The site is secure. Res. 99 (9), 988995. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. 34 (4), 610618. The Clinical Benefits of Chinese Patent Medicines against COVID-19 Based on Current Evidence. 11, 1708. doi:10.3389/fimmu.2020.01708, Thanh Le, T., Andreadakis, Z., Kumar, A., Gmez Romn, R., Tollefsen, S., Saville, M., et al. Prc, N. H. C. o. t. (2020). Salmeterol for the Prevention of High-Altitude Pulmonary Edema. -, Ahmed M. H., Hassan A. Rev. Before Hormonal Regulation and Genomic Organization of the Human Amiloride-Sensitive Epithelial Sodium Channel Subunit Gene. Pharmacol. COPD and asthma cause your airways to swell and become blocked with mucus, which can make it hard to breathe. Therefore, severe infections, which are induced by influenza virus, target the distal lung epithelial cells, inhibit the ENaC via activating protein kinase C (Kunzelmann et al., 2000), and damage the pulmonary surfactant (Hofer et al., 2015; Ito et al., 2015; Woods et al., 2015). Physiol. Creative Commons Attribution License (CC BY). Large Conductance Ca2+-Activated K+ Channels Sense Acute Changes in Oxygen Tension in Alveolar Epithelial Cells. 146 (6), 14541455. Ijerph 17 (15), 5320. doi:10.3390/ijerph17155320, Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. See this image and copyright information in PMC. In addition, natural compounds and TCMs which generally have multiple targets should also be investigated, both in terms of their efficacy and safety. Pulmonary edema is an abnormal buildup of fluid in the lungs. Bookshelf It has been shown that SARS-CoV-2 infects human cells via specific binding of S-protein to angiotensin-converting enzyme 2 (ACE2) (Figure 2 Infection and replication process of SARS-CoV-2) (Xu et al., 2020) and the binding affinity between these two proteins is 1020 times greater than that of SARS-CoV and ACE2 (Yan et al., 2020; Wrapp et al., 2020). Maresin Conjugates in Tissue Regeneration 1 Improves Alveolar Fluid Clearance by Upregulating Alveolar ENaC, Na, KATPase in Lipopolysaccharideinduced Acute Lung Injury. Circ. doi:10.1001/jama.2020.6775, Rogosnitzky, M., Okediji, P., and Koman, I. Raising evidences suggest that the effect of kinins on bradykinin receptor triggers the inflammatory responses, which have been observed in patients with COVID-19. 35 (5), 684688. N. Engl. 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. 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. COVID-DSNet: A novel deep convolutional neural network for detection of coronavirus (SARS-CoV-2) cases from CT and Chest X-Ray images. Nature 590, 635641. (2020a). Clipboard, Search History, and several other advanced features are temporarily unavailable. 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). Physiol. Infection, pulmonary edema, lung cancer, aspiration, and pulmonary hemorrhage are some of the diseases that can cause consolidation. Idiopathic pulmonary fibrosis is also a risk factor for severe COVID-19 which can be observed in the CT scans of COVID-19 patients (Xu et al., 2020; George et al., 2020). 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. Theaflavin from black tea was found to present a lower binding energy when it docks in the catalytic pocket of SARS-CoV-2 RdRp. FIGURE 3. medRxiv. Immunopathol 38 (3), 321329. Pflugers Arch. COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. When to. Virol. The stimulation of TRPA1 can cause coughing, hypersecretion of mucus, rapid shallow breathing as well as bronchoconstriction (Bessac and Jordt, 2008; Birrell et al., 2009), which, if persistent, may cause ARDS and other chronic diseases. PCTR1 Improves Pulmonary Edema Fluid Clearance through Activating the Sodium Channel and Lymphatic Drainage in Lipopolysaccharideinduced ARDS. J. Physiology-Lung Cell Mol. 108 (6), 11851194. (2020). 19 (5), 305306. 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. SODIUM CHANNELS IN ALVEOLAR EPITHELIAL CELLS: Molecular Characterization, Biophysical Properties, and Physiological Significance. (2020). 183 (1), G9G15. Mil. Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. doi:10.1007/s00134-007-0962-y, Niu, F., Xu, X., Zhang, R., Sun, L., Gan, N., and Wang, A. . doi:10.1126/science.abb2762, Yang, G., Tan, Z., Zhou, L., Yang, M., Peng, L., Liu, J., et al. Other therapeutic options including organ support, glucocorticoid therapy, nutritional support have been applied to COVID-19 clinical treatment without much knowledge of their efficacy. 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. Pharmacol. 2022 Dec;134:102427. doi: 10.1016/j.artmed.2022.102427. Also, thrombocytopenia and thrombosis have been mostly reported after AstraZeneca (ChAdOx1 nCoV-19) and Johnson & Johnson/Janssen COVID-19 vaccines [ 3 ]. Chloroquine and Hydroxychloroquine in Covid-19. Mechanism of BK inducing pulmonary edema and potential drugs. -, Ai J.-W., Zhang H.-C., Xu T., Wu J., Zhu M., Yu Y.-Q., et al. doi:10.1146/annurev.pa.17.040177.001053, Fronius, M. (2013). Thorax 69 (1), 4654. JAMA 323 (16), 15821589. Pathol. We observed a case of a delayed local reaction in a 38-year-old woman who had received the first dose of the BNT162b2 vaccine. Repurposing Antimalarials and Other Drugs for COVID-19. Hemost. Res. A., and Cook, D. I. Other anti-viral drugs, such as arbidol, chloroquine phosphate and ritonavir, did not exhibit efficacy in randomized, placebo-controlled trials in COVID-19 patients. In COVID-19, lung manifestations present as a slowly evolving pneumonia with insidious early onset interstitial pulmonary edema that undergoes acute exacerbation in the late stages and microvascular thrombosis. 171 (10), 24742507. (2008). HHS Vulnerability Disclosure, Help Heart Circ. Med. SARS-CoV-2 is an enveloped RNA coronavirus of the genus , and is the seventh coronavirus which can infect human (Xu et al., 2020). Medicines 16 (11), 811828. (2020). The integrity of PG molecules in the vascular capillary basement membrane can make sure that endothelial permeability to fluid and solutes in a low level. Transient Receptor Potential (TRP) Channels: a Clinical Perspective. 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). Mol. 64 (15), 20062012. 2, 26372646. doi:10.1161/01.RES.0000247065.11756.19, Andr, E., Gatti, R., Trevisani, M., Preti, D., Baraldi, P., Patacchini, R., et al. Mechanism of BK inducing pulmonary edema and potential drugs. 282 (8), 55975607. Med. 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. (2020). The Pfizer study defined their primary endpoint as cases of symptomatic, confirmed COVID-19 occurring at least seven days after the second injection, while Moderna counted symptomatic, confirmed COVID-19 cases occurring at least 14 days after the second injection. Toxicol. 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%). 308 (7), L628L638. Association between Early Treatment with Qingfei Paidu Decoction and Favorable Clinical Outcomes in Patients with COVID-19: A Retrospective Multicenter Cohort Study. 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. FOIA (1998). Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. Chem. doi:10.1007/s00424-018-2232-y, Woods, P. S., Tazi, M. F., Chesarino, N. M., Amer, A. O., and Davis, I. C. (2015). (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. JAMA 324 (8), 782793. 382 (18), 17081720. Cmp 6 (1), 1327. It's normal to experience side effects after a vaccine. Allergy Clin. (2001). Who (2021). Epub 2020 Jun 20. It has been reported that transepithelial ion transport in alveolar monolayers can be activated by K+ channel openers in vitro under physiological conditions (Leroy et al., 2006). 10.5582/ddt.2020.03070 (2020). The Serum and Glucocorticoid Kinase Sgk Increases the Abundance of Epithelial Sodium Channels in the Plasma Membrane of Xenopus Oocytes. J. Cel Physiol 234 (11), 2005720065. doi:10.3390/v4040557, Ho, T., Wu, S., Chen, J., Li, C., and Hsiang, C. (2007). Pharmacol. 46 (7), 835837. XC analyzed and reviewed the research articles as well as drafting the manuscript. 2020 Aug 14;15(1):103. doi: 10.1186/s13000-020-01017-8. Quantitative mRNA Expression Profiling of ACE 2, a Novel Homologue of Angiotensin Converting Enzyme. doi:10.3969/j.issn.10065725.2019.19.008, Rasaeifar, B., Gomez-Gutierrez, P., and Perez, J. J. (2020). (2021). Emodin Blocks the SARS Coronavirus Spike Protein and Angiotensin-Converting Enzyme 2 Interaction. 1, 2 More recently, six cases of. doi:10.1002/jmv.25848, Cutts, S., Talboys, R., Paspula, C., Prempeh, E., Fanous, R., and Ail, D. (2017). 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. Abdullah H., Heaney L. G., Cosby S. L., McGarvey L. P. A. Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage Is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients with Hypertension. Preprint. There are also several natural compounds which were previously shown to have positive effects on the lung edema-associated targets described in this paper (Zhou et al., 2006; Ho et al., 2007; Ji et al., 2014; Wang et al., 2015; Qu, 2019; Fan et al., 2020; Lung et al., 2020). Some patients also have leucopenia and lymphopenia, suggesting a weak immune function, and high prothrombin time and D-dimer level, indicating abnormal blood clotting function (Wang et al., 2020), which can all lead to lung damage and the severer pulmonary edema. 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). 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). J. Respir. Careers. 160, 105073. doi:10.1016/j.phrs.2020.105073, Maronde, R. F., Milgrom, M., Vlachakis, N. D., and Chan, L. (1983). Res. Amiloride. doi:10.1056/NEJMoa2007764, Bessac, B. F., and Jordt, S.-E. (2008). 383 (19), 18131826. Pharmaceuticals 13 (9), 259. doi:10.3390/ph13090259, Ren, J.-l., Zhang, A.-H., and Wang, X.-J. Chinese Medicine (TCMs), already widely used in China, may also be beneficial in addressing pulmonary edema in COVID-19 patients (Zhang et al., 2020; Yang et al., 2020d). Currently, these symptoms are the primary consequences of pulmonary virus infection. Zhongguo Zhong Yao Za Zhi 40 (21), 42454250. medRxiv. Repurposed drugs with proofs of antiviral effects for other viral infections have been tried. 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). doi:10.1136/bmj.m1432, Fleckenstein, A. 275(3), L631L635. eCollection 2021. JAMA 323 (20), 20522059. SN Compr. 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). Resolving D1 (Wang et al., 2014), generated from -3 fatty docosahexaenoic acids, and ursodeoxycholic acid (Niu et al., 2019) can stimulate AFC and Na-K-ATPase in LPS-induced pulmonary edema via alveolar epithelial sodium channel and ALX/cAMP/PI3K pathway, respectively. sharing sensitive information, make sure youre on a federal doi:10.1016/j.molimm.2018.09.003, Solymosi, E. A., Kaestle-Gembardt, S. M., Vadasz, I., Wang, L., Neye, N., Chupin, C. J. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. Am. (2016). Exp. A vision of coronavirus with the minimal set of structural proteins. COVID-19 Treatment and Diagnosis Guideline (7th version, trial) [Online]. Besides chemical drugs and compounds we discussed above, natural compounds and TCMs also possess promising antiviral effects against SARS-CoV-2 and had notably contribution in curing COVID-19, especially in alleviating pulmonary edema and preventing the disease development from mild to severe. HA is degraded by hyaluronidases encoded by HYAL1 and HYAL2, whose activity depends on CD44, an HA receptor (Harada and Takahashi, 2007). Federal government websites often end in .gov or .mil. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. (2020). Annu. doi:10.1111/j.1365-2125.1986.tb02859.x, Negrini, D., Passi, A., de Luca, G., and Miserocchi, G. (1998). The abnormal humoral metabolism and pulmonary edema contribute to the severity of symptoms and fatality of COVID-19 patients. doi:10.1165/ajrcmb.20.5.3382, Pascarella, G., Strumia, A., Piliego, C., Bruno, F., Del Buono, R., Costa, F., et al. 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. Clinical and Computed Tomographic Imaging Features of Novel Coronavirus Pneumonia Caused by SARS-CoV-2. (2013). Currently, many clinical trials are in progress to test coronavirus treatment, including new drugs and drug repurposing or repositioning. Crit. The abnormal humoral metabolism in lungs and the resulting pulmonary edema have become the main life-threatening factors in COVID-19 patients. (2021). Struct. CD44-dependent Intracellular and Extracellular Catabolism of Hyaluronic Acid by Hyaluronidase-1 and -2. The activation of -adrenergic receptor, especially 2 (Mutlu et al., 2004), was found to stimulate Na+ and fluid reabsorption. Response of Thiazide-Induced Hypokalemia to Amiloride. Dexmedetomidine can upregulate AQP-1 and AQP-5 expression in rats with acute lung injury induced by LPS and thus induce pulmonary edema (Jiang et al., 2015). Crit. 2023 Feb 13;11(2):435. doi: 10.3390/vaccines11020435. 