11. Physiol. Repurposed drugs with proofs of antiviral effects for other viral infections have been tried. medRxiv. COVID-19 Infection: the Perspectives on Immune Responses. doi:10.1002/jcp.29758, Zhang, W., Xia, X., Reisenauer, M. R., Rieg, T., Lang, F., Kuhl, D., et al. Proc. J. Physiology-Lung Cell Mol. Epithelial Sodium Channel Regulated by Aldosterone-Induced Protein Sgk. SODIUM CHANNELS IN ALVEOLAR EPITHELIAL CELLS: Molecular Characterization, Biophysical Properties, and Physiological Significance. Care Med. Disclaimer. Pharmacol. (2020). Ursodeoxycholic Acid Stimulates Alveolar Fluid Clearance in LPSinduced Pulmonary Edema via ALX/cAMP/PI3K Pathway. However, the efficacy and safety of these drugs in COVID-19 patients are unclear. doi:10.1152/ajplung.00078.2015, Wsten-van Asperen, R. M., Lutter, R., Specht, P. A., Moll, G. N., van Woensel, J. Pulmonary Edema. 64 (15), 20062012. The activation of -adrenergic receptor, especially 2 (Mutlu et al., 2004), was found to stimulate Na+ and fluid reabsorption. doi:10.1001/jama.2020.4783, Shi, N., Liu, B., Liang, N., Ma, Y., Ge, Y., Yi, H., et al. Pharmacol. doi:10.3969/j.issn.10065725.2019.19.008, Rasaeifar, B., Gomez-Gutierrez, P., and Perez, J. J. 1, 2 More recently, six cases of. 10.1136/thoraxjnl-2013-203894 A., Weber, D., Addison, E., Liedtke, W., and Townsley, M. I. EM did the language polishing. Dis. As such, the S protein is essential for viral infection (Heald-Sargent and Gallagher, 2012; Li, 2016; Walls et al., 2020). 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). The Clinical Benefits of Chinese Patent Medicines against COVID-19 Based on Current Evidence. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. 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. 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). A pulmonary edema was the cause of the death of a woman who died short after a vaccine on Tuesday an autopsy has shown. Thus, the relieve of pulmonary edema should be one of the critical concerns in terms of the treatment of COVID-19 patients. 10.1101/2020.02.13.20022673 The Potential Chemical Structure of antiSARSCoV2 RNAdependent RNA Polymerase. The Serum and Glucocorticoid Kinase Sgk Increases the Abundance of Epithelial Sodium Channels in the Plasma Membrane of Xenopus Oocytes. Life Sci. (2020). 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. Acad. Therefore, drugs targeted at the humoral mechanisms might turn out to be highly effective against SARS-COV-2 infections. (2020). This should ease some symptoms. doi:10.1111/nyas.14472, Adil, M. S., Narayanan, S. P., and Somanath, P. R. (2020). Not everyone gets side effects. Epub 2022 Oct 17. 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. Impact of -adrenergic Agonist on Na+ Channel and Na+-K+-ATPase Expression in Alveolar Type II Cells. 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. - Eur. Drug Discov. Papi A, Stapleton RD, Shore PM, Bica MA, Chen Y, Larbig M, Welte T. Lung. B., et al. 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). Chin. doi:10.2174/1874467211306010003, Gabazza, E. C., Kasper, M., Ohta, K., Keane, M., D'Alessandro-Gabazza, C., Fujimoto, H., et al. doi:10.1016/j.bbagen.2005.09.009, Zhuo, X.-J., Hao, Y., Cao, F., Yan, S.-F., Li, H., Wang, Q., et al. A., Auerbach, S. D., Husted, R. F., Volk, K. A., Ageloff, S., Knepper, M. A., et al. Can COVID-19 cause pulmonary embolism? Mil. N. Engl. Sci. Clin. COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. (2020a). Clin. Atractylenolide I Inhibits Lipopolysaccharide-Induced Inflammatory Responses via Mitogen-Activated Protein Kinase Pathways in RAW264.7 Cells. (2020c). Effect and Mechanism of Astragaloside A on Acute Respiratory Failure in Rats. (2007). JAMA 323 (16), 15821589. Pathol. 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. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. Further studies may determine if CD44 inhibitors can be of use to in COVID-19. medRxiv. Care Med. An official website of the United States government. The https:// ensures that you are connecting to the People with pneumonia, lung cancer, or heart disease may experience chest pain or wheezing. FIGURE 5. Moreover, the constituent Ephedra can trigger bronchodilation, relieve breathing disorders and alleviate pulmonary edema (Zhang et al., 2018). 108 (6), 11851194. No use, distribution or reproduction is permitted which does not comply with these terms. (2011). Inhibition of ACE2 by SARS-CoV-2 impairs the hydrolysis of des-arg9-bradykinin. J. Pract. HA-related hydrogel has been found in both, ARDS and SARS. 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. Biochem. 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. It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. Structure, Function, and Evolution of Coronavirus Spike Proteins. Clin. N.Y. Acad. Involvement of Lung Interstitial Proteoglycans in Development of Hydraulic- and Elastase-Induced Edema. Careers. 46 (2), 208214. doi:10.1074/jbc.M100322200, Udugama, B., Kadhiresan, P., Kozlowski, H. N., Malekjahani, A., Osborne, M., Li, V. Y. C., et al. 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. 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. 46 (7), 835837. 50 (4), 113. doi:10.1203/00006450-199908000-00014, Christ-Crain, M., Hoorn, E. J., Sherlock, M., Thompson, C. J., and Wass, J. 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). 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). FEBS Lett. (Imai et al., 2007; Zhang and Baker, 2017). RNA-dependent RNA polymerase (RdRp) is a crucial protease that catalyzes RNA replication from RNA templates and is an appealing therapeutic target. Yes. (1977). et al., 2020). Diagnosing COVID-19: The Disease and Tools for Detection. You might run a fever and experience body aches, headaches and tiredness for a day or two. *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. Pain at the injection site had completely resolved within 2 days. (2004). 54 (3), 678811. 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. Pharmacol. Lung Cel Mol Physiol 282, L631L641. (2015). Infection, pulmonary edema, lung cancer, aspiration, and pulmonary hemorrhage are some of the diseases that can cause consolidation. (1999). 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. Some natural compounds along with their antiviral and reducing pulmonary edema mechanisms are shown in Table 2. Physiol. SN Compr. J. Med. Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. It not only can induce de novo synthesis of ENaC and affect ENaC regulatory pathway, but also has an impact on cytokines. Am. 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). Consequently, drugs that can normalize humoral metabolism should be clinically evaluated for their use in the treatment of COVID-19 patients (Table 1). doi:10.1001/jama.2020.6775, Rogosnitzky, M., Okediji, P., and Koman, I. (2020c). 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). (2009). Amiloride, a prototypic inhibitor of ENaC, might also have a potential in treating COVID-19 patients. His lab findings and clinical course were consistent with those of MIS after COVID-19 vaccination. Lancet Respir. doi:10.1111/j.1365-2125.1986.tb02859.x, Negrini, D., Passi, A., de Luca, G., and Miserocchi, G. (1998). The Neutrophil-To-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19. (Engl) 133 (9), 10511056. Cryptotanshinone Inhibits Endothelin-1 Expression and Stimulates Nitric Oxide Production in Human Vascular Endothelial Cells. Res. RAS plays a significant role in ARDS as well as pulmonary edema processes. However, it is still unclear how the vaccination will proceed and how fast can vaccinations be done. National Library of Medicine Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. Biophys. 1 (4), 100052. doi:10.1016/j.xcrm.2020.100052, Shen, C., Wang, Z., Zhao, F., Yang, Y., Li, J., Yuan, J., et al. Chloride Transport-Driven Alveolar Fluid Secretion Is a Major Contributor to Cardiogenic Lung Edema. 