J. Biol. doi:10.1038/d41573-020-00073-5, Thorneloe, K. S., Cheung, M., Bao, W., Alsaid, H., Lenhard, S., Jian, M.-Y., et al. annals 99 (1), 1216. Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. doi:10.1056/NEJMoa2028836, Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., and Wen, C. (2020). (2003). J. Physiology-Lung Cell Mol. Am. Regulation of ENaC and CFTR Expression with K+ Channel Modulators and Effect on Fluid Absorption across Alveolar Epithelial Cells. (2021). Before doi:10.1172/JCI29850, Zhao, J., Tian, S., Lu, D., Yang, J., Zeng, H., Zhang, F., et al. Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) - anatomic pathology perspective on current knowledge. COVID-19 vaccine-related interstitial lung disease: a case study Biophys. -. Evolution of the Novel Coronavirus from the Ongoing Wuhan Outbreak and Modeling of its Spike Protein for Risk of Human Transmission. Mil. Not everyone gets side effects. Clipboard, Search History, and several other advanced features are temporarily unavailable. Epub 2023 Mar 31. Inhibiting these TRPs may benefit the treatment of pulmonary edema. Systems Pharmacological Study Illustrates the Immune Regulation, Anti-infection, Anti-inflammation, and Multi-Organ protection Mechanism of Qing-Fei-Pai-Du Decoction in the Treatment of COVID-19. A., et al. Am. doi:10.1111/j.1440-1827.2004.01754.x, Garvin, M. R., Alvarez, C., Miller, J. I., Prates, E. T., Walker, A. M., Amos, B. K., et al. Wiersinga, W. J., Rhodes, A., Cheng, A. C., Peacock, S. J., and Prescott, H. C. (2020). Optimizing Diagnostic Strategy for Novel Coronavirus Pneumonia, a Multi-center Study in Eastern China. Front. Repurposing of Clinically Approved Drugs for Treatment of Coronavirus Disease 2019 in a 2019-novel Coronavirus-Related Coronavirus Model. Medicines 16 (11), 811828. Arek Sarkissian. COVID-19 and its Implications for Thrombosis and Anticoagulation. doi:10.1152/ajplung.00244.2017, Looney, M. R., Sartori, C., Chakraborty, S., James, P. F., Lingrel, J. As of Sunday, at least 16,183 people had filed complaints with the Centers for Disease Control and Prevention that they'd developed tinnitus, or ringing in their ears, after receiving a Covid vaccine. 97 (5), 543554. A Mechanistic Model and Therapeutic Interventions for COVID-19 Involving a RAS-Mediated Bradykinin Storm. Electrolyte Imbalances in Patients with Severe Coronavirus Disease 2019 (COVID-19). Theaflavin from black tea was found to present a lower binding energy when it docks in the catalytic pocket of SARS-CoV-2 RdRp. FOIA 2, 1019. Since pulmonary edema can be promoted by decreased expression of alveolar Na-K-ATPase (Woods et al., 2015), drugs or compounds which activate the sodium channel and Na-K-ATPase may be putative therapeutics. Acad. 104, 81125. (2009). Proc. Most of the published data about this association come from case reports and series. Pathol. Am. 46 (7), 835837. Moreover, it has been revealed that exosomes derived from human adipocyte can inhibit TRPV4-mediated calcium influx and thus protect mice against ventilator-induced lung injury (Yu et al., 2020). Xue-Bi-Jing injection may act in COVID-19 by anti-inflammatory, anticoagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms (Li et al., 2021). 17, 149166. In addition, HA is a part of a three-dimensional matrix in pulmonary interstitial, which consists of HA, PGs and fibrillar macromolecules providing resistance to tissue compression and interstitial fluid expansion (Negrini et al., 2008).When PGs and HA interact with collagen IV, a fibrillar macromolecule modulating capillary permeability in the vascular basement membrane, the compound substance limit fluid influx into the interstitium. Authors Mabrouk Bahloul 1 . KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers can greatly recover AFC in mice intratracheally administrated verapamil, which is the first generation of the phenylalkylamine class of calcium channel antagonists (Fleckenstein, 1977; Nayler and Dillon, 1986), suggesting that K+ channel openers might be potential drugs for treating pulmonary edema (Han et al., 2010). B., van der Loos, C. M., et al. (2020c). 2023 Feb 13;11(2):435. doi: 10.3390/vaccines11020435. JACC: Basic Translational Sci. 313 (5), L859L872. Intensive Care Med. Clinical Characteristics of Coronavirus Disease 2019 in China. (2015). Cel Rep. Med. -, Adil M. S., Narayanan S. P., Somanath P. R. (2020). Naunyn-schmiedeberg's Arch. Pharmacol. (2020a). Am. It is also highly expressed in cardiomyocytes, epithelial cells of renal proximal convoluted tubule, urothelial cells, esophagus, and ileum (Harmer et al., 2002; Zhang et al., 2020), facilitating a quick invasion of the human body by SARS-COV-2 and causing complications. Decreased Expression of Aquaporin-5 in Bleomycin-Induced Lung Fibrosis in the Mouse fibrosis in the Mouse. doi:10.1136/gutjnl-2020-320953, Zhang, J.