A health care provider monitors the oxygen level. 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. Mechanism of BK inducing pulmonary edema and potential drugs. Epub 2020 Jun 29. 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. Xue-Bi-Jing injection may act in COVID-19 by anti-inflammatory, anticoagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms (Li et al., 2021). Respir. Rev. 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. 158 (6), 16211628. Clin. Pflugers Arch. J. Biol. J. Pract. (2020a). See this image and copyright information in PMC. Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. 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). Blood 135 (23), 20332040. 2021 Jun 7;12:664349. doi: 10.3389/fphar.2021.664349. Woman dies half an hour after vaccine: Autopsy shows pulmonary edema Theaflavin from black tea was found to present a lower binding energy when it docks in the catalytic pocket of SARS-CoV-2 RdRp. Br. J. Clin. Summary of potential TCM formulae against COVID-19. COVID-19 Vaccine-Induced Myocarditis: A Systemic Review and - PubMed eCollection 2023. Circulation 37 (1), 4553. 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. 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It shows the vaccine is teaching your body's immune system how to protect itself from the disease. 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. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Technol. Natl. doi:10.1016/j.cmet.2021.01.002, Chen, S.-y., Bhargava, A., Mastroberardino, L., Meijer, O. C., Wang, J., Buse, P., et al. 2023 Feb 13;11(2):435. doi: 10.3390/vaccines11020435. Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. 1 (4), 100052. doi:10.1016/j.xcrm.2020.100052, Shen, C., Wang, Z., Zhao, F., Yang, Y., Li, J., Yuan, J., et al. These cytokine storms can be treated with steroids, IL-1 antagonists, TNF inhibitors, and Janus kinase inhibitor (JAK) inhibitors (McCreary and Pogue, 2020). Cel Mol Biol 20 (5), 10281040. SARS-CoV-2 is an enveloped RNA coronavirus of the genus , and is the seventh coronavirus which can infect human (Xu et al., 2020). J. Intern. doi:10.1152/ajplung.00290.2014, Ji, G., Chen, R., and Zheng, J. Clipboard, Search History, and several other advanced features are temporarily unavailable. J. Pharmacol. Mol. Respir. Res. Dis. 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. Pharmacol. Res. Physiol. Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. Infect. Am J Physiol Lung Cell Mol Physiol. 50 (4), 113. Lancet Respir. Ion channels, AQPs, RAS, bradykinin and hyaluronic acid are factors influencing the pulmonary edema. 160, 105073. doi:10.1016/j.phrs.2020.105073, Maronde, R. F., Milgrom, M., Vlachakis, N. D., and Chan, L. (1983). doi:10.1007/s00018-007-6228-6, Itani, O. Fedratinib, an FDA approved JAK2 inhibitor, may be used to reduce the mortality associated with hyperinflammation by suppressing the production of several Th17 cytokines (i.e., IL1b and TNF-alpha, IL21, IL22, IL17) and the formation of pulmonary edema in combination with anti-viral drugs (Yang et al., 2020e). Chloride Transport-Driven Alveolar Fluid Secretion Is a Major Contributor to Cardiogenic Lung Edema. (2020). doi:10.1152/ajplung.00373.2014, Hu, F., Chen, J., Chen, H., Zhu, J., Wang, C., Ni, H. B., et al. Thorax 69 (1), 4654. Vaccination of Adults with Lung Disease Including Asthma | CDC Cepharanthine: a Review of the Antiviral Potential of a Japanese-approved Alopecia Drug in COVID-19. Epithelial Sodium Channel Regulated by Aldosterone-Induced Protein Sgk. 4 (159), 159ra148. doi:10.1007/s00424-018-2232-y, Woods, P. S., Tazi, M. F., Chesarino, N. M., Amer, A. O., and Davis, I. C. (2015). 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 blocked upper airway causes negative pressure in the lungs from trying to breathe through the blockage. (2020a). Protectin DX Increases Alveolar Fluid Clearance in Rats with Lipopolysaccharide-Induced Acute Lung Injury. (Imai et al., 2007; Zhang and Baker, 2017). 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. Chem. Systemic Reactions. SARS-CoV-2 may act in a similar way. (2020e). 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). Impaired Breakdown of Bradykinin and its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection. 10.1007/s42399-020-00610-8 2, 26372646. 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). (2015). (1998). N. Engl. Symptoms that are common to all of these conditions include cough and shortness of breath. Res. 532 (1), 4. doi:10.1016/s0014-5793(02)03640-2, Heald-Sargent, T., and Gallagher, T. (2012). 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 . Thorax 69 (1), 4654. J. Biol. Chem. JACC: Basic Translational Sci. Atractylenolide-I, the active component of atractylodes, could minimize the formation of IL-6 and TNF- (Ji et al., 2014), inhibiting the generation of inflammatory cytokines causing inflammatory response, thus lowering the possibility of developing pulmonary edema. 