Pharmacol. 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). Virol. However, it is still unclear how the vaccination will proceed and how fast can vaccinations be done. Cell Death Differ 27 (5), 14511454. Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. Other anti-viral drugs, such as arbidol, chloroquine phosphate and ritonavir, did not exhibit efficacy in randomized, placebo-controlled trials in COVID-19 patients. Physiol. 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). The Lancet 395 (10223), 497506. Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. doi:10.1007/s00134-007-0962-y, Niu, F., Xu, X., Zhang, R., Sun, L., Gan, N., and Wang, A. The frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Thorax 69 (1), 4654. doi:10.1152/ajplung.00085.2001, Ito, Y., Correll, K., Zemans, R. L., Leslie, C. C., Murphy, R. C., and Mason, R. J. Here, we summarized several natural compounds and TCM formulas which are very likely to be potential drugs or have already shown predominant efficacy of COVID-19 patients. The site is secure. J. Cel Physiol 234 (11), 2005720065. Adult Respiratory Distress Syndrome. As Towne et al., (2001) reported, AQP-5 expression significantly declined during pulmonary inflammation and edema, and TNF- decreased AQP5 mRNA and protein expression levels via TNFR1 and NF-B pathway (Towne et al., 2001). 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). Before doi:10.1016/j.cell.2020.02.058, Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., et al. TRPV1, expressed in C-fibers of the vagus nerves innervating airways (Cui et al., 2016), has been considered to play a key role in cough reflex and increased airway sensitivity caused by various diseases (Andr et al., 2009; Couto et al., 2013). (2013). (Engl) 133 (9), 10511056. Decreased expression of alveolar Na-K-ATPase, dysregulation of sodium and potassium channels, aquaporins, and renin angiotensin system, and abnormal metabolism of bradykinin and hyaluronic acid as well as cytokine inflammatory storm all lead to ARDS and pulmonary edema. (2020). Pharmacol. (2004). Aquaporins in the Lung. Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection. 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). COVID-19 and its Implications for Thrombosis and Anticoagulation. doi: 10.1152/ajplung.00161.2020. EM did the language polishing. 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. Res. doi:10.3109/08923973.2014.968256, Jiang, Y.-x., Dai, Z.-l., Zhang, X.-p., Zhao, W., Huang, Q., and Gao, L.-k. (2015). (2002). Intensive Care Med. 1 (4), 100052. doi:10.1016/j.xcrm.2020.100052, Shen, C., Wang, Z., Zhao, F., Yang, Y., Li, J., Yuan, J., et al. Immunopathol 38 (3), 321329. Chansu Injection Improves the Respiratory Function of Severe COVID-19 Patients. Crit. J. Physiology-Lung Cell Mol. (2017). (2021). Clipboard, Search History, and several other advanced features are temporarily unavailable. A., et al. doi:10.5114/pdia.2013.37040, Cui, M., Gosu, V., Basith, S., Hong, S., and Choi, S. (2016). Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control. As Gabazza et al., (2004) reported, lung fibrosis is linked to decreased mRNA and protein expression of AQP-5 in the lung. (2020). Proteoglycan Involvement during Development of Lesional Pulmonary Edema. Artif Intell Med. The clinical manifestations and CT scans show the presence of ARDS in critical COVID-19 patients (Ai et al., 2020; Guan et al., 2020; Huang et al., 2020). Virol. J. Intern. doi:10.1074/jbc.274.18.12431, Schlagenhauf, P., Grobusch, M. P., Maier, J. D., and Gautret, P. (2020). As the infection progresses, the immune function is impaired, causing damage to multiple organs, additional complications, and eventually death (Yang et al., 2020). However, the efficacy and safety of these drugs in COVID-19 patients are unclear. 7 (4). Repurposing Antimalarials and Other Drugs for COVID-19. (2020). (2007). J. Biol. Natl. doi:10.1007/s00281-016-0557-1, de Maat, S., de Mast, Q., Danser, A. H. J., van de Veerdonk, F. L., and Maas, C. (2020). Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy. doi:10.7554/eLife.59177, George, P. M., Wells, A. U., and Jenkins, R. G. (2020). 8 (4), 420422. Can COVID-19 cause pulmonary embolism? Am. Therefore, the excessive release and decreased hydrolysis of BK through activating BKB1 and BKB2 receptors result in extra vascular leakage and pulmonary edema (Figure 5 Mechanism of BK inducing pulmonary edema and potential drugs) (Zwaveling et al., 2020). doi:10.1101/2020.03.02.20029975, Yin, J., Hoffmann, J., Kaestle, S. M., Neye, N., Wang, L., Baeurle, J., et al. J. Physiol. (2013). 10.1136/thoraxjnl-2013-203894 Existing drugs and inhibitors targeting the components of humoral metabolism may serve as potential treatments for COVID-19 and should be further investigated. It has already been shown that the dysregulated release of cytokines is one of the key factors behind poor outcomes in COVID-19 patients. In this review, we discuss the clinical characteristics of COVID-19, current as well as potential new treatments based on the reduction of lung edema through various means, drugs, TCMs or natural compounds. Unable to load your collection due to an error, Unable to load your delegates due to an error. Am J Physiol Lung Cell Mol Physiol. Chills and swollen lymph nodes can also occur. No use, distribution or reproduction is permitted which does not comply with these terms. doi:10.1021/acsnano.0c02624, Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., and Veesler, D. (2020). Epub 2023 Mar 31. Circulation 37 (1), 4553. Med. National Library of Medicine Res. Further studies may determine if CD44 inhibitors can be of use to in COVID-19. 35 (5), 684688. Physiol. Zhou et al. Mechanism of inhibiting ENaC inducing pulmonary edema. Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. Lipoxin A4 (LXA4) can stabilize the permeability of pulmonary microvascular endothelial cell by regulating the expression of AQP-5 and MMP-9, and reduce alveolar fluid exudation (Shi et al., 2018). So far, only remdesivir was approved by FDA for the compassionate use in severe infected COVID-19 patients (Beigel et al., 2020). Supportive cares for COVID-19 include respiratory support and circulatory support. Infect. Semin. Amiloride. 2020 Jul;57:102833. doi: 10.1016/j.ebiom.2020.102833. You might run a fever and experience body aches, headaches and tiredness for a day or two. Yes. CD44 inhibition reduces the IL-2 induced vascular leakage syndrome, revealing that CD44 may act as a potential target in COVID-19 treatment. 1480 (1), 73103. 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). The imbalance of fluid metabolism, pulmonary fluid clearance (PFC) and rich-protein fluid entrance, may be a key reason for the acute exacerbation of pulmonary edema in COVID-19 patients. Front Pharmacol. Rev. Am. 6, 331345. Regulation of Alveolar Fluid Clearance and ENaC Expression in Lung by Exogenous Angiotensin II. COVID-19: Long-term effects - Mayo Clinic TRPA1 distributes on C-fibers throughout the respiratory system (De Logu et al., 2016). (2020a). Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. 383 (19), 18131826. The Role of Proteoglycans in Pulmonaryedema Development. 276 (22), 1865718664. 54 (3), 678811. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. AQP-5 plays a significant role in pulmonary edema and decreased expression of AQP-5 has been observed during the disease process. Thus, it could be a potential RdRp inhibitor for SARS-CoV-2 (Lung et al., 2020). Optimizing Diagnostic Strategy for Novel Coronavirus Pneumonia, a Multi-center Study in Eastern China. Infect. A type of pulmonary edema called neurogenic pulmonary edema can occur after a head injury, seizure or brain . COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. Acta (Bba) - Gen. Decreased Expression of Aquaporin-5 in Bleomycin-Induced Lung Fibrosis in the Mouse fibrosis in the Mouse. Patients with SARS-CoV-2-Induced Viral Sepsis Simultaneously Show Immune Activation, Impaired Immune Function and a Procoagulatory Disease State. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. (2020). -, Achanta S., Jordt S. E. (2020). 11. Traditional Chinese Medicine for COVID-19 Treatment. medRxiv. Phytomedicine 85, 153242. doi:10.1016/j.phymed.2020.153242, Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. These proteins include ion channels (Na channel, K channel and TRPV4), aquaporins (AQP), renin angiotensin system (RAS) proteins, and bradykinin/hyaluronic acid-related enzymes. (2020a). doi:10.1111/bph.12414, Kaur, S. P., and Gupta, V. (2020). 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). In the meantime, we urgently need potent reduction in fatality of COVID-19. Jiangsu Qing Lan Project for Young Academic Leaders of China. Mohanty SK, Satapathy A, Naidu MM, Mukhopadhyay S, Sharma S, Barton LM, Stroberg E, Duval EJ, Pradhan D, Tzankov A, Parwani AV. Aspirin: Generic, Uses, Side Effects, Dosages, Interactions - RxList COVID-19 can cause lung complications such as pneumonia and, in the most severe cases, acute respiratory distress syndrome, or ARDS . doi:10.1172/JCI29850, Zhao, J., Tian, S., Lu, D., Yang, J., Zeng, H., Zhang, F., et al. Chem. (2020b). FIGURE 3. doi:10.1308/rcsann.2016.0238, de la Rosa, D. A., Zhang, P., Nray-Fejes-Tth, A., Fejes-Tth, G., and Canessa, C. M. (1999). Most side effects are mild and normally last only a day or two. Circulation 96 (6), 18471852. Clinical and Computed Tomographic Imaging Features of Novel Coronavirus Pneumonia Caused by SARS-CoV-2. Res. [Effect of Astragali Radix in Improving Early Renal Damage in Metabolic Syndrome Rats through ACE2/Mas Pathway]. Respir. The combination of the two can lead to pneumonia and other serious respiratory illnesses. Respir. Ion Channels of the Lung and Their Role in Disease Pathogenesis. doi:10.1101/2020.03.31.20038935, Yang, R., Liu, H., Bai, C., Wang, Y., Zhang, X., Guo, R., et al. 46 (7), 835837. A. H. (2020). Biophys. J. Respir. Rev. Am. 39 (270), H2000H2007. sharing sensitive information, make sure youre on a federal 102 (8), 966974. Pharmacol. J. Pract. He was medicated with methylprednisolone 1 mg/kg and diuretics and recovered rapidly. doi:10.1126/science.abb2507, Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., et al. Res. Thromb. In TCM theory, evils of COVID-19 are derived from cold-dampness, whose core pathogenesis are toxin and dampness. J. Physiology-Lung Cell Mol. Med. Drug Discov. J. Physiology-Lung Cell Mol. (2020). COVID-19: Vaccine-induced immune thrombotic thrombocytopenia - UpToDate 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). TABLE 1. doi:10.1002/jcp.28602, Otulakowski, G., Rafii, B., Bremner, H. R., and O'Brodovich, H. (1999). Immune responses to COVID-19 vaccinations may trigger acute exacerbations in idiopathic pulmonary fibrosis among susceptible patients, according to data published in the American Journal of. Perplexingly, among the currently pursued therapeutic strategies against COVID-19, none is designed to directly protect the alveolo-capillary barrier. COVID-19: Urgent Reconsideration of Lung Edema as a Preventable Outcome: Inhibition of TRPV4 As a Promising and Feasible Approach. Pathological Findings of COVID-19 Associated with Acute Respiratory Distress Syndrome. Diagnosing COVID-19: The Disease and Tools for Detection. eCollection 2023. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. 74 (2), 92101. 