Rudel
- Chair of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany;
| | - Jürgen Heesemann
- Max von Pettenkofer Institute, Ludwig Maximilian University of Munich, 80336 München, Germany; (J.H.); (W.G.)
| | - Werner Goebel
- Max von Pettenkofer Institute, Ludwig Maximilian University of Munich, 80336 München, Germany; (J.H.); (W.G.)
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Raj ST, Bruce AW, Anbalagan M, Srinivasan H, Chinnappan S, Rajagopal M, Khanna K, Chandramoorthy HC, Mani RR. COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens. Front Cell Infect Microbiol 2024; 14:1384939. [PMID: 38863829 PMCID: PMC11165100 DOI: 10.3389/fcimb.2024.1384939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 05/13/2024] [Indexed: 06/13/2024] Open
Abstract
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.
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Affiliation(s)
- Sterlin T. Raj
- Department of Molecular Biology, Ekka Diagnostics, Chennai, Tamil Nadu, India
| | - Alexander W. Bruce
- Faculty of Science, University of South Bohemia, České Budějovice, Czechia
| | - Muralidharan Anbalagan
- Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, LA, United States
| | - Hemalatha Srinivasan
- School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science and Technology, Chennai, India
| | - Sasikala Chinnappan
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, University College of Sedaya International UCSI University, Kuala Lumpur, Malaysia
| | - Mogana Rajagopal
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, University College of Sedaya International UCSI University, Kuala Lumpur, Malaysia
| | - Kushagra Khanna
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia
| | - Harish C. Chandramoorthy
- Department of Microbiology and Clinical Parasitology, College of Medicine, King Khalid University, Abha, Saudi Arabia
- Center for Stem Cell Research, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Ravishankar Ram Mani
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, University College of Sedaya International UCSI University, Kuala Lumpur, Malaysia
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Yousef M, Rob M, Varghese S, Rao S, Zamir F, Paul P, Chaari A. The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review. Life Sci 2024; 342:122535. [PMID: 38408636 DOI: 10.1016/j.lfs.2024.122535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 02/28/2024]
Abstract
AIMS Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes. MATERIALS AND METHODS We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19. KEY FINDINGS The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0 % to 11 % in the intervention groups, as compared to 3 % to 30 % in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders. SIGNIFICANCE The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.
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Affiliation(s)
- Mahmoud Yousef
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Mlaak Rob
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Sanish Varghese
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Shrinidhi Rao
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Fahad Zamir
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Pradipta Paul
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Ali Chaari
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar.
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Mullins N, Alashraf AR, McDermott K, Brown RS, Payne SJ. Polyethylenimine mediated recovery of SARS-CoV-2 and total viral RNA: Impact of aqueous conditions on behaviour and recovery. WATER RESEARCH 2024; 253:121207. [PMID: 38401469 DOI: 10.1016/j.watres.2024.121207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 10/28/2023] [Accepted: 01/26/2024] [Indexed: 02/26/2024]
Abstract
Wastewater-based epidemiology (WBE) is an emerging, practical surveillance tool for monitoring community levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, SC2). However, a paucity of data exists regarding SARS-CoV-2 and viral biomarker behaviour in aqueous and wastewater environments. Therefore, there is a pressing need to develop efficient and robust methods that both improve method sensitivity and reduce time and cost. We present a novel method for SARS-CoV-2, Human Coronavirus 229E (229E), and Pepper Mild Mottle Virus (PMMoV) recovery utilizing surface charge-based attraction via the branched cationic polymer, polyethylenimine (PEI). Initially, dose-optimization experiments demonstrated that low concentrations of PEI (0.001% w/v) proved most effective at flocculating suspended viruses and viral material, including additional unbound SC2 viral fragments and/or RNA from raw wastewater. A design-of-experiments (DOE) approach was used to optimize virus and/or viral material aggregation behaviour and recovery across varying aqueous conditions, revealing pH as a major influence on recoverability in this system, combinatorially due to both a reduction in viral material surface charge and increased protonation of PEI-bound amine groups. Overall, this method has shown great promise in significantly improving quantitative viral recovery, providing a straightforward and effective augmentation to standard centrifugation techniques.
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Affiliation(s)
- Nathan Mullins
- Queen's University, Department of Civil Engineering, Kingston, Ontario, K7L 3N6, Canada; McMaster University, Department of Chemical Engineering, Hamilton, Ontario, L8S 4L7, Canada
| | - Abdul Rahman Alashraf
- Queen's University, Department of Civil Engineering, Kingston, Ontario, K7L 3N6, Canada; Queen's University, Beaty Water Research Centre, Department of Civil Engineering, Kingston, Ontario, K7L 3N6, Canada
| | | | - R Stephen Brown
- Queen's University, Department of Chemistry and School of Environmental Studies, Kingston, Ontario, K7L 3N6, Canada; Queen's University, Beaty Water Research Centre, Department of Civil Engineering, Kingston, Ontario, K7L 3N6, Canada.
| | - Sarah Jane Payne
- Queen's University, Department of Civil Engineering, Kingston, Ontario, K7L 3N6, Canada; Queen's University, Beaty Water Research Centre, Department of Civil Engineering, Kingston, Ontario, K7L 3N6, Canada.
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Xiao Z, Pan M, Li X, Zhao C. Impact of SARS-CoV2 infection on gut microbiota dysbiosis. MICROBIOME RESEARCH REPORTS 2023; 3:7. [PMID: 38455085 PMCID: PMC10917619 DOI: 10.20517/mrr.2023.48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 11/12/2023] [Accepted: 11/28/2023] [Indexed: 03/09/2024]
Abstract
The composition and function of the gut microbiota constantly influence health. Disruptions in this delicate balance, termed gut microbiota dysbiosis, have been implicated in various adverse health events. As the largest global epidemic since 1918, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had devastating consequences. While the primary impact of Corona Virus Disease 2019 (COVID-19) has been on the respiratory system, a growing body of research has unveiled the significant involvement of the gastrointestinal tract as well. Emerging evidence underscores notable alterations in the gut microbiome of COVID-19 patients. In addition, the gut microbiome is also characterized by an abundance of opportunistic pathogens, which is related to disease manifestations of COVID-19 patients. The intricate bidirectional interaction between the respiratory mucosa and the gut microbiota, known as the gut-lung axis, emerges as a crucial player in the pathological immune response triggered by SARS-CoV-2. Here, we discuss microbiota-based gut characteristics of COVID-19 patients and the long-term consequences of gut microbiota dysregulation. These insights could potentially transform the development of long-term interventions for COVID-19, offering hope for improved outcomes and enhanced patient recovery.
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Affiliation(s)
- Zhenming Xiao
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Miaomiao Pan
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Xinyao Li
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Chao Zhao
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Frontiers Science Center, Shanghai 200032, China
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10
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Elbeltagi R, Al-Beltagi M, Saeed NK, Bediwy AS. COVID-19-induced gastrointestinal autonomic dysfunction: A systematic review. World J Clin Cases 2023; 11:5246-5266. [DOI: 10.12998/wjcc.v11.i22.5246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/10/2023] [Accepted: 07/03/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND It is common for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to occur in the gastrointestinal tract, which can present itself as an initial symptom. The severity of coronavirus disease 2019 (COVID-19) is often reflected in the prevalence of gastrointestinal symptoms. COVID-19 can damage the nerve supply to the digestive system, leading to gastrointestinal autonomic dysfunction. There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract.
AIM To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction, including its manifestations, potential mechanisms, diagnosis, differential diagnosis, impact on quality of life, prognosis, and management and prevention strategies.
