However, the activation of matrix metalloproteinases (MMPs), which may be triggered by inflammatory factors (Shapiro, 2001), brings PG degradation, inducing pulmonary edema. (2020). J. Physiology-Lung Cell Mol. The combination of the two can lead to pneumonia and other serious respiratory illnesses. Comment on "Organprotective Effect of Angiotensinconverting Enzyme 2 and its Effect on the Prognosis of COVID19". Res. doi:10.1136/thoraxjnl-2013-203894, PubMed Abstract | CrossRef Full Text | Google Scholar, Achanta, S., and Jordt, S. E. (2020). SARS-CoV-2 is an enveloped RNA coronavirus of the genus , and is the seventh coronavirus which can infect human (Xu et al., 2020). Moreover, exogenous delivery of Ang (17) was shown to play a part in reducing inflammation and improving pulmonary function in ARDS models (Wosten-van Asperen et al., 2011). Pulmonary Edema in COVID-19: Explained by Bradykinin?. Infect. The University of Connecticut Foundation, Inc. Office of Development and Alumni Relations 10 Talcott Notch Road Suite 100 Farmington, CT 06032 official website and that any information you provide is encrypted Mechanism of BK inducing pulmonary edema and potential drugs. Influenza Virus Inhibits Amiloride-Sensitive Na+ Channels in Respiratory Epithelia. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. People with pneumonia, lung cancer, or heart disease may experience chest pain or wheezing. Sci. This site needs JavaScript to work properly. National Library of Medicine However, further researches into the mode of action, efficacy and safety of these drugs are required. doi:10.1016/j.resp.2011.11.009, Fan, H.-H., Wang, L.-Q., Liu, W.-L., An, X.-P., Liu, Z.-D., He, X.-Q., et al. Several cases of vaccine-induced thrombotic thrombocytopenia from a similar viral vector vaccine (Oxford-AstraZeneca [ChAdOx1 nCoV-19]) have been reported. Structure, Function, and Evolution of Coronavirus Spike Proteins. Furosemide, a NKCC inhibitor, has been acknowledged as first-line therapeutic drug for pulmonary edema all the time (Pickkers et al., 1997; Solymosi et al., 2013). (2005). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). doi:10.1001/jama.249.2.237, Matalon, S. (1999). Phytomedicine 85, 153282. doi:10.1016/j.phymed.2020.153282, Ma, Q., Pan, W., Li, R., Liu, B., Li, C., Xie, Y., et al. doi:10.1007/s11427-020-1637-5, Xu, Y.-H., Dong, J.-H., An, W.-M., Lv, X.-Y., Yin, X.-P., Zhang, J.-Z., et al. Physiol. medRxiv. (2004). doi:10.1002/path.2987, Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. Lianhuaqingwen Exerts Anti-viral and Anti-inflammatory Activity against Novel Coronavirus (SARS-CoV-2). includes glycoproteins, membranes and nucleic acids. doi:10.1152/physrev.1974.54.3.678, Steinritz, D., Stenger, B., Dietrich, A., Gudermann, T., and Popp, T. (2018). Biochem. J. Biol. Clin. J. A., Auerbach, S. D., Husted, R. F., Volk, K. A., Ageloff, S., Knepper, M. A., et al. Some of these TCMs along with their constituent and antiviral and reducing pulmonary edema mechanisms are shown in Table 3. Inhibiting these TRPs may benefit the treatment of pulmonary edema. However, clinical evidence showing that glucocorticoids can reduce pulmonary edema by regulating fluid absorption in alveolar and glucocorticoids is missing. doi:10.1074/jbc.M608358200, Harmer, D., Gilbert, M., and Borman, R. (2002). 97 (18), 1028210287. Federal government websites often end in .gov or .mil. A., et al. [Effect of Astragali Radix in Improving Early Renal Damage in Metabolic Syndrome Rats through ACE2/Mas Pathway]. Coronavirus Disease 2019 Treatment A Review of Early and Emerging Options. N. Engl. Physiol. 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. Bookshelf Here, we describe molecular mechanisms of PFC and propose that proteins functioning in this process might serve as an underappreciated, but yet promising targets for reducing lung edema in severe COVID-19 patients. (2001). DD&T 14 (5), 256258. J. Investig. (2000). (1998). Association between Early Treatment with Qingfei Paidu Decoction and Favorable Clinical Outcomes in Patients with COVID-19: A Retrospective Multicenter Cohort Study. Med. Is Amiloride a Promising Cardiovascular Medication to Persist in the COVID-19 Crisis?. 19 (5), 305306. Glucocorticoids were shown to have the ability of inducing de novo synthesis of ENaC (Chow et al., 1999; Otulakowski et al., 1999; Sayegh et al., 1999) and affecting ENaC regulatory pathway via serum and glucocorticoids-inducible kinase-1 (SGK-1) (Chen et al., 1999; de la Rosa et al., 1999; Itani et al., 2001; Zhang et al., 2007). Epub 2023 Mar 31. Res. 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). It shows the vaccine is teaching your body's immune system how to protect itself from the disease. doi:10.4268/cjcmm20152124, Wang, Q., Zheng, X., Cheng, Y., Zhang, Y.-L., Wen, H.-X., Tao, Z., et al. J. Cel Mol Med 24 (8), 47364747. The -Agonist Lung Injury Trial (Balti). This condition is generally referred to as pulmonary edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Antiviral Res. Transient Receptor Potential Vanilloid 4-Mediated Disruption of the Alveolar Septal Barrier. Acad. (2006) reported that the cryptotanshinone in Salvia miltiorrhiz can inhibit the synthesis of cGMP and NO in vein endothelial cells, activate NO/cGMP pathway and improve the blood circulation. doi:10.1007/s42399-020-00610-8, Ai, J.