2020 Jul;57:102833. doi: 10.1016/j.ebiom.2020.102833. doi:10.1001/jama.2020.6775, Rogosnitzky, M., Okediji, P., and Koman, I. Ion Channels of the Lung and Their Role in Disease Pathogenesis. Rev. (1997). J. Physiology-Lung Cell Mol. doi:10.1101/2020.03.20.20039586, Londino, J. D., Lazrak, A., Collawn, J. F., Bebok, Z., Harrod, K. S., and Matalon, S. (2017). It promotes the clearance of surplus fluid in alveoli and keeps alveolar space dry (Wittekindt and Dietl, 2019). FIGURE 3. 17, 149166. 2021 May 7;8:644678. doi: 10.3389/fmed.2021.644678. COVID-19 and its Implications for Thrombosis and Anticoagulation. Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2 Vaccination in After getting vaccinated for COVID-19, you might experience some temporary symptoms similar to those you might notice when you get a flu shot, such as a sore, swollen arm where you got the shot. 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. Further, ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). (2021). 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. Biol. doi:10.1021/acsnano.0c02624, Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., and Veesler, D. (2020). COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. Pulmonary edema is an abnormal buildup of fluid in the lungs. Infection of Mice with Influenza A/WSN/33 (H1N1) Virus Alters Alveolar Type II Cell Phenotype. doi:10.1152/ajplung.00464.2004, Lung, J., Lin, Y. S., Yang, Y. H., Chou, Y. L., Shu, L. H., Cheng, Y. C., et al. ACS Nano 14 (4), 38223835. doi:10.1203/00006450-199908000-00014, Christ-Crain, M., Hoorn, E. J., Sherlock, M., Thompson, C. J., and Wass, J. COVID-19 Lung Damage | Johns Hopkins Medicine Arek Sarkissian. COVID-19: Evaluation and management of adults with - UpToDate 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). Science 367 (6485), 14441448. 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). doi:10.1016/j.jaci.2020.08.038, Keywords: COVID-19, pulmonary edema, abnormal lung humoral metabolism, syndrome coronavirus 2, drug, traditional Chinese medicine, Citation: Cui X, Chen W, Zhou H, Gong Y, Zhu B, Lv X, Guo H, Duan J, Zhou J, Marcon E and Ma H (2021) Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential. Moreover, the constituent Ephedra can trigger bronchodilation, relieve breathing disorders and alleviate pulmonary edema (Zhang et al., 2018). 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. Inhibiting these TRPs may benefit the treatment of pulmonary edema. It has been reported that infection with a respiratory-associated virus can significantly increase the expression and activity of TRPV1 (Abdullah et al., 2014). doi:10.1007/s00134-007-0962-y, Niu, F., Xu, X., Zhang, R., Sun, L., Gan, N., and Wang, A. (2020). Adv. (2020b). Cause of COVID-19 pulmonary edema. Exuberant Elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 Infection Is Associated with Disease Severity and Fatal Outcome. COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). (2020b). (2009). doi: 10.1152/ajplung.00161.2020. Immunol. Other therapeutic options including organ support, glucocorticoid therapy, nutritional support have been applied to COVID-19 clinical treatment without much knowledge of their efficacy. However, so far, no effective inhibitors have been developed against HAS2. doi:10.1152/ajplung.00085.2001, Ito, Y., Correll, K., Zemans, R. L., Leslie, C. C., Murphy, R. C., and Mason, R. J. A., Auerbach, S. D., Husted, R. F., Volk, K. A., Ageloff, S., Knepper, M. A., et al. (2020c). Nat. 1480 (1), 73103. Am. It is worth mentioning that, except alveoli, which is widely known as the target tissue, cardiomyocyte can be infected as well. Crit. Pharmacol. TABLE 3. Mol. doi:10.1152/ajplung.00244.2017, Looney, M. R., Sartori, C., Chakraborty, S., James, P. F., Lingrel, J. Treatment of Severe Cardiogenic Pulmonary Edema with Continuous doi:10.1056/NEJMoa2028836, Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., and Wen, C. (2020). We speculate that treatment of lung-edema will lead to a lower mortality in COVID-19 patients with severe infections. Gut 69 (6), 10101018. doi:10.1146/annurev.pa.17.040177.001053, Fronius, M. (2013). Sci. These supportive approaches have been shown to be beneficial as adjuvant therapies in COVID-19 patients. Bethesda, MD 20894, Web Policies New theories of the possible link between Covid shots and tinnitus are It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. However, it is still unclear how the vaccination will proceed and how fast can vaccinations be done. J. Respir. (2011). Sodium transport is the main ion transport involved in the AFC. Ijerph 17 (15), 5320. doi:10.3390/ijerph17155320, Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. COVID-19: Vaccine-induced immune thrombotic thrombocytopenia - UpToDate K+ Channel Openers Restore Verapamil-Inhibited Lung Fluid Resolution and Transepithelial Ion Transport. Pulmonary edema secondary to congestive heart failure doi:10.1152/ajplung.00395.2015, Birrell, M. A., Belvisi, M. G., Grace, M., Sadofsky, L., Faruqi, S., Hele, D. J., et al. What's the Link Between ARDS and COVID-19? - Health J. Respir. 