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Background: HIV is a risk factor for severe acute COVID-19, but it is unknown whether HIV is a risk factor for long COVID. Method(s): We conducted a prospective observational cohort study of US adults with HIV (PWH) and HIV-seronegative adults with first SARS-CoV-2 infection within 4 weeks together with people who never had COVID-19. At enrollment, participants recalled the presence and severity of 49 long COVID-associated symptoms in the month prior to COVID-19. The same symptom survey was administered at 1, 2, 4, and 6 months post-COVID or post-enrollment for never- COVID participants. Post-COVID participants donated blood 1 and 4 months post-COVID, and never-COVID participants donated blood 0-1 times. Antibody titers to 18 coronavirus antigens and levels of 30 cytokines and hormones were quantified (Meso Scale Discovery). The Mann Whitney U test was used to compare continuous variables between groups, and Pearson's chi-squared test for categorical variables. Spearman correlation analyses were used to build networks of associations between cytokines and symptoms. Result(s): 341 participants enrolled between June 2021 and September 2022. Of these, 73 were PWH post-COVID, 121 were HIV-seronegative post-COVID, 78 were PWH never-COVID, and 69 were HIV-seronegative never-COVID. Over 85% of participants were vaccinated prior to COVID-19. Most participants with HIV were male sex at birth (83% post-COVID, 59% never-COVID), on ART ( >95%), with median CD4 counts >500. Over 60% of participants reported 1+ new or worsened symptoms 2-6 months post-COVID, with higher percentages in PWH at 2 months post-COVID (p< 0.05). PWH were more likely to report body ache, pain, confusion, memory problems, and thirst and had higher levels of creatine phosphokinase post-COVID than HIV-seronegative people. SARS-CoV-2 and non-SARS human coronavirus antibody titers did not differ between PWH and HIV-seronegative post-COVID participants. Cytokine associations with each other (network density) were significantly enriched at 1 month post-COVID in both PWH and HIV-seronegative people, with significantly less enrichment at 4 months post-COVID and in never- COVID participants. Levels of four analytes (cortisol, C5a, TGF-beta1, and TIM-3) associated with specific symptoms of long COVID. Conclusion(s): PWH may experience more symptoms post-COVID with a slightly different symptom profile than people without HIV. Inflammatory networks were active in PWH and people without HIV at 1 month post-COVID.
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Atrial fibrillation (AF) is the most frequent form of cardiac arrhythmia in COVID-19 infected patients. The occurrence of AF paroxysms is often associated with the acute period of infection in time. At the same time, the pathophysiological mechanisms of the occurrence of AF associated with COVID-19 remain insufficiently studied. The review considers the available literature data on the influence of factors such as reduced availability of angiotensin-converting enzyme 2 receptors, interaction of the virus with the cluster of differentiation 147 and sialic acid, increased inflammatory signaling, "cytokine storm", direct viral damage to the endothelium, electrolyte and acid-alkaline balance in the acute phase of severe illness and increased sympathetic activity.Copyright © Autors 2023.
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Background: Infections with SARS-CoV- 2 cause the coronavirus disease 2019 (COVID-19) pandemic. Alterations in immune cells of COVID-19 patients may predict the subsequent severity of disease. The changes in composition of immune cells in COVID-19 patients include lymphopenia, lower neutrophil to lymphocyte-ratios and an eosinopenia in about 50 to 80% of hospitalized patients. Eosinophils and neutrophils can interact with T cells via immune checkpoints receptors such as programmed death (PD)-1 on T cells and its counterpart PD-ligand 1 (PD-L1) on eosinophils or neutrophils. There are only limited studies on PD-1 and PD-L1 expressions in viral infections, we aimed to elucidate the interplay of T cells and other peripheral cells by analysing the immune checkpoints PD-1 and PD-L1 in expression during COVID-19. Method(s): Using flow cytometry, we have now analysed the immune checkpoint receptor expressions on whole blood cells from a total of 38 COVID-19 patients. The patient cohort comprises all ages and both sexes with the disease severity ranging from mild, moderate to severe, with ~10% mortality. We have further been investigating 21 biomarkers (G-CSF, GM-CSF, IFN-gamma, TGF-beta1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-23, IL-33, IP-10, MCP-1, MIP-1beta, TNF-alpha, and YKL-40) in plasma on a cohort of 76 COVID-19 patients using the MesoScale Multiplex Assay platform, with 48 healthy controls. Result(s): PD-L1 expression on eosinophils was significantly lower in COVID-19 patients in initial stages of infection, relative to healthy controls. There was an inverse relationship between disease progression and the expression of PD-1 on CD8+ T cells. These data suggests that analysis of PD-L1- PD1 cell networks in immune cells of EDTA blood of COVID-19 patients can predict disease outcomes. While most detectable biomarkers are strongly increased in COVID samples overall compared to healthy controls, the more severe the disease the higher the blood biomarker concentration. Conclusion(s): Taken together, the analysis of PD-L1- PD1 cell networks in immune cells together with plasma biomarkers of COVID-19 patients can predict disease outcomes.
