The COVID-19 pandemic has experienced unprecedented limitations and extraordinary scientific efforts to address this exceptional situation. Despite blanket closures that have resulted in significant financial constraints and losses around the world, research has an “unlimited” budget, with an exceptional concentration of medical and scientific care on a single topic: understanding the mechanisms for overcoming the disease. A large number of clinical trials have been launched with different drugs that have been behind different concepts and solutions. I would like to focus on the complexity aspect of COVID-19. Living systems are organized in a complex way, which implies dynamic stochastic phenomena, and deterministic reductionism can mislead research. When research focuses on individual molecules or pathways as products, it is distracted from the processes in which these products operate, thus neglecting the complex interactions between regulations and feedback controls. Common problems in product-oriented research are articulated as “double-edged swords”, “Janus behavior”, “two-sided action”, with a simple question: “friend or foe?” I focus on the missing complexity. I propose a bioelectromagnetic process that can maintain a complex approach, affecting processes rather than products. This hypothetical proposal is not a comprehensive solution. Complexity itself limits the overall effects of causing “miracles”. Well-designed electromagnetic effects can support current efforts and, in combination with intensively developed pharmaceuticals, bring us closer to a pharmaceutical solution against COVID-19.
References
[1]
Peiris, J.S., Lai, S.T., Poon, L.L. and SARS Study Group (2003) Coronavirus as a Possible Cause of Severe Acute Respiratory Syndrome. The Lancet, 361, 1319-1325. https://doi.org/10.1016/S0140-6736(03)13077-2
[2]
Drosten, C., Gunther, S., Preiser, W., et al. (2003) Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome. The New England Journal of Medicine, 348, 1967-1976. https://doi.org/10.1056/NEJMoa030747
[3]
Gorbalenya, A.E., Baker, S.C., Baric, R.S., de Groot, R.J., Drosten, C., Gulyaeva, A.A., et al. (2020) The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-nCoV and Naming It SARS-CoV-2. Nature Microbiology, 5, 536-544. https://doi.org/10.1038/s41564-020-0695-z
[4]
Ducharme, J. (2020) World Health Organization Declares COVID-19 a “Pandemic”. Here’s What That Means, time.com. https://time.com/5791661/who-coronavirus-pandemic-declaration/
[5]
Barry, C.A. (1983) Pareto Distributions. International Co-Operative Publishing House, Fairland.
[6]
Galvani, A.P. and May, R.M. (2005) Epidemiology: Dimensions of Superspreading. Nature, 438, 293-295. https://doi.org/10.1038/438293a
[7]
Chin, W.C.B. and Bouffanais, R. (2020) Spatial Super-Spreaders and Super-Susceptibles in Human Movement Networks. https://arxiv.org/abs/2005.05063 https://doi.org/10.1038/s41598-020-75697-z
[8]
Bergmann, K. (2014) UV-C Irradiation: A New Viral Inactivation Method for Biopharmaceuticals. America Pharmaceutical Review, Thursday, November 20, 2014. https://www.americanpharmaceuticalreview.com/Featured-Articles/169257-UV-C- Irradiation-A-New-Viral-Inactivation-Method-for-Biopharmaceuticals/
[9]
Van Doremalen, N., Morris, D.H., Holbrook, M.G., et al. (2020) Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. The New England Journal of Medicine, 382, 16. https://doi.org/10.1056/NEJMc2004973
[10]
Liu, M. (2020) Overlapping and Discrete Aspects of the Pathology of SARS-CoV, MERS-CoV, and 2019-nCoV. Journal of Medical Virology, 92, 491-494. https://doi.org/10.1002/jmv.25709
[11]
Raoult, D., Zumla, A., Locatelli, F., et al. (2020) Coronavirus Infections: Epidemiological, Clinical and Immunological Features and Hypotheses. Cell Stress, 4, 66-75. https://doi.org/10.15698/cst2020.04.216
[12]
Pathak, N. (2020) The “Great Imitator”: How COVID-19 Can Look like Almost Any Condition? https://www.medicinenet.com/the_great_imitator_covid-19_coronavirus-news.htm
[13]
Amaghashlag, D., Kandasami, G., Almanasef, M., et al. (2020) Review on the Coronavirus Disease (COVID-19) Pandemic: Its Outbreak and Current Status. International Journal of Clinical Practice, 74, e13637. https://doi.org/10.1111/ijcp.13637
[14]
Scarpetta, S., Pearson, M., Colombo, F., et al. (2020) OECD Treatments and a Vaccine for COVID-19: The Need for Coordinating Policies on R&D, Manufacturing and Access.
[15]
Mather, N. (2020) How We Accelerated Clinical Trials in the Age of Coronavirus. Nature, 584, 326. https://doi.org/10.1038/d41586-020-02416-z
[16]
Coronavirus Research Database, Stanford University. https://covdb.stanford.edu/search/?study=clinical-studies&virus=SARS-CoV-2
[17]
Weinrauch, Y. and Zychlinsky, A. (1999) The Induction of Apoptosis by Bacterial Pathogens. Annual Review of Microbiology, 53, 155-187. https://doi.org/10.1146/annurev.micro.53.1.155
[18]
Feys, B.J. and Parker, J.E. (2000) Interplay of Signaling Pathways in Plant Disease Resistance. Trends in Genetics, 16, 4449-4555. https://doi.org/10.1016/S0168-9525(00)02107-7
[19]
Jacobson, M.D., Weil, M. and Raff, M.C. (1997) Programmed Cell Death in Animal Development. Cell, 88, 347-354. https://doi.org/10.1016/S0092-8674(00)81873-5
[20]
Kerr, J.F., Wyllie, A.H. and Currie, A.R. (1972) Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics. British Journal of Cancer, 26, 239-257. https://doi.org/10.1038/bjc.1972.33
[21]
Wyllie, A.H. (1980) Glucocorticoid-Induced Thymocyte Apoptosis Is Associated with Endogenous Endonuclease Activation. Nature, 284, 555-556. https://doi.org/10.1038/284555a0
[22]
Núñez, G., Benedict, M.A., Hu, Y. and Inohara, N. (1998) Caspases: The Proteases of the Apoptotic Pathway. Oncogene, 17, 3237-3245. https://doi.org/10.1038/sj.onc.1202581
[23]
Kumar, S. (1999) Mechanisms Mediating Caspase Activation in Cell Death. Cell Death & Differentiation, 6, 1060-1066. https://doi.org/10.1038/sj.cdd.4400600
[24]
Ganz, T. (2003) Defensins: Antimicrobial Peptides of Innate Immunity. Nature Reviews Immunology, 3, 710-720. https://doi.org/10.1038/nri1180
[25]
Yousefifard, M., Zali, A., Ali, K.M., et al. (2020) Antiviral Therapy in Management of COVID-19: A Systematic Review on Current Evidence. Archives of Academic Emergency Medicine, 8, e45. https://doi.org/10.1111/ijcp.13557
[26]
Nitolescu, G.M., Paunescu, H., Moschos, S.A., et al. (2020) Comprehensive Analysis of Drugs to Treat SARS-CoV-2 Infection: Mechanistic Insights into Current Covid-19 Therapies (Review). International Journal of Molecular Medicine, 46, 467-488. https://doi.org/10.3892/ijmm.2020.4608
[27]
Callawy, E. (2020) The Race for Coronavirus Vaccines. Nature, 580, 576-577. https://doi.org/10.1038/d41586-020-01221-y
[28]
Siemieniuk, R.A.C., Bartoszko, J.J., Ge, L., et al. (2020) Drug Treatments for Covid-19: Living Systematic Review and Network Meta-Analysis. BMJ, 370, m2980.
[29]
NIH Halts Clinical Trial of Hydroxychloroquine. https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine
[30]
Chen, C., Huang, J., Cheng, Z., Wu, J., Chen, S., Zhang, Y., et al. (2020) Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. https://doi.org/10.1101/2020.03.17.20037432
[31]
Grein, J., Ohmagari, N., Shin, D., et al. (2020) Compassionate Use of Remdesivir for Patients with Severe COVID-19. New England Journal of Medicine, 382, 2327-2336. https://doi.org/10.1056/NEJMoa2007016
[32]
Beigel, J.H., Tomashek, K.M., Dodd, L.E., Mehta, A.K., Zingman, B.S., Kalil, A.C., et al. (2020) Remdesivir for the Treatment of Covid-19—Preliminary Report. New England Journal of Medicine, 383, 993. https://doi.org/10.1056/NEJMoa2007764
[33]
Sheahan, T.P., Sims, A.C., Leist, S.R., Schäfer, A., Won, J., Brown, A.J., et al. (2020) Comparative Therapeutic Efficacy of Remdesivir and Combination Lopinavir, Ritonavir, and Interferon Beta against MERS-CoV. Nature Communications, 11, 222. https://doi.org/10.1038/s41467-019-13940-6
[34]
Kim, U.J., Won, E.J., Kee, S.J., Jung, S.I. and Jang, H.C. (2016) Combination Therapy with Lopinavir/Ritonavir, Ribavirin and Interferon-α for Middle East Respiratory Syndrome. Antiviral Therapy, 21, 455-459. https://doi.org/10.3851/IMP3002
[35]
del Rio, C. and Malani, P.N. (2019) Novel Coronavirus—Important Information for Clinicians. JAMA, 323, 1039-1040. https://doi.org/10.1001/jama.2020.1490
[36]
Lim, J., Jeon, S., Shin, H.Y., Kim, M.J., Seong, Y.M., Lee, W.J., et al. (2020) Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: The Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR. Journal of Korean Medical Science, 35, e79. https://doi.org/10.3346/jkms.2020.35.e89
[37]
Cao, B., et al. (2020) A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. The New England Journal of Medicine, 382, 1787-1799. https://doi.org/10.1056/NEJMoa2001282
[38]
Jawhara, S. (2020) Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? International Journal of Molecular Sciences, 21, 2272. https://doi.org/10.3390/ijms21072272
[39]
Luo, P., Liu, Y., Qiu, L., Liu, X., Liu, D. and Li, J. (2020) Tocilizumab Treatment in COVID-19: A Single Center Experience. Journal of Medical Virology, 92, 814-848. https://doi.org/10.1002/jmv.25801
[40]
Ledford, H. (2020) US Widens Access to Covid-19 Plasma—Despite Lack of Data. Nature, 584, 505. https://doi.org/10.1038/d41586-020-02324-2
[41]
Sullivan, H.C. and Roback, J.D. (2020) Convalescent Plasma: Therapeutic Hope or Hopeless Strategy in the SARS-CoV-2 Pandemic. Transfusion Medicine Reviews, 34, 145-150. https://doi.org/10.1016/j.tmrv.2020.04.001
[42]
Cohrane-Targeted Update: Safety and Efficacy of Hydroxychloroquine or Chloroquine for Treatment of Covid-19. https://www.who.int/publications/m/item/targeted-update-safety-and-efficacy-of- hydroxychloroquine-or-chloroquine-for-treatment-of-covid-19
[43]
Zhou, Y., Chen, V., Shannon, C.P., et al. (2020) Interferon-α2b Treatment for Covid-19. Frontiers in Immunology, 11, 1061. https://doi.org/10.3389/fimmu.2020.01061
[44]
Fu, W., Liu, Y., Xia, L., et al. (2020) A Clinical Pilot Study on the Safety and Efficacy of Aerosol Inhalation Treatment of IFN-κ plus TFF2 in Patients with Moderate COVID-19. EClinicalMedicine, 25, Article ID: 100478. https://doi.org/10.1016/j.eclinm.2020.100478
[45]
Krammer, F. (2020) SARS-CoV-2 Vaccines in Development. Nature, 586, 516-527. https://doi.org/10.1038/s41586-020-2798-3
[46]
Li, W., Schafer, A., Kulkarni, S.S., et al. (2020) High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models. Cell, 183, 429-441.e16. https://doi.org/10.1016/j.cell.2020.09.007
[47]
Logunov, D.Y., Dolzhikova, I.V., Zubkova, O.V., et al. (2020) Safety and Immunogenicity of an rAd26 and rAd5 Vector-Based Heterologous Prime-Boost Covid-19 Vaccine in Two Formulations: Two Open, Non-Randomised Phase 1/2 Studies from Russia. The Lancet, 396, 887-897. https://doi.org/10.1016/S0140-6736(20)31866-3
[48]
Burki, T.K. (2020) The Russian Vaccine for COVID-19. The Lancet Respiratory Medicine, 8, E85-E86. https://doi.org/10.1016/S2213-2600(20)30402-1
[49]
Bar-Zeev, N. and Inglesby, T. (2020) COVID-19 Vaccines: Early Success and Remaining Challenges. The Lancet, 396, 868-869. https://doi.org/10.1016/S0140-6736(20)31867-5
[50]
Coronavirus: Oxford University Vaccine Trial Paused after Participant Falls Ill. https://www.bbc.com/news/world-54082192
[51]
Foster, R. and Mundell, E.J. (2020) Details Emerge on Unexplained Illness in AstraZeneca COVID Vaccine Trial. Medical Press. https://medicalxpress.com/news/2020-09-emerge-unexplained-illness-astrazeneca-covid.html
[52]
Cyranoski, D. and Malapaty, S. (2020) Relief as Coronavirus Vaccine Trials Restart—But Transparency Concerns Remain. Nature, 585, 331-332. https://doi.org/10.1038/d41586-020-02633-6
[53]
Pan, H.-C., Peto, R., Karim, Q.A., Alejandria, M., Henao-Restrepo, A.M., García, C.H., Kieny, M.-P., Malekzadeh, R., Murthy, S., Preziosi, M.-P., Reddy, S., Periago, M.R., Sathiyamoorthy, V., Røttingen, J.-A., Swaminathan, S. and WHO Solidarity Trial Consortium (2020) Repurposed Antiviral Drugs for COVID-19-Interim WHO Solidarity Trial Results.
[54]
Fox, M. (2020) Johnson & Johnson Pauses Covid-19 Vaccine Trial after “Unexplained Illness”. https://edition.cnn.com/2020/10/12/health/johnson-coronavirus-vaccine-pause-bn/index.html
[55]
Lovelace, B. and Farr, C. (2020) U.S. Pauses Eli Lilly’s Trial of a Coronavirus Antibody Treatment over Safety Concerns. https://www.cnbc.com/2020/10/13/us-pauses-eli-lillys-trial-of-a-coronavirus-antibody-treatment-over-safety-concerns.html
[56]
Horby, P., Lim, W.S., Emberson, J.R., et al. (2020) The Recovery Collaborative Group, Dexamethasone in Hospitalized Patients with Covid-19—Preliminary Report. NEJM.
[57]
Wolf, Y.I., Katsnelson, M.I. and Koonin, E.V. (2018) Physical Foundations of Biological Complexity. PNAS, 115, E8678-E8687. https://doi.org/10.1073/pnas.1807890115
[58]
Wu, M. and Higgs, P.G. (2012) The Origin of Life Is a Spatially Localized Stochastic Transition. Biology Direct, 7, 42. https://doi.org/10.1186/1745-6150-7-42
[59]
Hegyi, G., Vincze, Gy. and Szasz, A. (2012) On the Dynamic Equilibrium in Homeostasis. Open Journal of Biophysics, 2, 64-71. https://doi.org/10.4236/ojbiphy.2012.23009
[60]
Modell, H., Cliff, W., Michael, J., et al. (2015) A Physiologist’s View of Homeostasis. Advances in Physiology Education, 39, 259-266. https://doi.org/10.1152/advan.00107.2015
[61]
Billman, G.E. (2020) Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Frontiers in Physiology, 11, 200. https://doi.org/10.3389/fphys.2020.00200
[62]
Eskov, V.M., Filatova, O.E., Eskov, V.V., et al. (2017) The Evolution of the Idea of Homeostasis: Determinism, Stochastics, and Chaos—Self-Organization. Biophysics, 62, 809-820. https://doi.org/10.1134/S0006350917050074
[63]
von Bertalanffy, K.L. (1934) Untersuchungen über die Gesetzlichkeit des Wachstums. I. Allgemeine Grundlagen der Theorie; mathematische und physiologische Gesetzlichkeiten des Wachstums bei Wassertieren. Wilhelm Roux’ Archive für Entwicklungsmechanik der Organismen, 131, 613-652. https://doi.org/10.1007/BF00650112
[64]
Jakubik, J., Randáková, A., Rudajev, V., et al. (2019) Application and Limitations of Fitting of the Operational Model to Determine Relative Efficacies of Agonists. Scientific Reports, 9, Article No. 4637. https://doi.org/10.1038/s41598-019-40993-w
[65]
Turing, A.M. (1952) The Chemical Basis of Morphogenesis. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 237, 37-72. https://doi.org/10.1098/rstb.1952.0012
[66]
Aronson, J.K. (2016) The Hitchhiker’s Guide to Clinical Pharmacology, Pharmacodynamics: How Drugs Work. https://www.cebm.net/wp-content/uploads/2016/05/Pharmacodynamics-How-drugs-work.pdf
[67]
Wierman, M.J. (2010) An Introduction to Mathematics of Uncertainty. Hoors Program, Creighton University, College of Arts and Sciences, Omaha. http://typo3.creighton.edu/fileadmin/user/CCAS/programs/fuzzy_math/docs/MOU.pdf
[68]
Nurgali, K., Jagoe, R.T. and Abalo, R. (2018) Editorial-Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae? Frontiers in Pharmacology, 9, 245. https://doi.org/10.3389/fphar.2018.00245
[69]
Devaux, C. and Schoepffler, P. (1979) Side-Effects of Mixed Agonist-Antagonist Analgesics Used in Sequential Anaesthesia. British Journal of Clinical Pharmacology, 7, 323S-326S. https://doi.org/10.1111/j.1365-2125.1979.tb04708.x
[70]
Rosenberg, S.M. and Queitsch, C. (2014) Combating Evolution to Fight Disease. Science, 343, 1088-1089. https://doi.org/10.1126/science.1247472
[71]
West, B.J. (2006) Where Medicine Went Wrong: Rediscovering the Path to Complexity. World Scientific, London. https://doi.org/10.1142/6175
[72]
Pei, Y. (2015) From Determinism and Probability to Chaos: Chaotic Evolution towards Philosophy and Methodology of Chaotic Optimization. The Scientific World Journal, 2015, Article ID: 704587. https://doi.org/10.1155/2015/704587
[73]
Brown, J.H. and West, G.B. (2000) Scaling in Biology, Santa Fe Institute Studies in the Sciences of Complexity. Oxford University Press, Oxford.
[74]
Calder, W.A. (1996) Size, Function and Life History. Dover Publications, Inc., Mineola, New York.
[75]
Cohen, I.R. and Harel, D. (2007) Explaining a Complex Living System: Dynamics, Multi-Scaling and Emergence. Journal of the Royal Society Interface, 4, 175-182. https://doi.org/10.1098/rsif.2006.0173
[76]
Szasz, O., Szigeti, Gy.P. and Szasz, A. (2017) On the Self-Similarity in Biological Processes. Open Journal of Biophysics, 7, 183-196. https://doi.org/10.4236/ojbiphy.2017.74014
West, B.J. (1990) Fractal Physiology and Chaos in Medicine. World Scientific, Singapore, London.
[79]
Bassingthwaighte, J.B., Leibovitch, L.S. and West, B.J. (1994) Fractal Physiology. Oxford Univ. Press, New York, Oxford. https://doi.org/10.1007/978-1-4614-7572-9
[80]
Sego, T.J., Gianlupi, J.F., Aponte-Serrano, J., et al. (2020) A Modular Framework for Multiscale Multicellular Spatial Modeling of Viral Infection, Immune Response and Drug Therapy Timing and Efficacy in Epithelial Tissues. https://doi.org/10.1101/2020.04.27.064139
[81]
He, J.-H. (2008) Fatalness of Virus Depends upon Its Cell Fractal Geometry. Chaos, Solitons and Fractals, 38, 1390-1393. https://doi.org/10.1016/j.chaos.2008.04.018
[82]
Frolich, H. (1988) Biological Coherence and Response to External Stimuli. Springer Verlag, Berlin Heidelberg. https://doi.org/10.1007/978-3-642-73309-3
[83]
Szendro, P., Vincze, G. and Szasz, A. (2001) Pink Noise Behaviour of the Bio-Systems. European Biophysics Journal, 30, 227-231. https://doi.org/10.1007/s002490100143
[84]
Mode, C.J., Durrett, R., Klebaner, F., et al. (2013) Applications of Stochastic Processes in Biology and Medicine. International Journal of Stochastic Analysis, 2013, Article ID: 790625. https://doi.org/10.1155/2013/790625
[85]
Thimann, K.V. (1956) Promotion and Inhibition: Twin Themes of Physiology. American Naturalist, 90, 145-162. https://doi.org/10.1086/281921
[86]
Nickson, C., Iwashyna, J. and Young, P. (2020) COVID-19: Keeping the Baby in the Bath. https://litfl.com/covid-19-keeping-the-baby-in-the-bath
[87]
Ortiz-Prado, E., Simbana-Rivera, K., Gomez-Barreno, L., et al. (2020) Clinical, Molecular and Epidemiological Characterization of the SARS-CoV-2 Virus and the Coronavirus Disease 2019 (COVID-19), a Comprehensive Literature Review. Diagnostic Microbiology and Infectious Disease, 98, Article ID: 115094. https://doi.org/10.1016/j.diagmicrobio.2020.115094
[88]
Chen, I.-Y., Chang, S.-C., Wu, H.-Y., et al. (2010) Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway. Journal of Virology, 84, 7703-7712. https://doi.org/10.1128/JVI.02560-09
[89]
Verdecchia, P., Cavallini, C., Spanevello, A., et al. (2020) The Pivotal Link between ACE2 Deficiency and SARS-CoV-2 Infection. European Journal of Internal Medicine, 76, 14-20. https://doi.org/10.1016/j.ejim.2020.04.037
[90]
Chung, M.K., Karnik, S., Saef, J., et al. (2020) SARS-CoV-2 and ACE2: The Biology and Clinical Data Settling the ARB and ACEI Controversy. EBioMedicine, 58, Article ID: 102907. https://doi.org/10.1016/j.ebiom.2020.102907
[91]
Belouzard, S., Millet, J.K., Licitra, B.N., et al. (2012) Mechanisms of Coronavirus Cell Entry Mediated by the Viras Spike Protein. Viruses, 4, 1011-1033. https://doi.org/10.3390/v4061011
[92]
Breidenbach, J.D., Dude, P., Gosh, S., et al. (2020) Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes. Journal of Personalized Medicine, 10, 146. https://doi.org/10.3390/jpm10040146
[93]
Hoffman, M., Kleine-Weber, H., Schroeder, S., et al. (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181, 271-280. https://doi.org/10.1016/j.cell.2020.02.052
[94]
Heurich, A., Hofmann-Winkler, H., Giere, S., et al. (2020) 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, 88, 1293-1307. https://doi.org/10.1128/JVI.02202-13
[95]
Ou, X., Liu, Y., Lei, X., et al. (2020) Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and Its Immune Cross-Reactivity with SARS-CoV. Nature Communications, 11, 1620. https://doi.org/10.1038/s41467-020-15562-9
[96]
Kim, S.Y., Jin, W., Sood, A., Montgomery, D.W., Grant, O.C., Fuster, M.M., Fu, L., Dordick, J.S., Woods, R.J., Zhang, F., et al. (2020) Characterization of Heparin and Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Spike Glycoprotein Binding Interactions. Antiviral Research, 181, Article ID: 104873. https://doi.org/10.1016/j.antiviral.2020.104873
[97]
Hudak, A., Szilak, L. and Letoha, T. (2020) Contribution of Syndecans to the Cellular Entry of SARS-CoV-2. Research Square. https://doi.org/10.21203/rs.3.rs-70340/v1
[98]
Schött, U., Solomon, C., Fries, D., et al. (2016) The Endothelial Glycocalyx and Its Disruption, Protection and Regeneration: A Narrative Review. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 24, 48. https://doi.org/10.1186/s13049-016-0239-y
[99]
de Haan, C.A., Haijema, B.J., Schellen, P., Wichgers Schreur, P., te Lintelo, E., Vennema, H. and Rottier, P.J. (2018) Cleavage of Group 1 Coronavirus Spike Proteins: How Furin Cleavage Is Traded off against Heparan Sulfate Binding upon Cell Culture Adaptation. Journal of Virology, 82, 6078-6083. https://doi.org/10.1128/JVI.00074-08
[100]
Ren, L., Zhang, Y., Li, J., et al. (2015) Genetic Drift of Human Coronavirus OC43 Spike Gene during Adaptive Evolution. Scientific Reports, 5, Article No. 11451. https://doi.org/10.1038/srep11451
[101]
Bermejo-Jambrina, M., Eder, J., Kaptein, T.M., et al. (2020) SARS-CoV-2 Infection and Transmission Depends on Heparan Sulfates and Is Blocked by Low Molecular Weight Heparins. https://doi.org/10.1101/2020.08.18.255810
[102]
Negri, E.M., Piloto, B.M., Morinaga, L.K., et al. (2020) Heparin Therapy Improving Hypoxia in COVID-19 Patients a Case Series. https://doi.org/10.1101/2020.04.15.20067017
[103]
Thachil, J. (2020) The Versatile Heparin in COVID-19. Journal of Thrombosis and Haemostasis, 18, 1020-1022. https://doi.org/10.1111/jth.14821
[104]
Park, P.W. (2020) Extracellular Matrix: Surface Proteoglycans. In: Encyclopedia of Respiratory Medicine, 2nd Edition, Elsevier, Amsterdam, 1-8. https://doi.org/10.1016/B978-0-12-801238-3.11650-2
[105]
Shang, J., Wan, Y., Luo, C., et al. (2020) Cell Entry Mechanisms of SARS-CoV-2. PNAS, 117, 11727-11734. https://doi.org/10.1073/pnas.2003138117
[106]
Terali, K., Baddal, B. and Gulcan, H.O. (2020) Prioritizing Potential ACE2 Inhibitors in the COVID-19 Pandemic: Insights from a Molecular Mechanics-Assisted Structure-Based Virtual Screening Experiment. Journal of Molecular Graphics and Modelling, 100, Article ID: 107697. https://doi.org/10.1016/j.jmgm.2020.107697
[107]
Goldberg, A. (2020) ACE2 in COVID-19: Is It Friend or Foe? Labtag Blog. https://blog.labtag.com/ace2-in-covid-19-is-it-friend-or-foe
[108]
Guan, W.-J., Ni, Z.-Y., Liang, W.-H., et al. (2020) Clinical Characteristics of Coronavirus Disease 2019 in China. The New England Journal of Medicine, 382, 1708-1720. https://doi.org/10.1056/NEJMoa2002032
[109]
Crackower, M.A., Sarao, R., Oliveira-dos-Santos, A.J., Da Costa, J., Zhang, L., et al. (2002) Angiotensin-Converting Enzyme 2 Is an Essential Regulator of Heart Function. Nature, 417, 822-828. https://doi.org/10.1038/nature00786
[110]
Turner, A.J. (2015) ACE2 Cell Biology, Regulation, and Physiological Functions. In: The Protective Arm of the Renin-Angiotensin System (RAS), Elsevier, Amsterdam, 185-189, Chapter 25. https://doi.org/10.1016/B978-0-12-801364-9.00025-0
[111]
Banu, N., Panikar, S.S., Leal, L.R., et al. (2020) Protective Role of ACE2 and Its Downregulation in SARS-CoV-2 Infection Leading to Macrophage Activation Syndrome: Therapeutic Implications. Life Sciences, 256, Article ID: 117905. https://doi.org/10.1016/j.lfs.2020.117905
[112]
Gonzalez-Villalobos, R.A., Shen, X.Z., Bernstein, E.A., Janjulia, T., Taylor, B., Giani, J.F., et al. (2013) Rediscovering ACE: Novel Insights into the Many Roles of the Angiotensin-Converting Enzyme. Journal of Molecular Medicine, 91, 1143-1154. https://doi.org/10.1007/s00109-013-1051-z
[113]
Cheng, H., Wang, Y. and Wang, G. (2020) Organ-Protective Effect of Angiotensin-Converting Enzyme 2 and Its Effect on the Prognosis of COVID-19. Journal of Medical Virology, 92, 726-730. https://doi.org/10.1002/jmv.25785
[114]
Bernstrein, K.E., Khan, Z., Giani, J.F., et al. (2017) Angiotensin-Converting Enzyme in Innate and Adaptive Immunity. Nature Reviews Nephrology, 14, 325-336. https://doi.org/10.1038/nrneph.2018.15
[115]
Bosso, M., Thanaraj, T.A., Abu-Farha, M., Alanbaei, M., et al. (2020) The Two Faces of ACE2: The Role of ACE2 Receptor and Its Polymorphysms in Hyperthension and COVID-19. Molecular Therapy—Methods and Clinical Development, 18, 321-327. https://doi.org/10.1016/j.omtm.2020.06.017
[116]
Tsioufis, C., Dimitriadis, K. and Tousoulis, D. (2020) The Interplay of Hypertension, ACE-2 and SARS-CoV-2: Emerging Data as the “Ariadne’s Thread” for the “Labyrinth” of COVID-19. Hellenic Journal of Cardiology, 61, 31-33. https://doi.org/10.1016/j.hjc.2020.05.003
[117]
Devaux, C.A., Rolain, J.-M. and Raoult, D. (2020) ACE2 Receptor Polymorphism: Susceptibility to SARS-CoV-2, Hypertension, Multi-Organ Failure, and COVID-19 Disease Outcome. Journal of Microbiology, Immunology and Infection, 53, 425-435. https://doi.org/10.1016/j.jmii.2020.04.015
[118]
Ruiz, C.M.T., Balarin, Spadotto, M.A., Tanaka, S.C.S., Silva Mota da, V.I., Trovó de, M.A.B., et al. (2018) Polycystic Ovarian Syndrome: rs1799752 Polymorphism of ACE Gene. Revista da Associação Médica Brasileira, 64, 1017-1022. https://doi.org/10.1590/1806-9282.64.11.1017
[119]
Zheng, H. and Cao, J.J. (2020) Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019. The American Journal of Pathology, 190, 1-5. https://doi.org/10.1016/j.ajpath.2020.07.009
[120]
Reynolds, H.R., Adhikari, S., Pulgarin, C., Troxel, A.B., Iturrate, E., Johnson, S.B., Hausvater, A., Newman, J.D., Berger, J.S., Bangalore, S., et al. (2020) Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19. The New England Journal of Medicine, 382, 2441-2448. https://doi.org/10.1056/NEJMoa2008975
[121]
Vaduganathan, M., Vardeny, O., Michel, T., McMurray, J.J.V., Pfeffer, M.A. and Solomon, S.D. (2020). Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. The New England Journal of Medicine, 382, 1653-1659. https://doi.org/10.1056/NEJMsr2005760
[122]
Li, Y., Zhou, W., Yang, L., et al. (2020) Physiological and Pathological Regulation of ACE2, the SARS-CoV-2 Receptor. Pharmacological Research, 1587, Article ID: 104833. https://doi.org/10.1016/j.phrs.2020.104833
[123]
Kalberg, J., Chong, D.S.Y. and Lai, W.Y.Y. (2004) Do Men Have a Higher Case Fatality Rate of Severe Acute Respiratory Syndrome than Women Do? American Journal of Epidemiology, 159, 229-231. https://doi.org/10.1093/aje/kwh056
[124]
Chakravarty, D., Nair, S.S., Hammouda, N., et al. (2020) Sex Differences in SARS-CoV-2 Infection Rates and the Potential Link to Prostate Cancer. Communications Biology, 3, 374. https://doi.org/10.1038/s42003-020-1088-9
[125]
Poletti, P., Tirani, M., Cereda, D., et al. (2020) Age-Specific SARS-CoV-2 Infection Fatality Ratio and Associated Risk Factors, Italy, February to April 2020. Eurosurveillance, 25, pii=2001383. https://doi.org/10.2807/1560-7917.ES.2020.25.31.2001383
[126]
Zhang, J., Wu, J., Sun, X., et al. (2020) Association of Hypertension with the Severity of SARS-CoV-2 Infection: A Meta-Analysis. Epidemiology and Infection, 148, e106. https://doi.org/10.1017/S095026882000117X
[127]
Mazucanti, C.H. and Egan, J.M. (2020) SARS-CoV-2 Disease Severity and Diabetes: Why the Connection and What Is to Be Done? Immunity and Ageing, 17, 21. https://doi.org/10.1186/s12979-020-00192-y
[128]
Nishiga, M., Wang, D.W., Han, Y., et al. (2020) COVID-19 and Cardiovascular Disease: From Basic Mechanisms to Clinical Perspectives. Nature Reviews Cardiology, 17, 543-558. https://doi.org/10.1038/s41569-020-0413-9
[129]
Schultze, A., Walker, A.J., MacKenna, B., et al. (2020) Risk of COVID-19-Related Death among Patients with Chronic Obstructive Pulmonary Disease or Asthma Prescribed Inhaled Corticosteroids: An Observational Cohort Study Using the OpenSAFELY Platform. The Lancet Respiratory Medicine, 8, 1106-112. https://doi.org/10.1016/S2213-2600(20)30415-X
[130]
Wu, V.-C., Hsueh, P.-R., Lin, W.-C., et al. (2014) Acute Renal Failure in SARS Patients: More than Rhabdomyoliysis. Nephrology Dialysis Transplantation, 19, 3180-3182. https://doi.org/10.1093/ndt/gfh436
[131]
Rubino, F., Amiel, S.A., Zimmet, P., et al. (2020) New-Onset Diabetes in Covid-19. New England Journal of Medicine, 383, 789-790. https://doi.org/10.1056/NEJMc2018688
[132]
Malapaty, S. (2020) Evidence Suggests the Coronavirus Might Trigger Diabetes. Nature, 583, 16-17. https://doi.org/10.1038/d41586-020-01891-8
[133]
Diao, B., Wang, C., Wang, R., et al. (2020) Human Kidney Is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. https://doi.org/10.1101/2020.03.04.20031120
[134]
Madjid, M., Safavi-Naeini, P., Solomon, S., et al. (2020) Potential Effects of Coronaviruses on the Cardiovascular System—A Review. JAMA Cardiology, 5, 831-840. https://doi.org/10.1001/jamacardio.2020.1286
[135]
Puelles, V.G., Lütgehetmann, M., Lindenmeyer, M.T., et al. (2020) Multiorgan and Renal Tropism of SARS-CoV-2. The New England Journal of Medicine, 383, 590-592. https://doi.org/10.1056/NEJMc2011400
[136]
Radzikowska, U., Ding, M., Tan, G., et al. (2020) Distribution of ACE2, CD147, CD26, and Other SARS-CoV-2 Associated Molecules in Tissues and Immune Cells in Health and in Asthma, COPD, Obesity, Hypertension, and COVID-19 Risk Factors. Allergy, 75, 2829-2845. https://doi.org/10.1111/all.14429
[137]
Tian, S.F., Hu, W.D., Niu, L., et al. (2020) Pulmonary Pathology of Early Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients with Lung Cancer. Journal of Thoracic Oncology, 15, 700-704. https://doi.org/10.1016/j.jtho.2020.02.010 https://pubmed.ncbi.nlm.nih.gov/32114094
[138]
Crowley, S.D. and Rudemiller, N.P. (2017) Immunologic Effects of the Renin-An-giotensin System. Journal of the American Society of Nephrology, 28, 1350-1361. https://doi.org/10.1681/ASN.2016101066
[139]
Silhol, F., Sarlon, G., Deharo, J.-C., et al. (2020) Downregulation of ACE2 Induces Overstimulation of the Renin-Angiotensin System in COVID-19: Should We Block the Renin-Angiotensin System? Hypertension Research, 43, 854-856. https://doi.org/10.1038/s41440-020-0476-3
Luo, H., Wang, X., Chen, C., et al. (2015) Oxidative Stress Causes Imbalance of Renal Renin Angiotensin System (RAS) Components and Hyperthension in Obese Zucker Rats. Journal of the American Heart Association, 4, e001559. https://doi.org/10.1161/JAHA.114.001559
[142]
Dambic, V., Pojatic, D., Stazic, A., et al. (2020) Significance of the Renin-Angioten-sin System in Clinical Conditions. In: Kibel, A., Ed., Selected Chapter from the Renin-Angiotensin System, IntechOpen, London. https://doi.org/10.5772/intechopen.92309
[143]
Tolouian, R., Vahed, S.Z., Ghiyasvand, S., et al. (2020) COVID-19 Interactions with Angiotensin-Converting Enzyme 2 (ACE2) and the Kinin System: Looking at a Potential Treatment. Journal of Renal Injury Prevention, 9, e19. https://doi.org/10.34172/jrip.2020.19
[144]
Tschope, C., Schultheiss, H.-P. and Walther, T. (2002) Multiple Interactions between Renin-Angiotensin and the Kallikrein-Kinin Systems: Role of ACE Inhibition and AT1 Receptor Blockade. Journal of Cardiovascular Pharmacology, 39, 478-487. https://doi.org/10.1097/00005344-200204000-00003
[145]
Sidarta-Oliveira, D., Jara, C.P., Ferruzzi, A.J., et al. (2020) SARS-CoV-2 Receptor Is Co-Expressed with Elements of the Kinin-Kallikrein, Renin-Angiotensin and Coagulation Systems in Alveolar Cells. https://doi.org/10.1101/2020.06.02.20120634
[146]
Zuo, W., Zhao, X. and Chen, Y.-G. (2020) SARS Coronavirus and Lung Fibrosis. In: Lal, S.K., Ed., Molecular Biology of the SARS-Coronavirus, Springer-Verlag, Berlin, Chapter 15, 247-258. https://doi.org/10.1007/978-3-642-03683-5_15
[147]
Golias, Ch., Charalabopoulos, A., Stagikas, D., et al. (2007) The Kinin System— Bradykinin: Biological Effects and Clinical Implications. Multiple Role of the Kinin System—Bradykinin. Hippokratia, 11, 124-128.
[148]
Garvin, M.R., Alvarez, C., Miller, J.I., et al. (2020) A Mechanistic Model and Therapeutic Interventions for COVID-19 Involving a RAS-Mediated Bradykinin Storm. eLife, 9, e59177. https://doi.org/10.7554/eLife.59177
[149]
van de Veerdonk, F.L., Netea, M.G., van Deuren, M., et al. (2020) Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach. https://doi.org/10.20944/preprints202004.0023.v1
[150]
Delpino, M.V. and Quarleri, J. (2020) SARS-CoV-2 Pathogenesis: Imbalance in the Renin-Angiotensin System Favors Lung Fibrosis. Frontiers in Cellular Infection Microbiology, 10, 340. https://doi.org/10.3389/fcimb.2020.00340
[151]
Cereceda, R. and Beswick, E. (2020) A Supercomputer Analysed Data on COVID-19 and Helped Come Up with This New Hypothesis. Euronews. https://www.euronews.com/2020/09/05/a-supercomputer-analysed-data-on-covid-19-and-helped-come-up- with-this-new-hypothesis
[152]
Kaplan, A.P. (2008) Angioedema. WAO Journal, 1, 103-113. https://doi.org/10.1097/WOX.0b013e31817aecbe
[153]
Meini, S., Zanichelli, A., Sbrojavacca, R., et al. (2020) Understanding the Pathophysiology of COVID-19? Could the Contact System Be the Key? Frontiers in Immunology, 11, 2014. https://doi.org/10.3389/fimmu.2020.02014
[154]
LaRusch, G.A., Mahdi, F., Shariat-Madar, Z., Adams, G., Sitrin, R.G., Zhang, W.M., et al. (2010) Factor XII Stimulates ERK1/2 and Akt through uPAR, Integrins, and the EGFR to Initiate Angiogenesis. Blood, 115, 5111-5120. https://doi.org/10.1182/blood-2009-08-236430
[155]
Wujak, L., Didiasova, M., Zakrzewicz, D., Frey, H., Schasfer, L. and Wygrecka, M. (2015) Heparan Sulfate Proteoglycans Mediate Factor XIIa Binding to the Cell Surface. Journal of Biological Chemistry, 290, 7027-7039. https://doi.org/10.1074/jbc.M114.606343
[156]
Yong, S.J. (2020) Overlooked Receptors in Covid-19: What ACE2 Alone Cannot Explain. https://medium.com/microbial-instincts/overlooked-receptors-could-explain-quirks-of-covid-19-that-ace2- alone-cannot-9470817f59d0
[157]
Wang, K., Chen, W., Zhou, Y.-S., et al. (2020) SARS-CoV-2 Invades Host Cells via a Novel Route: CD147-Spike Protein. https://doi.org/10.1101/2020.03.14.988345
[158]
Ulrich, H. and Pillat, M.M. (2020) CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement. Stem Cell Reviews and Reports, 16, 434-440. https://doi.org/10.1007/s12015-020-09976-7
[159]
(2020) CD147 a New Target of SARS-CoV-2 Invasion. Cusabio. https://www.cusabio.com/c-20985.html
[160]
Xiong, L., Edwards, C.K. and Zhou, L. (2014) The Biological Function and Clinical Utilization of CD147 in Human Diseases: A Review of the Current Scientific Literature. International Journal of Molecular Sciences, 15, 17411-17441. https://doi.org/10.3390/ijms151017411
[161]
Luan, J., Zhao, Y., Zhang, Y., et al. (2017) CD147 Blockade as a Potential and Novel Treatment of Graft Rejection. Molecular Medicine Reports, 16, 4593-4602. https://doi.org/10.3892/mmr.2017.7201
[162]
Kendrick, A.A., Schafer, J., Dzieciatkowska, M., et al. (2016) CD147: A Small Molecule Transporter Ancillary Protein at the Crossroad of Multiple Hallmarks of Cancer and Metabolic Reprogramming. Oncotarget, 8, 6742-6762. https://doi.org/10.18632/oncotarget.14272
[163]
Li, X., Zhang, Y., Ma, W., et al. (2020) Enhanced Glucose Metabolism Mediated by CD147 Contributes to Immunesupression in Hepatocellular Carcinoma. Cancer Immunology, Immunotherapy, 69, 535-548. https://doi.org/10.1007/s00262-019-02457-y
[164]
Huang, Q., Li, J., Xing, J., Li, W., Li, H., Ke, X., Zhang, J., Ren, T., Shang, Y., Yang, H., Jiang, J. and Chen, Z. (2014) CD147 Promotes Reprogramming of Glucose Metabolism and Cell Proliferation in HCC Cells by Inhibiting p53-Dependent Signaling Pathway. Journal of Hepatology, 61, 859-866. https://doi.org/10.1016/j.jhep.2014.04.035
[165]
Vassilaki, N. and Frakolaki, E. (2017) Virus-Host Interactions under Hypoxia. Microbes and Infection, 19, 193-203. https://doi.org/10.1016/j.micinf.2016.10.004
[166]
Domingo, P., Mur, I., Pomar, V., Corominas, H., Casademont, J. and de Benito, N. (2020) The Four Horsemen of a Viral Apocalypse: The Pathogenesis of SARS-CoV-2 Infection (COVID-19). EBioMedicine, 58, Article ID: 102887. https://doi.org/10.1016/j.ebiom.2020.102887
[167]
Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B.-J. and Jiang, S. (2009) The Spike Protein of SARS-CoV—A Target for Vaccine and Therapeutic Development. Nature Reviews Microbiology, 7, 226-236. https://doi.org/10.1038/nrmicro2090
[168]
Walls, A.C., Park, Y.-J., Tortorici, M.A., et al. (2020) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, 180, 281-292. https://doi.org/10.1016/j.cell.2020.02.058
[169]
Szasz, O., Szigeti, G.P. and Szasz, A. (2019) The Intrinsic Self-Time of Biosystems. Open Journal of Biophysics, 9, 131-145.
[170]
Longo, G. and Montevil, M. (2014) Perspectives on Organisms, Biological Time, Symmetries and Singularities. Springer-Verlag, Berlin, Heidelberg.
[171]
Wang, F., Zhang, H. and Sun, Z. (2020) The Laboratory Tests and Host Immunity of COVID-19 Patients with Different Severity of Illness. JCI Insight, 5, e137799. https://doi.org/10.1172/jci.insight.137799
[172]
Banoun, H. (2020) Evolution of SARS-CoV-2 in Relation to the Host Immune System. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3637909 https://doi.org/10.2139/ssrn.3637909
[173]
Sun, X., Wang, T., Cai, D., et al. (2020) Cytokine Storm in the Early Stages of Covid-19 Pneumonia. Cytokine and Growth Factor Reviews, 53, 38-42. https://doi.org/10.1016/j.cytogfr.2020.04.002
[174]
McMillan, P. and Uhal, B.D. (2020) COVID-19—A Theory of Autoimmunity to ACE-2. MOJ Immunology, 7, 17-19.
[175]
Mahmudpour, M., Roozbeh, J., Kehavarz, M., et al. (2020) COVID-19 Cytokine Storm—The Anger of Inflammation. Cytokine, 133, Article ID: 155151. https://doi.org/10.1016/j.cyto.2020.155151
[176]
Channappanavar, R. and Perlman, S. (2017) Pathogenic Human Coronavirus Infections: Causes and Consequences of Citokine Storm and Immunopathology. Seminars in Immunopathology, 39, 529-539. https://doi.org/10.1007/s00281-017-0629-x
[177]
Maisch, B. (2019) Cardio-Immunology of Myocarditis: Focus on Immune Mechanisms and Treatment Options. Frontiers in Cardiovascular Medicine, 6, 48. https://doi.org/10.3389/fcvm.2019.00048
[178]
Anoop, U.R. and Verma, K. (2020) Pulmonary Edema in COVID19—A Neural Hypothesis. ACS Chemical Neuroscience, 11, 2048-2050. https://doi.org/10.1021/acschemneuro.0c00370
[179]
MsGrath, B.A., Wallace, S. and Goswamy, J. (2020) Laryngeal Oedema Associated with COVID-19 Complicating Airway Management. Anaesthesia, 75, 972. https://doi.org/10.1111/anae.15092
[180]
Tse, G.M.-K., To, K.-F., Chan, P.K.-S., et al. (2014) Pulmonary Pathological Features in Coronavirus Associated Severe Acute Respiratory Syndrome (SARS). Journal of Clinical Pathology, 57, 260-265. https://doi.org/10.1136/jcp.2003.013276
[181]
Luks, A.M., Freer, L., Grissom, C.K., et al. (2020) COVID-19 Lung Injury Is Not High Altitude Pulmonary Edema. High Altitude Medicine and Biology, 21, 192-193. https://doi.org/10.1089/ham.2020.0055
[182]
Zhu, Z., Tang, J., Chai, X., et al. (2020) How to Differentiate COVID-19 Pneumonia from Heart Failure with Computed Tomography at Initial Medical Contact during Epidemic Period. https://doi.org/10.1101/2020.03.04.20031047
[183]
Gattinoni, L., Coppola, S., Cressoni, M., Busana, M., Rossi, S. and Chiumello, D. (2020) Covid-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome. American Journal of Respiratory and Critical Care Medicine, 201, 1299-1300. https://doi.org/10.1164/rccm.202003-0817LE
[184]
Okada, H., Yoshida, S., Hara, A., et al. (2020) Vascular Endothelial Injury Exacerbates Coronavirus Disease 2019: The Role of Endothelial Glycocalyx Protection. Microcirculation, e12654. https://doi.org/10.1111/micc.12654
[185]
Lang, M., Som, A., Carey, D., et al. (2020) Pulmonary Vascular Manifestations of COVID-19 Pneumonia. Radiology: Cardiothoracic Imaging, 2, e200277. https://doi.org/10.1148/ryct.2020200277
[186]
Coperchini, F., Chiovato, L., Croce, L., et al. (2020) The Cytokine Storm in COVID-19: An Overview of the Involvement of the Chemokine/Chemokine-Receptor System. Cytokine and Growth Factor Reviews, 53, 25-32. https://doi.org/10.1016/j.cytogfr.2020.05.003
[187]
Maisch, B. (2020) SARS-CoV-2 as Potential Cause of Cardiac Inflammation and Heart Failure. Is It the Virus, Hyperinflammation, or MODS? Herz, 45, 321-322. https://doi.org/10.1007/s00059-020-04925-z
[188]
Huertas, A., Montani, D., Savale, L., et al. (2020) Endothelial Cell Dysfunction: A Major Player in SARS-CoV-2 Infection (COVID-19)? European Respiratory Journal, 56, Article ID: 2001634. https://doi.org/10.1183/13993003.01634-2020
[189]
Arteriograph, Interesting Facts—Innovative Method to Ease Arterial Stiffness Measurement. https://www.tensiomed.com/interesting-facts
[190]
De Andrea, M., Ravera, R., Gioia, D., Gariglio, M. and Landolfo, S. (2002) The Interferon System: An Overview. European Journal of Paediatric Neurology, 6, A41-A46. https://doi.org/10.1053/ejpn.2002.0573
[191]
Parkin, J. and Cohen, B. (2001) An Overview of the Immune System. The Lancet, 357, 1777-1789. https://doi.org/10.1016/S0140-6736(00)04904-7
[192]
Liu, J., Zheng, X., Tong, Q., Li, W., Wang, B., Sutter, K., et al. (2020) Overlapping and Discrete Aspects of the Pathology and Pathogenesis of the Emerging Human Pathogenic Coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. Journal of Medical Virology, 92, 491-494. https://doi.org/10.1002/jmv.25709
[193]
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., et al. (2020) Pathological Findings of COVID-19 Associated with Acute Respiratory Distress Syndrome. The Lancet Respiratory Medicine, 8, 420-422. https://doi.org/10.1016/S2213-2600(20)30076-X
[194]
Pacha, O., Sallman, M.A. and Evans, S.E. (2020) COVID-19: A Case for Inhibiting IL-17? Nature Reviews, Immunology, 20, 345-346. https://doi.org/10.1038/s41577-020-0328-z
[195]
Haller, O., Kochs, G. and Weber, F. (2007) Interferon, Mx, and Viral Countermeasures. Cytokine & Growth Factor Reviews, 18, 425-433. https://doi.org/10.1016/j.cytogfr.2007.06.001
[196]
Seder, R.A., Gazzinelli, R., Sher, A. and Paul, W.E. (1993) Interleukin 12 Acts Directly on CD4+ T Cells to Enhance Priming for Interferon γ Production and Diminishes Interleukin 4 Inhibition of Such Priming. Proceedings of the National Academy of Sciences of the United States of America, 90, 10188-10192. https://doi.org/10.1073/pnas.90.21.10188
[197]
Karupiah, G., Xie, Y.-W., Buller, M.L., et al. (1993) Inhibition of Viral Replication by Interferon-γ-Induced Nitric Oxide Synthase. Science, 261, 1445-1448. https://doi.org/10.1126/science.7690156
[198]
Hu, X., Li, W.P., Meng, C., et al. (2003) Inhibition of IFN-γ Signaling by Glucocorticoids. The Journal of Immunology, 170, 4833-4839. https://doi.org/10.4049/jimmunol.170.9.4833
[199]
Liu, P.P., Blet, A., Symth, D., et al. (2020) The Science Underlying COVID-19. Circulation, 142, 68-78. https://doi.org/10.4049/jimmunol.170.9.4833
[200]
Ong, E.Z., Chan, Y.F.Z., Leong, W.Y., Lee, N.M.Y., Kalimuddin, S., Mohideen, S.M.H., Chan, K.S., Tan, A.T., Bertoletti, A., Ooi, E.E. and Low, J.G.H. (2020) A Dynamic Immune Response Shapes COVID-19 Progression. Cell Host & Microbe, 27, 879-882. https://doi.org/10.1016/j.chom.2020.03.021
[201]
Caruana, G., Croxatto, A., Coste, A.T., et al. (2020) Diagnostic Strategies for SARS-CoV-2 Infection and Interpretation of Microbiological Results. Clinical Microbiology and Infection, 26, 1178-1182. https://doi.org/10.1016/j.cmi.2020.06.019
[202]
Skevaki, C., Fragkou, P.C., Cheng, C., et al. (2020) Laboratory Characteristics of Patients Infected with the Novel SARS-CoV-2 Virus. Journal of Infection, 81, 205-212. https://doi.org/10.1016/j.jinf.2020.06.039
[203]
Ruiz de Morales, J.M.G., Puig, L., Dauden, E., et al. (2019) Critical Role of Interleukin (IL)-17 in Inflammatory and Immune Disorders: An Updated Review of the Evidence Focusing in Controversies. Autoimmunity Reviews. https://doi.org/10.1016/j.autrev.2019.102429
[204]
Fu, Y., Cheng, Y. and Wu, Y. (2020) Understanding SARS CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools. Virologica Sinica, 35, 266-271. https://doi.org/10.1007/s12250-020-00207-4
[205]
Yale University (2020) Common Cold Combats Influenza. https://healthcare-in-europe.com/en/news/common-cold-combats-influenza.html
[206]
Wu, A., Mihaylova, V.T., Landry, M.L., et al. (2020) Interference between Rhinovirus and Influenza A Virus: A Clinical Data Analysis and Experimental Infection Study. The Lancet Microbe.
[207]
Turner, R.B., Felton, A., Kosak, K., et al. (1986) Prevention of Experimental Coronavirus Colds with Intranasal Alpha-2b Interferon. The Journal of Infectious Diseases, 154, 443-447. https://doi.org/10.1093/infdis/154.3.443
[208]
Manduffie, D. (2020) Scientists Say the Common Cold Can Keep the Flu at Bay. Can It Do the Same for Covid-19? https://www.courthousenews.com/scientists-say-the-common-cold-can-keep-the-flu-at-bay-can-it-do -the-same-for-covid-19
[209]
Sette, A. and Crotty, S. (2020) Pre-Existing Immunity to SARS-CoV-2: The Knowns and Unknowns. Nature Reviews, Immunology. https://doi.org/10.1038/s41577-020-00430-w
[210]
Foxman, E.F., Storer, J.A., Fitzgerald, M.E., et al. (2015) Temperature-Dependent Innate Defense against the Common Cold Virus Limits Viral Replication at Warm Temperature in Mouse Airway Cells. PNAS, 112, 827-832. https://doi.org/10.1073/pnas.1411030112
[211]
Brenner, I.K.M., Castellani, J.W., Gabaree, C., et al. (1999) Immune Changes in Humans during Cold Exposure: Effects of Prior Heating and Exercise. Journal of Applied Physiology, 87, 699-710. https://doi.org/10.1152/jappl.1999.87.2.699
[212]
Kamat, S. and Kumari, M. (2020) BCG against SARS-CoV-2: Second Youth of an Old Age Vaccine? Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2020.01050
[213]
Luke, A., O’Neill, J. and Netea, M.G. (2020) BCG-Induced Trained Immunity: Can It Offer Protection against COVID-19? Nature Reviews/Immunology. https://doi.org/10.1038/s41577-020-0337-y
[214]
Chumakov, K., Benn, C.S., Aaby, P., Kottilil, S. and Gallo, R. (2020) Can Existing Live Vaccines Prevent COVID-19? Science, 368, 1187-1188. https://doi.org/10.1126/science.abc4262
Fidel, P.L. and Noverr, M.C. (2020) Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure to Dampen Septic Inflammation Associated with COVID-19 Infection? mBio, 11, e00907-20. https://doi.org/10.1128/mBio.00907-20
[217]
Imami, A.S., O’Donovan, S.M., Creeden, J.F., Wu, X., Eby, H., McCullumsmith, C.B., Uvnäs-Moberg, K., McCullumsmith, R.E. and Andari, E. (2020) Oxytocin’s Anti-Inflammatory and Proimmune Functions in COVID-19: A Transcriptomic Signature-Based Approach. Physiological Genomics, 52, 401-407. https://doi.org/10.1152/physiolgenomics.00095.2020
[218]
Voronov, S., Zueva, N., Orlov, V., et al. (2002) Temperature-Induced Selective Death of the C-Domain within Angiotensin-Converting Enzyme Molecule. FEBS Letters, 522, 77-82. https://doi.org/10.1016/S0014-5793(02)02888-0
[219]
Tharakan, S, Nomoto, K., Miyashita, S., et al. (2020) Body Temperature Correlates with Mortality in COVID-19 Patients. Critical Care, 24, 298. https://doi.org/10.1186/s13054-020-03045-8
[220]
Kang, D. and Ellgen, C. (2020) The Role of Temperature in COVID-19 Disease Severity and Transmission Rates. http://www.preprints.org https://doi.org/10.20944/preprints202005.0070.v1
[221]
Szasz, A., Szasz, N. and Szasz, O. (2010) Oncothermia—Principles and Practices. Springer Science, Heidelberg. http://www.springer.com/gp/book/9789048194971 https://doi.org/10.1007/978-90-481-9498-8
[222]
Chi, K.-H. (2020) Tumour-Directed Immunotherapy: Clinical Results of Radiotherapy with Modulated Electro-Hyperthermia. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars, Newcastle upon Tyne, Ch. 12, 206-226. https://www.cambridgescholars.com/challenges-and-solutions-of-oncological-hyperthermia
[223]
Pang, L.K.C. (2012) Clinical Research on Integrative Treatment of Colon Carcinoma with Oncothermia and Clifford TCM Immune Booster. Oncothermia Journal, 5, 24-41.
[224]
Krenacs, T. and Benyo, Z. (2017) Tumor Specific Stress and Immune Response Induced by Modulated Electrohyperthermia in Relation to Tumor Metabolic Profiles. Oncothermia Journal, 20, 264-272.
[225]
Szasz, A.M., Minnaar, C.A., Szentmartoni, Gy., et al. (2019) Review of the Clinical Evidences of Modulated Electro-Hyperthermia (mEHT) Method: An Update for the Practicing Oncologist. Frontiers in Oncology, 9, Article No. 1012. https://doi.org/10.3389/fonc.2019.01012
[226]
Szasz, A.M., Arkosy, P., Arrojo, E.E., et al. (2020) Guidelines for Local Hyperthermia Treatment in Oncology. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars, Newcastle upon Tyne, Ch. 2, 32-71.
[227]
Minnaar, C.A., Kotzen, J.A., Naidoo, T., et al. (2020) Analysis of the Effects of mEHT on the Treatment-Related Toxicity and Quality of Life of HIV-Positive Cervical Cancer Patients. International Journal of Hyperthermia, 37, 263-272. https://doi.org/10.1080/02656736.2020.1737253
[228]
Minnaar, C.A., Szasz, A.M., Arrojo, E., Lee, S.-Y., Giorentini, G., Borbenyi, E., et al. (2020) Summary and Update of the Method Modulated Electro-Hyperthermia. Oncothermia Journal, Special Edition, 49-130. https://oncotherm.com/sites/oncotherm/files/2020-09/specialedition01_1.pdf
[229]
Szasz, A. (2020) Towards the Immunogenic Hyperthermic Action: Modulated Electro-Hyperthermia. Clinical Oncology and Research, Science Repository, 3, 5-6. https://doi.org/10.31487/j.COR.2020.09.07
[230]
Minnaar, C.A., Baeyens, A., Aeni, O.A., et al. (2019) Defining Characteristics of Nodal Disease on PET/CT Scans in Patients with HIV-Positive and -Negative Locally Advanced Cervical Cancer in South Africa. Tomography, 5, 339-345. https://doi.org/10.18383/j.tom.2019.00017
[231]
Minnaar, C.A., Kotzen, J.A., Ayeni, O.A., et al. (2019) The Effect of Modulated Electro-Hyperthermia on Local Disease Control in HIV-Positive and -Negative Cervical Cancer Women in South Africa: Early Results from a Phase III Randomized Controlled Trial. PLoS ONE, 14, e0217894. https://doi.org/10.1371/journal.pone.0217894
[232]
Szasz, A. (2015) Bioelectromagnetic Paradigm of Cancer Treatment Oncothermia. In: Rosch, P.J., Ed., Bioelectromagnetic and Subtle Energy Medicine, CRC Press, Taylor & Francis Group, Boca Raton, 323-336.
[233]
Szasz, A. and Szasz, O. (2013) Oncothermia Protocol. Oncothermia Journal, 8, 13-45. https://doi.org/10.1155/2013/159570 https://oncotherm.com/sites/oncotherm/files/2019-10/Oncothermia%20protocol.pdf
[234]
Minnaar, C.A., Szasz, A.M., Arrojo, E., Lee, S.-Y., Giorentini, G., Borbenyi, E., et al. (2020) Summary and Update of the Method Modulated Electro-Hyperthermia. Oncothermia Journal, Special Edition, 49-130. https://oncotherm.com/sites/oncotherm/files/2020-09/specialedition01_1.pdf
[235]
Szasz, O., Szasz, A.M. Minnaar, C. and Szasz, A. (2017) Heating Preciosity—Trends in Modern Oncological Hyperthermia. Open Journal of Biophysics, 7, 116-144. https://doi.org/10.4236/ojbiphy.2017.73010
[236]
Sanchez, E.L. and Lagunoff, M. (2015) Viral Activation of Cellular Metabolism. Virology, 479-480, 609-618. https://doi.org/10.1016/j.virol.2015.02.038
[237]
Mayer, K.A., Stöckl, J., Zlabinger, G.J., et al. (2019) Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction. Frontiers in Immunology, 10, 1533. https://doi.org/10.3389/fimmu.2019.01533
[238]
Thaker, S.K., Ch’ng, J. and Christofk, H.R. (2019) Viral Hijacking of Cellular Metabolism. BMC Biology, 17, 59. https://doi.org/10.1186/s12915-019-0678-9
[239]
Andocs, G., Rehman, M.U., Zhao, Q.L., Papp, E., Kondo, T. and Szasz, A. (2015) Nanoheating without Artificial Nanoparticles Part II. Experimental Support of the Nanoheating Concept of the Modulated Electro-Hyperthermia Method, Using U937 Cell Suspension Model. Biology and Medicine, 7, 1-9. https://doi.org/10.4172/0974-8369.1000247
[240]
Szasz, O. and Szasz, A. (2014) Oncothermia—Nano-Heating Paradigm. Journal of Cancer Science and Therapy, 6, 4. https://doi.org/10.4172/1948-5956.1000259
[241]
Hegyi, G., Szigeti, G.P. and Szasz, A. (2013) Hyperthermia versus Oncothermia: Cellular Effects in Complementary Cancer Therapy. Evidence-Based Complementary and Alternative Medicine, 2013, Article ID: 672873. https://doi.org/10.1155/2013/672873
[242]
Conti, C., De Marco, A., Mastromarino, P., et al. (1999) Antiviral Effect of Hyperthermic Treatment in Rhinovirus Infection. Antimicrobial Agents and Chemotherapy, 43, 822-829. https://doi.org/10.1128/AAC.43.4.822
[243]
Szasz, A., Vincze, Gy., Szasz, O. and Szasz, N. (2003) An Energy Analysis of Extracellular Hyperthermia. Magneto- and Electro-Biology, 22, 103-115. https://doi.org/10.1081/JBC-120024620
[244]
Szasz, O., Szasz, A.M., Minnaar, C. and Szasz, A. (2017) Heating Preciosity—Trends in Modern Oncological Hyperthermia. Open Journal of Biophysics, 7, 116-144. https://doi.org/10.4236/ojbiphy.2017.73010
[245]
Wust, P., Kortum, B., Strauss, U., Nadobny, J., Zschaeck, S., Beck, M., et al. (2020) Non-Thermal Effects of Radiofrequency Electromagnetic Fields. Scientific Reports, 10, Article No. 13488. https://doi.org/10.1038/s41598-020-69561-3
[246]
Szasz, A. (2019) Thermal and Nonthermal Effects of Radiofrequency on Living State and Applications as an Adjuvant with Radiation Therapy. Journal of Radiation and Cancer Research, 10, 1-17. https://doi.org/10.4103/jrcr.jrcr_25_18
[247]
Szasz, O., Szigeti, Gy.P., Vancsik, T. and Szasz, A. (2018) Hyperthermia Dosing and Depth of Effect. Open Journal of Biophysics, 8, 31-48. https://doi.org/10.4236/ojbiphy.2018.81004
[248]
Simons, K. and Sampaio, L. (2011) Membrane Organization and Lipid Rafts. Cold Spring Harbor Perspectives in Biology, 3, a004697. https://doi.org/10.1101/cshperspect.a004697
[249]
Simons, K. and Toomre, D. (2000) Lipid Rafts and Signal Transduction. Nature Reviews Molecular Cell Biology, 1, 31-41. https://doi.org/10.1038/35036052
[250]
Rajendran, L. and Simons, K. (2005) Lipid Rafts and Membrane Dynamics. Journal of Cell Science, 118, 1099-1102. https://doi.org/10.1242/jcs.01681
[251]
Vincze, Gy., Szigeti, Gy., Andocs, G. and Szasz, A. (2015) Nanoheating without Artificial Nanoparticles. Biology and Medicine, 7, 4.
[252]
Papp, E., Vancsik, T., Kiss, E. and Szasz, O. (2017) Energy Absorption by the Membrane Rafts in the Modulated Electro-Hyperthermia (mEHT). Open Journal of Biophysics, 7, 216-229. https://doi.org/10.4236/ojbiphy.2017.74016
[253]
Prasad, B., Kim, S., Cho, W., et al. (2018) Effect of Tumor Properties on Energy Absorption, Temperature Mapping, and Thermal Dose in 13,56-MHz Radiofrequency Hyperthermia. Journal of Thermal Biology, 74, 281-289. https://doi.org/10.1016/j.jtherbio.2018.04.007
[254]
Nagy, G., Meggyeshazi, N. and Szasz, O. (2013) Deep Temperature Measurements in Oncothermia Processes. Conference Papers in Medicine, 2013, Article ID: 685264. https://doi.org/10.1155/2013/685264
[255]
Csoboz, B., Balogh, G.E., Kusz, E., et al. (2013) Membrane Fluidity Matters: Hyperthermia from the Aspects of Lipids and Membranes. International Journal of Hyperthermia, 29, 491-499. https://doi.org/10.3109/02656736.2013.808765
[256]
Li, G.-M., Li, Y.-G., Yamate, M., et al. (2007) Lipid Rafts Play an Important Role in the Early Stage of Severe Acute Respiratory Syndrome-Coronavirus Life Cycle. Microbes and Infection, 9, 96-102. https://doi.org/10.1016/j.micinf.2006.10.015
[257]
Manes, S., del Real, G. and Martinez, A. (2003) Pathogens: Raft Hijackers. Nature Reviews Immunology, 3, 557-568. https://doi.org/10.1038/nri1129
[258]
Takahashi, T. and Suzuki, T. (2009) Role of Membrane Rafts in Viral Infection. The Open Dermatology Journal, 3, 178-194. https://doi.org/10.2174/1874372200903010178
[259]
Baglivo, M., Baronio, M., Natalini, G., et al. (2020) Natural Small Molecules as Inhibitors of Coronavirus Lipid Dependent Attachment to Host Cells: A Possible Strategy for Reducing SARS-COV-2 Infectivity? Acta BioMedica, 91, 161-164.
[260]
Wang, T.T., Lien, C.Z., Liu, S., et al. (2020) Effective Heat Inactivation of SARS-CoV-2. https://doi.org/10.1101/2020.04.29.20085498
[261]
Kiss, B., Kis, Z., Palyi, B., et al. (2020) Topography, Spike Dynamics and Nanomechanics of Individual Native SARS-CoV-2 Virions. https://doi.org/10.1101/2020.09.17.302380
[262]
Lee, Y.-N., Chen, L.-K., Ma, H.-C., et al. (2005) Thermal Aggregation of SARS-CoV Membrane Protein. Journal of Virological Methods, 129, 152-161. https://doi.org/10.1016/j.jviromet.2005.05.022
[263]
Maruyama, H., Kimura, T., Liu, H., et al. (2018) Influenza Virus Replication Raises the Temperature of Cells. Virus Research. https://doi.org/10.1016/j.virusres.2018.09.011
[264]
De Maio, A. (1999) Heat Shock Proteins: Facts, Thoughts, and Dreams. Shock, 11, 1-12. https://doi.org/10.1097/00024382-199901000-00001
[265]
Feder, M.E. and Hofmann, G.E. (1999) Heat-Shock Proteins, Molecular Chaperones, and the Stress Response: Evolutionary and Ecological Physiology. Annual Review of Physiology, 61, 243-282. https://doi.org/10.1146/annurev.physiol.61.1.243
[266]
Santoro, M.G. (2000) Heat Shock Factors and the Control of the Stress Response. Biochemical Pharmacology, 59, 55-63. https://doi.org/10.1016/S0006-2952(99)00299-3
[267]
Blank, M. (2012) Evidence for Stress Response. https://bioinitiative.org/wp-content/uploads/pdfs/sec07_2007_Evidence_for _Stress_Response.pdf
[268]
Milani, A., Basirnejad, M. and Bolhassani, A. (2019) Heat-Shock Proteins in Diagnosis and Treatment: An Overview of Different Biochemical and Immunological Functions. Immunotherapy, 11, 215-239. https://doi.org/10.2217/imt-2018-0105
[269]
Kregel, K.C. (2002) Molecular Biology of Thermoregulation Invited Review: Heat Shock Proteins: Modifying Factors in Physiological Stress Responses and Acquired Thermotolerance. Journal of Applied Physiology, 92, 2177-2186. https://doi.org/10.1152/japplphysiol.01267.2001
[270]
De Marco, A. and Santoro, M.G. (1193) Antiviral Effect of Short Hyperthermic Treatment at Specific Stages of Vesicular Stomatitis Virus Replication Cycle. Journal of General Virology, 74, 1685-1690. https://doi.org/10.1099/0022-1317-74-8-1685
[271]
Yerusameli, A., Karman, S. and Lwoff, A. (1982) Treatment of Perennial Allergic Rhinitis by Local Hyperthermia. Proceedings of the National Academy of Sciences of the United States of America, 79, 4766-4769. https://doi.org/10.1073/pnas.79.15.4766
[272]
Roulston, A., Marcellus, R.C. and Branton, P.E. (1999) Viruses and Apoptosis. Annual Review of Microbiology, 53, 577-628. https://doi.org/10.1146/annurev.micro.53.1.577
[273]
Hardwick, J.M. (2001) Apoptosis in Viral Pathogenesis. Cell Death & Differentiation, 8, 109-110. https://doi.org/10.1038/sj.cdd.4400820
[274]
Benedict, C.A., Norris, P.S. and Ware, C.F. (2002) To Kill or Be Killed: Viral Evasion of Apoptosis. Nature Immunology, 3, 1013-1018. https://doi.org/10.1038/ni1102-1013
[275]
Wan, Y., Song, D., Li, H., et al. (2020) Stress Proteins: The Biological Functions in Virus Infection, Present and Challenges for Target-Based Antiviral Drug Development. Signal Transduction and Targeted Therapy, 5, 125. https://doi.org/10.1038/s41392-020-00233-4
[276]
Ren, L., Yang, R., Gou, L., et al. (2005) Apoptosis Induced by the SARS-Associated Coronavirus in Vero Cells Is Replication-Dependent and Involves Caspase. DNA and Cell Biology, 24, 496-502. https://doi.org/10.1089/dna.2005.24.496
[277]
Fung, T.S. and Liu, D.X. (2014) Coronavirus Infection, ER Stress, Apoptosis and Innate Immunity. Frontiers in Microbiology, 5, 296. https://doi.org/10.3389/fmicb.2014.00296
[278]
Tan, Y.-X., Tan, T.H.P., Lee, M.J.-R., et al. (2007) Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-XL Protein. Journal of Virology, 81, 6346-6355. https://doi.org/10.1128/JVI.00090-07
[279]
Andocs, G., Renner, H., Balogh, L., Fonyad, L., Jakab, C. and Szasz, A. (2009) Strong Synergy of Heat and Modulated Electro-Magnetic Field in Tumor Cell Killing, Study of HT29 Xenograft Tumors in a Nude Mice Model. Strahlentherapie und Onkologie, 185, 120-126. https://doi.org/10.1007/s00066-009-1903-1
[280]
Meggyeshazi, N., Andocs, G. and Krenacs, T. (2013) Programmed Cell Death Induced by Modulated Electro-Hyperthermia. Conference Papers in Medicine, 2013, Article ID: 187835. https://doi.org/10.1155/2013/249563
[281]
Cummins, N. and Badley, A. (2009) The Trail to Viral Pathogenesis: The Good, the Bad and the Ugly. Current Molecular Medicine, 9, 495-505. https://doi.org/10.2174/156652409788167078
[282]
Peteranderi, C. and Herold, S. (2017) The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond. Frontiers in Immunology, 8, 313. https://doi.org/10.3389/fimmu.2017.00313
[283]
Lugade, A.A., Sorensen, E.W., Gerber, S.A., Moran, J.P., Frelinger, J.G. and Lord, E.M. (2008) Radiation-Induced IFN-Gamma Production within the Tumor Microenvironment Influences Antitumor Immunity. The Journal of Immunology, 180, 3132-3139. https://doi.org/10.4049/jimmunol.180.5.3132
[284]
Tsang, Y.-W., Huang, C.-C., Yang, K.-L., Chi, M.-S., Chiang, H.-C., Wang, Y.-S., Andocs, G., Szasz, A., Li, W.-T. and Chi, K.-H. (2015) Improving Immunological Tumor Microenvironment Using Electro-Hyperthermia Followed by Dendritic Cell Immunotherapy. BMC Cancer, 15, 708. https://doi.org/10.1186/s12885-015-1690-2
[285]
Vancsik, T., Kovago, Cs., Kiss, E., et al. (2018) Modulated Electro-Hyperthermia Induced Loco-Regional and Systemic Tumor Destruction in Colorectal Cancer Allografts. Journal of Cancer, 9, 41-53. https://doi.org/10.7150/jca.21520
[286]
Meggyeshazi, N., Andocs, G., Balogh, L., et al. (2014) DNA Fragmentation and Caspase-Independent Programmed Cell Death by Modulated Electrohyperthermia. Strahlentherapie und Onkologie, 190, 815-822. https://doi.org/10.1007/s00066-014-0617-1
[287]
Andocs, G., Rehman, M.U., Zhao, Q.-L., Tabuchi, Y., Kanamori, M. and Kondo, T. (2016) Comparison of Biological Effects of Modulated Electro-Hyperthermia and Conventional Heat Treatment in Human Lymphoma U937 Cell. Cell Death Discovery (Nature Publishing Group), 2, 16039. https://doi.org/10.1038/cddiscovery.2016.39
[288]
Forika, G., Balogh, A., Vancsik, T., Zalatnai, A., et al. (2020) Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis in Vitro. International Journal of Molecular Sciences, 21, 5100. https://pubmed.ncbi.nlm.nih.gov/32707717 https://doi.org/10.3390/ijms21145100
[289]
Kao, P.H.-J., Chen, C.-H., Chang, Y.-W., et al. (2020) Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia. Scientific Reports, 10, Article No. 8936. https://doi.org/10.1038/s41598-020-65823-2 https://www.nature.com/articles/s41598-020-65823-2
[290]
Graner, M.W. (2016) HSP90 and Immune Modulation in Cancer. Advances in Cancer Research, 129, 191-224. https://doi.org/10.1016/bs.acr.2015.10.001
[291]
Murshid, A., Gong, J. and Calderwood, K. (2012) Role of Heat Shock Proteins in Antigen Cross Presentation. Frontiers in Immunology, 3, 63. https://doi.org/10.3389/fimmu.2012.00063
[292]
Yang, K.-L., Huang, C.-C., Chi, M.-S., Chiang, H.-C., Wang, Y.-S., Andocs, G., et al. (2016) In Vitro Comparison of Conventional Hyperthermia and Modulated Electro-Hyperthermia. Oncotarget, 7, 84082-84092. https://doi.org/10.18632/oncotarget.11444
[293]
Meggyeshazi, N. (2015) Studies on Modulated Electrohyperthermia Induced Tumor Cell Death in a Colorectal Carcinoma Model. Thesis, Pathological Sciences Doctoral School, Semmelweis University, Budapest. http://repo.lib.semmelweis.hu/handle/123456789/3956
[294]
Andocs, G., Meggyeshazi, N., Balogh, L., et al. (2014) Upregulation of Heat Shock Proteins and the Promotion of Damage-Associated Molecular Pattern Signals in a Colorectal Cancer Model by Modulated Electrohyperthermia. Cell Stress and Chaperones, 20, 37-46. https://doi.org/10.1007/s12192-014-0523-6
[295]
Qin, W., Akutsu, Y., Andocs, G., et al. (2014) Modulated Electro-Hyperthermia Enhances Dendritic Cell Therapy through an Abscopal Effect in Mice. Oncology Reports, 32, 2373-2379. https://doi.org/10.3892/or.2014.3500
[296]
Binder, R.J. (2014) Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System. Journal of Immunology, 193, 5765-5771. https://doi.org/10.4049/jimmunol.1401417
[297]
Deffit, S.N. and Blum, J.S. (2015) A Central Role for HSC70 in Regulating Antigen Trafficking and MHC Class II Presentation. Molecular Immunology, 68, 85-88. https://doi.org/10.1016/j.molimm.2015.04.007
[298]
Hernandez, C., Huebener, P. and Schwabe, R.F. (2016) Damage-Associated Molecular Patterns in Cancer: A Double-Edged Sword. Oncogene, 35, 5931-5941. https://doi.org/10.1038/onc.2016.104
[299]
Keep, O., Galluzzi, L., Senovilla, L., et al. (2009) Viral Subversion of Immunogenic Cell Death. Cell Cycle, 8, 860-869. https://doi.org/10.4161/cc.8.6.7939
[300]
Klune, J.R., Dhuper, R., Cardinal, J., et al. (2008) HMGB1: Endogenous Danger Signaling. Molecular Medicine, 14, 476-484. https://doi.org/10.2119/2008-00034.Klune
[301]
Foel, D. (2007) Mechanisms of Disease: A “DAMP” View of Inflammatory Arthritis. Nature Clinical Practice Rheumatology, 3, 382-390. https://doi.org/10.1038/ncprheum0531
[302]
Bosteels, C., Neyt, K., Vanheerswynghels, M., et al. (2020) Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection. Immunity, 52, 1039-1056. https://doi.org/10.1016/j.immuni.2020.04.005
[303]
Xu, Z., Yang, Y., Zhou, J., et al. (2019) Role of Plasma Calreticulin in the Prediction of Severity in Septic Patients. Disease Makers, 2019, