Impaired Breakdown of Bradykinin and its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection. TRP Functions in the Broncho-Pulmonary System. 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). Generalized Edema and Pseudothrombocytopenia After ChAdOx1 nCoV-19 COVID-19 Vaccination: A Case Report Reports of side effects of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasing worldwide. Exp. doi:10.1177/0004563220922255, Liu, Y., Huang, F., Xu, J., Yang, P., Qin, Y., Cao, M., et al. (2020a). Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area. SN Compr. Pflugers Arch. 92 (9), 14231424. A vision of coronavirus with the minimal set of structural proteins. COVID-DSNet: A novel deep convolutional neural network for detection of coronavirus (SARS-CoV-2) cases from CT and Chest X-Ray images. Am. Pulmonary vessels and perfusion are frequently abnormal in coronavirus disease 2019 (COVID-19) pneumonia and may point to a key role of pulmonary vascular pathology and hypoxemia in COVID-19. (2020). The available adenoviral vaccines appear to stimulate autoantibodies to platelet factor 4 (PF4), which . 388 (4), 421436. doi:10.1152/ajplung.00290.2014, Ji, G., Chen, R., and Zheng, J. Recently, several companies came out with vaccines against COVID-19 which have been approved for use. 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. Allergol. 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. Care Med. 46 (7), 835837. (2020). Optimizing Diagnostic Strategy for Novel Coronavirus Pneumonia, a Multi-center Study in Eastern China. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. [Med. Thorax 69 (1), 4654. Annu. Diagn Pathol. 158, 104850. doi:10.1016/j.phrs.2020.104850, Ma, Q., Qiu, M., Zhou, H., Chen, J., Yang, X., Deng, Z., et al. Am. Clipboard, Search History, and several other advanced features are temporarily unavailable. Mol. (Engl) 133 (9), 10511056. 2023 Feb 15;12(4):1542. doi: 10.3390/jcm12041542. However, clinical evidence showing that glucocorticoids can reduce pulmonary edema by regulating fluid absorption in alveolar and glucocorticoids is missing. FIGURE 6. doi:10.1146/annurev.pa.17.040177.001053, Fronius, M. (2013). Traditional Chinese Medicine for COVID-19 Treatment. 104, 81125. (2014). Dis. Specific Pharmacology of Calcium in Myocardium, Cardiac Pacemakers, and Vascular Smooth Muscle. Serum sodium shows a decrease trend in CODIV-19 development (Krolicka et al., 2020). 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. Br. Respir. The general regulation approaches of AFC. Chem. doi:10.1111/joim.13091, Passi, A., Negrini, D., Albertini, R., de Luca, G., and Miserocchi, G. (1998). J. Respir. doi:10.1016/j.jinf.2020.02.017, Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., et al. doi:10.1111/nyas.14472, Adil, M. S., Narayanan, S. P., and Somanath, P. R. (2020). doi:10.1056/NEJMoa013183, Sayegh, R., Auerbach, S. D., Li, X., Loftus, R. W., Husted, R. F., Stokes, J. (2012). Repurposing of Clinically Approved Drugs for Treatment of Coronavirus Disease 2019 in a 2019-novel Coronavirus-Related Coronavirus Model. Phytochemistry and Pharmacology of Genus Ephedra. Involvement of Lung Interstitial Proteoglycans in Development of Hydraulic- and Elastase-Induced Edema. Lab. However, the activation of matrix metalloproteinases (MMPs), which may be triggered by inflammatory factors (Shapiro, 2001), brings PG degradation, inducing pulmonary edema. doi:10.1002/jcp.28602, Otulakowski, G., Rafii, B., Bremner, H. R., and O'Brodovich, H. (1999). Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. 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). J. Endocrinol. Chem. 103, 7888. 161, 105290. doi:10.1016/j.phrs.2020.105290, Shi, Y., Wang, Y., Shao, C., Huang, J., Gan, J., Huang, X., et al. 