-L., Zhuo, X.-J., Lin, J., Luo, L.-C., Ying, W.-Y., Xie, X., et al. Polymodal Transient Receptor Potential Vanilloid Type 1 Nocisensor. A blocked upper airway causes negative pressure in the lungs from trying to breathe through the blockage. doi:10.1165/rcmb.2002-0101OC, Kaneko, Y., and Szallasi, A. Virol. Gut 69 (6), 10101018. Invest. CDC/FDA announce pause in use of Janssen COVID-19 Vaccine after identification of 6 cases of CVST with thrombocytopenia. Natl. The Study on the Treatment of Xuebijing Injection (XBJ) in Adults with Severe or Critical Corona Virus Disease 2019 and the Inhibitory Effect of XBJ against SARS-CoV-2. A health care provider monitors the oxygen level. Moreover, other drugs which can regulate immune system like hydroxychloroquine and azithromycin may also show effects in treating SARS-COV-2-induced pulmonary edema and their effectiveness in treating SARS-COV-2 infections should be further investigated. SARS-CoV-2 invasion leads to alveolar and vascular epithelial cells damage impelling the formation of minimal thrombus, increasing pulmonary venous pressure and vascular permeability and leading to massive loss of tissue fluid. J. Physiology-Lung Cell Mol. These in turn, lead to severe lung damage in COVID-19 patients. Dis. (2020). Other anti-viral drugs, such as arbidol, chloroquine phosphate and ritonavir, did not exhibit efficacy in randomized, placebo-controlled trials in COVID-19 patients. includes glycoproteins, membranes and nucleic acids. Angiotensin-converting Enzyme 2 in Acute Respiratory Distress Syndrome. 11 (1), 65. doi:10.1186/1465-9921-11-65, Han, J., Li, H., Bhandari, S., Cao, F., Wang, X. Y., Tian, C., et al. -, Ahmed M. H., Hassan A. doi:10.1007/s00134-007-0962-y, Niu, F., Xu, X., Zhang, R., Sun, L., Gan, N., and Wang, A. The -Agonist Lung Injury Trial (Balti). Impact of -adrenergic Agonist on Na+ Channel and Na+-K+-ATPase Expression in Alveolar Type II Cells. Physiol. doi:10.1152/ajplung.1998.275.3.L631, Perkins, G. D., McAuley, D. F., Thickett, D. R., and Gao, F. (2006). J. Physiology-Lung Cell Mol. 10.1101/2020.02.13.20022673 117 (3), 773783. Circuits between Infected Macrophages and T Cells in SARS-CoV-2 Pneumonia. doi:10.1152/ajplung.00395.2015, Birrell, M. A., Belvisi, M. G., Grace, M., Sadofsky, L., Faruqi, S., Hele, D. J., et al. (2020b). (2016). You might run a fever and experience body aches, headaches and tiredness for a day or two. Physiol. Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. (2013). Fedratinib, an FDA approved JAK2 inhibitor, may be used to reduce the mortality associated with hyperinflammation by suppressing the production of several Th17 cytokines (i.e., IL1b and TNF-alpha, IL21, IL22, IL17) and the formation of pulmonary edema in combination with anti-viral drugs (Yang et al., 2020e). Besides those direct causes of COVID-19 pulmonary edema, there are other factors that can be described as abnormal humoral metabolism which can influence the AFC and PFC, resulting the manifestation of pulmonary edema (Figure 3 Cause of COVID-19 pulmonary edema). Hemost. Ann. China Life Sci. Res. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. Janssen COVID-19 Vaccine. doi:10.1002/jmv.25848, Cutts, S., Talboys, R., Paspula, C., Prempeh, E., Fanous, R., and Ail, D. (2017). Physiol. doi:10.1001/jama.2020.12839, Wittekindt, O. H., and Dietl, P. (2019). doi:10.1016/j.antiviral.2006.04.014, Hofer, C. C., Woods, P. S., and Davis, I. C. (2015). doi:10.1101/2020.03.20.20039586, Londino, J. D., Lazrak, A., Collawn, J. F., Bebok, Z., Harrod, K. S., and Matalon, S. (2017). Physiol. Can COVID-19 cause pulmonary embolism? J. Respir. TRPs regulate their functions through sensory neuronal and nonneuronal pathways and play an important role in complicated pulmonary pathophysiologic events, such as increased intracellular calcium levels, recruitment of pro-inflammatory cells, cough reflex, blocked mucus clearance, epithelia integrity disruption, pulmonary edema, fibrosis and so on (De Logu et al., 2016). The COVID-19 test was negative but with low blood pressure, leukocytosis, skin rash, pulmonary edema, and increased inflammation markers. So far, only remdesivir was approved by FDA for the compassionate use in severe infected COVID-19 patients (Beigel et al., 2020). doi:10.1152/ajplung.00290.2014, Ji, G., Chen, R., and Zheng, J. Na+/K+-ATPase and ion channels (sodium, potassium, AQPs, and TRPs) are all involved in the regulation of AFC. Amiloride, a prototypic inhibitor of ENaC, might also have a potential in treating COVID-19 patients. [Effect of Astragali Radix in Improving Early Renal Damage in Metabolic Syndrome Rats through ACE2/Mas Pathway]. sharing sensitive information, make sure youre on a federal 276 (22), 1865718664. EBioMedicine. (2006). After getting vaccinated for COVID-19, you might experience some temporary symptoms similar to those you might notice when you get a flu shot, such as a sore, swollen arm where you got the shot. -, Achanta S., Jordt S. E. (2020). BMJ 369, m1432. Disclaimer. Existing drugs and inhibitors targeting the components of humoral metabolism may serve as potential treatments for COVID-19 and should be further investigated. (1997). FIGURE 1. 