SARS-CoV-2-the Unforeseen Peril of David Winning Against Goliath: the Immune Giant Collapsing Under Its Own Rampaging Cytokine Storm

Authors

  • Xanya Sofra City University, London;New School for Social Research, New York

DOI:

https://doi.org/10.30564/jer.v2i1.2517

Abstract

We examined SARS-CoV-2 (Covid-19) available treatments and prophylactic methods that included interventions associated with inhibiting the “type II transmembrane serine protease” (TMPRSS2) to limit the fusion between the Covid-19 Spike proteins and ACE2 receptors, or newly developed therapeutics like Remdesivir that interferes with the viral RNA replication. We explored the dilemma of ACE2 receptors that have a protective function against high blood pressure associated disorders, yet,they serve as the viral points of entry, elevating the probability of infection. Human tissues’ analysis reveals a higher ACE2 expression in adipose tissue, placing obesity-related conditions in the eye of the pandemic storm. It primarily exposes males due to the surge of ACE2 receptors in the testes along with other tissues. Males manifest a relatively higher positive ACE2 orrelations with certain immune cells in the lungs,thyroid, adrenals, liver and colon, while females evidence higher ACE2 correlations with immune cells in the heart. The remaining tissues’ ACE2/immunity expressions are equivalent in both sexes, indicating that despite its preference for males, the threat of Covid-19 can easily target females.Recent reports indicate that Covid-19 is empowered by hindering the critical process of viral recognition during the adaptive immune response leading to the “cytokine storm”, the aggravated immune response that indiscriminately perseveres, rampaging the host’s vital organs. Sedentary lifestyle, age-related hormonal imbalance, and adiposity induced inflammation predispose the body to the immune collapse following Covid-19 invasion, spotlighting the detrimental aftermath of metabolic dysfunction,and excess food consumption provoked by elevated cortisol and dysregulated appetite hormones. ACE 2 expression is suppressed in the skeletal muscle, rendering fitness and weight management an effective Covid-19 preventive intervention, along with social distancing, hygiene, and facial coverings. Physical activity, or exercise alternative methods have recently demonstrated statistically significant reductions of the inflammatory marker C-Reactive Protein (CRP), triglycerides, visceral fat, cortisol and the orexigenic hormone ghrelin, juxtaposed by optimal increases of IGF-1, skeletal muscle mass, Free T3, HDL, and the anorexic hormone leptin.

Keywords:

SARS-CoV-2; Covid-19; Cytokine Storm; ACE2; Skeletal Muscle Mass; Visceral Fat; Triglycerides; CRP; Cortisol; Remdesivir; Leptin; Ghrelin; Free T3; IGF-1; HDL; TMPRSS2; ADAM17; Angiotensin; nsp12

References

[1] Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, Bolling MC,Dijkstra G,Voors AA, Osterhaus AD, van der Voort PH, Mulder DJ, van Goor H.ngiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol.,2020, 251(3): 228-248.DOI: 10.1002/path.5471 Epub 2020 Jun 10. PMID:32418199;PMCID:PMC7276767

[2] Ferrario, C.M., Trask, A.J., Jessup, J.A. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1-7) in regulation of cardiovascular function.American Journal ofPhysiology-Heart and Circulatory Physiology, 2005,289(6):H2281-H2290.https://doi.org/10.1152/ajpheart.00618.2005

[3] Benter, I.F., Yousif, M.H., Dhaunsi, G.S., Kaur, J.,Chappell, M.C., Diz, D.I. Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats. American journal of nephrology, 2008, 28(1): 25-33.https://doi.org/10.1159/000108758

[4] El-Hashim, A.Z., Renno, W.M., Raghupathy, R., Abduo, H.T., Akhtar, S., Benter, I.F.Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2-and NF-κB-dependent pathways. British journal of pharmacology,2012, 166(6): 1964-1976.https://doi.org/10.1111/j.1476-5381.2012.01905.x

[5] Ocaranza, M.P., Jalil, J.E.. Protective role of the ACE2/Ang-(1-9) axis in cardiovascular remodeling.International journal of hypertension, 2012.DOI: 10.1155/2012/594361 PMCID:PMC3270559.PMID: 22315665

[6] Danser, A.J., Epstein, M. and Batlle, D. Renin-angio tensin 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.https://doi.org/10.1161/HYPERTENSIONAHA.120.15082

[7] 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

[8] 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. J Virol., 2014, 88(2): 1293-307.DOI: 10.1128/JVI.02202-13. Epub 2013 Nov 13.PMID: 24227843; PMCID: PMC3911672

[9] Cheng H, Wang Y, Wang GQ. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol., 2020,92(7): 726-730.DOI: 10.1002/jmv.25785. Epub 2020 Apr 5. PMID:32221983; PMCID: PMC7317908.