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). Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. Toxin means various pathogenic microorganism and inflammatory storm presenting in infected patients, and dampness means the abnormal humoral metabolism like inflammatory exudation. 157, 104882. doi:10.1016/j.phrs.2020.104882, Zhang, H., and Baker, A. eCollection 2021. Transient Receptor Potential Vanilloid 4-Mediated Disruption of the Alveolar Septal Barrier. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma. Maresin Conjugates in Tissue Regeneration 1 Improves Alveolar Fluid Clearance by Upregulating Alveolar ENaC, Na, KATPase in Lipopolysaccharideinduced Acute Lung Injury. Angiotensin-converting Enzyme 2 in Acute Respiratory Distress Syndrome. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Abdullah H., Heaney L. G., Cosby S. L., McGarvey L. P. A. -, Ahmed M. H., Hassan A. J. Respir. The Origin, Transmission and Clinical Therapies on Coronavirus Disease 2019 (COVID-19) Outbreak - an Update on the Status. 318 (4), L723L741. doi:10.1001/jama.2020.1585, Wang, Q. Y., Liang, W., Jiang, C., Li, N. Y., Xu, H., Yang, M. N., et al. 192 (8), 37653777. doi:10.1161/01.cir.96.6.1847. Invited Review: Active Fluid Clearance from the Distal Air Spaces of the Lung. J. Clin. doi:10.1055/s-0040-1712960, Deng, J., Wang, D.-x., Deng, W., Li, C.-y., Tong, J., and Ma, H. (2012). 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. 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). Prc, N. H. C. o. t. (2020). 2021 Jan;93(1):94-96. doi: 10.1002/jmv.26152. (2020). J. Physiology-Lung Cell Mol. It not only can induce de novo synthesis of ENaC and affect ENaC regulatory pathway, but also has an impact on cytokines. J. Physiology-Lung Cell Mol. Am. Inflammatory cytokines and inflammatory storm in COVID-19 patients can strongly induce the expression of HA-synthase-2 (HAS2), while hyaluronidase level decreases, resulting in the accumulation of HA and inducing ARDS and pulmonary edema (Shi. The Role of Proteoglycans in Pulmonaryedema Development. Accessibility J. Physiology-Lung Cell Mol. Disclaimer. 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. Preprint. When there, the virus itself and virus-mediated protein-protein interactions lead to the lung inflammatory storm responsible for the observed increasing vascular permeability in lung and pulmonary edema (Tang et al., 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. 34, 101658. doi:10.1016/j.tmaid.2020.101658. PCTR1 Improves Pulmonary Edema Fluid Clearance through Activating the Sodium Channel and Lymphatic Drainage in Lipopolysaccharideinduced ARDS. (2005). doi:10.1136/bmj.m1432, Fleckenstein, A. doi: 10.1152/ajplung.00161.2020. Science 367 (6483), 12601263. (2020). 11 (1), 65. doi:10.1186/1465-9921-11-65, Han, J., Li, H., Bhandari, S., Cao, F., Wang, X. Y., Tian, C., et al. Immunol. Glucocorticoids, especially dexamethasone, have already been applied in the clinical treatment of COVID-19. A type of pulmonary edema called neurogenic pulmonary edema can occur after a head injury, seizure or brain . doi:10.1074/jbc.M100322200, Udugama, B., Kadhiresan, P., Kozlowski, H. N., Malekjahani, A., Osborne, M., Li, V. Y. C., et al. doi:10.1001/jama.2020.10044, Lippi, G., South, A. M., and Henry, B. M. (2020). Pathological Findings of COVID-19 Associated with Acute Respiratory Distress Syndrome. (2020a). Hormonal Regulation and Genomic Organization of the Human Amiloride-Sensitive Epithelial Sodium Channel Subunit Gene. Since the inhibition of ENaC induces pulmonary edema formation, targeting ENaC is rational in order to enhance fluid clearance from the alveoli. Alternative Names Lung congestion; Lung water; Pulmonary congestion; Heart failure - pulmonary edema Causes Pulmonary edema is often caused by congestive heart failure. N.Y. Acad. Was this helpful? Physiol. Science 367 (6485), 14441448. 