Like other types of organ injury, SARS-CoV-2 infection causes AKI by both direct and indirect mechanisms, including endotheliitis, thrombosis and glucolipid derangement. The IL-1, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. volume44,pages 695709 (2023)Cite this article. Emerging evidence has suggested that thinning of endothelial glycocalyx layer is associated with COVID-19, and thus the glycocalyx integrity was perceived as an important therapeutic target in COVID-19 [109, 110]. Activation of IL-6 trans-signaling in LSECs leads to coagulopathy, elevation of pro-inflammatory factors, and platelet adhesion to LSECs. Before Sansone A, Jannini EA. 2017BT01S131), Hefei Comprehensive National Science Center (Grant No. Several clinical trials are ongoing to evaluate the safety and efficacy of JAK/STAT inhibitors [146]. ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19. 2020;9:1652. 2022, https://doi.org/10.1002/ptr.7574. The net consequence is the extravasation of inflammatory and immune cell infiltrations [74]. Ma Z, Yang KY, Huang Y, Lui KO. Xu S, Ilyas I, Little PJ, Li H, Kamato D, Zheng X, et al. Fiziol Zh Im I M Sechenova. Endothelial dysfunction in COVID-19: an overview of evidence Arterioscler Thrombosis Vasc Biol. J Hepatol. MeSH Front Physiol. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1, IL-6, IL-15 and TNF-. 2022;17:e0268296. Cheng X, Liu YM, Li H, Zhang X, Lei F, Qin JJ, et al. Heat exhaustion; Heat stroke; Hypohidrosis; Hypothermia; Rewarming; Small fiber neuropathy; Thermoregulation. Management includes warming measures, hydration, and cardiovascular support. Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19. 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These vasoactive molecules tightly control the fine balance between vasodilatory and vasoconstrictory, pro-proliferative and anti-proliferative, pro-thrombotic and anti-thrombotic, pro-oxidant and antioxidant, fibrinolytic and anti-fibrinolytic, and pro-inflammatory and anti-inflammatory responses (Fig. 2020;7:629413. It is possible that these cytokines will disrupt the integrity of various types of junctional proteins, including VE-cadherin, ZO-1, -catenin and gap junction proteins. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection [87, 130]. Eur J Clin Invest. Ding Y, Zhou Y, Ling P, Feng X, Luo S, Zheng X, et al. Chang R, Mamun A, Dominic A, Le NT. Unexpectedly, propensity score-weighted analysis showed that treatment with ACEI/ARB was not significantly associated with the occurrence of defined end-points. COVID-19 can present with multiple manifestations arising from endothelial dysfunction/endotheliopathy as below (Fig. Thermoregulation is the biological mechanism responsible for maintaining a steady internal body temperature. 2020;314:5862. 2022;13:830061. 2020;32:17687. Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H, et al. Pulm Circ. Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Biomedicines. The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in 18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells. Glycocalyx layer regulates vascular barrier integrity, leukocyte adhesion, mechanosensing, mechanotransduction, anti-inflammatory and anti-thrombotic functions [109]. 2020;73:123140. Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients. We determined the pooled prevalence of such chemosensory deficits in a systematic review and meta-analysis. Employing mechanical ventilation techniques on venovenous extracorporeal membrane oxygenation (VV ECMO . Microorganisms. Copyright 2016 The Author. Data from multi-center registry support that ST-segment elevation myocardial infarction (STEMI) patients enrolled during the first-wave of COVID-19 experience longer time of ischemia and a higher rate of adverse events [30, 31], suggesting the need for COVID-19 vaccines. The Burden of Cognitive Dysfunction in COVID-19 These include tachycardia, shortness of breath, fatigue and post-exercise exhaustion. 2023 Apr 10;638:122941. doi: 10.1016/j.ijpharm.2023.122941. Aye YN, Mai AS, Zhang A, Lim OZH, Lin N, Ng CH, et al. 2020;10:40. Angiogenesis. The post-COVID-19 cardiovascular autonomic dysfunction can affect global circulatory control, producing not only a POTS-like pattern but also tachycardia at rest, blood pressure instability with . Pharmacol Res. Acta Pharmacol Sin 44, 695709 (2023). 2020;10:2045894020966547. 2021;221:153419. 2022;36:e22052. 2021;133:489507. Endothelial cell infection and dysfunction, immune activation in severe COVID-19. Post-COVID-19 conditions alter a person's immune response. Sholzberg M, Tang GH, Rahhal H, AlHamzah M, Kreuziger LB, inle FN, et al. It is well-established that SARS-CoV-2 enters host cells including ECs via ACE2 and coreceptor TMPRSS2. Choudhary S, Sharma K, Singh PK. In this regard, miR-24-3p has recently been identified as an essential regulator of Neuropilin-1 gene transcription, thereby maintaining barrier integrity via suppressing VEGF-induced endothelial leakage in human brain ECs [99]. JAK/STAT pathway is a canonical pathway in driving inflammation. J Mol Cell Cardiol. 17-Estradiol, a potential ally to alleviate SARS-CoV-2 infection. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. 2022;23:6196. Lancet Rheumatol. Qin Z, Liu F, Blair R, Wang C, Yang H, Mudd J, et al. MacKenzie MA, Hermus AR, Wollersheim HC, Binkhorst RA, Pieters GF. Front Immunol. Resistin associated with cytokines and endothelial cell adhesion molecules is related to worse outcome in COVID-19. Khider L, Gendron N, Goudot G, Chocron R, Hauw-Berlemont C, Cheng C, et al. 2020;142:160911. Mller R, Rink G, Uzun G, Bakchoul T, Wuchter P, Klter H, et al. The glycocalyx, a protective microstructure layer on the vascular endothelium, consists of glycoproteins and regulates capillary homeostasis by controlling vascular inflammation [109]. ACS Cent Sci. 2021;96:256175. Cardiovasc Res. SARS-CoV-2 infection relies on ACE2 expression in ECs [48]. 