thermoregulatory dysfunction in covid 19 thermoregulatory dysfunction in covid 19

Taken together, the concerted actions of above factors lead to dysfunctional status of the vascular endothelium (endothelial dysfunction) (Fig. Acute kidney injury in severe COVID-19 has similarities to sepsis-associated kidney injury: a multi-omics study. Complement activation induces excessive T cell cytotoxicity in severe COVID-19. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. Metformin represents the first-line therapy for T2DM [123]. Satarker S, Tom AA, Shaji RA, Alosious A, Luvis M, Nampoothiri M. JAK-STAT pathway inhibition and their implications in COVID-19 therapy. Would you like email updates of new search results? A retrospective study in COVID-19 patients with pre-existing T2DM indicated that metformin treatment was associated with the occurrence of acidosis as well as reduced heart failure and inflammation. 2021;12:18506. The glycocalyx, a protective microstructure layer on the vascular endothelium, consists of glycoproteins and regulates capillary homeostasis by controlling vascular inflammation [109]. This work was also supported by Program for Innovative Research Team of The First Affiliated Hospital of USTC (CXGG02), Anhui Provincial Key Research and Development Program (Grant No. Among these physiological functions, nitric oxide (NO) represents the key mechanism for maintaining endothelial homeostasis [2, 15]. In addition, heparan sulphate, as the major component in the glycocalyx, can also regenerate glycocalyx and promote the effective restoration of homeostatic EC gap junction [111]. Acute myocardial infarction in the Covid-19 era: Incidence, clinical characteristics and in-hospital outcomes-A multicenter registry. Google Scholar. Therefore, the therapeutic role of JIVC in treating severe COVID-19 patients warrants further investigation [160]. 2021;16:e0254167. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Pharmacopsychiatry. Hemil H, de Man AME. Maldonado F, Morales D, Daz-Papapietro C, Valds C, Fernandez C, Valls N, et al. and JavaScript. The vascular endothelium, the innermost layer of blood vessels, provides a dynamic interface between the circulating blood and various tissues/organs and thereby maintaining tissue homeostasis. Yang K, Holt M, Fan M, Lam V, Yang Y, Ha T, et al. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. 2022. https://doi.org/10.21203/rs.3.rs-1762855/v1. 2021;40:101125. Thermoregulatory physiology sustains health by keeping body core temperature within a degree or two of 37C, which enables normal cellular function. Severe COVID-19-induced cytokine storm (such as IL-6, IL-1, TNF-, MCP-1, etc) is a good predictor ofthe severity of COVID-19, which also aggravates multi-organ injury by propagating the vicious cycle of ECs damage, inflammation and thrombosis [93]. 2021;6:e148999. Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. 2020;98:31422. Cellular senescence is a primary stress response in virus-infected endothelial cells. The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. The .gov means its official. Raghavan S, Kenchappa DB, Leo MD. This study highlights the crucial role of IL-6 trans-signaling in endothelial dysfunction/endotheliopathy in COVID-19 [137]. 17-Estradiol, a potential ally to alleviate SARS-CoV-2 infection. MacKenzie MA, Hermus AR, Wollersheim HC, Binkhorst RA, Pieters GF. Cell Res. Virus-induced senescence is a driver and therapeutic target in COVID-19. McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, et al. Batabyal R, Freishtat N, Hill E, Rehman M, Freishtat R, Koutroulis I. Metabolic dysfunction and immunometabolism in COVID-19 pathophysiology and therapeutics. Because each symptom can be traced to the autonomic nervous system and its dysfunction, a platform for investigation is clear. Mechanistic studies in cultured human ECs suggest that COVID-19 induced endothelial inflammation and monocyte adhesion was ameliorated by atorvastatin and KLF2 overexpression, suggesting the possible utility of KLF2 activator in suppressing COVID-19 associated endothelial dysfunction [120]. Pharmacol Rev. Indications of persistent glycocalyx damage in convalescent COVID-19 patients: a prospective multicenter study and hypothesis. Thus, the endothelium is regarded as the Achilles heel in COVID-19 patients [8]. Cell Biosci. Recent randomized clinical trials revealed that treatment with fluvoxamine (a selective serotonin reuptake inhibitors, SSRI) reduced the need for COVID-19 hospitalization, reduced mortality and improved outcome over 15 days [148,149,150]. ACS Cent Sci. Kandhaya-Pillai R, Yang X, Tchkonia