2020 Jun 1;318(6):L1239-L1243. Protectin DX Increases Alveolar Fluid Clearance in Rats with Lipopolysaccharide-Induced Acute Lung Injury. XC analyzed and reviewed the research articles as well as drafting the manuscript. Physiol. Med. Chloride Transport-Driven Alveolar Fluid Secretion Is a Major Contributor to Cardiogenic Lung Edema. Circ. Life Sci. Systemic Reactions. 6, 331345. Moreover, the peripheral blood mononuclear lymphocyte of COVID-19 patients was also greatly improved, from 0.91 0.54 to 1.24 0.67 after being treated for a week, while there was no obvious change in control group (Hu et al., 2020). A Mechanistic Model and Therapeutic Interventions for COVID-19 Involving a RAS-Mediated Bradykinin Storm. (2004). (2001). 117 (3), 773783. Unable to load your collection due to an error, Unable to load your delegates due to an error. Quantitative mRNA Expression Profiling of ACE 2, a Novel Homologue of Angiotensin Converting Enzyme. For instance, angiotensin II (Ang II) can typically generate vasoconstriction and sodium retention when binding to the AGTR1 receptor and vice versa via the AGTR2 receptor (Garvin et al., 2020). Am. 54 (10), 774780. 19 (5), 305306. Med. 35 (5), 684688. HA is synthesized by HAS2. 4 (159), 159ra148. N.Y. Acad. FEBS Lett. 2021 Jun 7;12:664349. doi: 10.3389/fphar.2021.664349. doi:10.1007/s00210-014-1058-1, Grant, R. A., Morales-Nebreda, L., Morales-Nebreda, L., Markov, N. S., Swaminathan, S., Querrey, M., et al. Chansu Injection Improves the Respiratory Function of Severe COVID-19 Patients. Sci. Can COVID-19 cause pulmonary embolism? Int. 2023 Feb 14;14:1080962. doi: 10.3389/fphar.2023.1080962. 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. 12:664349. doi: 10.3389/fphar.2021.664349. (2013). (2021). Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. Physiol. The first treatment for acute pulmonary edema is oxygen. doi:10.1007/s00134-007-0962-y, Niu, F., Xu, X., Zhang, R., Sun, L., Gan, N., and Wang, A. ACS Nano 14 (4), 38223835. 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. Annu. This site needs JavaScript to work properly. 2, 26372646. Contact. sharing sensitive information, make sure youre on a federal People with pneumonia, lung cancer, or heart disease may experience chest pain or wheezing. The combination of the two can lead to pneumonia and other serious respiratory illnesses. A., and Cook, D. I. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. Multiple TCMs have been already clinical applied for COVID-19 in China and achieved high recovery rate. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Hongyue Ma, hongyuema@njutcm.edu.cn; Edyta Marcon, edyta.marcon@utoronto.ca; Jing Zhou, zhoujing_nj@126.com, Abnormal Lung Humoral Metabolism in COVID-19, Conventional Treatment of Pulmonary Edema in COVID-19 Patients, Putative Drug Targets for Pulmonary Edema in COVID-19 Patients, Natural Compounds and Traditional Chinese Medicines for the Treatment of Pulmonary Edema in COVID-19, https://doi.org/10.3389/fphar.2021.664349, https://www.frontiersin.org/articles/10.3389/fphar.2021.664349/full#supplementary-material, http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml. Liu Shen Capsule Shows Antiviral and Anti-inflammatory Abilities against Novel Coronavirus SARS-CoV-2 via Suppression of NF-b Signaling Pathway. Decreased Expression of Both the 1- and 2-subunits of the Na-K-ATPase Reduces Maximal Alveolar Epithelial Fluid Clearance. (2020c). J. Nat. doi:10.1165/rcmb.2002-0101OC, Kaneko, Y., and Szallasi, A. First, we could not entirely rule out infection, but results of blood cultures and COVID-19 testing were negative. (2020). B., and Matthay, M. A. (2020b). J. Physiology-Lung Cell Mol. TRPV4: Physiological Role and Therapeutic Potential in Respiratory Diseases. J. Physiol. 