Xanya Sofra
City University, London, New School for Social Research, New York, United States
The imminent danger of the Covid-19 pandemic has accelerated research in pharmaceuticals that either target the viral Spike proteins fusion with ACE2 receptors, or the infectious RNA replication that often overwhelms immune defences. The scope of this review was to elucidate the main human vulnerabilities to Covid-19, including the accumulation of ACE2 receptors in testes, adipose tissue, thyroid, heart and kidneys that escalate viral affinity in males, the aged, and certain medical conditions, including diabetes, CVD, and pulmonary diseases. Pre-existing inflammation inherent in obesity may exacerbate the “cytokine storm,” a rampaging immune reaction during the course of Covid-19 that is deleterious to the host. We examined the molecular dynamics illustrating the action of new therapeutics necessary for Covid-19 patients; the estradiol advantage hypothesis;alternative therapies including hormone replacement procedures and mesenchymal stem cells; plus preventive and protective interventions.The current perspective also explored the primary components of dysregulated health predisposing individuals to Covid-19, including hormonal imbalance, increased lipids and lipoproteins, thyroid dysfunction, degraded fitness, and age-related testosterone decline accompanied by cortisol increase that provokes stress eating behaviours and weight accumulation.Obesity increases the probability of Covid-19 infection due to its abundance of ACE2 receptors; while physical activity may decrease Covid-19 vulnerability, by reducing fat and increasing muscle mass that manifests a relatively inhibited ACE2 expression. Several weight management solutions feature lasers and radiofrequency which diminish subcutaneous adiposity but do not enhance fitness. A data metanalysis of seven recently published clinical studies on 95 obese individuals, 73 males and 22 females with an average BMI of 30.9, demonstrated visceral fat reduction combined with increased skeletal muscle mass. It also revealed a statistically significant decrease in BMI, lipids, lipoproteins, inflammation and toxicity as measured by CRP, Creatinine and Bilirubin respectively, juxtaposed by optimally healthier levels of Cortisol, Testosterone, Free T3,IGF-1, Insulin, and the appetite controlling hormones Leptin and Ghrelin.
[1] Boopathi, S., Poma, A. B., Kolandaivel, P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. Journal of biomolecular structure & dynamics, 2020, 1(10). Advance online publication. https://doi.org/10.1080/07391102.2020.1758788
[2] Walls A. C., Park Y. J., Tortorici M. A., Wall A., McGuire A. T., Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell, 2020, 181(2): 281 -212. DOI: https://doi.org/10.1016/j.cell.2020.02.058
[3] Wrapp D., Wang N., Corbett K. S., Goldsmith J. A., Hsieh C. L., Abiona O., Graham B. S., McLellan J. S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020, 367(6483): 1260-1263. DOI: 10.1126/science.abb2507
[4] Xu J, Sriramula S, Xia H, Moreno-Walton L, Culicchia F, Domenig O, Poglitsch M, Lazartigues E. Clinical relevance and role of neuronal AT1 receptors in ADAM17-mediated ACE2 shedding in neurogenic hypertension. Circ Res., 2017, 121: 43-55. DOI: https://doi.org/10.1161/CIRCRESAHA.116.310509
[5] Li, W., Moore, M., Vasilieva, N. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003, 426: 450-454 https://doi.org/10.1038/nature02145
[6] Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., Bao, L. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus -induced lung injury. Nature medicine, 2005, 11(8): 875-879. PMID: 16007097; PMCID: PMC7095783. DOI: 10.1038/nm1267
[7] Satarker S, Nampoothiri M. Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2. Arch Med Res., 2020, 51(6): 482-491. DOI: 10.1016/j.arcmed.2020.05.012. PMID: 32493627; PMCID: PMC7247499
[8] Kirchdoerfer R. N., Cottrell C. A., Wang N., Pallesen J., Yassine H. M., Turner H. L., Corbett K. S., Graham B. S., McLellan J. S., Ward A. B. Pre-fusion structure of a human coronavirus spike protein. Nature, 2016, 531(7592): 118-121.DOI: https://doi.org/10.1038/nature17200