2021;163:15362. ACE2 angiotensin-converting enzyme-2, AXL AXL receptor tyrosine kinase, EndoMT endothelial-to-mesenchymal transition, NO nitric oxide, SASP senescence-associated secretory phenotype. A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv from their inception until May 11, 2020, using the terms anosmia or hyposmia or dysosmia or olfactory dysfunction or olfaction disorder or smell dysfunction or ageusia or hypogeusia or dysgeusia or taste dysfunction or gustatory dysfunction or neurological and COVID-19 or 2019 novel coronavirus or . Severe COVID-19 patients had significantly higher levels of glycocalyx disruption (endocan and syndecan-1), endothelial damage (angiopoietin-2 and vWF), and inflammation (upregulation of soluble receptor for advanced glycation end-products, IL-6, ICAM-1 and VCAM-1). 2022. https://doi.org/10.21203/rs.3.rs-1762855/v1. Trends Microbiol. 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. Sulodexide significantly improves endothelial dysfunction and alleviates chest pain and palpitations in patients with long-COVID-19: Insights From TUN-EndCOV study. Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function. Clinical and pathological investigation of patients with severe COVID-19. Onorato D, Pucci M, Carpene G, Henry BM, Sanchis-Gomar F, Lippi G. Protective effects of statins administration in European and North American patients infected with COVID-19: a meta-analysis. The SARS-CoV-2 structural and non-structural proteins promote virus entry and its survival in host cells. However, compromised glycocalyx integrity promotes S protein/ACE2 interaction and facilitates viral entry [68]. Nat Med. Anti-coagulatory or anti-hypertensive drugs treatment before admission leads to reduced number of CECs, indicating that COVID-19-associated coagulopathy and endotheliopathy could be ameliorated by anti-coagulatory or anti-hypertensive therapy [115]. ACE2 angiotensin-converting enzyme-2, TMPRSS2 transmembrane protease serine 2, ICAM-1 intercellular adhesion molecule 1, VCAM-1 vascular cell adhesion molecule 1, MCP1 monocyte chemoattractant protein-1, TGF- transforming growth factor , VEGF vascular endothelial growth factor, NO nitric oxide, IL-1 interleukin-1, IL-6 interleukin 6, TNF- tumor necrosis factor. 2020;11:70722. Recent studied have shown that colchicine is able to reduce the length of stay in hospitalized COVID-19 patients with the possible mechanism of inhibition of NLRP3 inflammasome and resultant IL-1 production [143, 144]. Karakas M, Jarczak D, Becker M, Roedl K, Addo MM, Hein F, et al. BRD4 bromodomain-containing protein 4, CD31 cluster of differentiation 31, CXCLs chemokine (C-X-C motif) ligands, EndoMT endothelial-to-mesenchymal transition, eNOS endothelial nitric oxide synthase, ET-1 endothelin 1, FN fibronectin, GCLC glutamate-cysteine ligase catalytic subunit, GCLM glutamate-cysteine ligase modifier subunit, HO-1 heme oxygenase-1, IL-1 interleukin-1, IL-6 interleukin 6, JAK janus kinase, KLF2 krppel-like factor 2, MCP-1 monocyte chemoattractant protein-1, NF-B nuclear factor-kappa B, NLRP3 NLR family pyrin domain containing 3, NO nitric oxide, NQO1 NAD(P)H quinone oxidoreductase, Nrf2 nuclear factor erythroid 2-related factor 2, PAI-1 plasminogen activator inhibitor 1, RIG-I retinoic acid-inducible gene I, RIPK3 receptor-interacting protein kinase 3, SMA smooth muscle actin, STAT3 signal transducer and activator of transcription 3, TLR toll-like receptor, TLR9 toll-like receptor 9, TNF- tumor necrosis factor, VCAM1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor. QJM. It represents a potential biomarker for monitoring disease progression in COVID-19 patients [112]. 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. 2020;7:559811. Endothelial dysfunction, inflammation, and oxidative stress in COVID-19-mechanisms and therapeutic targets. Treatment with a humanized anti-IL-6 receptor antibody-tocilizumab, decreased the PAI-1 level and alleviated critical illness in severe COVID-19 patients. A new study by investigators from the Smidt Heart Institute at Cedars-Sinai suggests long COVID-19 might be caused by a dysfunction of . 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Han T, Ma S, Sun C, Zhang H, Qu G, Chen Y, et al. Yang RC, Huang K, Zhang HP, Li L, Zhang YF, Tan C, et al. The most common cardiovascular complications of COVID-19 include arrhythmia, cardiac injury (evidenced by elevated troponin I, creatine kinase, NT-proBNP levels), coagulation (evidenced by elevated level of D-dimer), fulminant myocarditis, heart failure and new-onset atherosclerosis [26]. 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. 2020;383:225573. The thermoregulation system includes the hypothalamus in the brain, as well as the sweat. As well, nAChR activators through interaction with diverse signaling pathways can reduce the risk of inflammatory disorders in COVID-19. 2022;13:930673. Flaumenhaft R, Enjyoji K, Schmaier AA. government site. Hemil H, de Man AME. The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. This article reviews what is known about the effects of severe acute respiratory syndrome . Thermoregulatory physiology sustains health by keeping body core temperature within a degree or two of 37C, which enables normal cellular function.