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Introduction: Renal fibrosis is a main outcome of acute kidney injury in COVID-19 survivors, which is emerging as a global public health concern. Lung damage in the COVID-19 patients leads to acute and chronic hypoxia, which results in inflammation, epithelial-mesenchymal transformation, and fibrosis in kidney. Quercetin is an abundant flavonoid in plant materials. Previous studies indicate that quercetin alleviates the decline of renal function, suppress epithelial to mesenchymal transformation in renal tubules, and reduce fibrosis. The study aimed to explore potential targets of quercetin on treating renal fibrosis in patients with COVID-19-induced hoxpia. Method(s): Gene/protein targets related to COVID-19, renal fibrosis, or quercetin were searched from ten databases, and Cytoscape 3.8.2 was then used to construct the protein-protein interaction network and to identify the core targets. The Metascape platform was used for bioconcentration analysis, while AutoDock Vina was used as the primary molecular docking tool. In vitro, the combination model of hypoxia- and transforming growth factor-beta (TGF-beta)- treated human proximal tubule epithelial cells (HK2 cells) was applied to determine the reno-protective effect of quercetin. Result(s): The network analysis showed that quercetin targeted on TGF-beta pathway in treating COVID-19 induced renal fibrosis. In the intersection PPI network, 115 targets were obtained, and gene enrichment analysis was conducted on 109 key nodes. Molecular docking analysis revealed that quercetin could spontaneously bind to eight targets on the TGF-beta pathway, and the binding energy of TGF-beta1 was 29.82 kJ/mol. The in vitro experiment further showed that quercetin significantly suppressed fibrosis in TGF-beta and hypoxia treated HK2 cells in a dose dependent manner by inhibiting TGF-beta/Smad3 pathway. Conclusion(s): Quercetin could attenuate renal fibrosis in patients with COVID-19 by suppressing TGF-beta/Smad3 pathway. No conflict of interestCopyright © 2023
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Background: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-ß1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19. Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-ß1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed. Results: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis. Conclusions: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-ß1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.
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Introduction: In the search of effective medicines against Coronavirus Disease-2019 (COVID-19) besides the conventional mode of treatment many medicines belonging to alternative therapeutics claimed to be effective in this disease. In homeopathy-a branch of alternative medicine some medicines are claimed to be effective in COVID-19 after human trials. Aim: To study whether ultradiluted preparation of Phosphorus 6CH (centesimal (C) dilutions, using Hanhemann's (H) dilution method) can protect damaging action of Delta Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) spike protein Receptor Binding Domain (RBD) in Gallus gallus embryo in relation to their gross appearances, histopathological changes and cytokine changes. Materials and Methods: An in-vivo fertilized chick embryo model experimental analysis was carried out at the Genetic Research Laboratory of Heritage Institute of Technology, Kolkata, West Bengal, India. The whole experimental study was done in a time period of November 2021 to January 2022 and the data collected were analysed using statistical software Minitab. About 14 days old Gallus gallus embryonated eggs were inoculated with the antigen along with the vehicle alcohol controls. The Phosphorus 6CH was used to see whether it can prevent or cure the damaging action of the spike protein in the embryo in different experimental sets. results: The notable finding in this experiment is the remarkable elevated expression of Interleukin (IL)-10 gene in the curative, preventive sets as well as in the medicine control sets in comparison to antigen and alcohol control sets. In case of Transforming Growth Factor, (TGF) β1 there was enhanced expression of TGF β1 gene in the alcohol 6C set and antigen set which gets ameliorated with Phosphorus 6CH. The morbid anatomy of the embryo and the histopathological picture of the liver of the embryo also reflected similar findings in these two experimental sets. After statistical analysis it was found that there was significant correlation in between Interferon (IF) γ and IL-10 in these experimental results which appears very important. conclusion: The homeopathic medicine phosphorus 6CH is capable of maintaining cytokine balance in Delta SARS-CoV-2 spike protein RBD induced pathogenecity in Gallus gallus embryo.
