Disease ⇒ Covid-19 {40000510} Record Keys Type:Disease Parent:[ ] Definition:Covid-19 Details Initialisation date:2021-04-19 Other Terms:[ ] Meta Information MedDra ID:[ ] MedDra Level:[ ] ICD:[ ] Category:[ ] Zone:[ ] Mechanism:[ ] Notes: - There is an unusual microbiomes in hospitalized COVID-19 patients. - There is a strong connection between gut microbes and COVID-19 severity. - In addition to the lungs and gut, the SARS-CoV-2 virus has been detected in the liver, kidney, heart, and brain. - Intestinal bacteria appear to influence the production of this important mucus barrier, which could prevent viruses in the gut from reaching other parts of the body. - Dysbiome can predispose to leaky gut and it is highly likely that viruses get access to organs other than the lungs and the gut through a leaky gut. - SARS-CoV-2 altered the gut microbiome by the tenth day of infection; with some of the changes persisting after 26 days. - There is a drop in bacterial species known to make short-chain fatty acids (SCFAs), which are important molecules that can regulate the immune system. - SCFAs produced by gut microbes in mouse travel via the bloodstream to other areas of the body, including the lungs, and can protect the from respiratory viruses. - Some bacteria manufacture a bacteriocin, that blocks the entry of viruses. - Bacteroidetes trigger intestinal immune cells to release interferons. Interferons are key factors that ramp up the body’s response to viruses and help eliminate cells that are infected.Shared Reference Notes [1.1] - Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. [1.2] - A disrupted gut microbiome (gut dysbiosis) can lead to epithelium breakdown and inflammation, which have been shown to increase levels of angiotensin-converting enzyme 2 (ACE2), the target of SARS-CoV-2. - Increased gut permeability can lead to pro-inflammatory bacterial products to leak out and circulate systemically, triggering inflammatory cascades. - A specific gut microbiota composition may predispose healthy individuals to severe COVID-19 infections; increased levels of pro-inflammatory bacterial species correlated with elevated levels of pro-inflammatory cytokines and increased disease severity. - A disrupted gut microbiome may also contribute to increased pro-inflammatory cytokine production (“cytokine storm”), known to worsen severity of SARS-CoV-2 infection. - Proteomic and metabolomic profiling has shown progression to severe COVID-19 infection can be predicted both in infected patients and in healthy individuals. - Elderly and immunocompromised populations are known to have reduced microbiota diversity. Since many of these vulnerable patients have had worse clinical outcomes for COVID-19, this strengthens the possibility that the gut microbiome is affecting clinical progression. - Reduced gut microbiome diversity may therefore be useful as a predictive biomarker of COVID-19 severity. Mechanisms underpinning gastrointestinal symptoms are thought to involve ACE2 receptors, which are highly expressed on intestinal epithelial cells , in particular the brush border membrane of small intestinal enterocytes. - ACE2 gene expression has been shown to increase with age, potentially accounting for differential susceptibility to more severe disease. [1.3] - #Bacteroidetes trigger intestinal immune cells to release interferons. Interferons are key factors that ramp up the body’s response to viruses and help eliminate cells that are infected. - #Bacteroidetes have a specific molecule on their cell surface called a #Glycolipid that causes intestinal immune cells to release antiviral interferons. - #Streptomycetes bacteria manufacture a bacteriocin, called duramycin, that blocks the entry of West Nile, dengue, and Ebola viruses into their host cells. Other bacteriocins halt the replication of herpes simplex viruses. [1.4] - The gut microbiota of moderate and severe Covid-19 patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial #Butyrate-producing bacteria such as Roseburia and Lachnospira genera. [1.5] - Faecal microbiota transplant (FMT) restores a damaged gut microbiome and may impact on immune responses,3 including in the respiratory system (‘gut–lung axis’); such microbiome-immune signalling may result in lung-epithelial resistance to SARS-CoV-2 - Patient 1: an 80-year-old man with multiple comorbidities, including prior CDI, was admitted to hospital with pneumonia/sepsis. Following meropenem treatment, pneumonic features resolved, but CDI relapse occurred. Sequential vancomycin treatment and nasojejunal FMT were administered. On the day of FMT, he developed further fever and C-reactive protein (CRP) increased; repeat microbiology cultures were negative, but SARS-CoV-2 PCR was positive. He commenced on remdesivir and convalescent plasma (CP). Unexpectedly, 2 days after FMT, the fever never recurred and his CRP decreased, without further pneumonia exacerbation. - Patient 2: a 19-year-old man with ulcerative colitis on immunosuppression was admitted to hospital because of a relapse of CDI. Vancomycin therapy was administered, and symptomatic improvement occurred; colonoscopic FMT was administered to prevent further recurrence. Fifteen hours post-FMT, he developed fever up to 39°C, with CRP and interleukin-6 (IL-6) levels increased; SARS-CoV-2 PCR returned positive. Subsequently, other than two isolated episodes of fever, his temperature did not exceed 36.6°C, and CRP and IL-6 normalised. [1.6] [1.7] [1.8] [1.9] [#Butyrate] [1.11] [#Lactobacillus rhamnosus] [#Probiotic (Bifidobacter and Lactobacilus)] - #Probiotic > Covid-19 > The proportion who developed symptoms was 26.4% with LGG versus 42.9% with placebo, a significant difference. [1.12] - Patients with very low #Vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected [1.13] [#Influenza A, #Pneumonia, #Tuberculosis] [1.14] [#Leptin] [1.15] - Severe Covid > higher abundance of four microbial species (i.e., #Burkholderia contaminans, #Bacteroides nordii, #Bifidobacterium longum, and #Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes > further associated with host immune response. - The abundance of Bu. contaminans > associated with higher levels of inflammation biomarkers and lower levels of immune cells. - human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. - The circulating levels of #Lipopolysaccharide-binding protein increased in patients with severe illness > associated with circulating inflammation biomarkers and immune cells. - proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. [1.16] - Calcitriol > increasing anti-inflammatory IL-10 production in B cells and reduces T cell activation by B cells and decreasing pro-inflammatory markers such as TNFα, IL-1β, IL-6, and cyclooxygenase-2 (COX-2) > anti-inflammatory effect. - #Vitamin D > induces the expression of antimicrobial peptides such as cathelicidin 1 and defensin β4 in lung epithelia. - The biologically active hydroxyderivatives of #Vitamin D > inhibit the action of the TMPRSS2 (the serine protease found on the host cell that primes the spike protein, which then binds to the angiotensin-converting enzyme 2 (ACE2) receptors). [1.17] - Bifidobacterium and Clostridium were depleted in those in the ICU. - The most severe COVID-19 patients had reduced Neisseria, Rothia, and Prevotella. - In contrast, Salmonella, Scardovia, Serratia, and Pseudomonadaceae were more abundant in the nasopharynx of ICU patients compared with those with mild or moderate symptoms, - Alloprevotella, Catonella, Lachnoanaerobaculum, Oribacterium, multiple Prevotella, Treponema, and Unclassified Erysipelotrichaceae operational taxonomic units (OTUs) to be more abundant and Unclassified Chloroplast to be less abundant in patients with severe compared with those with mild COVID-19 - #Corynebacterium accolens is a common nose inhabitant - #Corynebacterium accolens incidence was significantly decreased in the URT of patients with SARS-CoV-2 compared with uninfected controls. #Corynebacterium accolens can inhibit Streptococcus pneumoniae and Staphylococcus aureus growth, possibly through triolein hydrolysis, which releases #Oleic acid. - In addition to inhibiting bacterial pathogens, #Oleic acid is capable of inhibiting other enveloped viruses, such as herpes and influenza. - Oleoylethanolamide, an #Oleic acid derivative, may inhibit the release of proinflammatory cytokines induced by SARS-CoV-2, potetially reducing the risk of a patient developing a cytokine storm, which is associated with severe disease and high mortality. [1.18] [#Glycans] [1.19] [1.21] - SARS-CoV-2-infected participants with #Corynebacterium/#Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles [1.22] - Oral Bifidobacterium, Lactobacillus, and Solobacterium, all of which were depleted in patients with severe COVID-19. Nasopharyngeal Paracoccus was depleted while nasopharyngeal Proteus, Cupravidus, and Lactobacillus were increased in patients with severe COVID-19. - the abundance of oral #Bifidobacterium was negatively associated with plasma concentrations of known COVID-19 biomarkers interleukin 17F (IL-17F) and monocyte chemoattractant protein-1 (MCP-1) [1.23] - Methylcobalamin has a significant affinity to bind to the active site of the nsp12 protein of SARS-CoV-2, Thus, #Vitamin B12 may inhibit the RNA‐dependent RNA polymerase activity of nsp12 responsible for the replication of the viral genome. [1.24] - The serum #Zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum #Zonulin levels were not correlated with ESR, CRP, and other inflammation markers [1.25] -anti-inflammatory bacteria, including #Bifidobacteria species and #Eubacterium rectale, with lower severity, and pro-inflammatory bacteria such as #Prevotella copri with higher severity. [1.26] - #Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells [1.27] - Covid-19 > Mortality was associated with increased representation of #Proteobacteria in the fecal microbiota and decreased concentrations of fecal #Secondary bile acids and #Desaminotyrosine (DAT). - A microbiome metabolic profile (MMP) that accounts for fecal #Secondary bile acids and #Desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. [1.28] [#Parkinson’s Disease] [#Alpha-synuclein] - overexpression of α-synuclein in PD patients may limit SARS-CoV-2 neuroinvasion and degeneration of dopaminergic neurons; however, on the other hand, this virus can speed up the α-synuclein aggregation. [1.29] [#Human adenovirus, #Human coronavirus] [#Short Chain Fatty Acid] - Increased abundance of SCFA-producing bacteria appears to offer protection against many common respiratory viruses including #Rhinovirus, #Respiratory syncytial virus, adenovirus, #Influenza and severe acute respiratory syndrome #Coronavirus 2 (SARS-CoV-2) [#Post-acute infection syndrome] - PASC (post-acute sequelae of COVID-19 infection) and ME/CFS (myalgic encephalomyelitis/#Chronic fatigue syndrome) are two of the most recognized and prevalent PAIS conditions. [1.31] [#Diabetes Type 1] - COVID-19 patients have a significantly higher risk to develop subsequent autoimmune diseases such as #Rheumatoid Arthritis, #Ankylosing spondylitis, #Systemic sclerosis, type I diabetes mellitus. [#Chronic fatigue syndrome] - Covid-19 > The increased #Ornithine/#Citrulline ratio level in class B patients reflects abnormal metabolic activity in the urea cycle. - a similarly increased #Ornithine/#Citrulline ratio in CFS patients - long COVID-19 patients complain about extreme cognitive disorders (self-reported symptoms) but without any objective alterations - #IL-17A has been found to be associated with neurological sequelae and pulmonary #Fibrosis in post-COVID-19 patients - COVID-19 patients > higher levels of #Carnitine and some short, medium, and long #Acylcarnitines. - Covid-19 > increased levels of triacylglycerols, phosphatidylcholines, prostaglandin E2, #Arginine, and decreased levels of #Betaine and #Adenosine in patients with abnormal pulmonary function. - (1) supplementation of #Taurine (reducing musculoskeletal disorders); - (2) supplementation of #Citrulline (enhancing #Ammonia clearance and reducing blood #Lactate, as well as increasing #Arginine bioavailability for adequate NO production); - (3) supplementation of #Glutamine (primary source for #Neurotransmitters and immune function balancing); - (4) supplementation of antioxidants such as N-acetylcysteine or NAD + (redox balance); - (5) supplementation of #Arginine (targeting endothelial dysfunction in Long-COVID) - increased levels of #Proline associated with collagen metabolism in long COVID patients. - The #Glutamate/P5C synthase pathway in the intestine is responsible for most of the #Proline synthesis in the body. - The increased levels of #Proline may arise from #Arginine or #Glutamine pathways, potentially in response to hypoxia or tissue damage. - #Butyric acid and #Propionic acid, two short-chain fatty acids that were found to be altered during COVID-19 phase, also fell within normal levels in post-COVID-19 patients, probably indicating that the leaky gut phenomenon and gut dysbiosis detected during COVID infection could be partially reestablished - In the post-COVID phase, by the contrary, an increase in #Glutamine concentrations and a decrease in #Glutamate (higher #Glutamine/#Glutamate ratio) could be associated with long-term recovery, - During COVID-19 phase, a decrease in circulating levels of #Glutamine has been widely described. - Increased levels of #Hippuric acid in the long COVID-19 phase could be associated with a residual intestinal dysbiosis. - Covid-19 > Increased level of the #Lactate/#Pyruvate ratio in class B patients is another important indicator of mitochondrial dysfunction. - The #Lactate/#Pyruvate ratio has been proposed as a marker for mitochondrial disorders since it indirectly reflects the NADH/NAD + redox state56, lipid metabolism (fat oxidation), and ATP generation. - Increased plasma #Pyruvate levels could be both a consequence of glycolytic dysregulation and protein degradation. - #Taurine and #Spermidine were found significantly decreased in the long COVID phase. - increased levels of #kynurenine, and a trend towards normalization in #Tryptophan and the #kynurenine/#Tryptophan ratio in long COVID-19 patients. [1.32] - Both #Polyphenols and #Phytosterols reduce #Cholesterol levels in the cell membrane or destabilize the structure of lipid rafts, which are the main docking sites for COVID-19 entry and genome release [#Respiratory syncytial virus] - dietary polyphenol, lignan and #Phytosterol intake in reducing COVID-19 risk. - The antiviral efficacy of #Polyphenols including #Lignans and plant sterols has been confirmed against SARS-CoV, MERS-CoV, Ebola virus, HIV, #Influenza virus and other viruses causing respiratory tract infections. - their beneficial effects against the SARS-CoV-2 virus resulting from their ability to bind to peak protein sites on the ACE2 receptor used by SARS-CoV-2 to infect cells, regulate ACE2 expression and also interfere with SARS-CoV-2 replication by inhibiting the virus protease or inhibiting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) [1.33] - #Bifidobacterium dampens Th responses of severely ill COVID-19 patients likely contributing to resolution of harmful overreactions of the immune system. [1.34] [#Bacteroides dorei] - Higher neutralizing antibody levels at 6 months post-vaccination were associated with specific gut microbial compositions at baseline, such as Bifidobacterium adollescentis and #Bifidobacterium bifidum for BNT162b2 vaccines and #Phocaeicola dorei for CoronaVac vaccines. [#Niacin, #γ-Aminobutyric acid] - Distinct metabolites, including nicotinic acid (Vitamin B) and γ-Aminobutyric acid, were correlated with immune durability in BNT162b2 vaccines, while L-#Tryptophan showed significance for CoronaVac vaccines. [1.35] - #Eubacterium rectale and #Roseburia intestinalis, that were negatively correlated with SMR during the study period. - reduction of these species was associated with severer COVID-19 manifestation. [1.36] - elevated levels of #Candida albicans immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal Candida overgrowth, mycobiota dysbiosis and systemic neutrophilia. - Mice colonized with C. albicans patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. - sCOVID-19 patients treated with tocilizumab experienced sustained reductions in C. albicans IgG antibodies titers and GMP transcriptional changes [1.37] [#mRNA vaccine] - #Agathobacter, #Lactobacillus, #Bacteroides, and #Lachnospira were positively correlated with both spike IgG levels and spike-specific CD4+ T-cell responses. These #Bacteria with known immunomodulatory properties could contribute to higher immune responses to vaccinations [#Bifidobacterium adolescentis] [#mRNA vaccine] - B. adolescentis was also associated with a higher rate of neutralizing antibodies after CoronaVac immunization [#mRNA vaccine] - #Bifidobacterium and #Faecalibacterium showed significant association with high spike IgG titers, irrespective of other factors - Enrichment of #Bifidobacterium was correlated with CD4+ T-cell responses and higher antibody titers to parenteral and oral vaccinations. [#mRNA vaccine] - high spike IgG levels, with less abundance of bacterial groups belonging to #Clostridiales and #Methanobacteriales, such as #Ruminococcaceae #DTU089 and #Methanobrevibacter, respectively. [#Roseomonas mucosa] [#Short Chain Fatty Acid] [#mRNA vaccine] - different bacterial groups from #Lachnospiraceae to be associated with either high or low spike IgG levels. - bacterial members belonging to the family #Lachnospiraceae are well-known producers of SCFAs in colon mucosa-associated microbiota. - #Lachnospiracea FSC020, which shows a positive association with spike IgG levels > a potential positive association with the production of #Acetate and propionat [#Short Chain Fatty Acid] [#mRNA vaccine] - #Marvinbryantia was observed to be less abundant in the younger group. - enrichment of #Marvinbryantia spp., which are SCFA-producers, in the elderly > a lower response to vaccinations, - Elevated levels of spike-specific CD4+ T-cell responses were associated with reduced microbiome diversity, thus further validating the association of the microbiome with the immunogenicity of the BNT162b2 #mRNA vaccine. - certain bacterial genera at the baseline were associated with vaccine immunogenicity, measured by IgG spike and spike-specific CD4+ T-cell responses. [1.38] [#Thrombotic events] [#Acylcarnitines] [#Antibiotic Therapy] - #2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with major adverse cardiovascular events (MACEs). - 2MBC enhances platelet hyperreactivity and thrombus formation in mice. - 2MBC binds to integrin α2β1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. - Genetic depletion or pharmacological inhibition of integrin α2β1 largely reverses the pro-thrombotic effects of 2MBC. - 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. References Notes[ ]