532 (1), 4. doi:10.1016/s0014-5793(02)03640-2, Heald-Sargent, T., and Gallagher, T. (2012). Clinical Characteristics of Coronavirus Disease 2019 in China. The Potential Chemical Structure of antiSARSCoV2 RNAdependent RNA Polymerase. In the meantime, we urgently need potent reduction in fatality of COVID-19. 181 (1), 5361. 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). (2003). Role of Drugs Used for Chronic Disease Management on Susceptibility and Severity of COVID19: A Large CaseControl Study. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-Threatening COVID-19. Immunopathol 38 (3), 321329. 308 (11), L1178L1188. 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:10.7150/ijbs.45538, Yang, Y., Shen, C., Li, J., Yuan, J., Yang, M., Wang, F., et al. SARS-CoV-2 may act in a similar way. Mohanty SK, Satapathy A, Naidu MM, Mukhopadhyay S, Sharma S, Barton LM, Stroberg E, Duval EJ, Pradhan D, Tzankov A, Parwani AV. 346, 16311636. 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). (2008). Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy. doi:10.1203/00006450-199908000-00014, Christ-Crain, M., Hoorn, E. J., Sherlock, M., Thompson, C. J., and Wass, J. Digestive System Is a Potential Route of COVID-19: an Analysis of Single-Cell Coexpression Pattern of Key Proteins in Viral Entry Process. doi:10.1007/s11596-015-1490-6, Jovanovi, S., Crawford, R. M., Ranki, H. J., and Jovanovi, A. 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. Mol. Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection. Circ. Before The COVID-19 Vaccine Development Landscape. (2020). (2020d). official website and that any information you provide is encrypted 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). TALLAHASSEE, Fla. Florida Surgeon General Joseph Ladapo personally altered a state-driven study about Covid-19 vaccines last year to suggest that some doses pose a . Some of these TCMs along with their constituent and antiviral and reducing pulmonary edema mechanisms are shown in Table 3. Ann. Careers. Respir. Ijerph 17 (15), 5320. doi:10.3390/ijerph17155320, Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. PMC Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. 310 (10), L928L939. (2020b). (2020). Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. doi:10.1016/s2213-2600(20)30079-5, Yang, Y., Islam, M. S., Wang, J., Li, Y., and Chen, X. Santos JLF, Zanardi P, Alo V, Dos Santos V, Bovone L, Rodriguez M, Magdaleno F, De Langhe V, Villoldo A, Martinez Souvielle R, Alconcher J, Quiros D, Milicchio C, Garcia Saiz E. J Clin Med. FIGURE 2. doi:10.1093/ofid/ofaa105/5811022, Minakata, Y., Suzuki, S., Grygorczyk, C., Dagenais, A., and Berthiaume, Y. Pharmacol. COVID-19: Urgent Reconsideration of Lung Edema as a Preventable Outcome: Inhibition of TRPV4 As a Promising and Feasible Approach. doi:10.1016/j.cmet.2021.01.002, Chen, S.-y., Bhargava, A., Mastroberardino, L., Meijer, O. C., Wang, J., Buse, P., et al. 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). 61, 35. doi:10.1146/annurev.physiol.61.1.627, Matthay, M. A., Clerici, C., and Saumon, G. (2002). 99 (9), 988995. 288, 198114. doi:10.1016/j.virusres.2020.198114, Krlicka, A. L., Kruczkowska, A., Krajewska, M., and Kusztal, M. A. Received: 05 February 2021; Accepted: 25 May 2021;Published: 07 June 2021. Physiol. doi:10.1016/j.jacbts.2021.01.002, Bardou, O., Priv, A., Migneault, F., Roy-Camille, K., Dagenais, A., Berthiaume, Y., et al. J. Pract. 2 (6), 387396.doi:10.1038/35077544, Connors, J. M., and Levy, J. H. (2020). 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. 