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Rationale: The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions via the acute respiratory distress syndrome (ARDS). The early immune suppression of SARS-CoV-2 then subsequent inflammation suggests an unusual ability to cause immune dysregulation. Host transforming growth factor beta (TGF-β) is an immunesuppressing and profibrotic cytokine frequently “hijacked” by microbes to evade immune detection. We discovered a KRFK domain (a potent activating motif for latent TGF-β) in the SARS-CoV-2 nonstructural 15 (NSP15) protein. We hypothesized that this NSP15 protein causes immune dysregulation by activation of latent TGF-β and subsequent activation of immunosuppressive Tregulatory (Treg) cells, and that substantial TGF-β is present in the lungs of COVID-19 ARDS patients. Methods: We evaluated TGF-β1 concentrations in endotracheal aspirates (ETA) of 27 COVID-19 ARDS patients by ELISA. We produced recombinant SARS-CoV-2 NSP15 protein in E. coli and tested its ability to activate latent TGF-β1 using in vitro assays. TGF-β inhibitors were assessed for their ability to block effects. We obtained blood mononuclear cells from healthy subjects and isolated Tregs to assess their activation state via intracellular smad-2 phosphorylation (pSMAD2) using flow cytometry. Results: The KRFK domain was present in all SARS-CoV-2 variants. High concentrations of both active and total TGF-β1 were detected in ETA of COVID-19 ARDS patients (150 +/- 34 pg/ml active;1,819 +/- 304 pg/ml total) in a range previously shown to affect T cell function. NSP15 at 2.4 nM increased activation of latent TGF-β 12-fold (P < .001 vs. vehicle), compared to an 11% activation with the positive control thrombospondin-1 (TSP1;10 nM) (Figure). TGF-β receptor inhibitors blocked NSP15 effects on latent TGF-β activation and intracellular TGF-β1 signaling in a bioassay by over 95% (p<.01). At tested concentrations (25, 50, 100 nM) NSP15 increased Treg pSMAD2 levels via activation of latent TGF-β1, exceeding levels seen in Tregs stimulated with 400 pM of active TGF-β1 (+ control) (pSMAD2 + cells: vehicle 1.1%, active TGF-β1 43%, NSP15/latent TGF-β1 49-56%). Conclusions: High concentrations of active and total TGF-β1 are present in the lungs of COVID-19 ARDS patients, suggesting SARS-CoV-2 uses host TGF-β hijacking as a mechanism for immune evasion. The NSP15 protein of SARSCoV- 2 potently activates latent TGF-β, leading to Treg activation. TGF-β inhibitors are potent inhibitors of these NSP15 effects. A strategy to block NSP15-mediated effects with TGF-β inhibitors is an innovative therapy worthy of testing in animal models of COVID-19.
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A number of studies have previously provided evidence on the Anti-inflammatory properties of plant-derived compounds that can prevent lung injury. In this study, we attempted to analyze the therapeutic effects of PM 014 on inflammation and pulmonary fibrosis in COVID-19 as well as describing the treatment of one of the most challenging problems related to the coronavirus-19 (COVID-19). We believe that having a close look at all angles of the proposed mechanism goes beyond the physiological consequences of a way to design new strategies for providing an appropriate treatment.
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Background: The coronavirus disease 2019 (COVID-19) has spread around the world with high cardiovascular complications and mortality. Patients with heart pathology and diabetes mellitus were at greatest risk. An accurate and timely laboratory diagnosis is a vital step to help manage cardiovascular disease during this pandemic. Purpose: To conduct a prospective analysis of complete blood count parameters, inflammatory response, endothelial dysfunction of arterial wall and hemostasis in groups of patients undergoing COVID-19 associated pneumonia with and without type 2 diabetes mellitus (DM2);to highlight indicators of long-term adverse cardiovascular events. Methods: The study was carried out within register on one-year cardiac follow-up of patients after COVID-19-associated pneumonia. Patients (n=380) were identified in the period from April to July 2020 according to the data of medical information system of monoinfectious hospital. At the moment, data of the first 65 patients with cardiovascular pathology are obtained. Group 1 included 53 patients without DM2 (mean age 47.83±15.86 years), group 2 consisted of 12 patients with DM2 (61.71±9.12 years). Baseline parameters of complete blood count, biochemistry and hemostasis were assessed on the day of hospitalization. In-depth analysis of laboratory parameters was carried out in 3 months. Results: In group 1 significant decrease of coagulogram parameters: INR (p=0.004), fibrinogen, APTT, thrombocrit, large platelets level (p<0.0001), CRP level, liver enzymes (p<0.0001), leukocytes (p=0.015), erythrocytes (p=0.006) and increase in hematocrit (p<0.0001) were registered in 3 months compared to baseline data. In group 2 positive dynamics of CRP (p=0.018), platelets (p=0046), APTT (p=0.043) and erythrocytes (p=0.028) were revealed, while CRP concentration remained higher than reference values in 3 months. In group 2 in-depth analysis of biomarkers revealed values exceeding normal levels: hs-CRP (4.72±3.33 mg/L), homocysteine (13.17±7.95 μmol/L), myeloperoxidase (47.6±38.51), NT-proBNP (154.56±127.30 mg/ml), P-selectin (141.29±124.71) TgFb1 (6549.86±1987.87 pg/ml). Correlation analysis detected positive association of homocysteine level with platelets level (p=0.002. R=0.998), myeloperoxidase with fibrinogen (p=0.012. R=0.865). Conclusion: Three months after COVID-19 elevated levels of inflammatory markers (CRP, hs-CRP, homocysteine), endothelial dysfunction and thrombophilia (large platelets, P-selectin, TgFb1) are indicators of prolonged arterial inflammatory syndrome and increased predisposition to coagulopathy with thrombosis determining a very high risk of developing adverse cardiovascular events in patients with DM2.
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Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.