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:10.1056/NEJMoa2028836, Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., and Wen, C. (2020). (2021). Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. (2020c). annals 99 (1), 1216. Med. Digestive System Is a Potential Route of COVID-19: an Analysis of Single-Cell Coexpression Pattern of Key Proteins in Viral Entry Process. 308 (11), L1136L1144. (2020). medRxiv.doi:10.1101/2020.05.20.20107607, Hu, K., Guan, W.-j., Bi, Y., Zhang, W., Li, L., Zhang, B., et al. (2015). TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity-A Structured Review. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19). The activities of the molecules in RAS are ruled by dynamic changes responding to an injury. Thromb. A., et al. Abnormal humoral metabolism is mainly manifested as imbalances of water and electrolytes. Calcium Antagonists and Their Mode of Action: an Historical Overview. Adipose-derived Exosomes Protect the Pulmonary Endothelial Barrier in Ventilator-Induced Lung Injury by Inhibiting the TRPV4/Ca2+ Signaling Pathway. HA is synthesized by HAS2. Immunol. doi:10.1016/j.jinf.2020.02.017, Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., et al. We also obtain PFTs in recovering COVID-19 patients with severe pulmonary involvement or COVID-19-related ARDS, which applies to many patients who required hospitalization. (2020). J. Biol. doi:10.1073/pnas.96.5.2514, Chow, Y.-H., Wang, Y., Plumb, J., O'Brodovich, H., and Hu, J. Studies have shown that MCTR1 (Han et al., 2020), PCTR1 (Zhang et al., 2020) and protectin DX (Zhuo et al., 2018), endogenously produced lipid mediators, can effectively improve PFC, ameliorate morphological damage, reduce lung inflammation, and increase sodium channel and Na-K-ATPase expression and activity in vivo and in vitro in lipopolysaccharide (LPS)-induced ARDS rats model. (2018). Available: https://covid19.who.int/ (Accessed March 31, 2021). Pediatr. However, preliminary reports showed that some ACE inhibitors and ARBs have no significant clinical benefits in treating COVID-19 (Richardson et al., 2020), while others showed protective effects among patients with pre-existing hypertension (Yang et al., 2020; Liu et al., 2020). Acad. In addition, potassium channels can act as oxygen sensors in alveolar epithelium and thus adjust lung function to environmental changes in O2 levels (Bartoszewski et al., 2017). (2015). 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). 291 (6), L1207L1219. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. Sci. Immunopharmacology and Immunotoxicology 36 (6), 420425. 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). Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. 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). Yes. B., and Matthay, M. A. It is likely that alveolar fluid clearance (AFC) failure plays a major role in the pathogenesis of pulmonary edema. Notably, both vaccines have strong safety profiles, with the most common adverse events including injection site reactions, fever, chills, fatigue, headache, and muscle and joint aches. doi:10.1007/s00018-007-6228-6, Itani, O. Lung Injury in COVID-19 Has Pulmonary Edema as an Important Component and Treatment with Furosemide and Negative Fluid Balance (NEGBAL) Decreases Mortality. Rep. 72 (6), 15091516. TABLE 3. (2020). Crit. Inhibiting these TRPs may benefit the treatment of pulmonary edema. However, further researches into the mode of action, efficacy and safety of these drugs are required. doi:10.1152/ajplung.00255.2019, Zhang, B.-M., Wang, Z.-B., Xin, P., Wang, Q.-H., Bu, H., and Kuang, H.-X. J.I. J. Investig. 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. J. Physiology-Lung Cell Mol. Involvement of Lung Interstitial Proteoglycans in Development of Hydraulic- and Elastase-Induced Edema. Authors doi:10.1002/jmv.25761, Luo, X., Ni, X., Lin, J., Zhang, Y., Wu, L., Huang, D., et al. Sci. The https:// ensures that you are connecting to the
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