-W., Zhang, H.-C., Xu, T., Wu, J., Zhu, M., Yu, Y.-Q., et al. (2020). Rep. 72 (6), 15091516. Circulation 37 (1), 4553. Res. (2010). doi:10.1016/j.antiviral.2006.04.014, Hofer, C. C., Woods, P. S., and Davis, I. C. (2015). These in turn, lead to severe lung damage in COVID-19 patients. 2021 Jan;93(1):94-96. doi: 10.1002/jmv.26152. J. Physiology-Lung Cell Mol. One day before symptom onset, he had received a COVID-19 mRNA vaccine. Qing-Fei-Pai-Du Decoction, which is officially recommended for the treatment of COVID-19 patients as mentioned in the guideline issued by NHC (Trial 7th edition) (PRC, 2020), has an effective rate higher than 90% (2020) and can mediate the inflammatory storm induced by COVID-19 (Yang et al., 2020b), regulate the innate immune, cytokine activities (IL-17, NF-B, TNF etc. 2, 26372646. The COVID-19 Vaccine Development Landscape. N.Y. Acad. J. Physiol. 2020 Mar 23:3558887. doi: 10.2139/ssrn.3558887. Supportive cares for COVID-19 include respiratory support and circulatory support. 2021 May 7;8:644678. doi: 10.3389/fmed.2021.644678. doi:10.1161/01.RES.0000125623.56442.20, Nayler, W., and Dillon, J. Hormonal Regulation and Genomic Organization of the Human Amiloride-Sensitive Epithelial Sodium Channel Subunit Gene. 180 (11), 10421047. Sodium transport is the main ion transport involved in the AFC. 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. doi:10.1016/j.jaci.2020.08.038, Keywords: COVID-19, pulmonary edema, abnormal lung humoral metabolism, syndrome coronavirus 2, drug, traditional Chinese medicine, Citation: Cui X, Chen W, Zhou H, Gong Y, Zhu B, Lv X, Guo H, Duan J, Zhou J, Marcon E and Ma H (2021) Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential. Infection, pulmonary edema, lung cancer, aspiration, and pulmonary hemorrhage are some of the diseases that can cause consolidation. Abnormal humoral metabolism is mainly manifested as imbalances of water and electrolytes. (2020). HA-related hydrogel has been found in both, ARDS and SARS. 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). Infect. Res. (2015). COVID19 Diagnosis and Management: a Comprehensive Review. Amiloride was shown to induce the reduction of ACE2 expression in bronchial and alveolar epithelial cells (Adil et al., 2020) and can counteract the low cytosolic pH which has been observed in COVID-19 patients by acting on Na+/H+ exchanger (Cure and Cumhur Cure, 2020). Phytomedicine 85, 153242. doi:10.1016/j.phymed.2020.153242, Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. Mechanism of inhibiting ENaC inducing pulmonary edema. Am. Please enable it to take advantage of the complete set of features! TRPA1 distributes on C-fibers throughout the respiratory system (De Logu et al., 2016). Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. J. Biol. EM did the language polishing. (2020a). (2014). J. Endocrinol. 156, 104761. doi:10.1016/j.phrs.2020.104761, Sartori, C., Allemann, Y., Duplain, H., Lepori, M., Egli, M., Lipp, E., et al. Am. For patients recovering from COVID-19 who have persistent, progressive, or new respiratory symptoms, we obtain PFTs including spirometry, lung volumes, and diffusion capacity. J. Pharmacol. Direct Vascular Effects of Furosemide in Humans. 158, 104850. doi:10.1016/j.phrs.2020.104850, Ma, Q., Qiu, M., Zhou, H., Chen, J., Yang, X., Deng, Z., et al. In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. doi:10.1001/jama.2020.1585, Wang, Q. Y., Liang, W., Jiang, C., Li, N. Y., Xu, H., Yang, M. N., et al. 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). Am. FIGURE 6. Extensive studies have been conducted to identify the antiviral and pulmonary edema reducing efficacy of natural compounds, some of which have already been tested specifically against SARS-CoV and SARS-COV-2. Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. doi:10.1111/nyas.14472, Adil, M. S., Narayanan, S. P., and Somanath, P. R. (2020). Med. The project supported by Natural Science Foundation of China (grant number 81673563, 81102762, and 81274199); Open Project Program of Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXM-1-14, FJGJS-2015-15); Fund of Quality Standardization of Liu-Shen-Wan (BA2016104, ZYBZH-C-JS-30). 54 (3), 678811. In the meantime, we urgently need potent reduction in fatality of COVID-19. Protectin DX Increases Alveolar Fluid Clearance in Rats with Lipopolysaccharide-Induced Acute Lung Injury. Glucocorticoid Induction of Epithelial Sodium Channel Expression in Lung and Renal Epithelia Occurs via Trans-activation of a Hormone Response Element in the 5-Flanking Region of the Human Epithelial Sodium Channel Subunit Gene. doi:10.1164/rccm.200508-1302OC, Pickkers, P., Dormans, T. P. J., Russel, F. G. M., Hughes, A. D., Thien, T., Schaper, N., et al. Lancet Respir. Further, ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). J. Nat. doi:10.1001/jama.2020.4783, Shi, N., Liu, B., Liang, N., Ma, Y., Ge, Y., Yi, H., et al.

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