METHODS We conducted a thorough systematic search across various databases and performed an extensive literature review. Our review encompassed 113 studies published in English from January 2000 to April 18, 2023.
RESULTS According to most of the literature, gastrointestinal autonomic dysfunction can seriously affect a patient's quality of life and ultimate prognosis. Numerous factors can influence gastrointestinal autonomic nervous functions. Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues, and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways. These symptoms include anorexia, dysgeusia, heartburn, belching, chest pain, regurgitation, vomiting, epigastric burn, diarrhea, abdominal pain, bloating, irregular bowel movements, and constipation. Diarrhea is the most prevalent symptom, followed by anorexia, nausea, vomiting, and abdominal pain. Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms, COVID-19-induced autonomic effects significantly impact the patient's condition, general health, prognosis, and quality of life. Early diagnosis and proper recognition are crucial for improving outcomes. It is important to consider the differential diagnosis, as these symptoms may be induced by diseases other than COVID-19-induced autonomic dysfunction. Treating this dysfunction can be a challenging task.
CONCLUSION To ensure the best possible outcomes for COVID-19 patients, it is essential to take a multidisciplinary approach involving providing supportive care, treating the underlying infection, managing dysfunction, monitoring for complications, and offering nutritional support. Close monitoring of the patient's condition is crucial, and prompt intervention should be taken if necessary. Furthermore, conducting thorough research on the gastrointestinal autonomic dysfunction caused by COVID-19 is vital to manage it effectively.
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Affiliation(s)
- Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Medical University of Bahrain, Busiateen 15503, Muharraq, Bahrain
| | - Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
- Department of Paediatrics, University Medical Center, Arabian Gulf University, Manama 26671, Manama, Bahrain
- Department of Paediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr Sulaiman Al Habib Medical Group, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Pathology Department, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Microbiology Section, Pathology Department, The Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr Sulaiman Al Habib Medical Group, Manama 26671, Manama, Bahrain
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11
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Elbeltagi R, Al-Beltagi M, Saeed NK, Bediwy AS. COVID-19-induced gastrointestinal autonomic dysfunction: A systematic review. World J Clin Cases 2023; 11:5252-5272. [PMID: 37621592 PMCID: PMC10445067 DOI: 10.12998/wjcc.v11.i22.5252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/10/2023] [Accepted: 07/03/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND It is common for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to occur in the gastrointestinal tract, which can present itself as an initial symptom. The severity of coronavirus disease 2019 (COVID-19) is often reflected in the prevalence of gastrointestinal symptoms. COVID-19 can damage the nerve supply to the digestive system, leading to gastrointestinal autonomic dysfunction. There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract. AIM To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction, including its manifestations, potential mechanisms, diagnosis, differential diagnosis, impact on quality of life, prognosis, and management and prevention strategies. METHODS We conducted a thorough systematic search across various databases and performed an extensive literature review. Our review encompassed 113 studies published in English from January 2000 to April 18, 2023. RESULTS According to most of the literature, gastrointestinal autonomic dysfunction can seriously affect a patient's quality of life and ultimate prognosis. Numerous factors can influence gastrointestinal autonomic nervous functions. Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues, and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways. These symptoms include anorexia, dysgeusia, heartburn, belching, chest pain, regurgitation, vomiting, epigastric burn, diarrhea, abdominal pain, bloating, irregular bowel movements, and constipation. Diarrhea is the most prevalent symptom, followed by anorexia, nausea, vomiting, and abdominal pain. Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms, COVID-19-induced autonomic effects significantly impact the patient's condition, general health, prognosis, and quality of life. Early diagnosis and proper recognition are crucial for improving outcomes. It is important to consider the differential diagnosis, as these symptoms may be induced by diseases other than COVID-19-induced autonomic dysfunction. Treating this dysfunction can be a challenging task. CONCLUSION To ensure the best possible outcomes for COVID-19 patients, it is essential to take a multidisciplinary approach involving providing supportive care, treating the underlying infection, managing dysfunction, monitoring for complications, and offering nutritional support. Close monitoring of the patient's condition is crucial, and prompt intervention should be taken if necessary. Furthermore, conducting thorough research on the gastrointestinal autonomic dysfunction caused by COVID-19 is vital to manage it effectively.
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Affiliation(s)
- Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Medical University of Bahrain, Busiateen 15503, Muharraq, Bahrain
| | - Mohammed Al-Beltagi
- Department of Paediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
- Department of Paediatrics, University Medical Center, Arabian Gulf University, Manama 26671, Manama, Bahrain
- Department of Paediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr Sulaiman Al Habib Medical Group, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Pathology Department, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Microbiology Section, Pathology Department, The Royal College of Surgeons in Ireland-Medical University of Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr Sulaiman Al Habib Medical Group, Manama 26671, Manama, Bahrain
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12
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Pennarossa G, Arcuri S, Pasquariello R, Gandolfi F, Maranesi M, Brevini TAL. Cruciferous vegetable-derived indole-3-carbinol prevents coronavirus cell egression mechanisms in tracheal and intestinal 3D in vitro models. PHYTOCHEMISTRY 2023; 212:113713. [PMID: 37169138 PMCID: PMC10168192 DOI: 10.1016/j.phytochem.2023.113713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 05/04/2023] [Accepted: 05/05/2023] [Indexed: 05/13/2023]
Abstract
The potential antiviral effects of indole-3-carbinol (I3C), a phytochemical found in Cruciferous vegetables, were investigated. Fibroblasts and epithelial cells were co-cultured on Alvetex® scaffolds, to obtain ad hoc 3D in vitro platforms able to mimic the trachea and intestinal mucosae, which represent the primary structures involved in the coronavirus pathogenesis. The two barriers generated in vitro were treated with various concentrations of I3C for different incubation periods. A protective effect of I3C on both intestinal and trachea models was demonstrated. A significant reduction in the transcription of the two main genes belonging to the Homologous to E6AP C-terminus (HECT)-E3 ligase family members, namely NEDD4 E3 Ubiquitin Protein Ligase (NEDD4) and WW Domain Containing E3 Ubiquitin Protein Ligase 1 (WWP1), which promote virus matrix protein ubiquitination and inhibit viral egression, were detected. These findings indicate I3C potential effect in preventing coronavirus cell egression processes that inhibit viral production. Although further studies are needed to clarify the molecular mechanisms whereby HECT family members control virus life cycle, this work paves the way to the possible therapeutic use of new natural compounds that may reduce the clinical severity of future pandemics.
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Affiliation(s)
- Georgia Pennarossa
- Laboratory of Biomedical Embryology and Tissue Engineering, Department of Veterinary Medicine and Animal Sciences, Università Degli Studi di Milano, Via Dell'Università 6, 26900, Lodi, Italy
| | - Sharon Arcuri
- Laboratory of Biomedical Embryology and Tissue Engineering, Department of Veterinary Medicine and Animal Sciences, Università Degli Studi di Milano, Via Dell'Università 6, 26900, Lodi, Italy
| | - Rolando Pasquariello
- Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy, Università Degli Studi di Milano, Via Celoria 10, 20133, Milan, Italy
| | - Fulvio Gandolfi
- Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy, Università Degli Studi di Milano, Via Celoria 10, 20133, Milan, Italy
| | - Margherita Maranesi
- Department of Veterinary Medicine, University of Perugia, Via S. Costanzo 4, 06126, Perugia, Italy.
| | - Tiziana A L Brevini
- Laboratory of Biomedical Embryology and Tissue Engineering, Department of Veterinary Medicine and Animal Sciences, Università Degli Studi di Milano, Via Dell'Università 6, 26900, Lodi, Italy.
