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Med. doi:10.1111/bph.12414, Kaur, S. P., and Gupta, V. (2020). The abnormal humoral metabolism and pulmonary edema contribute to the severity of symptoms and fatality of COVID-19 patients. Serum sodium shows a decrease trend in CODIV-19 development (Krolicka et al., 2020). Moreover, the constituent Ephedra can trigger bronchodilation, relieve breathing disorders and alleviate pulmonary edema (Zhang et al., 2018). 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). (2021). Rep. 72 (6), 15091516. Pediatr. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration. In COVID-19 patients, pulmonary edema is diagnosed by lung ultrasound and a computerized tomography (CT) scan (Udugama et al., 2020). It is known that SARS-CoV-2 invades human cells by binding angiotensin-converting enzyme-2 (ACE-2) receptor and other membrane ectopeptidases (Xu et al., 2020). doi:10.1016/j.cell.2020.02.058, Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., et al. When to. 35 (19), 30142017. doi:10.1164/rccm.200905-0665OC, Bull, M. B., and Laragh, J. H. (1968). (2019). Sepsis, another possible complication of COVID-19, can also cause lasting harm to the lungs and other organs. 8600 Rockville Pike Gut 69 (6), 10101018. doi:10.1002/jcp.28602, Otulakowski, G., Rafii, B., Bremner, H. R., and O'Brodovich, H. (1999). 282 (8), 55975607. (2020). doi:10.1126/scitranslmed.3004276, Towne, J. E., Krane, C. M., Bachurski, C. J., and Menon, A. G. (2001). Cepharanthine, a bisbenzylisoquinoline alkaloid derived from tubers of Stephania Japonica, was shown to have a wide-spectrum inhibitor of pan--coronavirus (Fan et al., 2020; Rogosnitzky et al., 2020). Res. Pharmacol. Chem. The cystic fibrosis transmembrane conductance regulator (CFTR) and the ENaC located in the airway apical membranes and alveolar epithelial cells are essential in regulating lung fluid balance across airway as the chloride (Cl) and bicarbonate (HCO3) secretion conduits, and alveolar epithelia by sodium (Na+) ion absorption (Matalon, 1999; Birket et al., 2016; Londino et al., 2017). doi:10.4268/cjcmm20152124, Wang, Q., Zheng, X., Cheng, Y., Zhang, Y.-L., Wen, H.-X., Tao, Z., et al. Biol. Clin. The Clinical Benefits of Chinese Patent Medicines against COVID-19 Based on Current Evidence. Mechanism of BK inducing pulmonary edema and potential drugs. Consequently, the use of bradykinin antagonists is supposed to be regarded as a strategy for COVID-19 treatment interventions. The Serum and Glucocorticoid Kinase Sgk Increases the Abundance of Epithelial Sodium Channels in the Plasma Membrane of Xenopus Oocytes. However, so far, no effective inhibitors have been developed against HAS2. J. Huazhong Univ. doi:10.1038/s41418-020-0530-3, Shi, Z., Ye, W., Zhang, J., Zhang, F., Yu, D., Yu, H., et al. 275 (2), L414L422. 2020 Mar 23:3558887. doi: 10.2139/ssrn.3558887. The site is secure. doi:10.1073/pnas.96.5.2514, Chow, Y.-H., Wang, Y., Plumb, J., O'Brodovich, H., and Hu, J. Cause of COVID-19 pulmonary edema. ACS Nano 14 (4), 38223835. (2003). As reported, large-conductance calcium-activated potassium channels (BKCa) in alveoli can reduce alveoli opening during hypoxia, detect O2 variation, and adjust ion transport and fluid clearance (Jovanovi et al., 2003). Annu. - Eur. J. Nat. doi:10.1165/rcmb.2002-0101OC, Kaneko, Y., and Szallasi, A. N.Y. Acad. Cel Metab. Circ. (2020). WHO Coronavirus Disease (COVID-19) Dashboard [Online]. Other anti-viral drugs, such as arbidol, chloroquine phosphate and ritonavir, did not exhibit efficacy in randomized, placebo-controlled trials in COVID-19 patients. J. Physiology-Lung Cell Mol. Med Res 7 (1), 11. doi:10.1186/s40779-020-00240-0, Han, D.-Y., Nie, H.-G., Gu, X., Nayak, R. C., Su, X.-F., Fu, J., et al. (2008). 17, 149166. 2021 Jun 7;12:664349. doi: 10.3389/fphar.2021.664349. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Pharmacol. We speculate that treatment of lung-edema will lead to a lower mortality in COVID-19 patients with severe infections. Mil. (2021). A recent review has summarized the effects of TRPs in pulmonary chemical injuries, which includes the representative TRPA1, TRPV1 and TRPV4 antagonists which have participated in preclinical and clinical studies (Achanta and Jordt, 2020) (Supplementary Tables S1S3). Physiol. J. Cel Physiol 235 (12), 95109523. doi:10.1038/s41586-020-03148-w, Guan, W.-j., Ni, Z.-y., Hu, Y., Liang, W.-h., Ou, C.-q., He, J.-x., et al. This site needs JavaScript to work properly. Epithelial sodium channel (ENaC), present in human lungs, kidneys and other organs, plays a vital role in lung fluid clearance (Figure 4 Mechanism of inhibiting ENaC inducing pulmonary edema) (Matthay et al., 2002). Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. 10.1007/s42399-020-00610-8 (2020). Circ. Emodin, an anthraquinone compound from genus Rheum and Polygonum, can markedly prevent the binding of S protein and ACE2 in the study of SARS-CoV (Ho et al., 2007). Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control. doi:10.7150/ijbs.45538, Yang, Y., Shen, C., Li, J., Yuan, J., Yang, M., Wang, F., et al. Neurobiol. J. Physiology-Lung Cell Mol. Papi A, Stapleton RD, Shore PM, Bica MA, Chen Y, Larbig M, Welte T. Lung. In the meantime, we urgently need potent reduction in fatality of COVID-19. Ijerph 17 (15), 5320. doi:10.3390/ijerph17155320, Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. Patients receive high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), mechanical ventilation or ECMO as respiratory supports (Guo et al., 2020; Pascarella et al., 2020), a crystalloid fluid to ensure body fluid equilibrium (Christ-Crain et al., 2020), and anticoagulants for restraining the thrombus formation to aid in circulatory support (Connors and Levy, 2020). Currently, many clinical trials are in progress to test coronavirus treatment, including new drugs and drug repurposing or repositioning. Cel Mol Biol 28 (3), 363372. Not everyone gets side effects. Am. However, the efficacy and safety of these drugs in COVID-19 patients are unclear. doi:10.1073/pnas.160041997, Leroy, C., Priv, A., Bourret, J.-C., Berthiaume, Y., Ferraro, P., and Brochiero, E. (2006). J. Physiology-Lung Cell Mol. A., and Cook, D. I. (2020). In these patients, white blood cells count, neutrophil count and D-dimer level keep rising while lymphocyte count keeps decreasing as the disease progresses. Virol. 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. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. doi:10.1152/physiol.00026.2008, Birket, S. E., Chu, K. K., Houser, G. H., Liu, L., Fernandez, C. M., Solomon, G. M., et al. Immunopharmacology and Immunotoxicology 36 (6), 420425. 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). An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure. 23 (5), 289301. J. Med. The Liu Shen capsule, of which pharmacodynamic component is also toad venom, was shown to have antiviral and anti-inflammatory activity against SARS-CoV-2 in vitro, as it can inhibit the replication of SARS-CoV-2 in Vero E6 cells, reduce inflammatory cytokines production at the mRNA levels and suppress the NF-B signaling pathway to downregulate the expression of cytokines (Ma et al., 2020a). Physiol. Pharmacol. Biochim. 382 (18), 17081720. 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. The TRP Ion Channel Family. Clin. Rev. Pharmacol. J. Biol. (1986). Cells 7 (8), 98. doi:10.3390/cells7080098, Stone, J. H., Frigault, M. J., Serling-Boyd, N. J., Fernandes, A. D., Harvey, L., Foulkes, A. S., et al. Life Sci. Salmeterol for the Prevention of High-Altitude Pulmonary Edema. Respir. Additionally, other major ADRs were potentially linked to the BNT162b2 mRNA COVID-19 vaccine, including central nervous system thrombosis, deep vein thrombosis, and pulmonary embolism [3-5]. Who (2021). Am J Physiol Lung Cell Mol Physiol. Circulation 96 (6), 18471852. Yes. doi:10.1038/d41573-020-00073-5, Thorneloe, K. S., Cheung, M., Bao, W., Alsaid, H., Lenhard, S., Jian, M.-Y., et al. Effect and Mechanism of Astragaloside A on Acute Respiratory Failure in Rats. Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. Ready, Set, Fuse! Several cases of vaccine-induced thrombotic thrombocytopenia from a similar viral vector vaccine (Oxford-AstraZeneca [ChAdOx1 nCoV-19]) have been reported. (2020a). Also, thrombocytopenia and thrombosis have been mostly reported after AstraZeneca (ChAdOx1 nCoV-19) and Johnson & Johnson/Janssen COVID-19 vaccines [ 3 ]. RAS, especially several cleavage products of the peptide angiotensin (AGT) along with their receptors, maintains a balance of fluid volume and pressure. 532 (1), 4. doi:10.1016/s0014-5793(02)03640-2, Heald-Sargent, T., and Gallagher, T. (2012). Front. Med. Invest. Cough Reflex Testing with Inhaled Capsaicin and TRPV1 Activation in Asthma and Comorbid Conditions. Some of these TCMs along with their constituent and antiviral and reducing pulmonary edema mechanisms are shown in Table 3. He had no cough, expectoration, nasal discharge or sore throat. (1997). COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. TGF--induced IL-6 prevents development of acute lung injury in influenza A virus-infected F508del CFTR-heterozygous mice. COVID-19 Vaccine: A Comprehensive Status Report. 11. Repurposing Antimalarials and Other Drugs for COVID-19. TABLE 3. Optimizing Diagnostic Strategy for Novel Coronavirus Pneumonia, a Multi-center Study in Eastern China. It's normal to experience side effects after a vaccine. Am. doi:10.1146/annurev.pa.17.040177.001053, Fronius, M. (2013). Pulmonary Edema. Arek Sarkissian. doi:10.1016/bs.apcsb.2015.11.005, Cure, E., and Cumhur Cure, M. (2020). Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches, toothaches, common cold, and headaches.It may also be used to reduce pain and swelling in conditions such as arthritis.Aspirin is known as a salicylate and a nonsteroidal anti-inflammatory drug ().It works by blocking a certain natural substance in your body to reduce pain and swelling.