[10] Tikellis C, Bernardi S, Burns WC. Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease.Curr Opin Nephrol Hypertens., 2011, 20: 62-68 https://doi.org/10.1097/MNH.0b013e328341164a

[11] 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): 45.https://doi.org/10.1186/s40249-020-00662-x

[12] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y,Wei Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet, 2020.https://doi.org/10.1016/S0140-6736(20)30211-7

[13] Karlberg J, Chong D, Lai W. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol, 2004, 159(3): 229-31. https://doi.org/10.1093/aje/kwh056

[14] Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol., 2020, 108(1): 17-41.DOI:10.1002/JLB.3COVR0520-272R. Epub 2020 Jun 13. PMID: 32534467; PMCID:PMC7323250

[15] Tisoncik, J.R., Korth, M.J., Simmons, C.P., Farrar, J.,Martin, T.R. and Katze, M.G. Into the eye of the cytokine storm. Microbiology and Molecular Biology Reviews, 2012, 76(1): 16-32.DOI: 10.1128/MMBR.05015-11

[16] Brierley, M.M., Fish, E.N. IFN-α/β receptor interactions to biologic outcomes: understanding the circuitry. Journal of interferon & cytokine research, 2002,22(8): 835-845.https://doi.org/10.1089/107999002760274845

[17] Nguyen, K.B., Watford, W.T., Salomon, R.,Hofmann, S.R., Pien, G.C., Morinobu, A., Gadina,M., O’Shea, J.J., Biron, C.A. Critical role for STAT4 activation by type 1 interferons in the interferon-γ response to viral infection. Science, 2002, 297(5589):2063-2066.DOI: 10.1126/science.1074900

[18] Thomson, A.W., Lotze, M.T. eds. The Cytokine Handbook, Two-Volume Set. Elsevier, 2003.https://doi.org/10.1016/B978-012689663-3/50013-2

[19] Noh, M.K., Jung, M., Kim, S.H., Lee, S.R., Park,K.H., Kim, D.H., Kim, H.H. and Park, Y.G. Assessment of IL6, IL8 and TNFα levels in the gingival tissue of patients with periodontitis.Experimental and therapeutic medicine, 2013, 6(3): 847-851.https://doi.org/10.3892/etm.2013.1222

[20] Sun, L., Louie, M.C., Vannella, K.M., Wilke, C.A.,LeVine, A.M., Moore, B.B., Shanley, T.P..New concepts of IL-10-induced lung fibrosis: fibrocyte recruitment and M2 activation in a CCL2/CCR2 axis.American Journal of Physiology-Lung Cellular and Molecular Physiology, 2011, 300(3): L341-L353.https://doi.org/10.1152/ajplung.00122.2010

[21] Raman D, Sobolik-Delmaire T, Richmond A. Chemokines in health and disease. Exp. Cell Res,2011, 317:575-589.https://doi.org/10.1016/j.yexcr.2011.01.005

[22] Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol., 2008,8: 533-544.https://doi.org/10.1038/nri2356

[23] Kopf M, Bachmann MF, Marsland BJ. Averting inflammation by targeting the cytokine environment.Nat. Rev. Drug Discov., 2010, 9: 703-718.https://doi.org/10.1038/nrd2805

[24] Sethi G, Sung B, Kunnumakkara AB, Aggarwal BB.Targeting TNF for treatment of cancer and autoimmunity. Adv. Exp. Med. Biol., 2009, 647: 37-51.https://link.springer.com/chapter/10.1007/978-0-387-89520-8_3

[25] Pugin, J., Ricou, B., Steinberg, K.P., Suter, P.M.,Martin, T.R. Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1. American journal of respiratory and critical care medicine, 1996, 153(6):1850-1856.https://doi.org/10.1164/ajrccm.153.6.8665045 PubMed: 8665045

