doi:10.1056/NEJMoa2002032, Guo, Y.-R., Cao, Q.-D., Hong, Z.-S., Tan, Y.-Y., Chen, S.-D., Jin, H.-J., et al. 2020 Aug 14;15(1):103. doi: 10.1186/s13000-020-01017-8. Electrolyte Imbalances in Patients with Severe Coronavirus Disease 2019 (COVID-19). 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). Cough Reflex Testing with Inhaled Capsaicin and TRPV1 Activation in Asthma and Comorbid Conditions. Most of the published data about this association come from case reports and series. 92 (9), 14231424. Ann. Several cases of vaccine-induced thrombotic thrombocytopenia from a similar viral vector vaccine (Oxford-AstraZeneca [ChAdOx1 nCoV-19]) have been reported. BK is generated by cleavage of high-molecular-weight kininogen (HMWK) from plasma-kallikrein and binds to the BKB2 receptor, and thus results vascular hemorrhage (Garvin et al., 2020). Moreover, other drugs which can regulate immune system like hydroxychloroquine and azithromycin may also show effects in treating SARS-COV-2-induced pulmonary edema and their effectiveness in treating SARS-COV-2 infections should be further investigated. (2019). SODIUM CHANNELS IN ALVEOLAR EPITHELIAL CELLS: Molecular Characterization, Biophysical Properties, and Physiological Significance. A vision of coronavirus with the minimal set of structural proteins. Although NT-proBNP had an AUC of 0.89 in our patients with acute pulmonary edema, the study that reported an AUC of 0.96 did not include acute pulmonary edema or acute heart failure , and they excluded patients with eGFR < 60 mL/min/1.73 m 2, a group that constituted nearly half of our patients with hypertensive emergency. 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. doi:10.4049/jimmunol.1302421. A. H. (2020). Res. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. Care 21 (1), 305. doi:10.1186/s13054-017-1882-z, Zhang, H., Kang, Z., Gong, H., Xu, D., Wang, J., Li, Z., et al. The Origin, Transmission and Clinical Therapies on Coronavirus Disease 2019 (COVID-19) Outbreak - an Update on the Status. The functional inhibition of relevant lung enzymes and ion channels may disturb AFC, thus resulting pulmonary edema in COVID-19 patients. A health care provider monitors the oxygen level. doi:10.1152/ajpheart.1996.270.6.h2000, Negrini, D., Passi, A., and Moriondo, A. COVID-19 Treatment and Diagnosis Guideline (7th version, trial) [Online]. Rev. Biol. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. Na+/K+-ATPase and ion channels (sodium, potassium, AQPs, and TRPs) are all involved in the regulation of AFC. Evidences for TRPs as medium of lung injury are emerging from studies on various inhalational chemical threats (Achanta and Jordt, 2020). (2020). Mol. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area. Sci. 11. The project supported by Natural Science Foundation of China (grant number 81673563, 81102762, and 81274199); Open Project Program of Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXM-1-14, FJGJS-2015-15); Fund of Quality Standardization of Liu-Shen-Wan (BA2016104, ZYBZH-C-JS-30). Ann. Allergol. Maresin Conjugates in Tissue Regeneration 1 Improves Alveolar Fluid Clearance by Upregulating Alveolar ENaC, Na, KATPase in Lipopolysaccharideinduced Acute Lung Injury. Ion Channels of the Lung and Their Role in Disease Pathogenesis. Diagnosing COVID-19: The Disease and Tools for Detection. Toxicol. Eur. 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). J. Ethnopharmacology 265, 113301. doi:10.1016/j.jep.2020.113301, Li, F. (2016). Am. 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. J. Respir. (2014). Wiersinga, W. J., Rhodes, A., Cheng, A. C., Peacock, S. J., and Prescott, H. C. (2020). (2015). Exp. 11, 1708. doi:10.3389/fimmu.2020.01708, Thanh Le, T., Andreadakis, Z., Kumar, A., Gmez Romn, R., Tollefsen, S., Saville, M., et al. doi:10.5582/ddt.2020.03070, Ahmed, M. H., and Hassan, A. 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. (2016). Semin. Am. Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. 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. Potassium channels modulate the expression of ENaC. J. Med. - Eur. J. Respir. 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). (2020). Additionally, other major ADRs were potentially linked to the BNT162b2 mRNA COVID-19 vaccine, including central nervous system thrombosis, deep vein thrombosis, and pulmonary embolism [3-5]. doi:10.1136/thoraxjnl-2013-203894, PubMed Abstract | CrossRef Full Text | Google Scholar, Achanta, S., and Jordt, S. E. (2020). COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. Lab. These proteins include ion channels (Na channel, K channel and TRPV4), aquaporins (AQP), renin angiotensin system (RAS) proteins, and bradykinin/hyaluronic acid-related enzymes. As such, TRPV4 inhibition likely has protective and beneficial effect on mucus clearance and pulmonary edema. (2020). Comment on "Organprotective Effect of Angiotensinconverting Enzyme 2 and its Effect on the Prognosis of COVID19". Dis. medRxiv. The most common COVID-19 vaccine side effects include local injection site pain, fever, chills, myalgias, headache and fatigue, with resolution usually in a few days ( 1, 2 ). 