388 (4), 421436. Front. COVID-19 vaccines can cause mild side effects after the first or second dose, including: Pain, redness or swelling where the shot was given Fever Fatigue Headache Muscle pain Chills Joint pain Nausea and vomiting Swollen lymph nodes Feeling unwell Most side effects go away in a few days. Physiol. CDC interim clinical considerations and FDA Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. COVID-19 patients often have pathological features such as pulmonary interstitial or alveolar edema, diffuse tracheal phlegm thrombus and pulmonary inflammatory lymphoid infiltration, and are prone to acute respiratory distress syndrome (ARDS), causing lung injury (Cutts et al., 2017). COVID-19 Vaccine FAQ | American Lung Association COVID-19 Vaccination-related Lymphadenopathy: What To Be Aware Of 97 (18), 1028210287. The likelihood of hypertensive patients developing COVID-19, who were treated by ARBs, was reported to decrease by 76% (Yan et al., 2020). 97 (5), 543554. The Potential Chemical Structure of antiSARSCoV2 RNAdependent RNA Polymerase. J. Respir. SODIUM CHANNELS IN ALVEOLAR EPITHELIAL CELLS: Molecular Characterization, Biophysical Properties, and Physiological Significance. medRxiv.doi:10.1101/2020.05.20.20107607, Hu, K., Guan, W.-j., Bi, Y., Zhang, W., Li, L., Zhang, B., et al. Sci. Liu Shen Capsule Shows Antiviral and Anti-inflammatory Abilities against Novel Coronavirus SARS-CoV-2 via Suppression of NF-b Signaling Pathway. Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. The toad venom injection can significantly improve the pulmonary function of COVID-19 patients by regulating PaO2/FiO2 and ROX index and thus alleviate pulmonary edema. doi:10.1007/s43440-020-00132-z, Runfeng, L., Yunlong, H., Jicheng, H., Weiqi, P., Qinhai, M., Yongxia, S., et al. These in turn, lead to severe lung damage in COVID-19 patients. medRxiv. (2021). RAS plays a significant role in ARDS as well as pulmonary edema processes. doi:10.1016/s1875-5364(18)30123-7, Zhang, D., Zhang, B., Lv, J.-T., Sa, R.-N., Zhang, X.-M., and Lin, Z.-J. The University of Connecticut Foundation, Inc. Office of Development and Alumni Relations 10 Talcott Notch Road Suite 100 Farmington, CT 06032 (1999). This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). (2020a). (2020). Keywords: JAMA 323 (20), 20522059. Meanwhile, the number of patients in the treatment group presenting improved PaO2/FiO2 and ROX index was higher than that of the control group (95.2% vs. 68.4% and 73.7%). Indeed, in several preclinical studies, selective TRPV4 inhibition showed efficacy in preventing or attenuating lung edema (Thorneloe et al., 2012). Am. Symptoms that are common to all of these conditions include cough and shortness of breath. doi:10.1074/jbc.274.53.37834, De Logu, F., Patacchini, R., Fontana, G., and Geppetti, P. (2016). Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. We argue for expeditious clinical testing of this inhibitor in COVID-19 patients with respiratory malfunction and at risk for lung edema. As the activation of AT1 receptor promotes the pulmonary edema, AT1 receptor blockers (ARBs) like losartan, valsartan may be effective in decreasing pulmonary edema. (1985) 93 (4), 15331541. Mechanism of BK inducing pulmonary edema and potential drugs. Pharmacol. TRP channels are nonspecific cationic channels located throughout the respiratory system (Clapham et al., 2001), where TRPA1, TRPV1 and TRPV4 are the most abundant TRP subtypes (Kaneko and Szallasi, 2014; Steinritz et al., 2018). Moreover, the constituent Ephedra can trigger bronchodilation, relieve breathing disorders and alleviate pulmonary edema (Zhang et al., 2018). We are grateful to all of the colleagues who have given critical comments on this work. Repurposing of Clinically Approved Drugs for Treatment of Coronavirus Disease 2019 in a 2019-novel Coronavirus-Related Coronavirus Model. (2020b). Res. The activities of the molecules in RAS are ruled by dynamic changes responding to an injury. doi:10.1161/01.cir.96.6.1847. Molecular Features of Non-selective Small Molecule Antagonists of the Bradykinin Receptors. It was observed that the expression of ENaC and Na+/K+-ATPase in primary alveolar type II cells from rat lungs increased responding to terbutaline (Minakata et al., 1998).
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