T, Martin GM, Kirkland JL, Oshima J. TNF-/IFN- synergy amplifies senescence-associated inflammation and SARS-CoV-2 receptor expression via hyper-activated JAK/STAT1. Tan R, Xiang X, Chen W, Yang Z, Hu W, Qu H, et al. In addition to the spike protein, nucleocapsid protein of SARS-CoV-2 can also promotes endothelial activation via TLR2/NF-B and MAPK signaling pathways. Xu J, Zhang J, Lin H, Zhang J, Zhou R, Wu X, Niu Y, Zhang J. Lancet (Lond, Engl). Front Cardiovasc Med. Tocilizumab also protects against endothelial dysfunction by increasing glycocalyx thickness and reducing the burden of inflammation and oxidative stress. Redox Biol. SARS-CoV-2 can cross the blood brain barrier without affecting the expression of tight junctions (claudin5, ZO-1 and occludin) [41]. The Erectile Dysfunction Drugs report tracks competitive progresses, strategies, mergers and acquisitions and new product development. 2021;2021:8671713. CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. Jover E, Matilla L, Garaikoetxea M, Fernndez-Celis A, Muntendam P, Jaisser F, et al. Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial. JAMA. EBioMedicine. Targeting endothelial dysfunction in eight extreme-critically ill patients with COVID-19 using the anti-adrenomedullin antibody adrecizumab (HAM8101). Postgrad Med. Circulation. 2021;24:4036. A recent study has shown that increased levels of cellular senescence-associated markers, including PAI-1, p21 and sirtuin-1 in patient serum as well as lung ECs [89]. Recent studies have demonstrated that complement activation is associated with SARS-CoV-2 infection induced inflammation, endothelial injury, hypercoagulability and thrombosis [95]. Sci Rep. 2021;11:12157. 2020;5:e138070. Front Cardiovasc Med. Respir Med. Endothelial immunity trained by coronavirus infections, DAMP stimulations and regulated by anti-oxidant NRF2 may contribute to inflammations, myelopoiesis, COVID-19 cytokine storms and thromboembolism. Nutrients. 2020;75:e1980. 2022;55:57. Google Scholar. Zha D, Fu M, Qian Y. Vascular endothelial glycocalyx damage and potential targeted therapy in COVID-19. Hypothermia, defined as a core temperature of <35.0C, may present with shivering, respiratory depression, cardiac dysrhythmias, impaired mental function, mydriasis, hypotension, and muscle dysfunction, which can progress to cardiac arrest or coma. Schulthei C, Willscher E, Paschold L, Gottschick C, Klee B, Henkes SS, et al. Efficacy and mechanisms of traditional Chinese medicine for COVID-19: a systematic review. Recent studies have suggested that LSEC dysfunction is involved in COVID-19 associated liver injury [34]. Further, removal of the N-glycosylation site at N92 of L-SIGN enhances the binding of S-RBD with L-SIGN [21]. Endothelial dysfunction is generally defined as decreased NO bioavailability and an increase in vasoconstrictory substances (such as endothelin-1 (ET1), angiotensin II (AngII) and many others). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in The relationship between mechanisms and biomarkers of endothelial dysfunction in COVID-19 is provided in Fig. 2020;32:53747. Post-COVID-19 conditions alter a person's immune response. J Virol. Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury. 2021YFC2500500), National Natural Science Foundation of China (Grant No. https://doi.org/10.1038/s41401-022-00998-0, DOI: https://doi.org/10.1038/s41401-022-00998-0. After virus infection, ensuing cytokine storm occurs in severe COVID-19 patients, particularly the elevated secretion of pro-inflammatory cytokine interleukin 6 (IL-6). Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H, et al. Torices S, Motta C, da Rosa B, Marcos A, Alvarez-Rosa L, Siqueira M, et al. Severe COVID-19 is a microvascular disease. Proc Natl Acad Sci USA. Abraham GR, Kuc RE, Althage M, Greasley PJ, Ambery P, Maguire JJ, et al. Arterioscler Thrombosis Vasc Biol. Increased heparanase activity and heparan sulphate level have been observed in plasma derived from COVID-19 patients [113]. BJ9100000005), and Hefei Municipal Development and Reform Commission Emergency Funding for COVID-19 disease. SARS-CoV-2 infection relies on ACE2 expression in ECs [48]. EClinicalMedicine. Top manufacturers . 2021;20:66. Endothelial junctions (EJ) are crucial to maintain EC integrity and normal microvascular functions due to the adhesive properties of Vascular endothelial (VE)-cadherin to glue EC together. J Intern Med. Kang X, Jin D, Jiang L, Zhang Y, Zhang Y, An X, et al. Furthermore, it has been demonstrated that exosomes from severe COVID-19 patients trigger the activation of caspase-1 and NLRP3 inflammasome and release of IL-1 in ECs [64]. 