181 (1), 5361. doi:10.1007/s11596-015-1490-6, Jovanovi, S., Crawford, R. M., Ranki, H. J., and Jovanovi, A. doi:10.1152/ajplung.00244.2017, Looney, M. R., Sartori, C., Chakraborty, S., James, P. F., Lingrel, J. Rev. Phytomedicine 85, 153242. doi:10.1016/j.phymed.2020.153242, Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. It is likely that alveolar fluid clearance (AFC) failure plays a major role in the pathogenesis of pulmonary edema. Adipose-derived Exosomes Protect the Pulmonary Endothelial Barrier in Ventilator-Induced Lung Injury by Inhibiting the TRPV4/Ca2+ Signaling Pathway. J. Physiology-Lung Cell Mol. J. Physiology-Lung Cell Mol. doi:10.1146/annurev.pa.17.040177.001053, Fronius, M. (2013). Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. doi:10.1152/ajplung.1998.275.3.L631, Perkins, G. D., McAuley, D. F., Thickett, D. R., and Gao, F. (2006). Br. J. Physiology-Lung Cell Mol. Pulmonary capillary leak syndrome following COVID-19 virus infection. FIGURE 2. Pharmacol. TRPV4: Physiological Role and Therapeutic Potential in Respiratory Diseases. J. Med. Optimizing Diagnostic Strategy for Novel Coronavirus Pneumonia, a Multi-center Study in Eastern China. (2010). and transmitted securely. Chills and swollen lymph nodes can also occur. 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. Chin. Med. J. Endocrinol. doi:10.1016/j.jacbts.2021.01.002, Bardou, O., Priv, A., Migneault, F., Roy-Camille, K., Dagenais, A., Berthiaume, Y., et al. Lancet Respir. Acad. Sci. Am. 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). 2021 May 7;8:644678. doi: 10.3389/fmed.2021.644678. Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. Med. 8 (5), 475481. Blood 135 (23), 20332040. doi:10.1152/ajplung.00290.2014, Ji, G., Chen, R., and Zheng, J. getting a COVID-19 vaccine is one way to lower the chance of developing . Clipboard, Search History, and several other advanced features are temporarily unavailable. Immune-modulatory agents, supportive cares, and antiviral drugs have been tested as COVID-19 treatments in patients with severe infections (Pascarella et al., 2020; Ren et al., 2020). The abnormal expression of AQP is closely related to the abnormal alveolar fluid metabolism and the subsequent pulmonary fibrosis of COVID-19 patients. It has already been shown that the dysregulated release of cytokines is one of the key factors behind poor outcomes in COVID-19 patients. 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. 74 (2), 92101. (2003). J. Respir. Proc. The University of Connecticut Foundation, Inc. Office of Development and Alumni Relations 10 Talcott Notch Road Suite 100 Farmington, CT 06032 Med. Moreover, lower expression of alveolar Na-K-ATPase promotes pulmonary edema, and when the expression of Na-K-ATPase 1- and 2-subunits decreases, maximal alveolar epithelial fluid clearance is reduced (Looney et al., 2005). (2020). (2020). 11, 1708. doi:10.3389/fimmu.2020.01708, Thanh Le, T., Andreadakis, Z., Kumar, A., Gmez Romn, R., Tollefsen, S., Saville, M., et al. 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). Infection of Mice with Influenza A/WSN/33 (H1N1) Virus Alters Alveolar Type II Cell Phenotype. 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). J. Infect. Science 367 (6485), 14441448. 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 . Rhinovirus Upregulates Transient Receptor Potential Channels in a Human Neuronal Cell Line: Implications for Respiratory Virus-Induced Cough Reflex Sensitivity. J. Physiol. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. 383 (19), 18131826. Clinical Characteristics of Coronavirus Disease 2019 in China. Association between Early Treatment with Qingfei Paidu Decoction and Favorable Clinical Outcomes in Patients with COVID-19: A Retrospective Multicenter Cohort Study. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. TGF--induced IL-6 prevents development of acute lung injury in influenza A virus-infected F508del CFTR-heterozygous mice. 