(2013). 110 (25), E2308E2316. TRPA1 distributes on C-fibers throughout the respiratory system (De Logu et al., 2016). SARS-CoV-2 invasion leads to alveolar and vascular epithelial cells damage impelling the formation of minimal thrombus, increasing pulmonary venous pressure and vascular permeability and leading to massive loss of tissue fluid. We are grateful to all of the colleagues who have given critical comments on this work. (2020). COVID-DSNet: A novel deep convolutional neural network for detection of coronavirus (SARS-CoV-2) cases from CT and Chest X-Ray images. Large Conductance Ca2+-Activated K+ Channels Sense Acute Changes in Oxygen Tension in Alveolar Epithelial Cells. Rev. The structure of coronavirus (Figure 1 A vision of coronavirus with the minimal set of structural proteins.) J. Clin. (2020). Purpose To investigate pulmonary vascular abnormalities at CT pulmonary angiography (CT-PE) in patients with coronavirus disease 2019 (COVID-19) pneumonia. (2021). Physiol. The -Agonist Lung Injury Trial (Balti). "It is the macroscopic image of an old myocardial infarction and pulmonary edema under further laboratory investigation," medical examiner Nikos Kalogrias reportedly said on Wednesday. Pathol. It has been revealed that COVID-19 patients treated with Lian-Hua-Qing-Wen capsules for 14days resulted in a considerably higher recovery rate of 91.5%, a dramatically shorter median time to symptom recovery of 7days than the control group, which applied conventional treatment (Hu et al., 2021). Pharmacol. Ursodeoxycholic Acid Stimulates Alveolar Fluid Clearance in LPSinduced Pulmonary Edema via ALX/cAMP/PI3K Pathway. 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. Symptoms that are common to all of these conditions include cough and shortness of breath. 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). JACC: Basic Translational Sci. Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. Endocrinology in the Time of COVID-19: Management of Diabetes Insipidus and Hyponatraemia. Therefore, the infection along with the rapid replication of SARS-CoV-2 causes a large amount of body fluid permeating through pulmonary alveoli, leading to ADRS. (2008). Amiloride, a prototypic inhibitor of ENaC, might also have a potential in treating COVID-19 patients. Besides those direct causes of COVID-19 pulmonary edema, there are other factors that can be described as abnormal humoral metabolism which can influence the AFC and PFC, resulting the manifestation of pulmonary edema (Figure 3 Cause of COVID-19 pulmonary edema). FIGURE 5. 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). (1999). Emodin Blocks the SARS Coronavirus Spike Protein and Angiotensin-Converting Enzyme 2 Interaction. Semin. (2020). Pharmacol. A vision of coronavirus with the minimal set of structural proteins. (1999). Acta (Bba) - Gen. It is worth mentioning that, except alveoli, which is widely known as the target tissue, cardiomyocyte can be infected as well. Physiol. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. Infection and replication process of SARS-CoV-2. TRPV4: Physiological Role and Therapeutic Potential in Respiratory Diseases. 96 (5), 25142519. 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. Repurposing Antimalarials and Other Drugs for COVID-19. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. WHO Coronavirus Disease (COVID-19) Dashboard [Online]. J. Med. 2020 Mar 23:3558887. doi: 10.2139/ssrn.3558887. 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. Rhinovirus Upregulates Transient Receptor Potential Channels in a Human Neuronal Cell Line: Implications for Respiratory Virus-Induced Cough Reflex Sensitivity. J. Physiol. Am J Physiol Lung Cell Mol Physiol. ), cell growth and death, as well as the degradation of damaged cells (Zhao et al., 2020). Transient Receptor Potential (TRP) Channels: a Clinical Perspective. It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. Am. PMC Clin. Arek Sarkissian. The frequency and severity of systemic adverse events was higher after dose 2 than dose 1. 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). Physiol. (2020). 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. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma. Physiol. Moreover, it has been revealed that exosomes derived from human adipocyte can inhibit TRPV4-mediated calcium influx and thus protect mice against ventilator-induced lung injury (Yu et al., 2020). 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. Maresin1 Stimulates Alveolar Fluid Clearance through the Alveolar Epithelial Sodium Channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 Pathway. As RAS plays an important role in PFC and AFC, astragaloside IV from Astragalus propinquus is able to protect kidney and respiratory by activating the ACE2-Ang-(17)-Mas pathway in RAS and improving ACE2, Ang-(17), Mas level (Wang et l., 2015; Qu, 2019). doi:10.1007/s43440-020-00132-z, Runfeng, L., Yunlong, H., Jicheng, H., Weiqi, P., Qinhai, M., Yongxia, S., et al. Hemost. Some others will likely be approved soon (Kaur and Gupta, 2020; Thanh Le et al., 2020). This site needs JavaScript to work properly. (Engl) 133 (9), 10511056. Br. Res. Association between Early Treatment with Qingfei Paidu Decoction and Favorable Clinical Outcomes in Patients with COVID-19: A Retrospective Multicenter Cohort Study. (2020). 92 (9), 14231424. 94 (8), 10911100. COPD and asthma cause your airways to swell and become blocked with mucus, which can make it hard to breathe. Biochim. 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. 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. Hormonal Regulation and Genomic Organization of the Human Amiloride-Sensitive Epithelial Sodium Channel Subunit Gene. K+ Channel Openers Restore Verapamil-Inhibited Lung Fluid Resolution and Transepithelial Ion Transport. Pharmacol. As Towne et al., (2001) reported, AQP-5 expression significantly declined during pulmonary inflammation and edema, and TNF- decreased AQP5 mRNA and protein expression levels via TNFR1 and NF-B pathway (Towne et al., 2001). doi:10.1007/s11427-020-1637-5, Xu, Y.-H., Dong, J.-H., An, W.-M., Lv, X.-Y., Yin, X.-P., Zhang, J.-Z., et al. This should ease some symptoms. Sci. (2018). 23 (5), 289301. (2016). Recombinant Human ACE2: Acing Out Angiotensin II in ARDS Therapy. 181 (1), 5361. -, Achanta S., Jordt S. E. (2020). Dis. We speculate that treatment of lung-edema will lead to a lower mortality in COVID-19 patients with severe infections. doi:10.1136/thoraxjnl-2013-203894, PubMed Abstract | CrossRef Full Text | Google Scholar, Achanta, S., and Jordt, S. E. (2020). 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. Notably, both vaccines have strong safety profiles, with the most common adverse events including injection site reactions, fever, chills, fatigue, headache, and muscle and joint aches. the Coronavirus Spike Protein and Acquisition of Fusion Competence. doi:10.1152/physrev.1974.54.3.678, Steinritz, D., Stenger, B., Dietrich, A., Gudermann, T., and Popp, T. (2018). 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). Accessibility The most commonly reported symptoms of post- COVID-19 syndrome include: Fatigue Symptoms that get worse after physical or mental effort Fever Lung (respiratory) symptoms, including difficulty breathing or shortness of breath and cough Other possible symptoms include: Specific Pharmacology of Calcium in Myocardium, Cardiac Pacemakers, and Vascular Smooth Muscle. doi:10.1038/labinvest.2016.150, Zhang, P. h., Han, J., Cao, F., Liu, Y. j., Tian, C., Wu, C. h., et al. 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). Yes. Mechanism of inhibiting ENaC inducing pulmonary edema. SODIUM CHANNELS IN ALVEOLAR EPITHELIAL CELLS: Molecular Characterization, Biophysical Properties, and Physiological Significance. J. Physiol. J. Physiology-Lung Cell Mol. 318 (4), L723L741. 46 (2), 208214. The site is secure. Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. 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). Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. Atractylenolide I Inhibits Lipopolysaccharide-Induced Inflammatory Responses via Mitogen-Activated Protein Kinase Pathways in RAW264.7 Cells. 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). 313 (5), L845L858. Mechanism of BK inducing pulmonary edema and potential drugs. 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. Virus. medRxiv. doi:10.1126/science.abb2507, Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., et al. The cystic fibrosis transmembrane conductance regulator (CFTR) and the ENaC located in the airway apical membranes and alveolar epithelial cells are essential in regulating lung fluid balance across airway as the chloride (Cl) and bicarbonate (HCO3) secretion conduits, and alveolar epithelia by sodium (Na+) ion absorption (Matalon, 1999; Birket et al., 2016; Londino et al., 2017). A. H. (2020). People with pneumonia, lung cancer, or heart disease may experience chest pain or wheezing. Cel Rep. Med. 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. doi:10.1056/NEJMoa013183, Sayegh, R., Auerbach, S. D., Li, X., Loftus, R. W., Husted, R. F., Stokes, J. The Role of Proteoglycans in Pulmonaryedema Development. (2020). doi:10.1152/ajplung.00376.2005, Li, C., Wang, P., Li, M., Zheng, R., Chen, S., Liu, S., et al. Am. COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. J. 310 (10), L928L939. COVID-19, an infectious disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a global reach. 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). 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.