2022. https://doi.org/10.1164/rccm.202207-1258ED. Cell. Potential mechanisms of coronavirus disease 2019 (COVID-19)-induced olfactory dysfunction. Endothelial dysfunction-induced endotheliitis/endothelialitis/endotheliopathy following SARS-CoV-2 infection arises from a plethora of physiopathological mechanisms, including both direct mechanism of virus infection or indirect mechanisms such as paracrine effects of infected cells [2, 68]. Tetlow S, Segiet-Swiecicka A, OSullivan R, OHalloran S, Kalb K, Brathwaite-Shirley C, et al. 2020;7:559811. Schattner A. Colchicine-new horizons for an ancient drug. 2021: 1-15. The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers - PubMed. Viruses. 2021;75:5035. SARS-CoV-2 infection is associated with reduced krppel-like factor 2 in human lung autopsy. Furthermore, SARS-CoV-2 infection leads to decreased expression of tight junction protein (ZO-1, occluding and claudin5) and blood brain barrier permeability [75]. In light of the multiple endothelial protective effects exerted by SGLT2 inhibitors [127], this type of drug hold promises to treat COVID-19 patients with T2DM. Int J Infect Dis. The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction. Hess AL, Halalau A, Dokter JJ, Paydawy TS, Karabon P, Bastani A, et al. Fiziol Zh Im I M Sechenova. A meta-analysis revealed the favorable effect of statins in COVID-19 patients [118]. Mol Neurobiol. 2021;1867:166260. PubMed Central Cellular senescence was also associated with endothelial inflammation (augmented expression of ICAM-1 and VCAM-1), which is essential for promoting leukocyte adhesion to activated endothelium. Zheng H, Cheng J, Ho HC, Zhu B, Ding Z, Du W, Wang X, Yu Y, Fei J, Xu Z, Zhou J, Yang J. In addition, COVID-19 is an important risk factor for developing acute myocardial infarction [29]. 2021;10:e69314. 2021;290:43743. In addition, a recent study has shown that circulating level of ET-1, a potent vasoconstrictive peptide, was elevated in hospitalized patients with acute phase of COVID-19, indicating that ET-1 receptor blockers could potentially offer clinical benefits for COVID-19 patients [104]. An analysis of patients with a chief complaint of difficulty moving. 2022;11:1972. 2021;16:e0253524. S protein treatment of HAECs leads to increased secretion of inflammatory molecules (IL-6, MCP-1 and IL-18) and PAI-1, which can be attenuated by minerocorticoid receptor antagonists [56]. 2020;314:5862. 2022;10:812. de Rooij L, Becker LM, Carmeliet P. A role for the vascular endothelium in post-acute COVID-19? Am J Physiol Lung Cell Mol Physiol. Similar effects were observed in ECs infected with SARS-CoV-2 spike pseudovirions (SCV-2-S) [55]. Vollenberg R, Tepasse PR, Ochs K, Floer M, Strauss M, Rennebaum F, et al. 2017;12:e0186116. 2022;52:e13726. In addition, the levels of these endothelial markers are elevated in intensive care units (ICU) non-survivors compared to survivors. Intern Emerg Med. 2022;54:102362. Toscano O, Cosentino N, Campodonico J, Bartorelli AL, Marenzi G. Acute myocardial infarction during the COVID-19 pandemic: an update on clinical characteristics and outcomes. Role of traditional chinese medicine in treating severe or critical covid-19: a systematic review of randomized controlled trials and observational studies. Von Willebrand factor: A key glycoprotein involved in thrombo-inflammatory complications of COVID-19. Crit Care (Lond, Engl). We determined the pooled prevalence of such chemosensory deficits in a systematic review and meta-analysis. Life Sci. Therefore, IL-6 trans-signaling represents the mechanistic link between the coagulopathy/endotheliopathy and COVID-19 associated liver injury [35]. Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Falleni M, Tosi D, Savi F, Chiumello D, Bulfamante G. Endothelial-mesenchymal transition in COVID-19 lung lesions. N Engl J Med. Cardiovasc Res. Karakas M, Jarczak D, Becker M, Roedl K, Addo MM, Hein F, et al. : Experimental results and a cautionary note on challenges in translational research. Unable to load your collection due to an error, Unable to load your delegates due to an error. Like other types of organ injury, SARS-CoV-2 infection causes AKI by both direct and indirect mechanisms, including endotheliitis, thrombosis and glucolipid derangement. HHS Vulnerability Disclosure, Help 2021;13:1172. Cells. Bhowmik KK, Barek MA, Aziz MA, Islam MS. Impact of high-dose vitamin C on the mortality, severity, and duration of hospital stay in COVID-19 patients: a meta-analysis. Chen S, Zheng C, Chen T, Huang D, Pan Y, Chen S. Relationship between plasma vitamin C and COVID-19 susceptibility and