Clin. 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). Life Sci. Maresin1 Stimulates Alveolar Fluid Clearance through the Alveolar Epithelial Sodium Channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 Pathway. Med. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. This buildup of fluid leads to shortness of breath. Pathophysiology and incidence - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is an extremely rare syndrome that can occur in individuals who received certain adenoviral-vectored coronavirus disease 2019 (COVID-19) vaccines. (1985) 93 (4), 15331541. Aquaporins in the Lung. CFTR inhibitors, like glibenclamide and CFTRinh-172 inhibitor, distinctly reduced absorptive alveolar fluid transport (Solymosi et al., 2013). 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. Pulmonary edema is the disequilibrium between formation and reflux of lung tissue fluid leading to the absorption of massive tissue fluid by lung lymph and vein failure. Phytomedicine 85, 153282. doi:10.1016/j.phymed.2020.153282, Ma, Q., Pan, W., Li, R., Liu, B., Li, C., Xie, Y., et al. TRPs in Tox: Involvement of Transient Receptor Potential-Channels in Chemical-Induced Organ Toxicity-A Structured Review. Consequently, the use of bradykinin antagonists is supposed to be regarded as a strategy for COVID-19 treatment interventions. 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. (2014). PMC (2012). 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). Cause of COVID-19 pulmonary edema. FIGURE 6. XC analyzed and reviewed the research articles as well as drafting the manuscript. Impaired Breakdown of Bradykinin and its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection. A. H. (2020). Inhibiting the inflammatory storm can effectively alleviate pulmonary edema. 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. Exp. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients with Severe and Life-Threatening COVID-19. Some natural compounds along with their antiviral and reducing pulmonary edema mechanisms are shown in Table 2. Struct. Chloride Transport-Driven Alveolar Fluid Secretion Is a Major Contributor to Cardiogenic Lung Edema. Treatment of Pulmonary Edema by ENaC Activators/Stimulators. Treatment of 5 Critically Ill Patients with COVID-19 with Convalescent Plasma. Currently, these manifestations are considered to be only consequences of pulmonary SARS-CoV-2 virus infection. 2, 26372646. Fatal Systemic Capillary Leak Syndrome after SARS-CoV-2 Vaccination in Physiol. 2021 May 7;8:644678. doi: 10.3389/fmed.2021.644678. 39 (270), H2000H2007. Ijerph 17 (15), 5320. doi:10.3390/ijerph17155320, Kunzelmann, K., Beesley, A. H., King, N. J., Karupiah, G., Young, J. Res. Symptoms that are common to all of these conditions include cough and shortness of breath. Ion Channels of the Lung and Their Role in Disease Pathogenesis. Vaccines (Basel). N. Engl. J. Physiology-Lung Cell Mol. 8 (8), 807815. Currently, only icatibant has been approved as bradykinin antagonist for clinical treatment, and relevant studies have revealed that cefepime, cefpirome, imatinib, raloxifene, sildenafil, ponatinib, abemaciclib and entrectinib may also act as prospective non-selective bradykinin antagonists and have potential for treatment of COVID-19 (Rasaeifar et al., 2020). SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. Urgent reconsideration of lung edema as a preventable outcome in COVID-19: inhibition of TRPV4 represents a promising and feasible approach. (2020a). Rev. COVID-19: Vaccine-induced immune thrombotic thrombocytopenia - UpToDate Evolution of the Novel Coronavirus from the Ongoing Wuhan Outbreak and Modeling of its Spike Protein for Risk of Human Transmission. Transient Receptor Potential (TRP) Channels: a Clinical Perspective. China Life Sci. doi:10.1073/pnas.96.5.2514, Chow, Y.-H., Wang, Y., Plumb, J., O'Brodovich, H., and Hu, J. Nonetheless, little attention has been paid to CD44 in COVID-19 treatment. Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. 102 (8), 966974. Med. Treatment of Severe Cardiogenic Pulmonary Edema with Continuous KCa3.1 (1-EBIO) and KATP (minoxidil) channel openers can greatly recover AFC in mice intratracheally administrated verapamil, which is the first generation of the phenylalkylamine class of calcium channel antagonists (Fleckenstein, 1977; Nayler and Dillon, 1986), suggesting that K+ channel openers might be potential drugs for treating pulmonary edema (Han et al., 2010). COVID19 Diagnosis and Management: a Comprehensive Review. RAS, especially several cleavage products of the peptide angiotensin (AGT) along with their receptors, maintains a balance of fluid volume and pressure. COVID-19 vaccines can cause mild side effects after the first or second dose, including: Pain, redness or swelling where the shot was given Fever Fatigue Headache Muscle pain Chills Joint pain Nausea and vomiting Swollen lymph nodes Feeling unwell Most side effects go away in a few days. We also obtain PFTs in recovering COVID-19 patients with severe pulmonary involvement or COVID-19-related ARDS, which applies to many patients who required hospitalization. -, Adil M. S., Narayanan S. P., Somanath P. R. (2020). Some others will likely be approved soon (Kaur and Gupta, 2020; Thanh Le et al., 2020). doi:10.1101/2020.03.02.20029975, Yin, J., Hoffmann, J., Kaestle, S. M., Neye, N., Wang, L., Baeurle, J., et al. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration. Viruses 4 (4), 557580. Millions of people in the United States have received COVID-19 vaccines and they are safe and effective at protecting against COVID-19. HA is degraded by hyaluronidases encoded by HYAL1 and HYAL2, whose activity depends on CD44, an HA receptor (Harada and Takahashi, 2007). Res. Patients receive high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), mechanical ventilation or ECMO as respiratory supports (Guo et al., 2020; Pascarella et al., 2020), a crystalloid fluid to ensure body fluid equilibrium (Christ-Crain et al., 2020), and anticoagulants for restraining the thrombus formation to aid in circulatory support (Connors and Levy, 2020). COVID-19 Lung Damage | Johns Hopkins Medicine 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). doi:10.1101/2020.03.20.20039586, Londino, J. D., Lazrak, A., Collawn, J. F., Bebok, Z., Harrod, K. S., and Matalon, S. (2017). 183 (1), G9G15. 104, 81125. Gut 69 (6), 10101018. Am. Bookshelf HA is synthesized by HAS2. BMJ 369, m1432. 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). Pulmonary edema is an abnormal buildup of fluid in the lungs. Severe Acute Respiratory Syndrome. Biol. COVID-19; abnormal lung humoral metabolism; drug; pulmonary edema; syndrome coronavirus 2; traditional Chinese medicine. Impact of -adrenergic Agonist on Na+ Channel and Na+-K+-ATPase Expression in Alveolar Type II Cells. Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19. Case Report: Thrombotic Thrombocytopenia after COVID-19 Janssen the Coronavirus Spike Protein and Acquisition of Fusion Competence. Focusing on decreasing the formation of body fluid in lung or promoting the absorption of body fluid can contribute to a decrease in lung damage and decreased mortality in COVID-19 patients. Physiol. 92 (9), 14231424. Semin. J. Pathol. Biochem. (1977). Medicines 16 (11), 811828. 2021 Jun 7;12:664349. doi: 10.3389/fphar.2021.664349. Immunol. Lung Injury in COVID-19 Has Pulmonary Edema as an Important Component and Treatment with Furosemide and Negative Fluid Balance (NEGBAL) Decreases Mortality. Copyright 2021 Cui, Chen, Zhou, Gong, Zhu, Lv, Guo, Duan, Zhou, Marcon and Ma. Studies showed that ENaC activators or stimulators can regulate ENaC-dependent fluid absorption in alveolar and pulmonary edema (Fronius, 2013). J. Cell 181 (2), 281292. Sepsis, another possible complication of COVID-19, can also cause lasting harm to the lungs and other organs. J. Infect. Front. doi:10.1164/rccm.200508-1302OC, Pickkers, P., Dormans, T. P. J., Russel, F. G. M., Hughes, A. D., Thien, T., Schaper, N., et al. Nat. 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). Res. Acad. (2020a). Keywords: doi:10.1016/j.jacbts.2021.01.002, Bardou, O., Priv, A., Migneault, F., Roy-Camille, K., Dagenais, A., Berthiaume, Y., et al. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. Respir. (2019). -, Ai J.-W., Zhang H.-C., Xu T., Wu J., Zhu M., Yu Y.-Q., et al. medRxiv. Pharmacol. Shapiro, S. D. (2001). 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). It has been observed that MMP-2 and MMP-9, two most crucial MMPs in the lung are over-expressed in pulmonary edema (Negrini et al., 1996; Negrini et al., 1998; Passi et al., 1998), suggesting that MMPs may become a potential target for pulmonary edema treatment. J. Physiology-Lung Cell Mol. includes glycoproteins, membranes and nucleic acids. N. Engl. Invest. In these patients, white blood cells count, neutrophil count and D-dimer level keep rising while lymphocyte count keeps decreasing as the disease progresses. doi:10.1007/s11596-015-1490-6, Jovanovi, S., Crawford, R. M., Ranki, H. J., and Jovanovi, A. Its active absorption of Na+ is the main driving force of fluid clearance at birth and alveolar fluid absorption at adult stage (Bardou et al., 2012). 313 (5), L859L872. 1480 (1), 73103. Available: https://covid19.who.int/ (Accessed March 31, 2021). 289 (1), L104L110. Pathol. Sci. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Am. Biophys. His lab findings and clinical course were consistent with those of MIS after COVID-19 vaccination. doi:10.1016/j.cmet.2021.01.002, Chen, S.-y., Bhargava, A., Mastroberardino, L., Meijer, O. C., Wang, J., Buse, P., et al. 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. Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage Is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients with Hypertension. Several cases of vaccine-induced thrombotic thrombocytopenia from a similar viral vector vaccine (Oxford-AstraZeneca [ChAdOx1 nCoV-19]) have been reported. doi:10.1002/jcp.28602, Otulakowski, G., Rafii, B., Bremner, H. R., and O'Brodovich, H. (1999). (2020). Summary of potential TCM formulae against COVID-19. Res. Pulmonary Edema in COVID19-A Neural Hypothesis - PubMed
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