103, 7888. FEBS Lett. Thus, the relieve of pulmonary edema should be one of the critical concerns in terms of the treatment of COVID-19 patients. It is known that SARS-CoV-2 invades human cells by binding angiotensin-converting enzyme-2 (ACE-2) receptor and other membrane ectopeptidases (Xu et al., 2020). 388 (4), 421436. As such, the S protein is essential for viral infection (Heald-Sargent and Gallagher, 2012; Li, 2016; Walls et al., 2020). Chem. Existing drugs and inhibitors targeting the components of humoral metabolism may serve as potential treatments for COVID-19 and should be further investigated. Med. Physiol. Chills and swollen lymph nodes can also occur. Jiangsu Qing Lan Project for Young Academic Leaders of China. 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. doi:10.1001/jama.2020.4783, Shi, N., Liu, B., Liang, N., Ma, Y., Ge, Y., Yi, H., et al. J. Med. Med. Zhang J, Zhou N, Wang Y, Liu T, Cao Y, Feng W, Zheng X. JAMA 323 (20), 20522059. So far, only remdesivir was approved by FDA for the compassionate use in severe infected COVID-19 patients (Beigel et al., 2020). Amiloride, a prototypic inhibitor of ENaC, might also have a potential in treating COVID-19 patients. Since the inhibition of ENaC induces pulmonary edema formation, targeting ENaC is rational in order to enhance fluid clearance from the alveoli. Arek Sarkissian. Pharmacol. 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. Epub 2020 May 13. Pharmacol. Sodium transport is the main ion transport involved in the AFC. (2020). Diagn Pathol. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. (2020e). 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). Please enable it to take advantage of the complete set of features! Nervous system conditions or surgeries. Pathological Findings of COVID-19 Associated with Acute Respiratory Distress Syndrome. Some of these TCMs along with their constituent and antiviral and reducing pulmonary edema mechanisms are shown in Table 3. annals 99 (1), 1216. CFTR and NKCC inhibitors show promise in treating pulmonary edema. Ijerph 17 (15), 5320. doi:10.3390/ijerph17155320, Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. Mechanism of inhibiting ENaC inducing pulmonary edema. Currently, many clinical trials are in progress to test coronavirus treatment, including new drugs and drug repurposing or repositioning. Woman dies half an hour after vaccine: Autopsy shows pulmonary edema EBioMedicine. Blood 135 (23), 20332040. B., and Matthay, M. A. doi:10.1182/blood.2020006000, Couto, M., de Diego, A., Perpii, M., Delgado, L., and Moreira, A. doi:10.1126/science.abb2762, Yang, G., Tan, Z., Zhou, L., Yang, M., Peng, L., Liu, J., et al. It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. *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. J. Biol. The combination of the two can lead to pneumonia and other serious respiratory illnesses. doi:10.1021/acsnano.0c02624, Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., and Veesler, D. (2020). Clipboard, Search History, and several other advanced features are temporarily unavailable. However, so far, no effective inhibitors have been developed against HAS2. Hyponatremia in Infectious Diseases-A Literature Review. (2020a). J. Endocrinol. 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). 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). (1985) 93 (4), 15331541. 157, 104882. doi:10.1016/j.phrs.2020.104882, Zhang, H., and Baker, A. (2020a). 382 (18), 17081720. doi:10.1136/bmj.m1432, Fleckenstein, A. The general regulation approaches of AFC. Clin. Severe Acute Respiratory Syndrome. Physiol. Cell. 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). Immune responses to COVID-19 vaccinations may trigger acute exacerbations in idiopathic pulmonary fibrosis among susceptible patients, according to data published in the American Journal of. However, the efficacy and safety of these drugs in COVID-19 patients are unclear. Am. Unable to load your collection due to an error, Unable to load your delegates due to an error. J. Biol. Careers. Trav. 383, 23332344. Traditional Chinese Medicine for COVID-19 Treatment. 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. See this image and copyright information in PMC. The Role of Proteoglycans in Pulmonaryedema Development. JAMA 249 (2), 237241. Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2 Vaccination in COVID19 Diagnosis and Management: a Comprehensive Review. Physiol. JAMA 323 (16), 15821589. (2020). doi:10.1161/CIRCRESAHA.107.168724, Yin, J., Michalick, L., Tang, C., Tabuchi, A., Goldenberg, N., Dan, Q., et al. The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2021.664349/full#supplementary-material, Abdullah, H., Heaney, L. G., Cosby, S. L., and McGarvey, L. P. A. Clin. 308 (11), L1178L1188. Who (2021). 64 (15), 20062012. (2015). Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection.