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Infection of Mice with Influenza A/WSN/33 (H1N1) Virus Alters Alveolar Type II Cell Phenotype. 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%). J. Investig. Cause of COVID-19 pulmonary edema. Some natural compounds along with their antiviral and reducing pulmonary edema mechanisms are shown in Table 2. Physiol. Mil. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. However, clinical evidence showing that glucocorticoids can reduce pulmonary edema by regulating fluid absorption in alveolar and glucocorticoids is missing. Natural compounds can inhibit the binding between the virus and the ACE2 receptor of host cells. Creative Commons Attribution License (CC BY). EM did the language polishing. The abnormal expression of AQP is closely related to the abnormal alveolar fluid metabolism and the subsequent pulmonary fibrosis of COVID-19 patients. 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. Summary of potential TCM formulae against COVID-19. Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. 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. 158, 104850. doi:10.1016/j.phrs.2020.104850, Ma, Q., Qiu, M., Zhou, H., Chen, J., Yang, X., Deng, Z., et al. J. Huazhong Univ. doi:10.1152/ajplung.00373.2014, Hu, F., Chen, J., Chen, H., Zhu, J., Wang, C., Ni, H. B., et al. 1, 2 More recently, six cases of. 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However, as we discussed above, the inhibition of ENaC can also induce pulmonary edema and further studies are required to determine the potential use of ENaC inhibitors for COVID-19 treatment. doi:10.4049/jimmunol.1302421. 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). He had no cough, expectoration, nasal discharge or sore throat. Mol. 313 (5), L845L858. doi:10.1016/j.jinf.2020.02.017, Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., et al. Immunol. COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. 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). JAMA 323 (11), 10611069. . A pulmonary edema was the cause of the death of a woman who died short after a vaccine on Tuesday an autopsy has shown. Clinical and Computed Tomographic Imaging Features of Novel Coronavirus Pneumonia Caused by SARS-CoV-2. After internal reviews of the reports, the CDC "did not find any data suggesting a link between Covid-19 vaccines and tinnitus," an agency . official website and that any information you provide is encrypted Federal government websites often end in .gov or .mil. Bookshelf doi:10.1016/s2213-2600(20)30076-x, Yan, H., Valdes, A. M., Vijay, A., Wang, S., Liang, L., Yang, S., et al. An official website of the United States government. XC analyzed and reviewed the research articles as well as drafting the manuscript. Abstract Background Severe cardiogenic pulmonary edema is a . doi:10.1152/ajplung.1998.275.3.L631, Perkins, G. D., McAuley, D. F., Thickett, D. R., and Gao, F. (2006). Pharmacol. Respir. 10.1007/s42399-020-00610-8 Sci. Specific Pharmacology of Calcium in Myocardium, Cardiac Pacemakers, and Vascular Smooth Muscle. 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). N.Y. Acad. [Effect of Astragali Radix in Improving Early Renal Damage in Metabolic Syndrome Rats through ACE2/Mas Pathway]. Unable to load your collection due to an error, Unable to load your delegates due to an error. People with pneumonia, lung cancer, or heart disease may experience chest pain or wheezing. Nature 590, 635641. Fatigue, headache, chills, and new or worsened muscle pain were most common. Natl. J. Physiology-Lung Cell Mol. 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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. Ann. A type of pulmonary edema called neurogenic pulmonary edema can occur after a head injury, seizure or brain . Pulmonary Fibrosis and COVID-19: the Potential Role for Antifibrotic Therapy. CFTR and NKCC inhibitors show promise in treating pulmonary edema. medRxiv.doi:10.1101/2020.05.20.20107607, Hu, K., Guan, W.-j., Bi, Y., Zhang, W., Li, L., Zhang, B., et al. Angiotensin-converting Enzyme 2 in Acute Respiratory Distress Syndrome. ACIP reviews data. (2000). doi:10.1203/00006450-199908000-00014, Christ-Crain, M., Hoorn, E. J., Sherlock, M., Thompson, C. J., and Wass, J. However, among all current treatments mentioned above, little attention has been paid to the abnormal humoral metabolism and pulmonary edema, which is a key factor threatening patients lives. SODIUM CHANNELS IN ALVEOLAR EPITHELIAL CELLS: Molecular Characterization, Biophysical Properties, and Physiological Significance. CT images of COVID-19 patients revealed fluid and clear liquid jelly in their lungs, both closely linked to HA (Xu et al., 2020; Wang et al., 2020). 