pulmonary edema and covid vaccine

Researches proved that SARS-CoV-2 can directly infect human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as an engineered heart tissue (EHT), in cellular and organ level respectively, suggesting that the virus can replicate rapidly in the cardiomyocytes, infecting other cardiomyocytes, contributing to cardiomyocyte cell death, myocardial inflammation and even heart failure (Sharma et al., 2020; Bailey et al., 2021). 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: Pharmacol. J. Pract. Thus, PGs play a key role in the formation of pulmonary edema. Moreover, as a retrospective multicenter cohort study reported, early treatment with Qing-Fei-Pai-Du Decoction associated with better outcomes, faster recovery, and a shorter duration of hospital stay (Shi et al., 2020a). Amiloride, a prototypic inhibitor of ENaC, might also have a potential in treating COVID-19 patients. (2020). Liu Shen Capsule Shows Antiviral and Anti-inflammatory Abilities against Novel Coronavirus SARS-CoV-2 via Suppression of NF-b Signaling Pathway. Multiple TCMs have been already clinical applied for COVID-19 in China and achieved high recovery rate. Rev. 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). (2019). Transient Receptor Potential Channels in Pulmonary Chemical Injuries and as Countermeasure Targets. J. Med. doi:10.7150/ijbs.45538, Yang, Y., Shen, C., Li, J., Yuan, J., Yang, M., Wang, F., et al. Zhongguo Zhong Yao Za Zhi 40 (21), 42454250. J. Appl. eCollection 2021. 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. Diagnosing COVID-19: The Disease and Tools for Detection. Original Article Antibody Responses to Haemophilus influenzae Type b Vaccines in Men with Human . Med. Studies showed that ENaC activators or stimulators can regulate ENaC-dependent fluid absorption in alveolar and pulmonary edema (Fronius, 2013). In the meantime, we urgently need potent reduction in fatality of COVID-19. Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-Threatening COVID-19. Structural Basis for the Recognition of SARS-CoV-2 by Full-Length Human ACE2. (1999). Aquaporins in the Lung. Mil. See this image and copyright information in PMC. doi:10.1101/2020.03.31.20038935, Yang, R., Liu, H., Bai, C., Wang, Y., Zhang, X., Guo, R., et al. 2020. (2021). It shows the vaccine is teaching your body's immune system how to protect itself from the disease. TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity-A Structured Review. 274, L203L211. (2013). Calcium Antagonists and Their Mode of Action: an Historical Overview. 276 (22), 1865718664. PMC Abdullah H., Heaney L. G., Cosby S. L., McGarvey L. P. A. 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. (2020c). North America 33 (4), 869889. HA is a polysaccharide existing in most connective tissues which can trap approximately 1,000 times its weight in water and form hydrogel. Infect. doi:10.1016/j.jinf.2020.02.017, Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., et al. 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. However, clinical evidence showing that glucocorticoids can reduce pulmonary edema by regulating fluid absorption in alveolar and glucocorticoids is missing. This site needs JavaScript to work properly. Impact of -adrenergic Agonist on Na+ Channel and Na+-K+-ATPase Expression in Alveolar Type II Cells. 74 (2), 92101. Bookshelf 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). We argue for expeditious clinical testing of this inhibitor in COVID-19 patients with respiratory malfunction and at risk for lung edema. Virol. The Lancet 395 (10223), 497506. doi:10.1111/jcmm.15146, Harada, H., and Takahashi, M. (2007). Med. Cryptotanshinone Inhibits Endothelin-1 Expression and Stimulates Nitric Oxide Production in Human Vascular Endothelial Cells. It has been shown that the incidence and severity of COVID-19 are closely related to abnormal metabolism of inorganic salts. doi:10.1016/j.bbamem.2012.02.025, Bartoszewski, R., Matalon, S., and Collawn, J. F. (2017). Improving the blood circulation can advance the oxygen supply for organs, accelerate the absorption of fluid and eventually improve pulmonary edema. doi:10.1203/00006450-199908000-00014, Christ-Crain, M., Hoorn, E. J., Sherlock, M., Thompson, C. J., and Wass, J. Am. K+ Channel Openers Restore Verapamil-Inhibited Lung Fluid Resolution and Transepithelial Ion Transport. Med. J. Ethnopharmacology 265, 113301. doi:10.1016/j.jep.2020.113301, Li, F. (2016). Cmp 6 (1), 1327. (2001). Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective. Ion channels, AQPs, RAS, bradykinin and hyaluronic acid are factors influencing the pulmonary edema. 382 (18), 17081720. Respir. B., and Matthay, M. A. (2020). We speculate that treatment of lung-edema will lead to a lower mortality in COVID-19 patients with severe infections. doi:10.1164/rccm.200905-0665OC, Bull, M. B., and Laragh, J. H. (1968). Pulmonary capillary leak syndrome following COVID-19 virus infection J Med Virol. 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). Lancet Respir. *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. Annu. Mohanty SK, Satapathy A, Naidu MM, Mukhopadhyay S, Sharma S, Barton LM, Stroberg E, Duval EJ, Pradhan D, Tzankov A, Parwani AV. By March 31st of 2021, a total of 128.54 million cases of severe Coronavirus Disease (COVID-19) have been diagnosed globally, and a total of 2.81 million people have died from the disease (WHO, 2021). 275(3), L631L635. Zhang J, Zhou N, Wang Y, Liu T, Cao Y, Feng W, Zheng X. Nature 590, 635641. J. 1, 2 More recently, six cases of. doi:10.1161/01.RES.0000247065.11756.19, Andr, E., Gatti, R., Trevisani, M., Preti, D., Baraldi, P., Patacchini, R., et al. doi:10.1002/jmv.25761, Luo, X., Ni, X., Lin, J., Zhang, Y., Wu, L., Huang, D., et al. The condition presents itself as a slowly evolving pneumonia with insidious early onset interstitial pulmonary edema that undergoes acute exacerbation in the late stages and alveolar edema (Xu et al., 2020; Wiersinga et al., 2020). 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). Glucocorticoid Induction of Epithelial Sodium Channel Expression in Lung and Renal Epithelia Occurs via Trans-activation of a Hormone Response Element in the 5-Flanking Region of the Human Epithelial Sodium Channel Subunit Gene. (2017). TRPA1 Agonists Evoke Coughing in guinea Pig and Human Volunteers. doi:10.1016/j.cell.2020.02.058, Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., et al. Mechanism of inhibiting ENaC inducing pulmonary edema. 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. JAMA 323 (16), 15821589. The -Agonist Lung Injury Trial (Balti). As such, the S protein is essential for viral infection (Heald-Sargent and Gallagher, 2012; Li, 2016; Walls et al., 2020). doi:10.1152/physrev.1974.54.3.678, Steinritz, D., Stenger, B., Dietrich, A., Gudermann, T., and Popp, T. (2018). (1998). 383 (19), 18131826. [Med. 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). Med. Pathol. (2021). Since the inhibition of ENaC induces pulmonary edema formation, targeting ENaC is rational in order to enhance fluid clearance from the alveoli. Supportive cares for COVID-19 include respiratory support and circulatory support. Keywords: Res. Proc. (2015). 2 (6), 387396.doi:10.1038/35077544, Connors, J. M., and Levy, J. H. (2020). (2020). Semin. Cough Reflex Testing with Inhaled Capsaicin and TRPV1 Activation in Asthma and Comorbid Conditions. TRP channels are nonspecific cationic channels located throughout the respiratory system (Clapham et al., 2001), where TRPA1, TRPV1 and TRPV4 are the most abundant TRP subtypes (Kaneko and Szallasi, 2014; Steinritz et al., 2018). (2020). Clinical and Computed Tomographic Imaging Features of Novel Coronavirus Pneumonia Caused by SARS-CoV-2. Rhinovirus Upregulates Transient Receptor Potential Channels in a Human