3 (1), 237261. Med. Int. As in lipopolysaccharide-induced acute lung injury, docosahexaenoic acid and its derivatives stimulate AFC through alveolar ENaC, Na,K-ATPase via ALX/cAMP/PI3K pathway (Wang et al., 2014; Zhang et al., 2017). COVID-19 Lung Damage | Johns Hopkins Medicine Therefore, drugs targeted at the humoral mechanisms might turn out to be highly effective against SARS-COV-2 infections. Pain at the injection site had completely resolved within 2 days. 21, 97S107S. medRxiv. J. Respir. The expression of AQP-5 is regulated by inflammatory cytokines, like TNF-, elevated in the plasma of critical COVID-19 patients (Hui and Zumla, 2019). J. Biol. What's the Link Between ARDS and COVID-19? - Health Pulmonary Vascular Manifestations of COVID-19 Pneumonia Am. Received: 05 February 2021; Accepted: 25 May 2021;Published: 07 June 2021. Drugs targeting at least some of these proteins have already existed and could be repurposed to manage pulmonary edema seen in SARS-COV-2 infections. PDF Updates on Thrombosis with Thrombocytopenia Syndrome (TTS) Lancet Respir. Available: http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml (Accessed February 4, 2021). Pulmonary Interstitial Pressure and Proteoglycans during Development of Pulmonary Edema. The most commonly reported symptoms of post- COVID-19 syndrome include: Fatigue Symptoms that get worse after physical or mental effort Fever Lung (respiratory) symptoms, including difficulty breathing or shortness of breath and cough Other possible symptoms include: The fluid transudes into and accumulates in the interstitium of lungs and finally alveolars from lung capillary, leading to severe disorder of pulmonary ventilation and gas exchange (Staub, 1974). 288 (2), 192206. doi:10.4268/cjcmm20152124, Wang, Q., Zheng, X., Cheng, Y., Zhang, Y.-L., Wen, H.-X., Tao, Z., et al. Protectin DX Increases Alveolar Fluid Clearance in Rats with Lipopolysaccharide-Induced Acute Lung Injury. Overall, the decreased expression of alveolar Na-K-ATPase, misregulation of sodium, potassium, AQP, and RAS channels and abnormal metabolism of BK and HA can all lead to lung liquid clearance failure and pulmonary edema, resulting in severe lung damage and ARDS in COVID-19 patients (Figure 6 The general regulation approaches of AFC). [Med. 282 (8), 55975607. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. The first treatment for acute pulmonary edema is oxygen. (2020). Lian-Hua-Qing-Wen capsules significantly affect virus morphology, inhibit the SARS-CoV-2 replication with the IC50 value of 411.2g/ml, reduce pro-inflammatory cytokines production at the mRNA level, and show anti-inflammatory effect in vitro (Runfeng et al., 2020). Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. During the infection of SARS-CoV-2, RAS, BK and hyaluronic acid (HA) are all involved in the regulation of AFC and the formation of pulmonary edema (Garvin et al., 2020). Chansu Injection Improves the Respiratory Function of Severe COVID-19 Patients. Pharmacol. 54 (10), 774780. 532 (1), 4. doi:10.1016/s0014-5793(02)03640-2, Heald-Sargent, T., and Gallagher, T. (2012). A type of pulmonary edema called neurogenic pulmonary edema can occur after a head injury, seizure or brain . 1, 2 More recently, six cases of. XC analyzed and reviewed the research articles as well as drafting the manuscript. (1977). 2 (6), 387396.doi:10.1038/35077544, Connors, J. M., and Levy, J. H. (2020). Mechanism of inhibiting ENaC inducing pulmonary edema. As reported, PaO2/FiO2 and ROX index of patients receiving conventional treatment combined with toad venom injection (20ml/day) improved significantly (111.30 to 35.90 for PaO2/FiO2 and 7.56 to 2.94 for ROX). doi:10.1530/EJE-20-0338, Clapham, D. E., Runnels, L. W., and Strbing, C. (2001). Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. (2020). Authors Hyponatremia (low blood sodium concentration) as well as low concentrations of potassium and calcium in the blood serum are also associated with COVID-19 (Lippi et al., 2020). 102 (8), 966974. FIGURE 5. Mohanty SK, Satapathy A, Naidu MM, Mukhopadhyay S, Sharma S, Barton LM, Stroberg E, Duval EJ, Pradhan D, Tzankov A, Parwani AV.

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