63 (3), 457460. J. Med. Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. Physiol. Infection and replication process of SARS-CoV-2. 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Biol. ), cell growth and death, as well as the degradation of damaged cells (Zhao et al., 2020). doi:10.1073/pnas.96.5.2514, Chow, Y.-H., Wang, Y., Plumb, J., O'Brodovich, H., and Hu, J. Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. Am J Physiol Lung Cell Mol Physiol. 274 (53), 3783437839. doi:10.2174/1874467211306010003, Gabazza, E. C., Kasper, M., Ohta, K., Keane, M., D'Alessandro-Gabazza, C., Fujimoto, H., et al. Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. Oxygen flows through a face mask or a flexible plastic tube with two openings (nasal cannula) that deliver oxygen to each nostril. 388 (4), 421436. HA is synthesized by HAS2. Sepsis, another possible complication of COVID-19, can also cause lasting harm to the lungs and other organs. However, palpable lymphadenopathy commonly involving the axilla as an immune response to vaccination may present a clinical diagnostic dilemma especially in persons with . Studies have confirmed that selective TRPV4 activation induces rapid loss of alveolo-capillary barrier function and consequent alveolar edema formation (Alvarez et al., 2006). A type of pulmonary edema called neurogenic pulmonary edema can occur after a head injury, seizure or brain . the Coronavirus Spike Protein and Acquisition of Fusion Competence. Available: https://covid19.who.int/ (Accessed March 31, 2021). The .gov means its official. 161, 105290. doi:10.1016/j.phrs.2020.105290, Shi, Y., Wang, Y., Shao, C., Huang, J., Gan, J., Huang, X., et al. 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. 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). Pathol. Pharmacol. (2016). Pharmacol. Physiol. doi:10.1038/s41418-020-0530-3, Shi, Z., Ye, W., Zhang, J., Zhang, F., Yu, D., Yu, H., et al. (2020). (2020). Large Conductance Ca2+-Activated K+ Channels Sense Acute Changes in Oxygen Tension in Alveolar Epithelial Cells. With the presence of active basolateral Na+-K+-ATPase, inhibition of the entry of apical Na+ can generate a concentration gradient inducing the uptake of basolateral Na+ with Cl by Na+-K+-2Cl cotransporter (NKCC) and thus induce the apical secretion of Cl (Solymosi et al., 2013). doi:10.1001/jama.2020.1585, Wang, Q. Y., Liang, W., Jiang, C., Li, N. Y., Xu, H., Yang, M. N., et al. 110 (25), E2308E2316. doi:10.3969/j.issn.10065725.2019.19.008, Rasaeifar, B., Gomez-Gutierrez, P., and Perez, J. J. Acad. As the activation of AT1 receptor promotes the pulmonary edema, AT1 receptor blockers (ARBs) like losartan, valsartan may be effective in decreasing pulmonary edema. Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential Front Pharmacol. Yes. The -Agonist Lung Injury Trial (Balti). COPD and asthma cause your airways to swell and become blocked with mucus, which can make it hard to breathe. and transmitted securely. Studies showed that ENaC activators or stimulators can regulate ENaC-dependent fluid absorption in alveolar and pulmonary edema (Fronius, 2013). 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). 92 (6), 693697. CDC/FDA announce pause in use of Janssen COVID-19 Vaccine after identification of 6 cases of CVST with thrombocytopenia. Influenza Virus Infection Alters Ion Channel Function of Airway and Alveolar Cells: Mechanisms and Physiological Sequelae. Med. A recent review suggested that low-to-moderate doses of dexamethasone may lower the mortality rate in patients with severe infections (Ahmed and Hassan, 2020) and the latest finding indicated that the neutrophil-to-lymphocyte ratio determines the clinical efficacy of corticosteroid therapy in COVID-19 patients, as a neutrophil-to-lymphocyte ratio >6.11 associating with lower mortality in patients on corticosteroids (Cai et al., 2021). Electrolyte Imbalances in Patients with Severe Coronavirus Disease 2019 (COVID-19). CFTR and NKCC inhibitors show promise in treating pulmonary edema. The abnormal expression of AQP is closely related to the abnormal alveolar fluid metabolism and the subsequent pulmonary fibrosis of COVID-19 patients. *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. 12:664349. doi: 10.3389/fphar.2021.664349. EM did the language polishing. 155, 104743. doi:10.1016/j.phrs.2020.104743, Richardson, S., Hirsch, J. S., Narasimhan, M., Crawford, J. M., McGinn, T., Davidson, K. W., et al. Acad. Cell 181 (2), 281292. Also, thrombocytopenia and thrombosis have been mostly reported after AstraZeneca (ChAdOx1 nCoV-19) and Johnson & Johnson/Janssen COVID-19 vaccines [ 3 ].
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