Neuronal Cell Line: Implications for Respiratory Virus-Induced Cough Reflex Sensitivity. doi:10.1016/bs.apcsb.2015.11.005, Cure, E., and Cumhur Cure, M. (2020). Since pulmonary edema can be promoted by decreased expression of alveolar Na-K-ATPase (Woods et al., 2015), drugs or compounds which activate the sodium channel and Na-K-ATPase may be putative therapeutics. Cel Metab. Existing drugs and inhibitors targeting the components of humoral metabolism may serve as potential treatments for COVID-19 and should be further investigated. Lung Injury in COVID-19 Has Pulmonary Edema as an Important Component and Treatment with Furosemide and Negative Fluid Balance (NEGBAL) Decreases Mortality. ACIP reviews data. Am. doi:10.1101/2020.03.02.20029975, Yin, J., Hoffmann, J., Kaestle, S. M., Neye, N., Wang, L., Baeurle, J., et al. 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. Nervous system conditions or surgeries. medRxiv. Physiol. Rev. 8 (5), 475481. Pharmacol. 288, 198114. doi:10.1016/j.virusres.2020.198114, Krlicka, A. L., Kruczkowska, A., Krajewska, M., and Kusztal, M. A. Transient Receptor Potential (TRP) Channels: a Clinical Perspective. Thus, it could be a potential RdRp inhibitor for SARS-CoV-2 (Lung et al., 2020). Besides chemical drugs and compounds we discussed above, natural compounds and TCMs also possess promising antiviral effects against SARS-CoV-2 and had notably contribution in curing COVID-19, especially in alleviating pulmonary edema and preventing the disease development from mild to severe. Epub 2020 Jun 20. doi:10.1093/ofid/ofaa105/5811022, Minakata, Y., Suzuki, S., Grygorczyk, C., Dagenais, A., and Berthiaume, Y. TRP Functions in the Broncho-Pulmonary System. Am. Symptoms that are common to all of these conditions include cough and shortness of breath. 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). doi:10.1007/s11596-015-1490-6, Jovanovi, S., Crawford, R. M., Ranki, H. J., and Jovanovi, A. Circ. Recombinant ACE2 was also reported to be a potential therapy in the clinical study of ARDS, which can lead to rapid decrease of plasma Ang II level and IL-6 expression. doi:10.4268/cjcmm20152124, Wang, Q., Zheng, X., Cheng, Y., Zhang, Y.-L., Wen, H.-X., Tao, Z., et al. SN Compr. Authors Mabrouk Bahloul 1 . RAS, especially several cleavage products of the peptide angiotensin (AGT) along with their receptors, maintains a balance of fluid volume and pressure. Structure, Function, and Evolution of Coronavirus Spike Proteins. Am. 183 (1), G9G15. Impaired Breakdown of Bradykinin and its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection. Med. Br. FIGURE 2. 104, 81125. As Gabazza et al., (2004) reported, lung fibrosis is linked to decreased mRNA and protein expression of AQP-5 in the lung. 33, 258269. A pulmonary edema was the cause of the death of a woman who died short after a vaccine on Tuesday an autopsy has shown. Inhibiting these TRPs may benefit the treatment of pulmonary edema. doi: 10.1152/ajplung.00161.2020. doi:10.1001/jama.2020.6775, Rogosnitzky, M., Okediji, P., and Koman, I. MeSH doi:10.1002/path.2987, Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. Dis. doi:10.5114/pdia.2013.37040, Cui, M., Gosu, V., Basith, S., Hong, S., and Choi, S. (2016). Summary of potential natural compounds against COVID-19. J. Med. China Life Sci. Recently, several companies came out with vaccines against COVID-19 which have been approved for use. Angiotensin-converting Enzyme 2 in Acute Respiratory Distress Syndrome. J. Biol. The activities of the molecules in RAS are ruled by dynamic changes responding to an injury. Role of Drugs Used for Chronic Disease Management on Susceptibility and Severity of COVID19: A Large CaseControl Study. doi:10.1038/s12276-018-0075-4, Zwaveling, S., Gerth van Wijk, R., and Karim, F. (2020). Elife 9, e59177. (2020). COVID-19 Infection: the Perspectives on Immune Responses. doi:10.1016/j.bbagen.2005.09.009, Zhuo, X.-J., Hao, Y., Cao, F., Yan, S.-F., Li, H., Wang, Q., et al. In TCM theory, evils of COVID-19 are derived from cold-dampness, whose core pathogenesis are toxin and dampness. 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). Eur. medRxiv. Invest. Rev. 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. Physiol. Elevated pulmonary venous pressure leads to faster fluid infiltration into the interstitial lung than the ability of the pulmonary lymphatic vessel to drain away fluid, resulting in pulmonary edema. N. Engl. doi:10.1016/j.jacbts.2021.01.002, Bardou, O., Priv, A., Migneault, F., Roy-Camille, K., Dagenais, A., Berthiaume, Y., et al. Circulation 37 (1), 4553. IL6 monoclonal antibody or tocilizumab was thought to work by interrupting inflammatory storm after the infection, but the latest clinical study published in NEJM showed that Tocilizumab was not effective in preventing intubation or death in mild hospitalized COVID-19 patients (Stone et al., 2020). Immunopathol 38 (3), 321329. FEBS Lett. J. Cel Mol Med 24 (8), 47364747. Am. Am. Transient Receptor Potential Ankyrin Receptor 1 Is a Novel Target for Pro-tussive Agents. AQP-5 plays a significant role in pulmonary edema and decreased expression of AQP-5 has been observed during the disease process. 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). EM did the language polishing. Circ. (2021). Subjects 1760 (1), 19. Sepsis, another possible complication of COVID-19, can also cause lasting harm to the lungs and other organs. (2020b). 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). 2020 Mar 23:3558887. doi: 10.2139/ssrn.3558887. (2020). et al., 2020). doi:10.1136/thoraxjnl-2013-203894, PubMed Abstract | CrossRef Full Text | Google Scholar, Achanta, S., and Jordt, S. E. (2020). 160, 105073. doi:10.1016/j.phrs.2020.105073, Maronde, R. F., Milgrom, M., Vlachakis, N. D., and Chan, L. (1983). COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. It has already been shown that the dysregulated release of cytokines is one of the key factors behind poor outcomes in COVID-19 patients. doi:10.1056/NEJMoa013183, Sayegh, R., Auerbach, S. D., Li, X., Loftus, R. W., Husted, R. F., Stokes, J. Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. XC analyzed and reviewed the research articles as well as drafting the manuscript. Structure and Hormone Responsiveness of the Gene Encoding the -Subunit of the Rat Amiloride-Sensitive Epithelial Sodium Channel. Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. These channels are important in maintaining the optimum volume and ion constitution of bronchial periciliary fluid and alveolar lining fluid layers, which are necessary in appropriate pathogens mucociliary clearance and optimum gas exchange, respectively (Londino et al., 2017). 34 (4), 610618. 10.1111/nyas.14472 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. First post-authorization U.S. doses of Janssen COVID -19 Vaccine. Comment on "Organprotective Effect of Angiotensinconverting Enzyme 2 and its Effect on the Prognosis of COVID19". Front. These supportive approaches have been shown to be beneficial as adjuvant therapies in COVID-19 patients. 12:664349. doi: 10.3389/fphar.2021.664349. Potential drugs for normalizing humoral metabolism. (2002). Systemic Reactions. Glucocorticoids were shown to have the ability of inducing de novo synthesis of ENaC (Chow et al., 1999; Otulakowski et al., 1999; Sayegh et al., 1999) and affecting ENaC regulatory pathway via serum and glucocorticoids-inducible kinase-1 (SGK-1) (Chen et al., 1999; de la Rosa et al., 1999; Itani et al., 2001; Zhang et al., 2007). Is Amiloride a Promising Cardiovascular Medication to Persist in the COVID-19 Crisis?. FIGURE 6. In these patients, white blood cells count, neutrophil count and D-dimer level keep rising while lymphocyte count keeps decreasing as the disease progresses.

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