[26] Imai, Y., Parodo, J., Kajikawa, O., de Perrot, M.,Fischer, S., Edwards, V., Cutz, E., Liu, M., Keshavjee, S., Martin, T.R., Marshall, J.C.. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. Jama,2003, 289(16): 2104-2112. DOI: 10.1001/jama.289.16.2104

[27] Levy, M.M., Fink, M.P., Marshall, J.C., Abraham, E.,Angus, D., Cook, D., Cohen, J., Opal, S.M., Vincent,J.L., Ramsay, G.. 2001 sccm/esicm/accp/ats/sis international sepsis definitions conference.Intensive care medicine, 2003, 29(4): 530-538.https://doi.org/10.1007/s00134-003-1662-x

[28] Abraham, E., Glauser, M.P., Butler, T., Garbino, J.,Gelmont, D., Laterre, P.F., Kudsk, K.,Bruining, H.A.,Otto, C., Tobin, E., Zwingelstein, C. Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock: A randomized controlled multicenter trial. Jama, 1997,277(19): 1531-1538.DOI: 10.1001/jama.1997.03540430043031

[29] Wurfel, M.M., Gordon, A.C., Holden, T.D., Radella,F., Strout, J., Kajikawa, O., Ruzinski, J.T., Rona, G.,Black, R.A., Stratton, S. and Jarvik, G.P. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. American journal of respiratory and critical care medicine, 2008, 178(7):710-720.https://doi.org/10.1164/rccm.200803-462OC PubMed: 18635889

[30] 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

[31] 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

[32] 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.https://doi.org/10.1080/22221751.2020.1770129

[33] 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., Marron,T.U. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature medicine,2020:1-8.https://doi.org/10.1038/s41591-020-1051-9

[34] 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.https://doi.org/10.1002/jmv.26070

[35] 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.https://doi.org/10.1016/j.metabol.2009.04.025

[36] 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

[37] 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.https://doi.org/10.1038/nrmicro.2016.81 https://www.nature.com/articles/nrmicro.2016.81.pdf?origin=ppub

[38] Park WY, et al. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am. J.Respir. Crit. Care Med., 2001, 164: 1896-1903.https://doi.org/10.1164/ajrccm.164.10.2104013PubMed: 11734443

[39] Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC,Mou HM, Wang LH, Zhang HR, Fu WJ, Luo T, Liu F, Guo QN, Chen C, Xiao HL, Guo HT, Lin S, Xiang DF, Shi Y, Pan GQ, Li QR, Huang X, Cui Y, Liu XZ,Tang W, Pan PF, Huang XQ, Ding YQ, Bian XW. A pathological report of three COVID-19 cases by minimal invasive autopsies. Zhonghua Bing Li Xue Za Zhi, 2020, 49(5): 411-417. (in Chinese)DOI: 10.3760/cma.j.cn112151-20200312-00193 PMID: 32172546

[40] Gupta, R., Ghosh, A., Singh, A.K., Misra, A. Clinical Considerations for Patients with Diabetes in Times of COVID-19 Epidemic. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2020, 14: 211-212.https://doi.org/10.1016/j.dsx.2020.03.002

[41] Cameron, M.J., Ran, L., Xu, L., Danesh, A., Bermejo-Martin, J.F., Cameron, C.M., Muller, M.P., Gold,W.L., Richardson, S.E., Poutanen, S.M., Willey, B.M.Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. Journal of virology, , 2007, 81(16): 8692-8706.DOI: 10.1128/JVI.00527-07

[42] Cheung, C. Y., L. L. Poon, I. H. Ng, W. Luk, S. F.Sia, M. H. Wu, K. H. Chan, K. Y. Yuen, S. Gordon, Y.Guan, J. S. Peiris. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macro phages in vitro: possible relevance to pathogenesis. J.Virol., 2005, 79: 7819-7826.DOI: 10.1128/JVI.79.12.7819-7826.2005

[43] Lo, A.W., Tang, N.L., To, K.F. How the SARS coronavirus causes disease: host or organism?. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland, , 2006, 208(2):142-151.https://doi.org/10.1002/path.1897

[44] Prompetchara, E., Ketloy, C., Palaga, T.. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol, 2020, 38(1): 1-9.http://apjai-journal.org/wp-content/uploads/2020/03/1.pdf?fbclid=IwAR1kVlFnoc6mobqEy7FDz_93fX__AaY8ZgE4TUwtjzhh8oVqgs82rgf3QoU

[45] Faure, E., Poissy, J., Goffard, A., Fournier, C., Kipnis, E., Titecat, M., Bortolotti, P., Martinez, L., Dubucquoi, S., Dessein, R., Gosset, P. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside?. PloS one, 2014, 9(2):e88716.https://doi.org/10.1371/journal.pone.0088716

[46] Hamano, E., Hijikata, M., Itoyama, S., Quy, T., Phi,N.C., Long, H.T., Van Ban, V., Matsushita, I., Yanai,H., Kirikae, F., Kirikae, T. Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population. Biochemical and biophysical research communications, 2005,329(4): 1234-1239.https://doi.org/10.1016/j.bbrc.2005.02.101

[47] Tang, N.L.S., Chan, P.K.S., Wong, C.K., To, K.F.,Wu, A.K.L., Sung, Y.M., Hui, D.S.C., Sung, J.J.Y.,Lam, C.W.K. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clinical chemistry, 2005,51(12): 2333-2340.https://doi.org/10.1373/clinchem.2005.054460

[48] Shao, L., Sperber, K. Impaired regulation of HLADR expression in human immunodeficiency virus-infected monocytes. Clinical and Diagnostic Laboratory Immunology, 2002, 9(4): .739-746.DOI: 10.1128/CDLI.9.4.739-746.2002

[49] Kobasa, D., Jones, S.M., Shinya, K., Kash, J.C.,Copps, J., Ebihara, H., Hatta, Y., Kim, J.H.,Halfmann, P., Hatta, M., Feldmann, F. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature, 2007,445(7125): 319-323.https://doi.org/10.1038/nature05495

[50] Wong, C.K., Tsang, C.M., Ip, W.K., Lam, C.W.K.Molecular mechanisms for the release of chemokines from human leukemic mast cell line (HMC)-1 cells activated by SCF and TNF-α: roles of ERK, p38 MAPK, and NF-κB. Allergy, 2006, 61(3): 289-297.https://doi.org/10.1111/j.1398-9995.2006.00972.x

[51] Subissi L., Posthuma C. C., Collet A., Zevenhoven-Dobbe J. C., Gorbalenya A. E., Decroly E.,Snijder E. J., Canard B., Imbert I. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc. Natl. Acad. Sci. U.S.A., 2014,111: E3900-E3909.DOI: 10.1073/pnas.1323705111

[52] Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M.,Shi Z., Hu Z., Zhong W., Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res.,2020, 30: 269-271 DOI: 10.1038/s41422-020-0282-0

[53] Holshue M. L., DeBolt C., Lindquist S., Lofy K. H.,Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G., Cohn A., Fox L., Patel A.,Gerber S. I., Kim L., Tong S., Lu X., Lindstrom S.,Pallansch M. A., Weldon W. C., Biggs H. M., Uyeki T.M., Pillai S. K. Washington State 2019-nCoV Case Investigation Team , First Case of 2019 Novel Coronavirus in the United States. N. Engl. J. Med., 2020,382: 929-936 DOI: 10.1056/NEJMoa2001191

[54] Kirchdoerfer R. N., Ward A. B. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat. Commun., 2019, 10: 2342 DOI: 10.1038/s41467-019-10280-3

[55] Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M.,Shi Z., Hu Z., Zhong W., Xiao G.,Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res.,2020, 30: 269-271.DOI: 10.1038/s41422-020-0282-0

[56] Holshue M. L., DeBolt C., Lindquist S., Lofy K. H.,Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G., Cohn A., Fox L., Patel A.,Gerber S. I., Kim L., Tong S., Lu X.,Lindstrom S.,Pallansch M. A., Weldon W. C., Biggs H. M., Uyeki T.M., Pillai S. K., Washington State 2019-nCoV Case Investigation Team , First Case of 2019 Novel Coronavirus in the United States. N. Engl. J. Med., 2020,382: 929-936.DOI: 10.1056/NEJMoa2001191

[57] Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L.,Wang, T., Sun, Q., Ming, Z., Zhang, L., Ge, J. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 2020, 368(6492):779-782.DOI: 10.1126/science.abb7498

[58] Spinner, C.D., Gottlieb, R.L., Criner, G.J., López,J.R.A., Cattelan, A.M., Viladomiu, A.S.,Ogbuagu,O., Malhotra, P., Mullane, K.M., Castagna, A., Chai,L.Y.A. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA, 2020,324(11): 1048-1057.DOI: 10.1001/jama.2020.16349

[59] Rochwerg, B., Agarwal, A., Zeng, L., Leo, Y.S.,Appiah, J.A., Agoritsas, T., Bartoszko, J., Brignardello-Petersen, R., Ergan, B., Ge, L., Geduld, H.Remdesivir for severe covid-19: a clinical practice guideline. bmj, 2020, 370.https://doi.org/10.1136/bmj.m2924

[60] Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America Guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis;ciaa, 2020, 478.DOI: 10.1093/cid/ciaa478 pmid:32338708

[61] Ye W, Yao M, Dong Y, et al.. Remdesivir (GS-5734) impedes enterovirus replication through viral RNA synthesis inhibition. Front Microbiol, 2020, 11:1105.DOI: 10.3389/fmicb.2020.01105 pmid:32595613

[62] National Institutes of Health. COVID-19 treatment guidelines. 2020.https://www.covid19treatmentguidelines.nih.gov/whats-new/

[63] Gandhi, M., Beyrer, C., Goosby, E. Masks do more than protect others during COVID-19:educing the inoculum of SARS-CoV-2 to protect the wearer.Journal of general internal medicine, 2020: 1-4.https://doi.org/10.1007/s11606-020-06067-8

[64] Centers for Disease Control and Prevention. Regarding the Use of Cloth Face Coverings,Especially in Areas of Significant Community-Based Transmission, 2020.https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover.html

[65] World Health Organization. Advice on the use of masks in the context of COVID-19. Interim guidance, 2020. Accessible at:https://apps.who.int/iris/handle/10665/331693

[66] World Health Organization. Advice on the use of masks in the context of COVID-19, Interim guidance, 5 June 2020. Accessible at:https://www.who.int/publications/i/item/advice-on the-use-of-masks-in-the-community-during-homecare-and-in-healthcare-settings-in-the-context-of-thenovel-coronavirus-(2019-ncov)-outbreak

[67] Gandhi, M., Yokoe, D.S., Havlir, D.V. Asymptomatic transmission, the Achilles’ heel of current strategies to control COVID-19, 2020.DOI: 10.1056/NEJMe2009758

[68] He, X., Lau, E.H., Wu, P., Deng, X., Wang, J., Hao,X., Lau, Y.C., Wong, J.Y., Guan, Y., Tan, X., Mo, X.Temporal dynamics in viral shedding and transmissibility of COVID-19. Nature medicine, 2020, 26(5):672-675.https://doi.org/10.1038/s41591-020-0869-5

[69] Handel, A., Li, Y., McKay, B., Pawelek, K.A.,Zarnitsyna, V., Antia, R. Exploring the impact of inoculum dose on host immunity and morbidity to inform model-based vaccine design. PLoS computational biology, 2018, 14(10): e1006505.https://doi.org/10.1371/journal.pcbi.1006

[70] Miller, D.S., Kok, T., Li, P. The virus inoculum volume influences outcome of influenza A infection in mice. Laboratory animals, 2013, 47(1): 74-77.https://doi.org/10.1258/la.2012.011157

[71] McKenney, D.G., Kurath, G., Wargo, A.R. Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV). Virus research, 2016, 214: 80-89.https://doi.org/10.1016/j.virusres.2015.12.020

[72] Kai, D., Goldstein, G.P., Morgunov, A., Nangalia,V., Rotkirch, A. Universal masking is urgent in the covid-19 pandemic: Seir and agent based models,empirical validation, policy recommendations, 2020.arXiv preprint arXiv:2004.13553.arXiv:2004.1355 arXiv:2004.13553v1

[73] Niemietz B. Photo of 1918 college football fans wearing face masks points to the past and future.New York Daily News, 2020. Accessible at:https://www.nydailynews.com/coronavirus/ny-photo-mask-georgia-tech-1918-pandemic-flu-coronavirus-20200525-fbkqrf6tqjgf7plck2emfjdjvi-story.html

[74] Ward A. How masks helped Hong Kong control the coronavirus. Vox, 2020. Accessible at:https://www.vox.com/2020/5/18/21262273/coronavirus-hong-kong-masks-deaths-new-york

[75] Watanabe M, Caruso D, Tuccinardi D, Risi R,Zerunian M, Polici M, Pucciarelli F, Tarallo M, Strigari L, Manfrini S, Mariani S, Basciani S, Lubrano C,Laghi A, Gnessi L. Visceral fat shows the strongest association with the need of intensive care in patients with COVID-19. Metabolism, 2020, 111: 154319. DOI: 10.1016/j.metabol.2020.154319. Epub 2020 Jul 23. PMID: 32712222; PMCID: PMC7377788

[76] Petersen A, Bressem K, Albrecht J, Thieß HM,Vahldiek J, Hamm B, Makowski MR, Niehues A,Niehues SM, Adams LC. The role of visceral adiposity in the severity of COVID-19: Highlights from a unicenter cross-sectional pilot study in Germany.Metabolism, 2020, 110: 154317.DOI:10.1016/j.metabol.2020.154317. Epub. PMID:32673651; PMCID: PMC7358176

[77] Iacobellis G, Malavazos AE, Ferreira T. Sep 2.COVID-19 Rise in Younger Adults with Obesity:Visceral Adiposity Can Predict the Risk. Obesity (Silver Spring), 2020, 28(10): 1795.DOI:10.1002/oby.22951. Epub. PMID: 32619294;PMCID: PMC7361935

[78] Wajchenberg, B.L., Giannella-Neto, D., Da Silva,M.E.R., Santos, R.F. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome.Hormone and metabolic research, 2002, 34(11/12):616-621.DOI: 10.1055/s-2002-38256

[79] Pedersen, B.K., Febbraio, M.A. Muscles, exercise and obesity: skeletal muscle as a secretory organ.Nature Reviews Endocrinology, 2012, 8(8): 457-465.https://doi.org/10.1038/nrendo.2012.49

[80] Dyck, D.J., Putman, C.T., Heigenhauser, G.J., Hultman, E., Spriet, L.L. Regulation of fat-carbohydrate interaction in skeletal muscle during intense aerobic cycling. American Journal of Physiology-Endocrinology And Metabolism, 1993, 265(6): .E852-E859.https://doi.org/10.1152/ajpendo.1993.265.6.E852

[81] Romijn, J.A., Coyle, E.F., Sidossis, L.S., Zhang, X.J.,Wolfe, R.R. Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise.Journal of Applied Physiology, 1995, 79(6): 1939-1945.DOI: https://doi.org/10.1152/jappl.1995.79.6.1939

[82] Robergs, R.A., Frankel, C. Relationship between fatty acid delivery and fatty acid oxidation during exercise. Journal of Applied Physiology, 1996, 81(3):1450-1452.https://doi.org/10.1152/jappl.1996.81.3.1450

[83] Spriet, L.L. New insights into the interaction of carbohydrate and fat metabolism during exercise. Sports medicine, 2014, 44(1): 87-96.DOI: https://doi.org/10.1007/s40279-014-0154-1

[84] Hargreaves, M., Spriet, L.L. Exercise metabolism:fuels for the fire. Cold Spring Harbor perspectives in medicine, 2018, 8(8): a029744.DOI: 10.1101/cshperspect.a029744

[85] Robinson, S.L. Fat oxidation during exercise: significance, determinants and response to nutrition (Doctoral dissertation, University of Birmingham), 2016.http://etheses.bham.ac.uk/id/eprint/7079

[86] Glatz, J.F., Luiken, J.J., Bonen, A. Membrane fatty acid transporters as regulators of lipid metabolism:implications for metabolic disease. Physiological reviews, 2010.https://doi.org/10.1152/physrev.00003.2009

[87] Sahlin, K. Control of lipid oxidation at the mitochondrial level. Applied Physiology, Nutrition, and Metabolism, 2009, 34(3): 382-388.https://doi.org/10.1139/H09-027

[88] Smith, B.K., Bonen, A., Holloway, G.P. A dual mechanism of action for skeletal muscle FAT/CD36 during exercise. Exercise and sport sciences reviews, 2012,40(4): 211-217.DOI: 10.1097/JES.0b013e31825eb263

[89] Franco, C., Brandberg, J., Lönn, L., Andersson,B., Bengtsson, B.A., Johannsson, G. Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. The Journal of Clinical Endocrinology & Metabolism, 2005, 90(3):1466-1474.https://doi.org/10.1210/jc.2004-1657

