Inflammation In COVID-19 Research Articles

FPR1 signaling aberrantly regulates S100A8/A9 production by CD14+FCN1hi macrophages and aggravates pulmonary pathology in severe COVID-19

Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Necroptosis in alveolar epithelial cells drives lung inflammation and injury caused by SARS-CoV-2 infection

COVID-19, caused by SARS-CoV-2 infection, results in irreversible or fatal lung injury. We assumed that necroptosis of virus-infected alveolar epithelial cells (AEC) could promote local inflammation and further lung injury in COVID-19. Since CD8+ lymphocytes induced AEC cell death via cytotoxic molecules such as FAS ligands, we examined the involvement of FAS-mediated cell death in COVID-19 patients and murine COVID-19 model. We identified the occurrence of necroptosis and subsequent release of HMGB1 in the admitted patients with COVID-19. In the mouse model of COVID-19, lung inflammation and injury were attenuated in Fas-deficient mice compared to Fas-intact mice. The infection enhanced Type I interferon-inducible genes in both groups, while inflammasome-associated genes were specifically upregulated in Fas-intact mice. The treatment with necroptosis inhibitor, Nec1s, improved survival rate, lung injury, and systemic inflammation. SARS-CoV-2 induced necroptosis causes cytokine induction and lung damage, and its inhibition could be a novel therapeutic strategy for COVID-19.

Inflammation in COVID-19 is linked to pulmonary embolism and/or vascular tree-in-bud in hospitalized patients. The university hospital of Ioannina COVID-19 Registry, NCT05534074

Inflammation in COVID-19 is linked to pulmonary embolism and/or vascular tree-in-bud in hospitalized patients. The university hospital of Ioannina COVID-19 Registry, NCT05534074

The Link between Inflammation, Lipid Derivatives, and Microbiota Metabolites in COVID-19 Patients: Implications on Eating Behaviors and Nutritional Status.

Extreme inflammation that continues even after infections can lead to a cytokine storm. In recent times, one of the most common causes of cytokine storm activation has been SARS-CoV-2 infection. A cytokine storm leads to dysregulation and excessive stimulation of the immune system, producing symptoms typical of post-COVID syndrome, including chronic fatigue, shortness of breath, joint pain, trouble concentrating (known as "brain fog"), and even direct organ damage in the heart, lungs, kidneys, and brain. This work summarizes the current knowledge regarding inflammation and the cytokine storm related to SARS-CoV-2 infection. Additionally, changes in lipid metabolism and microbiota composition under the influence of inflammation in COVID-19, along with the possible underlying mechanisms, are described. Finally, this text explores potential health implications related to changes in eating behaviors and nutritional status in COVID-19 patients. Although research on the cytokine storm is still ongoing, there is convincing evidence suggesting that severe immune and inflammatory responses during the acute phase of COVID-19 may lead to long-term health consequences. Understanding these links is key to developing treatment strategies and supporting patients after infection.

Colchicine-The Divine Medicine against COVID-19.

Colchicine has a number of effects that suggest it may be useful in the treatment of COVID-19. Myeloid cells are a major source of dysregulated inflammation in COVID-19. The hyperactivation of the NLRP3 inflammasome and the subsequent cytokine storm take place precisely inside them and can lead to multiorgan damage and death. NLRP3 inflammasome inhibition has been assessed at micromolar colchicine concentrations which cannot be achieved in serum. However, colchicine has remarkable ability to accumulate intensively in leukocytes, where the cytokine storm is generated. Over 50 observational studies and randomized clinical trials, small randomized non-controlled trials, and retrospective cohort studies were initiated to test its healing effect in vivo, leading to conflicting, rather disappointing results. The WHO gives a "Strong recommendation against" the use of colchicine for COVID-19 treatment. This is because low doses of colchicine are always used, where the concentrations required to inhibit the NLRP3 inflammasome in leukocytes cannot be reached. Considering this, from March 2020, we started the administration of higher doses of colchicine. Our assumption was that a safe increase in colchicine doses to reach micromolar concentrations in leukocytes will result in NLRP3 inflammasome/cytokine storm inhibition. We demonstrated that in 785 inpatients treated with increasing doses of colchicine, mortality fell between two and seven times. Our data, including a large number of COVID-19 outpatients, showed that nearly 100% of the patients treated with this therapeutic regimen escaped hospitalization. In addition, post-COVID-19 symptoms in those treated with colchicine were significantly rarer. As a large number of viruses can overactivate the NLRP3 inflammasome (like seasonal influenza), we are convinced that higher colchicine doses would be useful in these cases as well.

Inflammasome-Mediated Mechanisms Of Systemic Inflammation In COVID-19 And Asthma

The review examines the formation of inflammasome-mediated mechanisms of systemic inflammation in asthma after COVID-19. It provides insight into the clinical and pathophysiological relationship between asthma and COVID-19. The review summarizes information about the role of the NLRP3 inflammasome in the pathogenesis of asthma and describes in detail its manifestations in various asthma phenotypes. Emphasizing the significance of the inflammatory-mediated immune response during coronavirus infection in patients with bronchopulmonary pathology, the review outlines the consequences of hyperactivation of the NLRP3 pathway, leading to increased production of cytokines, the appearance of neutrophil and monocyte-derived traps, induction of pyroptosis and the development of complications.

Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. The International Study of Inflammation in Covid-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients. Ten hospitals in the United States and Europe. Adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body-mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI≥35), those with BMI>40 (n=485) had 55% higher odds of the composite outcome (95% CI[1.21 to 1.98]) compared to non-obese individuals (BMI<30, n=2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.

Acellular Human Amniotic Fluid-Derived Extracellular Vesicles as Novel Anti-Inflammatory Therapeutics against SARS-CoV-2 Infection.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19.

Network-based pharmacology and UHPLC-Q-Exactive-Orbitrap-MS reveal Jinhua Qinggan granule's mechanism in reducing cellular inflammation in COVID-19.

The outbreak of SARS-CoV-2, leading to COVID-19, poses a major global health threat. While specific treatments and vaccines are under development, Traditional Chinese Medicine (TCM) has historically been effective against pandemics, including viral pneumonias. Our study explores the efficacy and mechanisms of Jinhua Qinggan Granules (JHQG) in treating COVID-19. We analyzed JHQG's components using UHPLC-Q-Exactive-Orbitrap-MS, identifying 73 compounds. Network pharmacology and single-cell RNA sequencing (scRNA-seq) were used to assess JHQG's effects on immune cells from peripheral blood mononuclear cells (PBMCs). Literature review supported the antiviral and anti-inflammatory effects of JHQG. JHQG targets were found to interact with immune cells, including neutrophils, monocytes, plasmablasts, and effector T cells, reducing their overactivation in severe COVID-19. JHQG's modulation of these cells' activity likely contributes to reduced inflammation and improved clinical outcomes. Our findings provide insights into JHQG's mechanism of action, highlighting its potential in controlling the inflammatory response in COVID-19 patients. The study supports the use of JHQG as a safe and effective treatment for COVID-19 and similar viral infections, leveraging its ability to modulate immune cell activity and reduce inflammation.

Blood Count, Markers of Inflammation and Coagulation factors in COVID-19 versus non COVID-19 patients having Medical Emergency in Qena University Hospital

Blood Count, Markers of Inflammation and Coagulation factors in COVID-19 versus non COVID-19 patients having Medical Emergency in Qena University Hospital

Some reflections on immunosuppressants and their delivery to the lungs by aerosol in the treatment of COVID-19

Disorders of immune homeostasis represent the key pathogenetic link of COVID-19, which often manifests as a hyperimmune response to the pathogen, leading to severe uncontrolled inflammation in lungs, followed by complications and death. Accordingly, a certain therapeutic potential is provided by different pharmacological drugs with distinct mechanisms of action, This class of drugs should, however, act in common direction by suppressing the immune response, thus being often classified as immunosuppressants (IS). Of them, the most promising are immunobiological preparations, which include monoclonal antibodies, as well as purinergic regulatory agents. There are several attempts to use the “classical” IS by a certain way, e.g., cytostatics and calcineurin inhibitors which found clinical application in transplantology and oncology. However, their usage for treatment of uncontrolled inflammation of respiratory tract was abandoned by the end of XX century. Meanwhile, the aerosol route of drug administration optimizes treatment, both in terms of their effectiveness, and the reduction of side effects thus promoting usage of IS for treatment of uncontrolled airway inflammation. Previously, the analysis of therapeutic opportunities for some IS delivered as aerosols to the lungs in COVID-19 therapy was not carried out, thus bein the purpose of our work. Methodological analysis was carried out using various databases of biomedical scientific information, including Index Medicus, PubMed, Embase, Cohrane Clinical Trials gov registry and patent databases.The efficiency of the impact of various IS subgroups in COVID-19, including their administration by inhalations into the respiratory ways, was assessed. The role of regulatory T cells considered the central regulator of immune response, in pathogenesis of COVID-19 was considered, and their therapeutic potential was characterized, dependent on phase and severity of the disease as well as drug dose dependence. Methods and approaches to the use of IP, advantages and disadvantages are discussed. The expediency and future prospects of their application are considered.One may conclude that the effectiveness of cytostatics and calcineurin inhibitors in the treatment of airway inflammation in COVID-19 remains unconfirmed and seems to be unpromising. Meanwhile, biological preparations, including monoclonal antibodies and purinergic regulatory agents, offer great promise in this respect.

Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.

Airway basal stem cells (BSCs) play a critical role in epithelial regeneration. Whether coronavirus disease (COVID-19) affects BSC function is unknown. Here, we derived BSC lines from patients with COVID-19 using tracheal aspirates (TAs) to circumvent the biosafety concerns of live-cell derivation. We show that BSCs derived from the TAs of control patients are bona fide bronchial BSCs. TA BSCs from patients with COVID-19 tested negative for severe acute respiratory syndrome coronavirus 2 RNA; however, these so-termed COVID-19-exposed BSCs invitro resemble a predominant BSC subpopulation uniquely present in patients with COVID-19, manifested by a proinflammatory gene signature and STAT3 hyperactivation. Furthermore, the sustained STAT3 hyperactivation drives goblet cell differentiation of COVID-19-exposed BSCs in an air-liquid interface. Last, these phenotypes of COVID-19-exposed BSCs can be induced in control BSCs by cytokine cocktail pretreatment. Taken together, acute inflammation in COVID-19 exerts a long-term impact on mucociliary differentiation of BSCs.

Coping with the COVID-19 pandemic by strengthening immunity as a nonpharmaceutical intervention: A major public health challenge.

The global Coronavirus-2 outbreak has emerged as a significant threat to majority of individuals around the world. The most effective solution for addressing this viral outbreak is through vaccination. Simultaneously, the virus's mutation capabilities pose a potential risk to the effectiveness of both vaccines and, in certain instances, newly developed drugs. Conversely, the human body's immune system exhibits a robust ability to combat viral outbreaks with substantial confidence, as evidenced by the ratio of fatalities to affected individuals worldwide. Hence, an alternative strategy to mitigate this pandemic could involve enhancing the immune system's resilience. The research objective of the review is to acquire a comprehensive understanding of the role of inflammation and immunity in COVID-19. The pertinent literature concerning immune system functions, the impact of inflammation against viruses like SARS-CoV-2, and the connection between nutritional interventions, inflammation, and immunity was systematically explored. Enhancing immune function involves mitigating the impact of key factors that negatively influence the immune response. Strengthening the immune system against emerging diseases can be achieved through nonpharmaceutical measures such as maintaining a balanced nutrition, engaging in regular exercise, ensuring adequate sleep, and managing stress. This review aims to convey the significance of and provide recommendations for immune-strengthening strategies amidst the ongoing COVID-19 pandemic.