2021 Jun 7;12:664349. doi: 10.3389/fphar.2021.664349. 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). Acad. 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. Nat. MeSH Med. 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. Impaired Breakdown of Bradykinin and its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection. (2020b). Therefore, AQP-5 may be a promising drug target for treating abnormal humoral metabolism as well as lung injury caused by COVID-19. Immunol. It is likely that alveolar fluid clearance (AFC) failure plays a major role in the pathogenesis of pulmonary edema. SARS-CoV-2 is an enveloped RNA coronavirus of the genus , and is the seventh coronavirus which can infect human (Xu et al., 2020). Am. (2020). Acute Respiratory Distress Syndrome Leads to Reduced Ratio of ACE/ACE2 Activities and Is Prevented by Angiotensin-(1-7) or an Angiotensin II Receptor Antagonist. 2, 1019. Circulation 96 (6), 18471852. Res. Physiol. Res. The latest research revealed that alveolar macrophages, which normally play a protective role, may also be infected by SARS-CoV-2 and release T cell chemokines, resulting large amounts of T cells gathering in lung and generating IFN. (2021). Reaffirms recommendation for Janssen COVID-19 Vaccine. Currently, no specific drug has been developed to against COVID-19, although some existing drugs have been repurposed and approved for treating hospitalized patients (Ferner and Aronson, 2020; Schlagenhauf et al., 2020). Med. Further, ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). Since hypokalemia is a major issue in severe COVID-19 patients (Lippi et al., 2020), amiloride with its potassium-sparing diuretic activity (Bull and Laragh, 1968) can potentially be used to restore normal serum potassium concentrations (Maronde et al., 1983). 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. Dis. doi:10.1161/01.RES.0000247065.11756.19, Andr, E., Gatti, R., Trevisani, M., Preti, D., Baraldi, P., Patacchini, R., et al. (2016). (2020). Structure, Function, and Evolution of Coronavirus Spike Proteins. Pharmacol. Papi A, Stapleton RD, Shore PM, Bica MA, Chen Y, Larbig M, Welte T. Lung. Biochim. Mechanism of BK inducing pulmonary edema and potential drugs. 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. Bradykinin (BK) is an important cellular mediator that causes vasodilatation and leaky blood vessels, leading to vascular leakage and edema (de Maat et al., 2020). 2020. Glucocorticoids, especially dexamethasone, have already been applied in the clinical treatment of COVID-19. 383, 23332344. 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). Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-Threatening COVID-19. Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. FEBS Lett. Therefore, the S protein determines the host cell of the virus, regulates the viral attachment and fusion with the host cell membrane, and promotes cellular invasion. (2020). Neurosci. J. Transient Receptor Potential (TRP) Channels: a Clinical Perspective. 275(3), L631L635. 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). doi:10.4268/cjcmm20152124, Wang, Q., Zheng, X., Cheng, Y., Zhang, Y.-L., Wen, H.-X., Tao, Z., et al. Res. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Med. (2011). Rhinovirus Upregulates Transient Receptor Potential Channels in a Human Neuronal Cell Line: Implications for Respiratory Virus-Induced Cough Reflex Sensitivity. 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. 54 (3), 678811. We are grateful to all of the colleagues who have given critical comments on this work. Supportive cares for COVID-19 include respiratory support and circulatory support. 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). Symptoms that are common to all of these conditions include cough and shortness of breath. 19 (5), 305306. Abnormal humoral metabolism is mainly manifested as imbalances of water and electrolytes. (2020). J. Biol. Open Forum Infect. 156, 104761. doi:10.1016/j.phrs.2020.104761, Sartori, C., Allemann, Y., Duplain, H., Lepori, M., Egli, M., Lipp, E., et al. Was this helpful? Oxygen flows through a face mask or a flexible plastic tube with two openings (nasal cannula) that deliver oxygen to each nostril. Lancet Respir. [Med. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ann. doi:10.2174/1874467211306010003, Gabazza, E. C., Kasper, M., Ohta, K., Keane, M., D'Alessandro-Gabazza, C., Fujimoto, H., et al. Decreased Expression of Aquaporin-5 in Bleomycin-Induced Lung Fibrosis in the Mouse fibrosis in the Mouse. Allergol. (2020). Natl. J. 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S1 facilitates virus infection by binding to host receptors, and S2 regulates the membranes fusion to enable viral RNA entering into host cells for further replication. 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. Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential Front Pharmacol. Ion Channels of the Lung and Their Role in Disease Pathogenesis. By March 31st of 2021, a total of 128.54 million cases of severe Coronavirus Disease (COVID-19) have been diagnosed globally, and a total of 2.81 million people have died from the disease (WHO, 2021). Med. The Clinical Benefits of Chinese Patent Medicines against COVID-19 Based on Current Evidence. 92 (6), 693697. doi:10.1016/s0140-6736(20)30183-5, Hui, D. S. C., and Zumla, A. The general regulation approaches of AFC. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. However, further researches into the mode of action, efficacy and safety of these drugs are required. Chemical Composition and Pharmacological Mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): In Silico and Experimental Study. Multiple TCMs have been already clinical applied for COVID-19 in China and achieved high recovery rate. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. Thorax 69 (1), 4654. J. Physiology-Lung Cell Mol. Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. Life Sci. Coronavirus Disease 2019 Treatment A Review of Early and Emerging Options. 2 (6), 387396.doi:10.1038/35077544, Connors, J. M., and Levy, J. H. (2020). Some people experience no side effects after vaccination while many will experience mild side effects, such as pain, swelling at the injection site, a headache, chills or a fever. Physiol. Potassium channels up-regulate ENaC expression via activating KvLQT1 pathway so as to control AFC (Bardou et al., 2012). 2023 Feb 15;12(4):1542. doi: 10.3390/jcm12041542. The Add-On Effect of Chinese Herbal Medicine on COVID-19: A Systematic Review and Meta-Analysis. Proc. Sci. 34, 101658. doi:10.1016/j.tmaid.2020.101658. doi:10.1152/ajplung.1998.275.2.L414, Mutlu, G. M., Dumasius, V., Burhop, J., McShane, P. J., Meng, F. J., Welch, L., et al. As the infection progresses, the immune function is impaired, causing damage to multiple organs, additional complications, and eventually death (Yang et al., 2020). Clipboard, Search History, and several other advanced features are temporarily unavailable. Chloride Transport-Driven Alveolar Fluid Secretion Is a Major Contributor to Cardiogenic Lung Edema. 80 (4), 394400. Nat. This site needs JavaScript to work properly. doi:10.1152/physrev.1974.54.3.678, Steinritz, D., Stenger, B., Dietrich, A., Gudermann, T., and Popp, T. (2018). 8600 Rockville Pike Would you like email updates of new search results? You might run a fever and experience body aches, headaches and tiredness for a day or two. Virol. J. Physiology-Lung Cell Mol. (2004). (2020). FIGURE 1. 16 (10), 17081717. Pathological Findings of COVID-19 Associated with Acute Respiratory Distress Syndrome. 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. 61, 35. doi:10.1146/annurev.physiol.61.1.627, Matthay, M. A., Clerici, C., and Saumon, G. (2002). doi:10.3390/v4040557, Ho, T., Wu, S., Chen, J., Li, C., and Hsiang, C. (2007). Recombinant ACE2 was also reported to be a potential therapy in the clinical study of ARDS, which can lead to rapid decrease of plasma Ang II level and IL-6 expression. 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). The Potential Chemical Structure of antiSARSCoV2 RNAdependent RNA Polymerase. Potential drugs for normalizing humoral metabolism. doi:10.1152/ajplung.00085.2001, Ito, Y., Correll, K., Zemans, R. L., Leslie, C. C., Murphy, R. C., and Mason, R. J. Acad. (2020). doi:10.1055/s-0040-1712960, Deng, J., Wang, D.-x., Deng, W., Li, C.-y., Tong, J., and Ma, H. (2012). Its active absorption of Na+ is the main driving force of fluid clearance at birth and alveolar fluid absorption at adult stage (Bardou et al., 2012).
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