[90] Ronnemaa, T., Karonen, S.L., Rissanen, A., Koskenvuo, M., Koivisto, V.A. Relation between plasma leptin levels and measures of body fat in identical twins discordant for obesity. Annals of internal medicine, 1997, 126(1): 26-31.https://doi.org/10.7326/0003-4819-126-1-199701010-00004

[91] Dua, A., Hennes, M.I., Hoffmann, R.G., Maas, D.L.,Krakower, G.R., Sonnenberg, G.E. and Kissebah,A.H. Leptin: a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African-American women. Diabetes, 1996, 45(11):1635-1637.https://doi.org/10.2337/diab.45.11.1635

[92] Banerji, M.A., Faridi, N., Atluri, R., Chaiken, R.L.,Lebovitz, H.E. Body composition, visceral fat, leptin,and insulin resistance in Asian Indian men. The journal of clinical endocrinology & metabolism, 1999,84(1): 137-144.DOI: https://doi.org/10.1210/jcem.84.1.5371

[93] Nam, J.S., Cho, M., Park, J.S., Ahn, C.W., Cha,B.S., Lee, E.J., Lim, S.K., Kim, K.R. and Lee, H.C.Triiodothyronine level predicts visceral obesity and atherosclerosis in euthyroid, overweight and obese subjects: T3 and visceral obesity. Obesity Research & Clinical Practice, 2010, 4(4): e315-e323.DOI: https://doi.org/10.1016/j.orcp.2010.08.003

[94] 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

[95] 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

[96] 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

[97] del Pino Emilia, M., Rosado, R.H., Azuela, A., Graciela, M.G., Argüelles, D., Rodríguez, C., 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

[98] 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

[99] Kapoor, R., Shome, D., 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

[100] 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/10.1080/14787210.2020.1794818

[101] Simpson, R. J., Kunz, H., Agha, N., Graff, R. Exercise and the regulation of immune functions. In Progress in molecular biology and translational science,Academic Press, 2015, 135: 355-380.DOI: https://doi.org/10.1016/bs.pmbts.2015.08.001

[102] 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

[103] 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, 2020.DOI: https://doi.org/10.1111/sms.13706

[104] Martin, S. A., Pence, B. D., Woods, J. A. Exercise and respiratory tract viral infections. Exercise and sport sciences reviews, 2009, 37(4): 157.

[105] 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

[106] 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

[107] 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.https://doi.org/10.1371/journal.pone.0002108

[108] 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

[109] 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

[110] 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:https://dx.doi.org/10.1016/j.psyneuen.2009.09.017

[111] 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.https://doi.org/10.2337/dc06-1267

[112] 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:https://dx.doi.org/10.1007/bf03345606

[113] Skoluda N, Dettenborn L, Stalder T, Kirschbaum C.Elevated hair cortisol concentrations in endurance athletes. Elsevier BV, 2012. Available from:https://dx.doi.org/101016/j.psyneuen.2011.09.001

[114] 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

[115] 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

[116] 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

[117] 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

[118] 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

[119] Sofra, X., Lampe, N. Technological Advances in Accelerated Wound Repair and Regeneration. Health,2020, 12(7): 717-737.DOI: 10.4236/health.2020.127053

[120] 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

[121] 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

[122] Sofra, X. Dynamics of Female Sexuality; Hidden Emotional Issues. Health, 2020, 12(6): 694-708.DOI: 10.4236/health.2020.126051

[123] 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

[124] Sofra, X. The Affinity between Obesity and COVID-19. J Endo Metabol Res, 2020, 1(2): 1-13.https://maplespub.com/webroot/files/The-Affinity-between-Obesity-and-COVID-19_1602748373.pdf

[125] Sofra X, Badami S. A Review of COVID19 associated factors: CRP, Creatinine, Bilirubin, VLDL, HDL,Triglycerides, Cortisol, and Thyroid Function.J Endo Metabol Res., 2020, 1(2):1-17.https://maplespub.com/article/A-Re-view-of-COVID19-associated-factors-CRP-Creatinine-Bilirubin-VLDL-HDL-Triglycerides-Cortisol-and-Thyroid-Function

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Sofra, X. (2020). SARS-CoV-2-the Unforeseen Peril of David Winning Against Goliath: the Immune Giant Collapsing Under Its Own Rampaging Cytokine Storm. Journal of Endocrinology Research, 2(1), 26–43. https://doi.org/10.30564/jer.v2i1.2517

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