• COVID-19
• SARS-CoV-2

• COVID-19
• Cancer
• Homology modeling
• Molecular dynamics simulations
• TMPRSS4

• Molecular Dynamics Simulation
• Humans
• Serine Endopeptidases/chemistry
• Serine Endopeptidases/metabolism
• Molecular Docking Simulation
• SARS-CoV-2/drug effects
• Protein Binding
• Membrane Proteins/chemistry
• Membrane Proteins/antagonists & inhibitors
• Membrane Proteins/metabolism
• COVID-19 Drug Treatment
• Binding Sites
• Serine Proteinase Inhibitors/chemistry
• Serine Proteinase Inhibitors/pharmacology

• RSPD2024R628 King Saud University

• COVID‐19
• Mendelian randomization
• colocalization analysis
• gastroesophageal reflux disease
• molecular pathway analysis
• shared genomic loci

• Humans
• COVID-19/genetics
• Mendelian Randomization Analysis
• Gastroesophageal Reflux/genetics
• Genetic Predisposition to Disease
• SARS-CoV-2
• Polymorphism, Single Nucleotide
• Linkage Disequilibrium
• Genome-Wide Association Study

• 2023-B-02 The Science and Technology Talents Incubation Project of Center for Disease Control and Prevention of Zhejiang Province

• Inflammation
• Long COVID-19
• Systemic effects
• Thrombosis

• Exacerbated GI-Related symptoms
• Inflammatory bowel disease
• Long COVID

• Humans
• COVID-19/complications
• COVID-19/epidemiology
• Taiwan/epidemiology
• Male
• Female
• Adult
• Middle Aged
• Inflammatory Bowel Diseases/complications
• SARS-CoV-2
• COVID-19 Vaccines
• Aged
• Diarrhea/etiology
• Diarrhea/epidemiology
• Abdominal Pain/etiology
• Risk Factors
• Gastrointestinal Diseases/epidemiology
• Gastrointestinal Diseases/etiology

• COVID-19
• COVID-19 testing
• COVID-19 treatment
• PASC
• United States
• Veterans Affairs
• clinician
• diagnosis
• health care support
• long COVID
• long COVID cause
• mobile phone
• pandemic
• policy initiatives
• postacute sequelae of COVID-19
• public health
• public safety

• Humans
• COVID-19/epidemiology
• COVID-19/complications
• Risk Factors
• Male
• Post-Acute COVID-19 Syndrome
• Female
• Cross-Over Studies
• Middle Aged
• United States/epidemiology
• Aged
• International Classification of Diseases
• Adult

• R21 AA026954 NIAAA NIH HHS
• R25 LM014213 NLM NIH HHS
• T15 LM012495 NLM NIH HHS
• UL1 TR001412 NCATS NIH HHS

• COVID-19
• Gut microbiota
• anxiety
• depression
• psychiatric symptoms

• Humans
• COVID-19/psychology
• Gastrointestinal Microbiome
• Dysbiosis
• Anxiety Disorders
• SARS-CoV-2
• Depressive Disorder

• COVID-19
• Omicron
• critical illness
• predictive models
• sex-specific

• COVID-19
• chronic kidney disease
• inflammation
• nutrition

• Humans
• COVID-19/complications
• Renal Insufficiency, Chronic/complications
• Diet
• Dietary Supplements
• Antioxidants/therapeutic use

• SARS-CoV-2
• asymptomatic
• infectious
• pediatric population
• stool
• symptomatic
• variants

• COVID-19
• Coronavirus disease 2019
• kidney transplantation
• meta-analysis
• systematic review

• COVID‐19
• Iran
• epidemiology
• gastrointestinal symptoms
• mortality

• COVID-19
• SARS-CoV-2
• angiotensin-converting enzyme 2
• gastroenteritis
• gut microflora
• immune responses
• inflammatory bowel disease
• pathogenesis
• therapeutics

• BT/PR4094/COT/142/20/2021 Department of Biotechnology
• HKBU 12103021 Research Grants Council of the Hong Kong Special Administrative Region, China

• bibliometric analysis
• immunity
• microbiota
• microecology
• mucosa dysfunction

• No.81830114, 82174253, 82104707 and 82004232 National Natural Science Foundation of China

• COVID-19
• SARS-CoV-2
• gastrointestinal symptoms
• gut-lung axis
• meta-analysis
• microbiota
• nutritional intervention

• Humans
• SARS-CoV-2
• COVID-19
• Exposome
• Lung
• Gastrointestinal Diseases
• Mucous Membrane

• National Research Foundation of Korea

• COVID-19
• Cancer
• Hypoxia
• IL-6
• SARS-CoV-2
• Therapeutics

• BILE
• COVID-19
• DIET
• GASTRIC ACID
• PANCREATIC ENZYMES

• COVID-19
• MIS-C
• SARS-CoV-2
• gut microbiome

• Humans
• SARS-CoV-2
• Gastrointestinal Microbiome
• COVID-19

• Bacteriocins
• Beta variant
• COVID-19
• MD simulations
• Protein–protein docking
• SARS-CoV-2

• clinical microbiology
• gastroenterology
• medical research

• Humans
• Gastrointestinal Microbiome/genetics
• COVID-19
• Metagenomics/methods
• Feces/microbiology
• Post-Acute COVID-19 Syndrome

• Food and Health Bureau of the Government of the Hong Kong Special Administrative Region | Health Care and Promotion Fund (HCPF)
• This work was supported by InnoHK, The Government of Hong Kong, Special Administrative Region of the People’s Republic of China.

• COVID-19
• COVID-19 recovery
• SARS-CoV-2
• gut microbiota
• microbiota-derived metabolites
• micronutrients

• Humans
• Aged
• Gastrointestinal Microbiome
• COVID-19
• Micronutrients/pharmacology
• Vitamins/pharmacology
• Coenzymes

• COVID-19
• gastrointestinal symptom
• laboratory indicator
• nongastrointestinal symptom

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.

• COVID-19
• Inflammation
• Gut microbiota
• Therapeutic

• Aged
• Dysbiosis/microbiology
• Gastrointestinal Microbiome
• Humans
• Inflammation
• SARS-CoV-2
• Severity of Illness Index
• COVID-19 Drug Treatment

• Probiotics
• coronavirus
• coronavirus disease 2019 (COVID-19)
• severe acute respiratory syndrome coronavirus (SARS-CoV)

• COVID-19
• Cytokine Release Syndrome
• Dysbiosis/therapy
• Humans
• Probiotics/therapeutic use
• SARS-CoV-2

• Kerman University of Medical Sciences

Proton Pump Inhibitors (PPI) are one of the most prescribed medications in the United States. However, PPIs have been shown to increase the risk of enteric infections. Our study aims to evaluate the correlation between PPI and COVID-19 severity. We performed a retrospective cohort study on patients who tested positive for SARS-CoV-2 from March to August 2020. Patients were categorized based on PPI user status. Primary outcomes included need for hospital or ICU admission and 30-day mortality. Secondary outcomes looked to determine the severity of COVID-19 infection and effect of comorbid conditions. 2,594 patients were reviewed. The primary outcomes of our study found that neither active nor past PPI use was associated with increased hospital admission or 30-day mortality following completion of multivariate analysis. Additionally, there was no association between COVID-19 infection and the strength of PPI dosing (low, standard, high). However, the following covariates were independently and significantly associated with increased admission: age, male gender, diabetes, COPD, composite cardiovascular disease, kidney disease, and obesity. The following covariates were associated with increased mortality: age, male gender, COPD, and kidney disease. In conclusion, the high risk features and comorbidities of PPI users were found to have a stronger correlation to severe COVID-19 infection and poor outcomes as opposed to the use of PPI therapy.

• COVID-19/complications
• Child
• Gastrointestinal Diseases
• Humans
• Pandemics
• SARS-CoV-2
• Systemic Inflammatory Response Syndrome

• adverse events
• covid-19
• covid-19 vaccine
• diverticulitis colon
• gastrointestinal complications.

• ACE-2
• COVID-19
• Crohn’s disease
• Inflammatory bowel disease
• SARS-CoV-2
• Ulcerative colitis

• R01 DK128143 NIDDK NIH HHS
• R03 DK123579 NIDDK NIH HHS

• COVID-19
• intestinal microbiology

• COVID-19/complications
• COVID-19/diagnosis
• COVID-19/microbiology
• Follow-Up Studies
• Gastrointestinal Microbiome/physiology
• Humans
• Metagenomics/methods
• Prospective Studies
• SARS-CoV-2
• Severity of Illness Index
• Post-Acute COVID-19 Syndrome

• by Hong Kong Special Administrative Region Government, China
• The Chinese University of Hong Kong

The diagnosis of coronavirus disease (COVID-19) has been a great challenge since the infection affects not only the respiratory system, but also different organs, given the intense inflammatory and autoimmune reaction triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein we present a case of a 36-year-old male patient, with some comorbidities and previous use of carbamazepine, who developed a severe condition triggered by COVID-19, including extensive exfoliative erythroderma and severe impairment of liver function, which lasted approximately 80 days.

• Adult
• Antigen-Antibody Complex
• COVID-19/complications
• Drug Hypersensitivity Syndrome/diagnosis
• Drug Hypersensitivity Syndrome/etiology
• Eosinophilia
• Exanthema
• Humans
• Male
• SARS-CoV-2

In addition to the angiotensin-converting enzyme 2 (ACE2), a number of host cell entry mediators have been identified for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), including transmembrane protease serine 4 (TMPRSS4). The authors have recently demonstrated the upregulation of TMPRSS4 in 11 different cancers, as well as its specific expression within the central nervous system using in silico tools. The present study aimed to expand the initial observations and, using immunohistochemistry, TMPRSS4 protein expression in the gastrointestinal (GI) tract and lungs was further mapped. Immunohistochemistry was performed on tissue arrays and lung tissues of patients with non-small cell lung cancer with concurrent coronavirus disease 2019 (COVID-19) infection using TMPRSS4 antibody. The results revealed that TMPRSS4 was abundantly expressed in the oesophagus, stomach, small intestine, jejunum, ileum, colon, liver and pancreas. Moreover, the extensive TMPRSS4 protein expression in the lungs of a deceased patient with COVID-19 with chronic obstructive pulmonary disease and bronchial carcinoma, as well in the adjacent normal tissue, was demonstrated for the first time, at least to the best of our knowledge. On the whole, the immunohistochemistry data of the present study suggest that TMPRSS4 may be implicated in the broader (pulmonary and extra-pulmonary) COVID-19 symptomatology; thus, it may be responsible for the tropism of this coronavirus both in the GI tract and lungs.

• coronavirus disease 2019
• gastrointestinal tract
• lung
• severe acute respiratory syndrome coronavirus‑2
• transmembrane protease serine 4
• tropism

SARS‐CoV‐2, the causative agent of COVID‐19, typically manifests as a respiratory illness, although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS‐CoV‐2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS‐CoV‐2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 postmortem cases and 16 biopsies with polymerase chain reaction (PCR)‐confirmed SARS‐CoV‐2 status from the peaks of the pandemic in 2020 and four pre‐COVID postmortem controls. SARS‐CoV‐2 anti‐NP staining in the postmortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS‐CoV‐2 NP in neurons of the myenteric plexus, a site of high ACE2 expression, the entry receptor for SARS‐CoV‐2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS‐CoV‐2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms with the organ tropism of SARS‐CoV‐2 in contemporary cases as well as providing insights into potential long‐term complications of COVID‐19. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

• COVID-19
• Enteric nervous system
• Gastrointestinal tract
• Immunohistochemistry
• Megakaryocytes
• Myenteric plexus
• Neurons
• Parkinson's Disease
• SARS-CoV-2
• Tropism

• SARS-CoV-2
• colon cancer
• gastrointestinal tract
• motif
• network

The ongoing coronavirus disease (COVID-19) pandemic has dramatically tested healthcare systems around the world, with serious repercussions on the measures of prevention and control of hospital-acquired infections (HAIs). Among HAIs, Clostridioides difficile infection (CDI) represents one of the most important global public health threats. Although the full impact of the COVID-19 pandemic on CDI remains undetermined, depending on the development of the pandemic in the coming months, in this review literature studies of the last three years have been considered in order to depict the current situation, and make some considerations about possible future developments. If on the one hand, a general reduction in CDI incidence has been reported in several settings, mainly due to the extraordinary reinforcement of infection prevention measures, on the other hand, the critical circumstances experienced in many hospitals have limited the effectiveness of these measures, particularly in the intensive care units (ICUs), increasing the possibility of the occurrence of hospital-acquired CDI (HA-CDI). New concerns have arisen from the decrease in C. difficile testing and the increased use of broad-spectrum antibiotics reported during the pandemic. In particular, overuse of antibiotics and disinfectants may lead to a selection of resistant C. difficile strains not only in hospitals but also in the community. Furthermore, patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and patients that have survived COVID-19 may represent a new group of frail patients potentially at a higher risk of CDI, a group that could potentially increase in size due to SARS-CoV-2 evolution. In the dramatic COVID-19 era, the multifactorial nature of CDI has emerged more clearly than before, highlighting the necessity of a strong refocus on efforts to improve prevention strategies and to integrate CDI surveillance in a One Health prospective in order to curtail the public health threat posed by this infection in the next future.

• Coronavirus
• Dose-response models
• Fecal-oral route
• Risk estimation
• SARS-CoV-2
• Sensitivity index

• COVID-19
• Humans
• Influenza A Virus, H5N1 Subtype
• Risk Assessment
• SARS-CoV-2
• Wastewater
• Water

• COVID-19/complications
• COVID-19/epidemiology
• COVID-19/metabolism
• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/etiology
• Cardiovascular Diseases/metabolism
• Female
• Humans
• Male
• Pandemics
• Risk Factors
• SARS-CoV-2/metabolism
• Severity of Illness Index
• Sex Characteristics
• Sex Factors

Gastrointestinal and respiratory tract diseases often occur together. There are many overlapping pathologies, leading to the concept of the ‘gut–lung axis’ in which stimulation on one side triggers a response on the other side. This axis appears to be implicated in infections involving severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has triggered the global coronavirus disease 2019 (COVID-19) pandemic, in which respiratory symptoms of fever, cough and dyspnoea often occur together with gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhoea. Besides the gut–lung axis, it should be noted that the gut participates in numerous axes which may affect lung function, and consequently the severity of COVID-19, through several pathways. This article focuses on the latest evidence and the mechanisms that drive the operation of the gut–lung axis, and discusses the interaction between the gut–lung axis and its possible involvement in COVID-19 from the perspective of microbiota, microbiota metabolites, microbial dysbiosis, common mucosal immunity and angiotensin-converting enzyme II, raising hypotheses and providing methods to guide future research on this new disease and its treatments.

• Coronavirus disease-19
• Dysbiosis
• Gut-lung axis
• Immunity
• Microbiota

• COVID-19
• Detection
• Diagnosis
• Metal-based nanoparticles
• Polymeric materials
• SARS-CoV-2
• Virus lifecycle