54 (3), 678811. Rev. doi:10.1016/s2213-2600(20)30076-x, Yan, H., Valdes, A. M., Vijay, A., Wang, S., Liang, L., Yang, S., et al. CFTR inhibitors, like glibenclamide and CFTRinh-172 inhibitor, distinctly reduced absorptive alveolar fluid transport (Solymosi et al., 2013). J. Cel Mol Med 24 (8), 47364747. SN Compr. 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. J.I. 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). 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). It has been observed that MMP-2 and MMP-9, two most crucial MMPs in the lung are over-expressed in pulmonary edema (Negrini et al., 1996; Negrini et al., 1998; Passi et al., 1998), suggesting that MMPs may become a potential target for pulmonary edema treatment. 275 (2), L414L422. Anti-hypertensive Angiotensin II Receptor Blockers Associated to Mitigation of Disease Severity in Elderly COVID-19 Patients. Ion channels, AQPs, RAS, bradykinin and hyaluronic acid are factors influencing the pulmonary edema. However, further researches into the mode of action, efficacy and safety of these drugs are required. TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity-A Structured Review. Am J Physiol Lung Cell Mol Physiol. 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). 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). Pharmacol. A., Weber, D., Addison, E., Liedtke, W., and Townsley, M. I. (2020). The TRP Ion Channel Family. Structural Basis for the Recognition of SARS-CoV-2 by Full-Length Human ACE2. 157, 104820. doi:10.1016/j.phrs.2020.104820, Yang, X., Yu, Y., Xu, J., Shu, H., Xia, J. a., Liu, H., et al. doi:10.1074/jbc.274.18.12431, Schlagenhauf, P., Grobusch, M. P., Maier, J. D., and Gautret, P. (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. J. Cel Physiol 234 (11), 2005720065. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. Vaccines (Basel). Zhongguo Zhong Yao Za Zhi 40 (21), 42454250. RAS, especially several cleavage products of the peptide angiotensin (AGT) along with their receptors, maintains a balance of fluid volume and pressure. KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers can greatly recover AFC in mice intratracheally administrated verapamil, which is the first generation of the phenylalkylamine class of calcium channel antagonists (Fleckenstein, 1977; Nayler and Dillon, 1986), suggesting that K+ channel openers might be potential drugs for treating pulmonary edema (Han et al., 2010). Inhibiting these TRPs may benefit the treatment of pulmonary edema. Further, ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). doi:10.3969/j.issn.10065725.2019.19.008, Rasaeifar, B., Gomez-Gutierrez, P., and Perez, J. J. (2020). Heart Circ. Theaflavin from black tea was found to present a lower binding energy when it docks in the catalytic pocket of SARS-CoV-2 RdRp. 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). 1 (4), 100052. doi:10.1016/j.xcrm.2020.100052, Shen, C., Wang, Z., Zhao, F., Yang, Y., Li, J., Yuan, J., et al. Transl. J. Huazhong Univ. Mechanism of BK inducing pulmonary edema and potential drugs. 1480 (1), 73103. Authors Mabrouk Bahloul 1 . Ann. Resolvin D1 Stimulates Alveolar Fluid Clearance through Alveolar Epithelial Sodium Channel, Na,K-ATPase via ALX/cAMP/PI3K Pathway in Lipopolysaccharide-Induced Acute Lung Injury. Adult Respiratory Distress Syndrome. Rhinovirus Upregulates Transient Receptor Potential Channels in a Human Neuronal Cell Line: Implications for Respiratory Virus-Induced Cough Reflex Sensitivity. For patients recovering from COVID-19 who have persistent, progressive, or new respiratory symptoms, we obtain PFTs including spirometry, lung volumes, and diffusion capacity. It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. Efficacy and Safety of Lianhuaqingwen Capsules, a Repurposed Chinese Herb, in Patients with Coronavirus Disease 2019: A Multicenter, Prospective, Randomized Controlled Trial.