[9] Gupta M. K., Vemula S., Donde R., Gouda G., Behera L., Vadde R. In silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. Journal of Biomolecular Structure and Dynamics, 2020. DOI: https://doi.org/10.1080/07391102.2020.175130 0
[10] Sarma, P., Sekhar, N., Prajapat, M., Avti, P., Kaur, H., Kumar, S., Singh, S., Kumar, H., Prakash, A., Dhibar, D. P., Medhi, B. In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). Journal of Biomolecular Structure & Dynamics, 2020. DOI: https://doi.org/10.1080/07391102.2020.1753580
[11] Shannon, A., Le, N.T.T., Selisko, B., Eydoux, C., Alvarez, K., Guillemot, J.C., Decroly, E., Peersen, O., Ferron, F., Canard, B. Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites. Antiviral Research, 2020: 104793. DOI: https://doi.org/10.1016/j.antiviral.2020.104793
[12] Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor [published ahead of print].Cell., 2020. DOI: 10.1016/j.cell.2020.02.052
[13] Ragia, G., Manolopoulos, V. G. Inhibition of SARSCoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies. European journal of clinical pharmacology, 2020, 1-8. DOI: https://doi.org/10.1007/s00228-020-02963-4
[14] Danser, A.J., Epstein, M., Batlle, D. Renin-angiotensin system blockers and the COVID-19 pandemic: at present there is no evidence to abandon renin-angiotensin system blockers. Hypertension, 2020, 75(6): 1382-1385. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.120.15082
[15] Xia H, Sriramula S, Chhabra KH, Lazartigues E. Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension. Circ Res., 2013, 113: 1087-1096. DOI: https://doi.org/10.1161/CIRCRESAHA.113.301811
[16] Jin, J.M., Bai, P., He, W., Wu, F., Liu, X.F., Han, D.M., Liu, S., Yang, J.K. Gender differences in patients with COVID-19: Focus on severity and mortality. Frontiers in Public Health, 2020, 8: 152.DOI: https://doi.org/10.3389/fpubh.2020.00152
[17] Karlberg, J., Chong, D.S.Y., Lai, W.Y.Y. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do?. American journal of epidemiology, 2004, 159(3): 229-231. DOI: https://doi.org/10.1093/aje/kwh056
[18] Mjaess, G., Karam, A., Aoun, F., Albisinni, S., Roumeguere, T. COVID-19 and the male susceptibility: the role of ACE2, TMPRSS2 and the androgen receptor. Progress En Urologie, 2020. DOI: https://doi.org/10.1016/j.purol.2020.05.007
[19] Wang, Z., Xu, X. scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia, Leydig and Sertoli cells. Cells, 2020, 9(4): 920. DOI: https://doi.org/10.3390/cells9040920
[20] Douglas, G. C., O’Bryan, M. K., Hedger, M. P., Lee, D. K., Yarski, M. A., Smith, A. I., Lew, R. A. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology, 2004, 145(10): 4703-4711. DOI: https://doi.org/10.1210/en.2004-0443
[21] Liu, X., Chen, Y., Tang, W., Zhang, L., Chen, W., Yan, Z., Yuan, P., Yang, M., Kong, S., Yan, L., Qiao, J. Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Sci. China Life Sci., 2020, 63: 1006 -1015 DOI: https://doi.org/10.1007/s11427-020-1705-0
[22] Wambier C.G. Goren A. SARS-COV-2 infection is likely to be androgen mediated. J Am Acad Dermatol., 2020. DOI: https://doi.org/10.1016/j.jaad.2020.04.032
[23] Heurich, A., Hofmann-Winkler, H., Gierer, S., Liepold, T., Jahn, O., Pöhlmann, S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. Journal of virology, 2014, 88(2): 1293-1307. DOI: 10.1128/JVI.02202-13
[24] Böttcher, E., Matrosovich, T., Beyerle, M., Klenk, H. D., Garten, W., Matrosovich, M. Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium. Journal of virology, 2006, 80(19): 9896-9898. DOI: 10.1128/JVI.01118-06
[25] Nie, X., Qian, L., Sun, R., Huang, B., Dong, X., Xiao, Q., Zhang, Q., Lu, T., Yue, L., Chen, S., Li, X. Multi-organ proteomic landscape of COVID-19 autopsies. medRxiv, 2020. DOI: https://doi.org/10.1101/2020.08.16.20176065
[26] Jansson, J.H., Boman, K., Brännström, M., Nilsson, T.K. High concentration of thrombomodulin in plasma is associated with hemorrhage: a prospective study in patients receiving long-term anticoagulant treatment. Circulation, 1997, 96(9): 2938-2943.
[27] Liu, T., Luo, S., Libby, P., Shi, G. P. Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients. Pharmacology & Therapeutics, 2020, 107587. DOI: https://doi.org/10.1016/j.pharmthera.2020.107587
[28] Li, M.Y., Li, L., Zhang, Y., Wang, X.S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infectious diseases of poverty, 2020, 9: 1-7. DOI: https://doi.org/10.1186/s40249-020-00662-x
[29] Montano, L. M., Espinoza, J., Flores-Soto, E., Chávez, J., Perusquia, M. Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm. J Endocrinol, 2014, 222(1): 1-13. DOI: 10.1530/JOE-14-0074
[30] Muller, I., Cannavaro, D., Dazzi, D., Covelli, D., Mantovani, G., Muscatello, A., Ferrante, E., Orsi, E., Resi, V., Longari, V., Cuzzocrea, M. SARS-CoV-2- related atypical thyroiditis. The Lancet Diabetes & Endocrinology, 2020, 8(9): 739-741. DOI: https://doi.org/10.1016/S2213-8587(20)30266-7
[31] Duntas LH, Orgiazzi J, Brabant G. The interface between thyroid and diabetes mellitus. Clinical endocrinology, 2011, 75(1): 1-9. DOI: https://doi.org/10.1111/j.1365-2265.2011.04029.x
[32] Cai, Z., Dai, M., Zhang, Y., Zhong, H., Tan, T., Bao, M. Imbalance of cardiac autonomic nervous activity and increase of ventricular repolarization dynamicity induced by thyroid hormones in hyperthyroidism. Autonomic Neuroscience, 2018, 213: 86-91. DOI: https://doi.org/10.1016/j.autneu.2018.06.006
[33] Wang, C. The relationship between type 2 diabetes mellitus and related thyroid diseases. Journal of diabetes research, 2013. DOI: https://doi.org/10.1155/2013/390534
[34] Baxter, J.D., Webb, P. Thyroid hormone mimetics: potential applications in atherosclerosis, obesity and type 2 diabetes. Nature reviews Drug discovery, 2009, 8(4): 308-320. DOI: https://doi.org/10.1038/nrd2830
[35] Tan, T., Khoo, B., Mills, E.G., Phylactou, M., Patel, B., Eng, P.C., Thurston, L., Muzi, B., Meeran, K., Prevost, A.T., Comninos, A.N. Association between high serum total cortisol concentrations and mortality from COVID-19. The Lancet Diabetes & Endocrinology, 2020, 8(8): 659-660. DOI: https://doi.org/10.1016/S2213-8587(20)30216-3
[36] Chiodini, I., Adda, G., Scillitani, A., Coletti, F., Morelli, V., Di Lembo, S., Epaminonda, P., Masserini, B., Beck-Peccoz, P., Orsi, E. and Ambrosi, B. Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications. Diabetes care, 2007, 30(1): 83-88. DOI: https://doi.org/10.2337/dc06-1267
[37] Chiodini, I., Adda, G., Beck-Peccoz, P., Orsi, E., Ambrosi, B., Arosio, M. Cortisol Secretion in Patients With Type 2 Diabetes: Relationship With Chronic Complications: Response to Castillo-Quan and Pérez-Osorio. Diabetes Care, 2007, 30(6): e50-e50. DOI: https://doi.org/10.2337/dc07-0271
[38] Sher, L. Type D personality: the heart, stress, and cortisol. Qjm, 2005, 98(5): 323-329. DOI: https://doi.org/10.1093/qjmed/hci064112
[39] Klein, S. L., Dhakal, S., Ursin, R. L., Deshpande, S., Sandberg, K., Mauvais-Jarvis, F. Biological sex impacts COVID-19 outcomes. PLoS pathogens, 2020, 16(6): e1008570. DOI: https://doi.org/10.1371/journal.ppat.1008570
[40] Liu J, Ji H, Zheng W, Wu X, Zhu JJ, Arnold AP, Sandberg K. Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17beta-estradiol-dependent and sex chromosome-independent. Biology of sex differences, 2010, 1(1): 6. pmid: 21208466. DOI: https://doi.org/10.1186/2042-6410-1-6
[41] Mauvais-Jarvis, F., Klein, S. L., Levin, E. R. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology, 2020, 161(9): bqaa127. DOI: https://doi.org/10.1210/endocr/bqaa127
[42] Seeland, U., Coluzzi, F., Simmaco, M., Mura, C., Bourne, P.E., Heiland, M., Preissner, R. and Preissner, S. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. MedRxiv, 2020. DOI: https://doi.org/10.1101/2020.08.21.20179671
[43] Wener, M.H., Daum, P. R., McQuillan, G.M. The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration. The Journal of rheumatology, 2000, 27(10): 2351. PMID: 11036829 DOI: https://pubmed.ncbi.nlm.nih.gov/11036829/
[44] Silvestri, A., Gebara, O., Vitale, C., Wajngarten, M., Leonardo, F., Ramires, J.A., Fini, M., Mercuro, G. and Rosano, G.M. Increased levels of C-reactive protein after oral hormone replacement therapy may not be related to an increased inflammatory response. Circulation, 2003, 107(25): 3165-3169.DOI: https://doi.org/10.1161/01.CIR.0000074208 .02226.5E
[45] Iba, T., Yagi, Y., Kidokoro, A. Kidokoro, A., Fukunaga, M., Fukunaga, T. Increased plasma levels of soluble thrombomodulin in patients with sepsis and organ failure. Surg Today,1995, 25: 585 -590. DOI: https://doi.org/10.1007/BF00311430
[46] Jansson, J.H., Boman, K., Brännström, M. and Nilsson, T.K. High concentration of thrombomodulin in plasma is associated with hemorrhage: a prospective study in patients receiving long-term anticoagulant treatment. Circulation, 1997, 96(9): 2938-2943. DOI: https://doi.org/10.1161/01.CIR.96.9.2938
[47] Sproston, N.R., Ashworth, J.J. Role of C-reactive protein at sites of inflammation and infection. Frontiers in immunology, 2018, 9: 754. DOI: https://doi.org/10.3389/fimmu.2018.00754
[48] Liang, B., Chen, J., Li, T., Wu, H., Yang, W., Li, Y., Li, J., Yu, C., Nie, F., Ma, Z., Yang, M. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine, 2020, 99(31). DOI: 10.1097/MD.0000000000021429
[49] Leng, Z., Zhu, R., Hou, W., Feng, Y., Yang, Y., Han, Q., Shan, G., Meng, F., Du, D., Wang, S. and Fan, J. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging and disease, 2020, 11(2): 216. DOI: 10.14336/AD.2020.0228
[50] Hashemian, S.M.R., Aliannejad, R., Zarrabi, M., Soleimani, M., Vosough, M., Hosseini, S.E., Hossieni, H., Keshel, S.H., Naderpour, Z., Hajizadeh-Saffar, E. and Shajareh, E., 2021. Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. Stem cell research & therapy, 12(1), pp.1-12. DOI: https://doi.org/10.1186/s13287-021-02165-4
[51] Kalligeros, M., Shehadeh, F., Mylona, E. K., Benitez, G., Beckwith, C. G., Chan, P. A., & Mylonakis, E. Association of Obesity with Disease Severity among Patients with COVID-19. Obesity (Silver Spring, Md.), 2020. DOI: http://ahajournals.org
[52] Dietz, W., Santos, Burgoa, C. Obesity and its Implications for COVID-19 Mortality. Obesity, 2020, 28(6): 1005-1005. DOI: https://doi.org/10.1002/oby.22818
[53] Gao, F., Zheng, K. I., Wang, X. B., Sun, Q. F., Pan, K. H., Wang, T. Y., Zheng, M. H. Obesity is a risk factor for greater COVID-19 severity. Diabetes Care, 2020. DOI: https://doi.org/10.2337/dc20-0682
[54] Park, H. S., Park, J. Y., Yu, R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes research and clinical practice, 2005, 69(1): 29-35. DOI: https://doi.org/10.1016/j.diabres.2004.11.007
[55] Gorini, F., Bianchi, F., Iervasi, G. COVID-19 and Thyroid: Progress and Prospects, 2020. DOI: https://doi.org/10.3390/ijerph17186630
[56] Peng YD, Meng K, Guan HQ, et al. Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV. Zhonghua Xin Xue Guan Bing Za Zhi., 2020, 48(0): E004. DOI: 10.3760/cma.j.cn112148-20200220-00105
[57] MUÑOZ, J. 2020 Covid-19 Epidemic Exercise or Not to Exercise; That is the Question. Asian J Sports Med, 2020, 11(1): 102630. DOI: 10.5812/asjsm.102630
[58] Jiménez-Pavón, D., Carbonell-Baeza, A., & Lavie, C. J. Physical exercise as therapy to fight against the mental and physical consequences of COVID-19 quarantine: Special focus in older people. Progress in cardiovascular diseases, 2020. DOI: 10.1016/j.pcad.2020.03.009
[59] Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect, 2020, 50(4): 332- 334. DOI: 10.1016/j.medmal.2020.03.007
[60] Tan C, Huang Y, Shi F, et al. C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early. J Med Virol., 2020, 92(7): 856-862. DOI: 10.1002/jmv.25871
[61] Han, H., Ma, Q., Li, C., Liu, R., Zhao, L., Wang, W., Zhang, P., Liu, X., Gao, G., Liu, F. and Jiang, Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerging Microbes & Infections, 2020, 9(1): 1123- 1130. DOI: https://doi.org/10.1080/22221751.2020.177012 9
[62] Del Valle, D.M., Kim-Schulze, S., Huang, H.H., Beckmann, N.D., Nirenberg, S., Wang, B., Lavin, Y., Swartz, T.H., Madduri, D., Stock, A. and Marron, T.U. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature medicine, 2020: 1-8. DOI: https://doi.org/10.1038/s41591-020-1051-9
[63] Ni, M., Tian, F. B., Xiang, D. D., Yu, B. Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19. Journal of Medical Virology, 2020. DOI: https://doi.org/10.1002/jmv.26070
[64] Cartier, A., Côté, M., Lemieux, I., Pérusse, L., Tremblay, A., Bouchard, C., & Després, J. P. Age-related differences in inflammatory markers in men: contribution of visceral adiposity. Metabolism, 2009, 58(10): 1452-1458. DOI: https://doi.org/10.1016/j.metabol.2009.04.025
[65] Gong, J., Dong, H., Xia, S.Q., Huang, Y.Z., Wang, D., Zhao, Y., Liu, W., Tu, S., Zhang, M., Wang, Q., Lu, F. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19 pneumonia. MedRxiv, 2020. DOI: https://doi.org/10.1101/2020.02.25.20025643
[66] de Wit, E., van Doremalen, N., Falzarano, D. et al. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol, 2016, 14: 523- 534. DOI: https://doi.org/10.1038/nrmicro.2016.81 https://www.nature.com/articles/nrmicro.2016.81. pdf?origin=ppub
[67] Channappanavar, R., Fehr, A.R., Vijay, R. Mack, M., Zhao, J., Meyerholz, D.K. et al. Dysregulated Type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe, 2016, 19(2): 181- 193. DOI: https://doi.org/10.1016/j.chom.2016.01.007
[68] Thevarajan, I., Nguyen, T.H.O., Koutsakos, M. et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med 26, 2020: 453-455. DOI: https://doi.org/10.1038/s41591-020-0819-2
[69] Gao, Y. M., Xu, G., Wang, B., Liu, B. C. Cytokine storm syndrome in coronavirus disease 2019: A narrative review. Journal of internal medicine, 2020. DOI: https://doi.org/10.1111/joim.13144
[70] Yohei Tanaka. Three-dimensional volumetric assessment of body sculpting using a uniform heating radio frequency device in Asians, Journal of Cosmetic and Laser Therapy, 2015, 17(4): 194-199. DOI: https://doi.org/10.3109/14764172.2015.1007059
[71] Franco, W., Kothare, A., Goldberg, D.J. Controlled volumetric heating of subcutaneous adipose tissue using a novel radiofrequency technology. Lasers in Surgery and Medicine: The Official Journal of the American Society for Laser Medicine and Surgery, 2009, 41(10): 745-750. DOI: https://doi.org/10.1002/lsm.20876
[72] Franco, W., Kothare, A., Ronan, S.J., Grekin, R.C., McCalmont, T.H. Hyperthermic injury to adipocyte cells by selective heating of subcutaneous fat with a novel radiofrequency device: feasibility studies. Lasers in surgery and medicine, 2010, 42(5): 361-370. DOI: https://doi.org/10.1002/lsm.20925
[73] Del Pino Emilia, M., Rosado, R.H., Azuela, A., Graciela, M.G., Argüelles, D., Rodríguez, C. and Rosado, G.M. Effect of controlled volumetric tissue heating with radiofrequency on cellulite and the subcutaneous tissue of the buttocks and thighs. Journal of drugs in dermatology: JDD, 2006, 5(8): 714-722. PMID: 16989185
[74] Paul, M., Mulholland, R.S. A new approach for adipose tissue treatment and body contouring using radiofrequency-assisted liposuction. Aesthetic plastic surgery, 2009, 33(5): 687-694. DOI: 10.1007/s00266-009-9342-z
[75] Kapoor, R., Shome, D. and Ranjan, A. Use of a novel combined radiofrequency and ultrasound device for lipolysis, skin tightening and cellulite treatment. Journal of Cosmetic and Laser Therapy, 2017, 19(5): 266-274. DOI: https://doi.org/10.1080/14764172.2017.1303169
[76] Abboud, S., Hachem, J.P. Heat Shock Lipolysis: Radiofrequency Combined with Cryolipolysis for the Reduction of Localized Subcutaneous Fat. Dermatology Research and Practice, 2020. DOI: https://doi.org/10.1155/2020/4093907
[77] Sabbour, A., Omar, H., El-Banna A. The Efficiency of Cavitation Ultrasound Therapy on Visceral Adiposity in Perimenopausal Women. Bull. Fac. Ph.Th. Cairo University, 2009, 14(1).
[78] Nomura, M., Yamakado, K., Nomoto, Y., Nakatsuka, A., Ii, N., Takaki, H., Yamashita, Y., Takeda, K. Complications after lung radiofrequency ablation: risk factors for lung inflammation. The British Journal of Radiology, 2008, 81(963): 244-249. DOI: https://doi.org/10.1259/bjr/84269673
[79] Richter, B., Gwechenberger, M., Socas, A., Zorn, G., Albinni, S., Marx, M., Bergler-Klein, J., Binder, T., Wojta, J. and Gössinger, H.D. Markers of oxidative stress after ablation of atrial fibrillation are associated with inflammation, delivered radiofrequency energy and early recurrence of atrial fibrillation. Clinical Research in Cardiology, 2012, 101(3): 217-225. DOI: https://doi.org/10.1007/s00392-011-0383-3
[80] Lim, H.S., Schultz, C., Dang, J., Alasady, M., Lau, D.H., Brooks, A.G., Wong, C.X., Roberts-Thomson, K.C., Young, G.D., Worthley, M.I., Sanders, P. Time course of inflammation, myocardial injury, and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation. Circulation: Arrhythmia and Electrophysiology, 2014, 7(1): 83-89. DOI: https://doi.org/10.1161/CIRCEP.113.000876
[81] Wanner, M., Avram, M., Gagnon, D., Mihm Jr, M.C., Zurakowski, D., Watanabe, K., Tannous, Z., Anderson, R.R., Manstein, D. Effects of non-invasive, 1,210nm laser exposure on adipose tissue: Results of a human pilot study. Lasers in Surgery and Medicine: The Official Journal of the American Society for Laser Medicine and Surgery, 2009, 41(6): 401-407. DOI: https://doi.org/10.1002/lsm.20785
[82] Badin AZ, Moraes LM, Gondek L, Chiaratti MG, Canta L. Laser lipolysis: flaccidity under control. Aesth Plast Surg., 2002, 26: 335 - 339 DOI: https://doi.org/10.1007/s00266-002-1510-3
[83] Dibernardo, B. E., Reyes, J., Chen, B. Evaluation of tissue thermal effects from 1064/1320-nm laser-assisted lipolysis and its clinical implications. Journal of Cosmetic and Laser Therapy, 2009, 11(2): 62-69. DOI: https://doi.org/10.1080/14764170902792181
[84] Youn, J. I., Holcomb, J. D. Ablation efficiency and relative thermal confinement measurements using wavelengths 1,064, 1,320, and 1,444 nm for laser-assisted lipolysis. Lasers in medical science, 2013, 28(2): 519-527. DOI: https://doi.org/10.1007/s10103-012-1100-9
[85] Janda P, Sroka R, Mundweil B, Betz Christian S, Baumgartner R, Leunig A. Comparison of thermal tissue effects induced by contact application of fiber guided laser systems. Lasers Surg Med., 2003, 33: 93 -101. DOI: https://doi.org/10.1002/lsm.10199
[86] Badin AZ, Gondek L, Garcia MJ, Valle LC, Flizikowski F, Noronha L. Analysis of laser lipolysis effects on human tissue samples obtained from liposuction. Aesth Plas Surg., 2005, 29: 281-286. DOI: https://doi.org/10.1007/s00266-004-0102-9
[87] Khoury JG, Saluja R, Keel D, Detwiler S, Goldman MP. Histologic evaluation of interstitial lipolysis comparting a 1064, 1320 and 2100 nm laser in an vivo model. Lasers Surg Med., 2008, 40: 402 -406. DOI: https://doi.org/10.1002/lsm.20649
[88] Ichikawa K, Tanino R, Wakaki M. Histologic and photonic evaluation of a pulsed Nd: YAG laser for ablation of subcutaneous adipose tissue. Tokai J Exp Clin Med., 2006, 31(4): 136 -140. PMID: 21302242.
[89] Tark KC, Jung JI, Song SY. Superior lipolytic effect of the 1,444 nm Nd:YAG laser: comparison with the 1,064 nm Nd:YAG laser. Lasers Surg Med., 2009, 41: 721 -727.
[90] Fakhouri, T. M., Tal, A. K. E., E. Abrou, A., Mehregan, D. A., Barone, F. Laser-assisted lipolysis: A review. Dermatologic surgery, 2012, 38(2): 155-169. DOI: https://doi.org/10.1111/j.1524-4725.2011 .02168.x
[91] Katz, B., McBean, J. Laser-assisted lipolysis: A report on complications. Journal of Cosmetic and Laser Therapy, 2008, 10(4): 231-233.DOI: https://doi.org/10.1080/14764170802524437
[92] Van Den Bos, R. R., Neumann, M., DE ROOS, K. P., Nijsten, T. Endovenous laser ablation -induced complications: review of the literature and new cases. Dermatologic surgery, 2009, 35(8): 1206-1214. DOI: https://doi.org/10.1111/j.1524-4725.2009 .01215.x
[93] Cotler HB, Chow RT, Hamblin MR, Carroll J. The use of Low Level Laser Therapy (LLLT) for musculoskeletal pain. MOJ Orthop Rheumatol, 2015, 2(5): 00068. DOI: 10.15406/mojor..02.00068
[94] Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys, 2017, 4(3): 337 -61. DOI: 10.3934/biophy.2017.3.337
[95] Bjordal JM, Lopes-Martins RAB, Iversen VV. The anti-inflammatory mechanism of low level laser therapy and its relevance for clinical use in physiotherapy. Medicine, 2010, 15: 286 -293 Corpus ID: 27687471. DOI: 10.1179/1743288X10Y.0000000001
[96] Derbenev VA, Mikhailov VA, Denisov IN. Use of low-level laser therapy (LLLT) in the treatment of some pulmonary diseases: ten-year experience. Proc SPIE, 2000, 4166: 323-5. DOI: 10.1117/12.389506
[97] Woodruff LD, Bounkeo JM, Brannon WM, et al. The efficacy of laser therapy in wound repair: a meta-analysis of the literature. Photomed Laser Surg., 2004, 22(3): 241. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15315732
[98] da Cunha Moraes G, Vitoretti LB, de Brito AA, et al. Low-level laser therapy reduces lung inflammation in an experimental model of chronic obstructive pulmonary disease involving P2X7 receptor. Oxid Med Cell Longev 2018, 4: 6798238. DOI: 10.1155/2018/6798238
[99] Mokmeli, S., Vetrici, M. Low level laser therapy as a modality to attenuate cytokine storm at multiple levels, enhance recovery, and reduce the use of ventilators in COVID-19. Canadian journal of respiratory therapy: CJRT= Revue canadienne de la therapie respiratoire: RCTR, 2020, 56(25). DOI: 10.29390/cjrt-2020-015
[100] Mokmeli, S., Vetrici, M. Low level laser therapy as a modality to attenuate cytokine storm at multiple levels, enhance recovery, and reduce the use of ventilators in COVID-19. Canadian journal of respiratory therapy: CJRT= Revue canadienne de la therapie respiratoire: RCTR, 2020, 56(25). DOI: 10.29390/cjrt-2020-015
[101] Duarte, F., Seme-Fiorese, M., Eduard de Aquino, A., Campos, R., Masquio, D., Tock, L., Duarte, A., Bagnato, V., Parizotto, N. Can low-level laser therapy (LLLT) associated with an aerobic plus resistance training change the cardiometabolic risk in obese women? A placebo-controlled clinical trial. Journal of Photochemistry and Photobiology B: Biology. 2015, 153: 103-110. DOI: https://doi.org/10.1016/j.jphotobiol.2015.08.026
[102] Duarte, F., Seme-Fiorese, M., Eduard de Aquino, A., Campos, R., Masquio, D., Tock, L., Duarte, A., Bagnato, V., Parizotto, N. The Effects of Exercise Training Associated With Low-Level Laser Therapy on Biomarkers of Adipose Tissue Transdifferentiation in Obese Women. Lasers Med Sci., 2018, 33(6): 1245- 1254. DOI: 10.1007/s10103-018-2465-1. Epub 2018 Feb 23. PMID: 29473115
[103] Ranasinghe, C., Ozemek, C., Arena, R. Exercise and well-being during COVID 19 -time to boost your immunity. Expert Review of Anti-infective Therapy, 2020, 1-6. DOI: https://doi.org/10.1080/14787210.2020.179481 8
[104] Simpson, R. J., Kunz, H., Agha, N., Graff, R. Exercise and the regulation of immune functions. In Progress in molecular biology and translational science, 2015, 135: 355-380. Academic Press. DOI: https://doi.org/10.1016/bs.pmbts.2015.08.001
[105] Nieman, D. C., Wentz, L. M. The compelling link between physical activity and the body’s defense system. Journal of sport and health science, 2019, 8(3): 201-217. DOI: https://doi.org/10.1016/j.jshs.2018.09.009
[106] Burtscher, J., Burtscher, M., Millet, G. P. (Indoor) isolation, stress and physical inactivity: vicious circles accelerated by Covid-19?. Scandinavian journal of medicine & science in sports. DOI: https://doi.org/10.1111/sms.13706
[107] Martin, S. A., Pence, B. D., Woods, J. A. Exercise and respiratory tract viral infections. Exercise and sport sciences reviews, 2009, 37(4): 157.
[108] KOSTKA, T., BERTHOUZE, S., LACOUR, J. R., BONNEFOY, M. The symptomatology of upper respiratory tract infections and exercise in elderly people. Medicine & Science in Sports & Exercise, 2000, 32(1). PMID: 10647528 DOI: 10.1097/00005768-200001000-00008
[109] Matthews, C. E., Ockene, I. S., Freedson, P. S., Rosal, M. C., Merriam, P. A., & Hebert, J. R. Moderate to vigorous physical activity and risk of upper-respiratory tract infection. Medicine and science in sports and exercise, 2002, 34(8): 1242-1248. DOI: 10.1097/00005768-200208000-00003 PMID: 12165677
[110] Wong, C. M., Lai, H. K., Ou, C. Q., Ho, S. Y., Chan, K. P., Thach, T. Q., Peiris, J. S. M. Is exercise protective against influenza-associated mortality?. PLoS One, 2008, 3(5): e2108. DOI: https://doi.org/10.1371/journal.pone.0002108
[111] Nieman, D. C., Johanssen, L. M., Lee, J. W. Infectious episodes in runners before and after a roadrace. The Journal of sports medicine and physical fitness, 1989, 29(3): 289-296. PMID: 2635263.
[112] Keating, S., Hackett, D., Parker, H, O’Connor, H., Gerofi, J., Sainsbury, A., Baker, M., Chuter, V., Caterson, I., George, J., Jhonson, N. Effect of aerobic exercise training dose on liver fat and visceral adiposity, Journal of Hematology, 2015, 63(1): 174-182. DOI: https://doi.org/10.1016/j.jhep.2015.02.022
[113] Kim, K., Valentine, R., Shin, Y., Gong, K. Associations of visceral adiposity and exercise participation with C-reactive protein, insulin resistance, and endothelial dysfunction in Korean healthy adults. Metabolism, 2008, 57: 1181-1189. DOI: https://doi.org/10.1016/j.metabol.2008.04.009
[114] McFadden Jr, E. R. Ingram Jr, R. H. Exercise-induced asthma: Observations on the initiating stimulus. New England Journal of Medicine, 1979, 301(14): 763-769. DOI: 10.1056/NEJM197910043011406
[115] George SA, Khan S, Briggs H, Abelson JL. CRH-stimulated cortisol release and food intake in healthy, non-obese adults. Psychoneuroendocrinology. 2010, 35(4): 607 -612. Available from: DOI: https://dx.doi.org/10.1016/j.psyneuen
[116] Chiodini I, Di Lembo S, Morelli V, Epaminonda P, Coletti F, Masserini B, Scillitani A, Arosio M, Adda G: Hypothalamic-pituitary-adrenal activity in type 2 diabetes: Diabetes Care. 2007, 30(1): 83-88. DOI: https://doi.org/10.2337/dc06-1267
[117] Hill EE, Zack E, Battaglini C, Viru M, Viru A, Hackney AC. Exercise and circulating cortisol levels: The intensity threshold effect. Journal of Endocrinological Investigation. 2008, 31(7): 587 -591. Available from: DOI: https://dx.doi.org/10.1007/bf03345606
[118] Skoluda N, Dettenborn L, Stalder T, Kirschbaum C. Elevated hair cortisol concentrations in endurance athletes. Elsevier BV; 2012. Available from: DOI: https://dx.doi.org/101016/j.psyneuen
[119] Landt, M., Lawson G., Helgeson J., Davila-Roman, V., Laderson J., Jaffe, A., Hickner, R. Prolonged exercise decreases serum leptin concentrations. Metabolism, 1997, 46(10): 1109-1112. DOI: https://doi.org/10.1016/S0026-0495(97)90200-6
[120] Bente Klarlund Pedersen, Adam Steensberg, Peter Schjerling. Muscle-derived interleukin-6: possible biological effects. J. of Physiology, 2001, 536 (Pt 2): 329-337. DOI: 10.1111/j.1469-7793.2001.0329c.xd https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2278876/
[121] Sofra, X. How to get rid of visceral fat: a randomised double-blind clinical trial. Journal of Aesthetic Nursing, 2020, 9(7): 268-275. DOI: https://doi.org/10.12968/joan.2020.9.7.268
[122] Sofra, X. Gain without pain: beyond sport effortless exercise solutions. Journal of Aesthetic Nursing, 2020, 9(5): 202-210. DOI: https://doi.org/10.12968/joan.2020.9.5.202
[123] Sofra X. The Importance of Systemic Balance in Safeguarding Health: A Randomized Double-Blind Clinical Trial on VLDL, Triglycerides, Free T3, Leptin, Ghrelin, Cortisol and Visceral Adipose Tissue. Health, 2020, 12(8). DOI: https://doi.org/10.4236/health.2020.128078
[124] Sofra, X., Badami, S. Adverse Effects of Sedentary Lifestyles: Inflammation, and High-Glucose Induced Oxidative Stress-A Double Blind Randomized Clinical Trial on Diabetic and Prediabetic Patients. Health, , 2020, 12(08): 1029. Article ID:102260, 20 pages. DOI: https://doi.org/10.4236/health.2020.128076
[125] Sofra, X., Lampe, N. Technological Advances in Accelerated Wound Repair and Regeneration. Health, 2020, 12(7): 717-737. DOI: 10.4236/health.2020.127053
[126] Sofra, X., Lampe, N. A Randomized Longitudinal Double-Blind Clinical Trial on Long-Term Neuropathic Symptomatology Relief & Pain Analgesia. Health, 2020, 12(07): 738. ID: 101363, 12 pages. DOI: 10.4236/health.2020.127054
[127] Sofra, X., Badami, S. A Review of COVID-19 associated factors: CRP, Creatinine, Bilirubin, VLDL, HDL, Triglycerides, Cortisol and Thyroid Function. J Endo Metabol Res, 2020, 1(2): 1-17. https://www.maplespub.com/webroot/files/A-Review-of-COVID19-associated-factors-CRP-Creatinine-Bilirubin-VLDL-HDL-Triglycerides-Cortisol-and-Thyroid-Function_1601046593.pdf
[128] Sofra, X. Dynamics of Female Sexuality; Hidden Emotional Issues. Health, 2020, 12(6): 694-708. DOI: 10.4236/health.2020.126051
[129] Sofra, X., Lampe, N. Empowering the woman: a comprehensive model of sexual anti-ageing. Journal of Aesthetic Nursing, 2020, 9(3): 118-127. DOI: https://doi.org/10.12968/joan.2020.9.3.118
Aims and Scope