Administration of N-Acetylcysteine (NAC) as Adjunctive Therapy for COVID-19 Patients by Improving Oxidative Stress and Inflammation Through Assessment of MDA, IL-6, IL-1β, TNF-α, and TGF-β

INTRODUCTION: Oxidative stress due to COVID-19 will trigger a widespread inflammatory reaction in the lungs. Malondialdehyde (MDA), Interleukin-6 (IL-6), Interleukin-1 β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Tumor Growth Factor- β (TGF-β) are pro-inflammatory cytokines which levels may rise in the presence of an inflammatory process. N-Acetylcysteine (NAC) is an antioxidant widely considered as adjunctive therapy in COVID-19. We aim to analyze the effect of NAC administration in improving oxidative stress and inflammation in COVID-19 through assessment of MDA, IL-6, IL-1β, TNF-α, and TGF-β. METHOD: This is a quasi-experimental study with pre-post design. MDA, IL-6, IL-1β, TNF-α, and TGF-β levels were measured in admission and day 8 of administration of 5000 mg/72 hours of NAC. RESULT: From 74 samples, between admission and day 8 of NAC therapy, There is a decrease of IL-6 (185.31 ± 181.30 to 97.60 ± 161.86 (p=0.003)), TNF-α (5.83 ± 3.51 to 4.37 ± 3.33 (p=0.019)), IL-1 β (4.65 ± 4.13 to 1.87 ± 0.96 (p&lt;0.001)), and MDA levels (3000.70 ± 2017.98 to 2116.54 ± 1109.58 (p&lt;0.001). However, TGF-β levels were increased from 5.47 ± 2.76 to 7.97 ± 3.24 (p&lt;0.001). DISCUSSION: From our patients we get a significant decrease of pro-inflammatory cytokines (MDA, IL-6, IL-1β, and TNF-α) after administration of NAC. However, we acquired a significant increased level of TGF-β in our patients despite NAC administration which implies the chronic immune response in COVID-19 patients. CONCLUSION: There is an improvement of oxidative stress and inflammation by administration of NAC as adjunctive therapy in COVID-19 patients assessed by decrease of MDA, IL-6, IL-1β, and TNF-α levels. There is no effect of NAC as adjunctive therapy in TGF-β levels in COVID-19 patients. Keywords: NAC, COVID-19, MDA, IL-6, IL-1β, TNF-α, TGF-β

Administration of N-acetylcysteine (Nac) as Adjunctive Therapy for Covid-19 Patients by Improving Oxidative Stress and Inflammation through Assessment of Ldh, Crp, D-dimer, and Ferritin

INTRODUCTION Lactate dehydrogenase (LDH), C-Reactive Protein (CRP), D-dimer and feritin are acute phase proteins which levels may rise in the presence of an inflammatory process of COVID-19. N-Acetylcysteine (NAC) is an antioxidant which has also been widely considered as adjunctive therapy in COVID-19. We aim to analyze the effect of NAC administration in improving oxidative stress and inflammation in COVID-19 through assessment of LDH, CRP, D-dimer, and feritin levels. METHOD A quasi-experimental study with pre-post design. LDH, CRP, D-dimer, and feritin levels were measured in admission and day 8 of administration of 5000 mg/72 hours of NAC. RESULT There is a significant decrease in CRP, LDH, D-dimer and Ferritin levels between admission and day 8 of NAC therapy. CRP levels were reduced from 185.31 ± 181.30 to 97.60 ± 161.86 (p&lt;0.001), LDH levels were reduced from 4.65 ± 4.13 to 1.87 ± 0.96 (p&lt;0.001), D-dimer levels were reduced from 185.31 ± 181.30 to 97.60 ± 161.86 (p&lt;0.001) and Ferritin levels were reduced from 4.65 ± 4.13 to 1.87 ± 0.96 (p&lt;0.001). DISCUSSION There is a significant decrease of LDH, CRP, D-dimer, and feritin levels from day-1 (admission) to day-8 of NAC administration in accordance with existing theories. This implies the ability of NAC to reduce oxidative stress and inflammation in COVID-19 patients. CONCLUSION There was a decrease in CRP, LDH, D-dimer and Ferritin after administration of NAC in COVID-19 patients and a positive correlation between severity and mortality towards acute phase protein in COVID-19 patients.

Reduced Vessel Density and Enlarged Foveal Avascular Zone in the Macula as a Result of Systemic Hypoxia Caused by SARS-CoV-2 Infection.

Infection with SARS-CoV-2 can lead to various long-term consequences, including those of an ophthalmic nature. This paper reviews the results of optical coherence tomography angiography (OCTA) performed among COVID-19 patients. The review included papers evaluating short- and long-term outcomes following the SARS-CoV-2 infection. Some differentiated the obtained retinal and choroidal vascularization parameters according to gender. Following COVID-19, patients reveal changes in retinal and choroidal vascular parameters based on OCTA, such as reduced vascular density and an increased foveal avascular zone, which can persist for several months. Routine ophthalmic follow-up with OCTA should be considered in patients after SARS-CoV-2 infection to assess the effects of inflammation and systemic hypoxia in COVID-19. Further research is needed to understand whether infection with particular viral variants/subvariants may vary in the risk of effects on retinal and choroidal vascularization and whether and to what extent these risks may also differ in relation to reinfected and vaccinated individuals.

COVID-19 associated coagulopathy: A bibliometric investigation

Infection with SARS-CoV-2 initiates an immune-hemostatic response. While both systems are intimately connected and necessary for an efficient immune response to contain the infection, excessive coagulation activation might exceed the valuable benefits by causing thrombotic consequences and excessive inflammation. This biological response is new to clinicians and researchers, and accordingly, tremendous studies have been conducted on coagulopathy and its relationship to COVID-19 disease during this pandemic. Therefore, it takes a research insight from a bibliometric perspective to determine research hotspots and trends of COVID-19 associated coagulopathy (C19-CA). The analysis relies on the Scopus database for bibliographic content and Visualization of Similarities viewer software to map bibliometric data of C19-CA. Our study finds the most eminent authors, journals, institutions, funding organizations, and countries that publish in the C19-CA. Additionally; this research employs bibliometric analysis of co-authorship, co-citations, bibliographic coupling, and co-occurrence of keywords. A total of 2242 studies were retrieved, and the number of annual publications of C19-CA showed remarkable growth. The top-publishing authors on C19-CA are Smadja, D.M., Diehl, J.L., and Gendron, N (France). The total number of articles published in English in these three years was 1241, with the original article accounting for 99.8% and conference papers accounting for 0.2%. Huazhong University of Science and Technology (China) is the top-productive institution, with the US being the top-publishing country. Journal of Thrombosis and Thrombolysis received the highest number of original articles. The research results were mainly published in the fields of Medicine, Biochemistry, Genetics, and Molecular Biology, Immunology and Microbiology. Yuanyuan Li, who is (China), is the top-collaborating author. China and its authors have the highest number of citations. Keywords' co-occurrence analyses of the authors and all keywords revealed the following themes in C19-CA; abnormal coagulation parameters, pulmonary coagulopathy, venous and arterial thrombotic disorders, distinct features of coagulopathy, inflammation, and thrombosis in COVID-19, and anticoagulants and thrombolytic therapies. By combining bibliometric analysis with VOSviewer software, we identified C19-CA's leaders, collaborating institutions, and research hotspots, as well as give references for future research paths.

Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome.

Immune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragments is mostly unknown. Here, we investigate the role of endostatin, a fragment of the BM protein collagen XVIIIα1, on ARDS associated cellular functions such as neutrophil recruitment, endothelial cell barrier integrity, and platelet aggregation in vitro. In our study we analyzed endostatin in plasma and post-mortem lung specimens of patients with COVID-19 and non-COVID-19 ARDS. Functionally, we investigated the effect of endostatin on neutrophil activation and migration, platelet aggregation, and endothelial barrier function in vitro. Additionally, we performed correlation analysis for endostatin and other critical plasma parameters. We observed increased plasma levels of endostatin in our COVID-19 and non-COVID-19 ARDS cohort. Immunohistochemical staining of ARDS lung sections depicted BM disruption, alongside immunoreactivity for endostatin in proximity to immune cells, endothelial cells, and fibrinous clots. Functionally, endostatin enhanced the activity of neutrophils, and platelets, and the thrombin-induced microvascular barrier disruption. Finally, we showed a positive correlation of endostatin with soluble disease markers VE-Cadherin, c-reactive protein (CRP), fibrinogen, and interleukin (IL)-6 in our COVID-19 cohort. The cumulative effects of endostatin on propagating neutrophil chemotaxis, platelet aggregation, and endothelial cell barrier disruption may suggest endostatin as a link between those cellular events in ARDS pathology.

The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin

The pandemic of COVID-19 has highlighted the intricate relationship between gut microbiome and overall health. Recent studies have shown that the Firmicutes/Bacteroidetes ratio in the gut microbiome may be linked to various diseases including COVID-19 and type 2 diabetes (T2D). Understanding the link between gut microbiome and these diseases is essential for developing strategies for prevention and treatment. In this study, 115 participants were recruited and divided into three groups: 1st group: T2D patients and healthy controls, 2nd group: COVID-19 patients with and without T2D, 3rd group: T2D patients with COVID-19 treated with or without metformin. Gut microbial composition at the phylum level was assessed using qRT-PCR with universal primers targeting the bacterial 16 S rRNA gene and specific primers for Firmicutes and Bacteroidetes. Data was analyzed using one-way ANOVA, logistic regression, and Spearman's rank correlation coefficient. The study found that the ratio of Firmicutes to Bacteroidetes (F/B) was higher in patients with both T2D and COVID-19 compared to those with only T2D or COVID-19. Additionally, the F/B ratio was positively correlated with C-reactive protein (CRP) in T2D and COVID-19 patients. The study also suggests that metformin treatment may affect this correlation. Logistic regression analysis showed that the F/B ratio was significantly associated with CRP. These findings suggest that the F/B ratio may be a potential biomarker for inflammation in T2D and COVID-19 patients and metformin treatment may have an effect on the correlation between F/B and CRP levels.

Paradoxically Increased Inflammation in Immunosuppressed Individuals with COVID-19

Abstract Dysregulated inflammation is central to the morbidity and mortality associated with COVID-19. Treatment with dexamethasone and IL-6 blockade can be life-saving in patients stratified for moderate - severe disease. Patients with suppressed immunity are often excluded from immune blockade therapy due to the assumption that additional suppression of an impaired immune system will be detrimental to viral clearance. We hypothesised that patients with suppressed immune systems would be slower to clear viral infection, leading to increased damage and therefore, paradoxically, a more intense acute phase response to SARS-CoV-2 infection. This was tested by a sub-group analysis of the Coronavirus Immune Response and Clinical Outcomes (CIRCO) cohort, an observational study of acute COVID-19 in Greater Manchester, UK. Patients were included if they were treated with dexamethasone and had a research blood sample retrieved within 48 hours of admission, and excluded if they were treated with IL-6 blockade or antiviral therapy prior to research sampling. Acute phase serum cytokine levels were compared between eight immunosuppressed and 12 immunocompetent patients positive for SARS-CoV-2. In support of our hypothesis, we found that immunosuppressed individuals had higher levels of the inflammatory cytokines IP-10 (p=0.03) and MCP-1 (p=0.01) compared to immunocompetent patients matched for COVID-19 severity. This suggests that immunosuppressed patients may benefit as much as immunocompetent individuals from systemic treatments to dampen inflammation in COVID-19, and current recommendations of excluding these patients from treatment solely on the basis of immune competence may need to be re-evaluated.