severity: a two-sample mendelian randomization study. Joffre J, Rodriguez L, Matthay ZA, Lloyd E, Fields AT, Bainton RJ, et al. Efficacy of diammonium glycyrrhizinate combined with vitamin C for treating hospitalized COVID-19 patients: a retrospective, observational study. These findings suggest that spike protein interactions with ECs contribute to inflammation, thrombosis, and the severity of COVID-19 and could offer novel mechanistic insights into SARS-CoV-2 induced vascular leakage and the development of targeted therapies [59]. Evaluating the short-term effect of ambient temperature on non-fatal outdoor falls and road traffic injuries among children and adolescents in China: a time-stratified case-crossover study. Gladka MM, Maack C. The endothelium as Achilles heel in COVID-19 patients. Chang R, Mamun A, Dominic A, Le NT. QJM. EBioMedicine. SARS-CoV-2 or viral proteins can infect endothelial cells and other host cells via reported receptors and the vicious cycle was perpetuated. In these cardiovascular complications, endothelial dysfunction plays a fundamental role [27]. Arterial stiffness in acute COVID-19 and potential associations with clinical outcome. 2022;13:868679. 2021;34:812. These studies illustrated that TCM in combination with standard care might be safe and potentially effective for COVID-19. Xu S, Ilyas I, Little PJ, Li H, Kamato D, Zheng X, et al. 2014;120:947-57. doi: 10.1016/B978-0-7020-4087-0.00062-0. Non-coding RNA. All the above evidence pinpoints the protective effect of heparin in COVID-19 could largely be attributable to glycocalyx-stabilizing effect. 2021;12:814. An unresolved question. Caccuri F, Bugatti A, Zani A, De Palma A, Di Silvestre D, Manocha E, et al. However, the reported prevalence of these deficits in smell and taste varies widely, and the reason for the differences between studies is unclear. Epub 2023 Apr 1. On the other hand, S1R agonism by fluvoxamine activates Akt-eNOS signaling in mouse aorta in a S1R-dependent manner. Treatment with a humanized anti-IL-6 receptor antibody-tocilizumab, decreased the PAI-1 level and alleviated critical illness in severe COVID-19 patients. Anakinra for severe forms of COVID-19: a cohort study. Before Mechanistically, patients with heart failure demonstrate increased ACE2 gene and protein expression, suggesting that if patients with heart failure were infected by the virus, they are more susceptible to severe COVID-19 and develop into a critically-ill conditions [28]. The net consequence is the extravasation of inflammatory and immune cell infiltrations [74]. Circ Res. Therefore, primary endothelial cell senescence or secondary senescence caused by SRAS-CoV-2 infected non-ECs can be exploited as a new therapeutic target for ameliorating COVID-19 associated endotheliitis [90]. 2021;22:4177. Excessive production of mtROS causes oxidative stress that perpetuates ECs inflammation, senescence and dysfunction. Histopathological observations demonstrate that COVID-19 is a (micro)vascular and endothelial disease in which endothelial dysfunction plays a fundamental role [4, 6, 9,10,11]. Katsoularis I, Fonseca-Rodrguez O, Farrington P, Lindmark K, Fors Connolly AM. PubMed Central 8600 Rockville Pike Am J Respiratory Cell Mol Biol. Signal Transduct Target Ther. eCollection 2023 Apr. Based on the important role of endothelial dysfunction in COVID-19, several categories of endothelial protective drugs are possible to ameliorate endothelial dysfunction in COVID-19. Endothelial senescence is an important aspect of endothelial dysfunction. A recent multi-omics study has revealed that COVID-19 associated AKI resembles AKI induced by sepsis, which involves the mechanism of mitochondria dysfunction, inflammation, necroptosis, capillary congestion and endothelial injury [37]. Xing D, Liu Z. Mansiroglu AK, Seymen H, Sincer I, Gunes Y. 2022;167:926. Analysis of ACE2 expression in autopsy tissues indicates that high expression of ACE2, transmembrane protease serine 2 (TMPRSS2) and associated endotheliitis in capillaries but less in arterioles/venules from COVID-19 patients, compared with COVID-19-free subjects. Employing mechanical ventilation techniques on venovenous extracorporeal membrane oxygenation (VV ECMO . Inflammatory cytokines, such as IL-6, promotes JAK and STATs phosphorylation [145]. In addition, due to the fact that trained immunity in ECs is an important mechanism in propagating endothelial response to inflammatory/immune insults after prior exposure to microbial stimuli [100], detailed mechanisms of epigenetic memory in transducing the SARS-COV-2 infection-induced immune signal needs further studies.