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. Clinical Course and Outcomes of Critically Ill Patients with SARS-CoV-2 Pneumonia in Wuhan, China: a Single-Centered, Retrospective, Observational Study. Kiener M, Roldan N, Machahua C, Sengupta A, Geiser T, Guenat OT, Funke-Chambour M, Hobi N, Kruithof-de Julio M. Front Med (Lausanne). doi:10.1016/j.resp.2011.11.009, Fan, H.-H., Wang, L.-Q., Liu, W.-L., An, X.-P., Liu, Z.-D., He, X.-Q., et al. Currently, these symptoms are the primary consequences of pulmonary virus infection. Res. doi:10.1152/ajplung.00285.2017, Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., et al. doi:10.1016/j.antiviral.2006.04.014, Hofer, C. C., Woods, P. S., and Davis, I. C. (2015). Jiangsu Qing Lan Project for Young Academic Leaders of China. Am. (2020e). Am. JAMA 323 (20), 20522059. Immunopathol 38 (3), 321329. Toxin means various pathogenic microorganism and inflammatory storm presenting in infected patients, and dampness means the abnormal humoral metabolism like inflammatory exudation. -, Ai J.-W., Zhang H.-C., Xu T., Wu J., Zhu M., Yu Y.-Q., et al. CFTR inhibitors, like glibenclamide and CFTRinh-172 inhibitor, distinctly reduced absorptive alveolar fluid transport (Solymosi et al., 2013). Decreased Expression of Both the 1- and 2-subunits of the Na-K-ATPase Reduces Maximal Alveolar Epithelial Fluid Clearance. All authors contributed to manuscript revision, read, and approved the submitted version. doi:10.1152/japplphysiol.01210.2001, McCreary, E. K., and Pogue, J. M. (2020). Anti-hypertensive Angiotensin II Receptor Blockers Associated to Mitigation of Disease Severity in Elderly COVID-19 Patients. Dexmedetomidine Alleviates Pulmonary Edema by Upregulating AQP1 and AQP5 Expression in Rats with Acute Lung Injury Induced by Lipopolysaccharide. Maresin1 Stimulates Alveolar Fluid Clearance through the Alveolar Epithelial Sodium Channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 Pathway. Comment on "Organprotective Effect of Angiotensinconverting Enzyme 2 and its Effect on the Prognosis of COVID19". Recently, several companies came out with vaccines against COVID-19 which have been approved for use. Physiol. Am. doi:10.1161/01.RES.0000247065.11756.19, Andr, E., Gatti, R., Trevisani, M., Preti, D., Baraldi, P., Patacchini, R., et al. Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. Accessibility Am. Med. Physiol. J. Res. 346, 16311636. Cel Mol Biol 20 (5), 10281040. Clin. 8600 Rockville Pike 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). Convalescent plasma have been initially shown to be beneficial for COVID-19 patients with severe infection stabilizing the immune system (Shen et al., 2020), but the subsequent randomized controlled trial did not show significant improvement within 28days (Li et al., 2020). 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). Infection and replication process of SARS-CoV-2. 275(3), L631L635. medRxiv.doi:10.1101/2020.05.20.20107607, Hu, K., Guan, W.-j., Bi, Y., Zhang, W., Li, L., Zhang, B., et al. (2020). doi:10.1016/s0140-6736(20)30183-5, Hui, D. S. C., and Zumla, A. Regardless, it seems reasonable that antiviral therapy might be adopted to patients with high risk factors as early as possible rather than wait for severe manifestation of the disease. medRxiv. J. Physiology-Lung Cell Mol. Med. 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). (2021). Inhibiting these TRPs may benefit the treatment of pulmonary edema. The -Agonist Lung Injury Trial (Balti). Int. Ther. 183 (1), G9G15. Remdesivir for the Treatment of Covid-19 - Final Report. Am. (2020a). 173 (3), 281287. 94 (8), 10911100. Am. Pharmacol. EBioMedicine. J. Cel Mol Med 24 (8), 47364747. 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. 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. J. Respir. CD44-dependent Intracellular and Extracellular Catabolism of Hyaluronic Acid by Hyaluronidase-1 and -2. travis beyond scared straight basketball, mizunos 16 craft cit invisible item frame pack,
Charles Ingalls Descendants Today, Articles P