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13
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Ailioaie LM, Ailioaie C, Litscher G. Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children. Int J Mol Sci 2023; 24:10874. [PMID: 37446047 DOI: 10.3390/ijms241310874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child's daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host's immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.
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Affiliation(s)
- Laura Marinela Ailioaie
- Department of Medical Physics, Alexandru Ioan Cuza University, 11 Carol I Boulevard, 700506 Iasi, Romania
| | - Constantin Ailioaie
- Department of Medical Physics, Alexandru Ioan Cuza University, 11 Carol I Boulevard, 700506 Iasi, Romania
| | - Gerhard Litscher
- President of the International Society for Medical Laser Applications (ISLA Transcontinental), German Vice President of the German-Chinese Research Foundation (DCFG) for TCM, Honorary President of the European Federation of Acupuncture and Moxibustion Societies, 8053 Graz, Austria
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14
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Malik JR, Acharya A, Avedissian SN, Byrareddy SN, Fletcher CV, Podany AT, Dyavar SR. ACE-2, TMPRSS2, and Neuropilin-1 Receptor Expression on Human Brain Astrocytes and Pericytes and SARS-CoV-2 Infection Kinetics. Int J Mol Sci 2023; 24:8622. [PMID: 37239978 PMCID: PMC10218482 DOI: 10.3390/ijms24108622] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 05/02/2023] [Accepted: 05/09/2023] [Indexed: 05/28/2023] Open
Abstract
Angiotensin Converting Enzyme 2 (ACE-2), Transmembrane Serine Protease 2 (TMPRSS-2) and Neuropilin-1 cellular receptors support the entry of SARS-CoV-2 into susceptible human target cells and are characterized at the molecular level. Some evidence on the expression of entry receptors at mRNA and protein levels in brain cells is available, but co-expression of these receptors and confirmatory evidence on brain cells is lacking. SARS-CoV-2 infects some brain cell types, but infection susceptibility, multiple entry receptor density, and infection kinetics are rarely reported in specific brain cell types. Highly sensitive Taqman ddPCR, flow-cytometry and immunocytochemistry assays were used to quantitate the expression of ACE-2, TMPRSS-2 and Neuropilin-1 at mRNA and protein levels on human brain-extracted pericytes and astrocytes, which are an integral part of the Blood-Brain-Barrier (BBB). Astrocytes showed moderate ACE-2 (15.9 ± 1.3%, Mean ± SD, n = 2) and TMPRSS-2 (17.6%) positive cells, and in contrast show high Neuropilin-1 (56.4 ± 39.8%, n = 4) protein expression. Whereas pericytes showed variable ACE-2 (23.1 ± 20.7%, n = 2), Neuropilin-1 (30.3 ± 7.5%, n = 4) protein expression and higher TMPRSS-2 mRNA (667.2 ± 232.3, n = 3) expression. Co-expression of multiple entry receptors on astrocytes and pericytes allows entry of SARS-CoV-2 and progression of infection. Astrocytes showed roughly four-fold more virus in culture supernatants than pericytes. SARS-CoV-2 cellular entry receptor expression and "in vitro" viral kinetics in astrocytes and pericytes may improve our understanding of viral infection "in vivo". In addition, this study may facilitate the development of novel strategies to counter the effects of SARS-CoV-2 and inhibit viral infection in brain tissues to prevent the spread and interference in neuronal functions.
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Affiliation(s)
- Johid Reza Malik
- Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.R.M.); (S.N.A.); (C.V.F.)
| | - Arpan Acharya
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA; (A.A.); (S.N.B.)
| | - Sean N. Avedissian
- Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.R.M.); (S.N.A.); (C.V.F.)
| | - Siddappa N. Byrareddy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA; (A.A.); (S.N.B.)
- Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, 17177 Stockholm, Sweden
| | - Courtney V. Fletcher
- Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.R.M.); (S.N.A.); (C.V.F.)
| | - Anthony T. Podany
- Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.R.M.); (S.N.A.); (C.V.F.)
| | - Shetty Ravi Dyavar
- Antiviral Pharmacology Laboratory, Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA; (J.R.M.); (S.N.A.); (C.V.F.)
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15
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Kozlov KV, Zhdanov KV, Ratnikova AK, Ratnikov VA, Tishkov AV, Grinevich V, Kravchuk YA, Miklush PI, Nikiforova PO, Gordienko VV, Popov AF, Andryukov BG. Hepatobiliary system and intestinal injury in new coronavirus infection (COVID-19): A retrospective study. World J Clin Cases 2023; 11:2226-2236. [PMID: 37122523 PMCID: PMC10131012 DOI: 10.12998/wjcc.v11.i10.2226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/22/2023] [Accepted: 03/06/2023] [Indexed: 03/30/2023] Open
Abstract
BACKGROUND An important area of effective control of the coronavirus disease 19 (COVID-19) pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection, including those based on assessing the state of the intestinal microbiota and permeability.
AIM To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization, to determine the role of hepatobiliary injury, intestinal permeability disorders, and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19.
METHODS The study was performed in 80 patients with COVID-19, with an average age of 45 years, 19 of whom had mild disease, and 61 had moderate disease severity. The scope of the examination included traditional clinical, laboratory, biochemical, instrumental, and radiation studies, as well as original methods for studying microbiota and intestinal permeability.
RESULTS The clinical course of COVID-19 was studied, and the clinical and biochemical features, manifestations of systemic inflammation, and intestinal microbiome changes in patients with mild and moderate severity were identified. Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines, insulin, faecal calprotectin, and zonulin.
CONCLUSION This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.
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Affiliation(s)
- Konstantin V Kozlov
- Department of Infectious Disease, Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Konstantin V Zhdanov
- Department of Infectious Disease, Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Anna K Ratnikova
- Department of Admission, Federal State Budgetary Institution "North-West District Scientific and Clinical Center Named After LG. Sokolov Federal Medical and Biological Agency", Saint-Petersburg 194291, Russia
| | - Vyacheslav A Ratnikov
- Department of Roentgenology, Federal State Budgetary Institution "North-West District Scientific and Clinical Center Named After LG. Sokolov Federal Medical and Biological Agency", Saint-Petersburg 194291, Russia
| | - Artem V Tishkov
- Department of Physics, Mathematics and Informatics, FSBEI HE IP. Pavlov SPbSMU MOH Russia, Saint-Petersburg 197022, Russia
| | - Vladimir Grinevich
- 2nd Department of Therapy (Advanced Medical Education), Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Yuriy A Kravchuk
- Department of Infectious Disease, Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Panteley I Miklush
- Department of Infectious Disease, Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Polina O Nikiforova
- Department of Infectious Disease, Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Vera V Gordienko
- Department of Infectious Disease, Military Medical Academy Named After SM. Kirov, Saint-Petersburg 194044, Russia
| | - Alexander F Popov
- School of Medicine, Far Eastern Federal University, Vladivostok 690922, Russia
| | - Boris G Andryukov
- School of Medicine, Far Eastern Federal University, Vladivostok 690922, Russia
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16
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Mahdi N, Nadeem I, Ur Rasool M, Ul Munamm SA, Khatana UF, Rashad F, Babu A. Pulmonary hypertension due to pulmonary embolism secondary to COVID-19: A district general hospital experience from the UK. J R Coll Physicians Edinb 2023; 53:9-12. [PMID: 36705094 PMCID: PMC9884629 DOI: 10.1177/14782715231152677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION Preliminary data suggest that the prevalence of pulmonary hypertension (PH) in patients with COVID-19 is around 13%, but its prognostic role remains unclear. Approximately 3% of patients develop chronic thrombo-embolic pulmonary hypertension (CTEPH) following diagnosis of acute pulmonary embolism (PE). It is recommended that patients are screened for CTEPH if they remain symptomatic 3 months following diagnosis of PE. AIMS The primary aim of the study was to assess the chances of persistent PH following PE secondary to COVID-19. METHODS We conducted a retrospective cohort study at a District General Hospital (DGH) in the United Kingdom. All patients diagnosed with COVID-19 and PE between April 2020 and October 2021 were examined. Patients were divided into two groups:·COVID-19 and PE with comorbidities (excluding pre-existing PH) and·COVID-19 and PE without comorbidities. We compared the ECHO features suggestive of PH between the two groups at the time of diagnosis of PE and at 3 months following treatment. RESULTS 80 patients were included in the study (49 with comorbidities and 31 with no comorbidities). Average age of comorbidities and no comorbidities groups were 73 years and 70 years, respectively. Average PaO2/FiO2 ratio for comorbidities and no comorbidities groups were 170 and 195, respectively. Fourteen patients (13 with comorbidities and 1 with no comorbidities) died in total. Results showed that risk of persistent PH and subsequent mortality following PE in COVID19 is 4.17 times and 1.32 times more in comorbidity group as compared to no comorbidity group, respectively (p < 0.001). CONCLUSION Patients with comorbidities are at high risk of persistent PH and mortality due to PE secondary to COVID19.
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Affiliation(s)
- Noor Mahdi
- Royal Papworth Hospital NHS Trust,
Cambridge, UK
| | - Iftikhar Nadeem
- Royal Papworth Hospital NHS Trust,
Cambridge, UK,Iftikhar Nadeem, Royal Papworth Hospital
NHS Trust, Cambridge, UK.
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17
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Rossini V, Tolosa-Enguis V, Frances-Cuesta C, Sanz Y. Gut microbiome and anti-viral immunity in COVID-19. Crit Rev Food Sci Nutr 2022; 64:4587-4602. [PMID: 36382631 DOI: 10.1080/10408398.2022.2143476] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
SARS-CoV-2 mainly affects the respiratory system, but the gastrointestinal tract is also a target. Prolonged gut disorders, in COVID-19 patients, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed viral clearance. Although there are no definitive conclusions, ample evidence would suggest that the gut microbiome composition and function play a role in COVID-19 progression. Microbiome modulation strategies for population stratification and management of COVID-19 infection are under investigation, representing an area of interest in the ongoing pandemic. In this review, we present the existing data related to the interaction between gut microbes and the host's immune response to SARS-CoV-2 and discuss the implications for current disease management and readiness to face future pandemics.
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Affiliation(s)
- V Rossini
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - V Tolosa-Enguis
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - C Frances-Cuesta
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
| | - Y Sanz
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
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18
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Assante G, Tourna A, Carpani R, Ferrari F, Prati D, Peyvandi F, Blasi F, Bandera A, Le Guennec A, Chokshi S, Patel VC, Cox IJ, Valenti L, Youngson NA. Reduced circulating FABP2 in patients with moderate to severe COVID-19 may indicate enterocyte functional change rather than cell death. Sci Rep 2022; 12:18792. [PMID: 36335131 PMCID: PMC9637119 DOI: 10.1038/s41598-022-23282-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 10/25/2022] [Indexed: 11/08/2022] Open
Abstract
The gut is of importance in the pathology of COVID-19 both as a route of infection, and gut dysfunction influencing the severity of disease. Systemic changes caused by SARS-CoV-2 gut infection include alterations in circulating levels of metabolites, nutrients and microbial products which alter immune and inflammatory responses. Circulating plasma markers for gut inflammation and damage such as zonulin, lipopolysaccharide and β-glycan increase in plasma along with severity of disease. However, Intestinal Fatty Acid Binding Protein / Fatty Acid Binding Protein 2 (I-FABP/FABP2), a widely used biomarker for gut cell death, has paradoxically been shown to be reduced in moderate to severe COVID-19. We also found this pattern in a pilot cohort of mild (n = 18) and moderately severe (n = 19) COVID-19 patients in Milan from March to June 2020. These patients were part of the first phase of COVID-19 in Europe and were therefore all unvaccinated. After exclusion of outliers, patients with more severe vs milder disease showed reduced FABP2 levels (median [IQR]) (124 [368] vs. 274 [558] pg/mL, P < 0.01). A reduction in NMR measured plasma relative lipid-CH3 levels approached significance (median [IQR]) (0.081 [0.011] vs. 0.073 [0.024], P = 0.06). Changes in circulating lipid levels are another feature commonly observed in severe COVID-19 and a weak positive correlation was observed in the more severe group between reduced FABP2 and reduced relative lipid-CH3 and lipid-CH2 levels. FABP2 is a key regulator of enterocyte lipid import, a process which is inhibited by gut SARS-CoV-2 infection. We propose that the reduced circulating FABP2 in moderate to severe COVID-19 is a marker of infected enterocyte functional change rather than gut damage, which could also contribute to the development of hypolipidemia in patients with more severe disease.
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Affiliation(s)
- G Assante
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
- Faculty of Life Sciences & Medicine, King's College, London, UK
| | - A Tourna
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
- Faculty of Life Sciences & Medicine, King's College, London, UK
| | - R Carpani
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - F Ferrari
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - D Prati
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - F Peyvandi
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
- Department of Pathophysiology and Transplantation, Università Degli Studi Di Milano, Milan, Italy
| | - F Blasi
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
- Department of Pathophysiology and Transplantation, Università Degli Studi Di Milano, Milan, Italy
| | - A Bandera
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
- Department of Pathophysiology and Transplantation, Università Degli Studi Di Milano, Milan, Italy
| | - A Le Guennec
- Randall Centre for Cell & Molecular Biophysics, King's College, London, UK
| | - S Chokshi
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
- Faculty of Life Sciences & Medicine, King's College, London, UK
| | - V C Patel
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
- Faculty of Life Sciences & Medicine, King's College, London, UK
- Institute of Liver Studies, King's College Hospital, London, UK
| | - I J Cox
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
- Faculty of Life Sciences & Medicine, King's College, London, UK.
| | - L Valenti
- Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
- Department of Pathophysiology and Transplantation, Università Degli Studi Di Milano, Milan, Italy.
| | - N A Youngson
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.
- Faculty of Life Sciences & Medicine, King's College, London, UK.
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Mozaffari SA, Salehi A, Mousavi E, Zaman BA, Nassaj AE, Ebrahimzadeh F, Nasiri H, Valedkarimi Z, Adili A, Asemani G, Akbari M. SARS-CoV-2-associated gut microbiome alteration; A new contributor to colorectal cancer pathogenesis. Pathol Res Pract 2022; 239:154131. [PMID: 36191449 PMCID: PMC9477615 DOI: 10.1016/j.prp.2022.154131] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/31/2022] [Accepted: 09/14/2022] [Indexed: 11/17/2022]
Abstract
The emergence of a novel coronavirus, COVID-19, in December 2019 led to a global pandemic with more than 170 million confirmed infections and more than 6 million deaths (by July 2022). Studies have shown that infection with SARS-CoV-2 in cancer patients has a higher mortality rate than in people without cancer. Here, we have reviewed the evidence showing that gut microbiota plays an important role in health and is linked to colorectal cancer development. Studies have shown that SARS-CoV-2 infection leads to a change in gut microbiota, which modify intestinal inflammation and barrier permeability and affects tumor-suppressor or oncogene genes, proposing SARS-CoV-2 as a potential contributor to CRC pathogenesis.
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Affiliation(s)
- Shahrooz Amin Mozaffari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Ali Salehi
- Department of Oral and Maxillofacial Radiology, School of Dentistry, Islamic Azad University, Isfahan (Khorasgan) Branch, Isfahan, Islamic Republic of Iran
| | - Elnaz Mousavi
- Dental Sciences Research Center, Department of Endodontics, School of Dentistry, Guilan University of Medical Sciences, Rasht, Islamic Republic of Iran
| | - Burhan Abdullah Zaman
- Department of Basic Sciences, College of Pharmacy, University of Duhok, Duhok, Kurdistan Region, Iraq
| | - Ali Eslambol Nassaj
- Department of Endodontics, School of Dentistry, Kerman University of Medical Sciences, Kerman, Islamic Republic of Iran
| | - Farnoosh Ebrahimzadeh
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
| | - Hadi Nasiri
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Zahra Valedkarimi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Ali Adili
- Senior Adult Oncology Department, Moffitt Cancer Center, University of South Florida, Tampa, USA; Department of Oncology, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Ghazaleh Asemani
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Morteza Akbari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.
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20
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Wais T, Hasan M, Rai V, Agrawal DK. Gut-brain communication in COVID-19: molecular mechanisms, mediators, biomarkers, and therapeutics. Expert Rev Clin Immunol 2022; 18:947-960. [PMID: 35868344 PMCID: PMC9388545 DOI: 10.1080/1744666x.2022.2105697] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 07/21/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Infection with COVID-19 results in acute respiratory symptoms followed by long COVID multi-organ effects presenting with neurological, cardiovascular, musculoskeletal, and gastrointestinal (GI) manifestations. Temporal relationship between gastrointestinal and neurological symptoms is unclear but warranted for exploring better clinical care for COVID-19 patients. AREAS COVERED We critically reviewed the temporal relationship between gut-brain axis after SARS-CoV-2 infection and the molecular mechanisms involved in neuroinvasion following GI infection. Mediators are identified that could serve as biomarkers and therapeutic targets in SARS-CoV-2. We discussed the potential therapeutic approaches to mitigate the effects of GI infection with SARS-CoV-2. EXPERT OPINION Altered gut microbiota cause increased expression of various mediators, including zonulin causing disruption of tight junction. This stimulates enteric nervous system and signals to CNS precipitating neurological sequalae. Published reports suggest potential role of cytokines, immune cells, B(0)AT1 (SLC6A19), ACE2, TMRSS2, TMPRSS4, IFN-γ, IL-17A, zonulin, and altered gut microbiome in gut-brain axis and associated neurological sequalae. Targeting these mediators and gut microbiome to improve immunity will be of therapeutic significance. In-depth research and well-designed large-scale population-based clinical trials with multidisciplinary and collaborative approaches are warranted. Investigating the temporal relationship between organs involved in long-term sequalae is critical due to evolving variants of SARS-CoV-2.
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Affiliation(s)
- Tameena Wais
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences. Pomona, CA 91766
| | - Mehde Hasan
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences. Pomona, CA 91766
| | - Vikrant Rai
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences. Pomona, CA 91766
| | - Devendra K. Agrawal
- Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences. Pomona, CA 91766
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21
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COVID-19 and Parkinson's Disease: Possible Links in Pathology and Therapeutics. Neurotox Res 2022; 40:1586-1596. [PMID: 35829997 DOI: 10.1007/s12640-022-00540-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/30/2022] [Accepted: 06/28/2022] [Indexed: 02/07/2023]
Abstract
The outbreak of SARs-CoV-2 with emerging new variants is leading to global health crisis and has brought a major concern for patients with comorbidities. Parkinson's disease (PD) is a motor neurodegenerative disease involving various metabolic and psychological ailments along with the common occurrence of hyposmia as observed in COVID-19 patients. In addition, the observed surplus inflammatory responses in both diseases are also alarming. Alongside, angiotensin-converting enzyme 2 (ACE2) receptor, essentially required by SARS-CoV-2 to enter the cell and dopamine decarboxylase (DDC), required for dopamine synthesis is known to co-regulate in the non-neuronal cells. Taken together, these conditions suggested the probable reciprocal pathological relation between COVID-19 and PD and also suggested that during comorbidities, the disease diagnosis and therapeutics are critical and may engender severe health complications. In this review, we discuss various events and mechanisms which may have implications for the exacerbation of PD conditions and must be taken into account during the treatment of patients.
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22
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Chakraborty C, Sharma AR, Bhattacharya M, Dhama K, Lee SS. Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity. World J Gastroenterol 2022; 28:2802-2822. [PMID: 35978881 PMCID: PMC9280735 DOI: 10.3748/wjg.v28.i25.2802] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/19/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.
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Affiliation(s)
| | - Ashish Ranjan Sharma
- Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University, Chuncheon-si 24252, South Korea
| | | | - Kuldeep Dhama
- Division of Pathology, Indian Council of Agricultural Research (ICAR)-Indian Veterinary Research Institute (IVRI), Bareilly 243122, Uttar Pradesh, India
| | - Sang-Soo Lee
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University, Chuncheon-si 24252, South Korea
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23
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Zyoud SH, Al-Jabi SW, Shahwan MJ, Jairoun AA. Global research production pertaining to gastrointestinal involvement in COVID-19: A bibliometric and visualised study. World J Gastrointest Surg 2022; 14:494-505. [PMID: 35734615 PMCID: PMC9160685 DOI: 10.4240/wjgs.v14.i5.494] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/26/2021] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a global pandemic that can cause diarrhoea, nausea/vomiting, and abdominal pain, among other gastrointestinal (GI) symptoms.
AIM To perform a bibliometric analysis of the global research production pertaining to GI involvement in COVID-19.
METHODS The Scopus database was used to search the global literature on GI involvement in COVID-19 during 2020. A bibliometric review of these publications was also performed using VOSviewer.
RESULTS Scopus had published 95615 documents on COVID-19 in all areas of research at the time of data collection. In total, 1267 publications on the topic of GI and COVID-19 were identified. Research articles (n = 606; 47.83%), letters (293; 23.13%), and reviews (186; 14.68%) were the most popular types of documents. The most productive countries and institutions in this field were the United States and Huazhong University of Science and Technology. The most cited paper was Xiao et al, which was published in Gastroenterology as a brief communication, with 798 citations. This paper provides evidence for GI infection of COVID-19 and its possible faecal–oral transmission route. In the term cluster analysis, there were two frontiers in this field: GI manifestations among COVID-19 patients and the implications of COVID-19 for the gastroenterologist.
CONCLUSION GI manifestations among COVID-19 patients and implications of COVID-19 for gastroenterologists were of interest, especially in the early stages of the pandemic.
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Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Samah W Al-Jabi
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
| | - Moyad Jamal Shahwan
- Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates
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24
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Tay DJW, Lew ZZR, Chu JJH, Tan KS. Uncovering Novel Viral Innate Immune Evasion Strategies: What Has SARS-CoV-2 Taught Us? Front Microbiol 2022; 13:844447. [PMID: 35401477 PMCID: PMC8984613 DOI: 10.3389/fmicb.2022.844447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 02/17/2022] [Indexed: 11/13/2022] Open
Abstract
The ongoing SARS-CoV-2 pandemic has tested the capabilities of public health and scientific community. Since the dawn of the twenty-first century, viruses have caused several outbreaks, with coronaviruses being responsible for 2: SARS-CoV in 2007 and MERS-CoV in 2013. As the border between wildlife and the urban population continue to shrink, it is highly likely that zoonotic viruses may emerge more frequently. Furthermore, it has been shown repeatedly that these viruses are able to efficiently evade the innate immune system through various strategies. The strong and abundant antiviral innate immunity evasion strategies shown by SARS-CoV-2 has laid out shortcomings in our approach to quickly identify and modulate these mechanisms. It is thus imperative that there be a systematic framework for the study of the immune evasion strategies of these viruses, to guide development of therapeutics and curtail transmission. In this review, we first provide a brief overview of general viral evasion strategies against the innate immune system. Then, we utilize SARS-CoV-2 as a case study to highlight the methods used to identify the mechanisms of innate immune evasion, and pinpoint the shortcomings in the current paradigm with its focus on overexpression and protein-protein interactions. Finally, we provide a recommendation for future work to unravel viral innate immune evasion strategies and suitable methods to aid in the study of virus-host interactions. The insights provided from this review may then be applied to other viruses with outbreak potential to remain ahead in the arms race against viral diseases.
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Affiliation(s)
- Douglas Jie Wen Tay
- Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Zhe Zhang Ryan Lew
- Infectious Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Justin Jang Hann Chu
- Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Collaborative and Translation Unit for Hand, Foot and Mouth Disease (HFMD), Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore
| | - Kai Sen Tan
- Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Infectious Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- *Correspondence: Kai Sen Tan,
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25
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Tam I, McNamara C, Dunbar J, O'Connor K, Manzano G, Cabana MD, Hametz PA. SARS-CoV-2 Gastrointestinal Shedding in Hospitalized Children. Hosp Pediatr 2022; 12:e78-e85. [PMID: 35028670 DOI: 10.1542/hpeds.2021-006304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that can cause gastrointestinal (GI) symptoms, with studies demonstrating detection of stool viral RNA weeks after respiratory tract clearance. It is unknown if children who test negative for SARS-CoV-2 on a nasopharyngeal (NP) swab may be shedding the virus in their stool. OBJECTIVE To measure the prevalence of SARS-CoV-2 stool shedding in children with positive and negative SARS-CoV-2 NP polymerase chain reactions (PCR) tests, and to determine clinical factors associated with GI shedding. METHODS In this cross-sectional study, we enrolled hospitalized patients 0 to 21 years old with a positive or a negative SARS-CoV-2 NP PCR test who had respiratory and/or GI symptoms. Participants were surveyed, and stool samples were sent for viral PCR testing. Fisher's exact test was used to evaluate bivariate associations of stool PCR test positivity with categorical variables. RESULTS Sixty-seven patients were consented; 34 patients did not provide stool samples so 33 patients were included: 17 NP-positive and 16 NP-negative for SARS-CoV-2. Eight of the 17 NP-positive patients had a positive stool PCR test for SARS-CoV-2, while none of the 16 SARS-CoV-2 NP-negative patients had a positive result (P < .01). For the 17 SARS-CoV-2 NP-positive patients, GI symptoms were associated with a positive stool PCR test (P = .05) for SARS-CoV-2, but this association was not found for all 33 patients (P = .11). No associations were found with patients in an immunocompromised state or those with a comorbid condition, fever and/or chills, respiratory symptoms, headache and/or myalgias, or anosmia and/or ageusia. CONCLUSIONS SARS-CoV-2 GI shedding is common and associated with GI symptoms in NP-positive children, with 47% having positive stool PCRs for SARS-CoV-2. GI shedding was not demonstrated in SARS-CoV-2 NP-negative children.
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26
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Logan AC, Berman BM, Prescott SL. Earth Dreams: Reimagining ARPA for Health of People, Places and Planet. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:12788. [PMID: 34886514 PMCID: PMC8657388 DOI: 10.3390/ijerph182312788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/29/2021] [Accepted: 12/02/2021] [Indexed: 12/28/2022]
Abstract
Bold new approaches are urgently needed to overcome global health challenges. The proposed Advanced Research Projects Agency for Health (ARPA-H) is intended to provide rapid health breakthroughs. While new technologies for earlier disease detection and more effective treatment are critical, we urge equal attention be given to the wider (physical, emotional, social, political, and economic) environmental ecosystems driving the non-communicable disease (NCD) crisis in the first place. This requires an integrated, cross-sectoral vision that spans the interwoven connections affecting health across the scales of people, places, and planet. This wider "exposome" perspective considers biopsychosocial factors that promote resilience and reduce vulnerabilities of individuals and communities over time-the many variables driving health disparities. Since life course health is strongly determined by early life environments, early interventions should be prioritized as a matter of effectiveness and social justice. Here, we explore the origins of the Advanced Research Project Agency and point to its potential to build integrated solutions, with wisdom and ethical value systems as a compass. Since the planned ARPA-H is anticipated to spawn international collaborations, the imagined concept is of relevance to a broad audience of researchers. With appropriate input, the quest for health equity through personalized, precision medicine while deconstructing unacceptable structural inequities may be accelerated.
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Affiliation(s)
- Alan C. Logan
- Nova Institute for Health of People, Places and Planet, 1407 Fleet Street, Baltimore, MD 21231, USA; (A.C.L.); (B.M.B.)
| | - Brian M. Berman
- Nova Institute for Health of People, Places and Planet, 1407 Fleet Street, Baltimore, MD 21231, USA; (A.C.L.); (B.M.B.)
- Center for Integrative Medicine, Department of Family and Community Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Susan L. Prescott
- Nova Institute for Health of People, Places and Planet, 1407 Fleet Street, Baltimore, MD 21231, USA; (A.C.L.); (B.M.B.)
- Center for Integrative Medicine, Department of Family and Community Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- inVIVO Planetary Health, Worldwide Universities Network (WUN), Baltimore, MD 21231, USA
- ORIGINS Project, Telethon Kids Institute, Perth Children’s Hospital, University of Western Australia, 15 Hospital Avenue, Nedlands, WE 6009, Australia
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27
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Wang Q, Liu L. On the Critical Role of Human Feces and Public Toilets in the Transmission of COVID-19: Evidence from China. SUSTAINABLE CITIES AND SOCIETY 2021; 75:103350. [PMID: 34540563 PMCID: PMC8433098 DOI: 10.1016/j.scs.2021.103350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 09/08/2021] [Accepted: 09/08/2021] [Indexed: 05/05/2023]
Abstract
The surprising spread speed of the COVID-19 pandemic creates an urgent need for investigating the transmission chain or transmission pattern of COVID-19 beyond the traditional respiratory channels. This study therefore examines whether human feces and public toilets play a critical role in the transmission of COVID-19. First, it develops a theoretical model that simulates the transmission chain of COVID-19 through public restrooms. Second, it uses stabilized epidemic data from China to empirically examine this theory, conducting an empirical estimation using a two-stage least squares (2SLS) model with appropriate instrumental variables (IVs). This study confirms that the wastewater directly promotes the transmission of COVID-19 within a city. However, the role of garbage in this transmission chain is more indirect in the sense that garbage has a complex relationship with public toilets, and it promotes the transmission of COVID-19 within a city through interaction with public toilets and, hence, human feces. These findings have very strong policy implications in the sense that if we can somehow use the ratio of public toilets as a policy instrument, then we can find a way to minimize the total number of infections in a region. As shown in this study, pushing the ratio of public toilets (against open defecation) to the local population in a city to its optimal level would help to reduce the total infection in a region.
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Affiliation(s)
- Qiuyun Wang
- School of Economics, Southwestern University of Finance and Economics, P.R China
| | - Lu Liu
- School of Economics, Southwestern University of Finance and Economics, P.R China
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28
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Al Kassaa I, El Omari S, Abbas N, Papon N, Drider D, Kassem II, Osman M. High association of COVID-19 severity with poor gut health score in Lebanese patients. PLoS One 2021; 16:e0258913. [PMID: 34673813 PMCID: PMC8530309 DOI: 10.1371/journal.pone.0258913] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 10/07/2021] [Indexed: 02/07/2023] Open
Abstract
Background Coronavirus disease 2019 (COVID-19) has affected millions of lives globally. However, the disease has presented more extreme challenges for developing countries that are experiencing economic crises. Studies on COVID-19 symptoms and gut health are scarce and have not fully analyzed possible associations between gut health and disease pathophysiology. Therefore, this study aimed to demonstrate a potential association between gut health and COVID-19 severity in the Lebanese community, which has been experiencing a severe economic crisis. Methods This cross-sectional study investigated SARS-CoV-2 PCR-positive Lebanese patients. Participants were interviewed and gut health, COVID-19 symptoms, and different metrics were analyzed using simple and multiple logistic regression models. Results Analysis of the data showed that 25% of participants were asymptomatic, while an equal proportion experienced severe symptoms, including dyspnea (22.7%), oxygen need (7.5%), and hospitalization (3.1%). The mean age of the participants was 38.3 ±0.8 years, and the majority were males (63.9%), married (68.2%), and currently employed (66.7%). A negative correlation was found between gut health score and COVID-19 symptoms (Kendall’s tau-b = -0.153, P = 0.004); indicating that low gut health was associated with more severe COVID-19 cases. Additionally, participants who reported unhealthy food intake were more likely to experience severe symptoms (Kendall’s tau-b = 0.118, P = 0.049). When all items were taken into consideration, multiple ordinal logistic regression models showed a significant association between COVID-19 symptoms and each of the following variables: working status, flu-like illness episodes, and gut health score. COVID-19 severe symptoms were more common among patients having poor gut health scores (OR:1.31, 95%CI:1.07–1.61; P = 0.008), experiencing more than one episode of flu-like illness per year (OR:2.85, 95%CI:1.58–5.15; P = 0.001), and owning a job (OR:2.00, 95%CI:1.1–3.65; P = 0.023). Conclusions To our knowledge, this is the first study that showed the impact of gut health and exposure to respiratory viruses on COVID-19 severity in Lebanon. These findings can facilitate combating the pandemic in Lebanon.
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Affiliation(s)
- Imad Al Kassaa
- Faculty of Public Health, Lebanese University, Beirut, Lebanon
- Doctoral School of Science and Technology, Lebanese University, Beirut, Lebanon
- * E-mail: (IAK); , (MO)
| | - Sarah El Omari
- Department of Epidemiology and Population Health, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Nada Abbas
- Department of Health Management and Policy, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
| | - Nicolas Papon
- Univ Angers, Univ Brest, GEIHP, SFR ICAT, Angers, France
| | - Djamel Drider
- UMR Transfrontalière BioEcoAgro1158, Univ. Lille, INRAE, Univ. Liège, UPJV, YNCREA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, Lille, France
| | - Issmat I. Kassem
- Center for Food Safety and Department of Food Science and Technology, University of Georgia, Griffin, GA, United States of America
| | - Marwan Osman
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America
- * E-mail: (IAK); , (MO)
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Hussain I, Cher GLY, Abid MA, Abid MB. Role of Gut Microbiome in COVID-19: An Insight Into Pathogenesis and Therapeutic Potential. Front Immunol 2021; 12:765965. [PMID: 34721437 PMCID: PMC8551858 DOI: 10.3389/fimmu.2021.765965] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 09/20/2021] [Indexed: 12/13/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome's potential as a biomarker and therapeutic target.
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Affiliation(s)
- Ikram Hussain
- Department of Gastroenterology, Khoo Teck Puat Hospital, Singapore, Singapore
| | | | - Muhammad Abbas Abid
- Department of Hematopathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan
| | - Muhammad Bilal Abid
- Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, WI, United States
- Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
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30
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Iglesias JI, Vassallo AV, Sullivan JB, Elbaga Y, Patel VV, Patel N, Ayad L, Benson P, Pittiglio M, Gobran E, Clark A, Khan W, Damalas K, Mohan R, Singh SP. Retrospective analysis of anti-inflammatory therapies during the first wave of COVID-19 at a community hospital. World J Crit Care Med 2021; 10:244-259. [PMID: 34616660 PMCID: PMC8462025 DOI: 10.5492/wjccm.v10.i5.244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/23/2021] [Accepted: 08/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Our understanding of the severe acute respiratory syndrome coronavirus 2 has evolved since the first reported cases in December 2019, and a greater emphasis has been placed on the hyper-inflammatory response in severely ill patients. The purpose of this study was to determine risk factors for mortality and the impact of anti-inflammatory therapies on survival.
AIM To determine the impact of various therapies on outcomes in severe coronavirus disease 2019 patients with a focus on anti-inflammatory and immune-modulating agents.
METHODS A retrospective analysis was conducted on 261 patients admitted or transferred to the intensive care unit in two community hospitals between March 12, 2020 and June 17, 2020. Totally 167 patients received glucocorticoid (GC) therapy. Seventy-three patients received GC alone, 94 received GC and tocilizumab, 28 received tocilizumab monotherapy, and 66 received no anti-inflammatory therapy.
RESULTS Patient survival was associated with GC use, either alone or with tocilizumab, and decreased vasopressor requirements. Delayed administration of GC was found to decrease the survival benefit of GC therapy. No difference in survival was found with varying anticoagulant doses, convalescent plasma, tocilizumab monotherapy; prone ventilation, hydroxychloroquine, azithromycin, or intravenous ascorbic acid use.
CONCLUSION This analysis demonstrated the survival benefit associated with anti-inflammatory therapy of GC, with or without tocilizumab, with the combination providing the most benefit. More studies are needed to assess the optimal timing of anti-inflammatory therapy initiation.
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Affiliation(s)
- Jose I Iglesias
- Department of Critical Care, Community Medical Center, Toms River, NJ 08757, United States
- Department of Nephrology, Community Medical Center, Toms River, NJ 08757, United States
- Department of Nephrology, Jersey Shore University Medical Center, Hackensack Meridian School of Medicine at Seton Hall, Neptune, NJ 07753, United States
| | - Andrew V Vassallo
- Department of Pharmacy, Community Medical Center, Toms River, NJ 08757, United States
| | - Jesse B Sullivan
- Fairleigh Dickinson University School of Pharmacy & Health Sciences, Fairleigh Dickinson University, Florham Park, NJ 07932, United States
| | - Yasmine Elbaga
- Department of Pharmancy, Monmouth Medical Center Southern Campus, Lakewood, NJ 08701, United States
| | - Vishal V Patel
- Department of Pharmacy, Community Medical Center, Toms River, NJ 08757, United States
| | - Nikunjkumar Patel
- Department of Medicine, Community Medical Center, Toms River, NJ 08757, United States
| | - Lydia Ayad
- Department of Medicine, Community Medical Center, Toms River, NJ 08757, United States
| | - Payam Benson
- Department of Medicine, Community Medical Center, Toms River, NJ 08757, United States
| | - Marina Pittiglio
- Department of Pharmacy, Community Medical Center, Toms River, NJ 08757, United States
| | - Emad Gobran
- Department of Medicine, Community Medical Center, Toms River, NJ 08757, United States
| | - Alexander Clark
- Department of Pharmancy, Monmouth Medical Center Southern Campus, Lakewood, NJ 08701, United States
| | - Wajahat Khan
- Department of Critical Care, Community Medical Center, Toms River, NJ 08757, United States
| | - Kaliope Damalas
- Department of Pharmacy, Community Medical Center, Toms River, NJ 08757, United States
| | - Rajesh Mohan
- Department of Cardiology, Monmouth Medical Center Southern Campus, Lakewood, NJ 08701, United States
| | - Satyendra P Singh
- Department of Medicine, Monmouth Medical Center Southern Campus, Lakewood, NJ 08701, United States
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Arnold CG, Monte AA, Littlefield K, Vest A, Palmer BE. Vaccination Hesitancy and Postacute Sequelae of SARS-CoV-2: Is It Time to Reconsider? Viral Immunol 2021; 34:666-668. [PMID: 34491119 DOI: 10.1089/vim.2021.0126] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Cosby G Arnold
- Department of Emergency Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA
| | - Andrew A Monte
- Department of Emergency Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA
| | - Katherine Littlefield
- Divisions of Allergy and Clinical Immunology, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA
| | - Alexis Vest
- Department of Emergency Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA
| | - Brent E Palmer
- Divisions of Allergy and Clinical Immunology, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA
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Vyhnalova T, Danek Z, Gachova D, Linhartova PB. The Role of the Oral Microbiota in the Etiopathogenesis of Oral Squamous Cell Carcinoma. Microorganisms 2021; 9:microorganisms9081549. [PMID: 34442627 PMCID: PMC8400438 DOI: 10.3390/microorganisms9081549] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/13/2021] [Accepted: 07/16/2021] [Indexed: 02/07/2023] Open
Abstract
Dysbiosis in the oral environment may play a role in the etiopathogenesis of oral squamous cell carcinoma (OSCC). This review aims to summarize the current knowledge about the association of oral microbiota with OSCC and to describe possible etiopathogenetic mechanisms involved in processes of OSCC development and progression. Association studies included in this review were designed as case–control/case studies, analyzing the bacteriome, mycobiome, and virome from saliva, oral rinses, oral mucosal swabs, or oral mucosal tissue samples (deep and superficial) and comparing the results in healthy individuals to those with OSCC and/or with premalignant lesions. Changes in relative abundances of specific bacteria (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus sp.) and fungi (especially Candida sp.) were associated with OSCC. Viruses can also play a role; while the results of studies investigating the role of human papillomavirus in OSCC development are controversial, Epstein–Barr virus was positively correlated with OSCC. The oral microbiota has been linked to tumorigenesis through a variety of mechanisms, including the stimulation of cell proliferation, tumor invasiveness, angiogenesis, inhibition of cell apoptosis, induction of chronic inflammation, or production of oncometabolites. We also advocate for the necessity of performing a complex analysis of the microbiome in further studies and of standardizing the sampling procedures by establishing guidelines to support future meta-analyses.
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Affiliation(s)
- Tereza Vyhnalova
- Environmental Genomics Research Group, RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; (T.V.); (D.G.); (P.B.L.)
- Department of Maxillofacial Surgery, Faculty of Medicine, Masaryk University, Jihlavská 20, 62500 Brno, Czech Republic
| | - Zdenek Danek
- Environmental Genomics Research Group, RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; (T.V.); (D.G.); (P.B.L.)
- Department of Maxillofacial Surgery, Faculty of Medicine, Masaryk University, Jihlavská 20, 62500 Brno, Czech Republic
- Department of Maxillofacial Surgery, University Hospital Brno, Jihlavská 20, 62500 Brno, Czech Republic
- Correspondence: ; Tel.: +420-777-550-596
| | - Daniela Gachova
- Environmental Genomics Research Group, RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; (T.V.); (D.G.); (P.B.L.)
| | - Petra Borilova Linhartova
- Environmental Genomics Research Group, RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; (T.V.); (D.G.); (P.B.L.)
- Department of Maxillofacial Surgery, Faculty of Medicine, Masaryk University, Jihlavská 20, 62500 Brno, Czech Republic
- Institute of Medical Genetics and Genomics, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
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Salivary Microbiome Diversity in Kuwaiti Adolescents with Varied Body Mass Index-A Pilot Study. Microorganisms 2021; 9:microorganisms9061222. [PMID: 34200004 PMCID: PMC8228046 DOI: 10.3390/microorganisms9061222] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/23/2021] [Accepted: 05/25/2021] [Indexed: 02/07/2023] Open
Abstract
The potential role of the salivary microbiome in human diseases has increasingly been explored. The salivary microbiome has been characterized in several global populations, except the Arabian Gulf region. Hence, in this pilot study, we profiled the salivary microbiome of Kuwaiti adolescents with varied body mass indexes (BMI). The analyses of core microbiome composition showed Firmicutes, Bacteroidota, Proteobacteria, Patescibacteria, Fusobacteriota, Actinobacteriota, and Campylobacterota as the common phylum found in the Kuwaiti adolescent population. We also illustrated a diverse microbial community among the sampled individuals grouped according to their BMI. Notably, the overweight group was found with a higher number of distinct taxa than other groups. As such, the core microbiome composition was found to be significantly different (p-value < 0.001) across different BMI groups. Overall, this pilot investigation outlined the microbial diversity and suggested that changes in salivary microbiome composition in people with obese or overweight BMI might reflect their susceptibility to oral diseases.
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Howell MC, Green R, McGill AR, Dutta R, Mohapatra S, Mohapatra SS. SARS-CoV-2-Induced Gut Microbiome Dysbiosis: Implications for Colorectal Cancer. Cancers (Basel) 2021; 13:2676. [PMID: 34071688 PMCID: PMC8198029 DOI: 10.3390/cancers13112676] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 05/22/2021] [Accepted: 05/24/2021] [Indexed: 12/12/2022] Open
Abstract
The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019 led to a worldwide pandemic with over 170 million confirmed infections and over 3.5 million deaths (as of May 2021). Early studies have shown higher mortality rates from SARS-CoV-2 infection in cancer patients than individuals without cancer. Herein, we review the evidence that the gut microbiota plays a crucial role in health and has been linked to the development of colorectal cancer (CRC). Investigations have shown that SARS-CoV-2 infection causes changes to the gut microbiota, including an overall decline in microbial diversity, enrichment of opportunistic pathogens such as Fusobacterium nucleatum bacteremia, and depletion of beneficial commensals, such as the butyrate-producing bacteria. Further, these changes lead to increased colonic inflammation, which leads to gut barrier disruption, expression of genes governing CRC tumorigenesis, and tumor immunosuppression, thus further exacerbating CRC progression. Additionally, a long-lasting impact of SARS-CoV-2 on gut dysbiosis might result in a greater possibility of new CRC diagnosis or aggravating the condition in those already afflicted. Herein, we review the evidence relating to the current understanding of how infection with SARS-CoV-2 impacts the gut microbiota and the effects this will have on CRC carcinogenesis and progression.
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Affiliation(s)
- Mark C. Howell
- Department of Veterans Affairs, James A. Haley Veterans Hospital, Tampa, FL 33612, USA; (M.C.H.); (R.G.); (A.R.M.)
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Ryan Green
- Department of Veterans Affairs, James A. Haley Veterans Hospital, Tampa, FL 33612, USA; (M.C.H.); (R.G.); (A.R.M.)
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Andrew R. McGill
- Department of Veterans Affairs, James A. Haley Veterans Hospital, Tampa, FL 33612, USA; (M.C.H.); (R.G.); (A.R.M.)
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
| | - Rinku Dutta
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA;
| | - Subhra Mohapatra
- Department of Veterans Affairs, James A. Haley Veterans Hospital, Tampa, FL 33612, USA; (M.C.H.); (R.G.); (A.R.M.)
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA;
| | - Shyam S. Mohapatra
- Department of Veterans Affairs, James A. Haley Veterans Hospital, Tampa, FL 33612, USA; (M.C.H.); (R.G.); (A.R.M.)
- Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
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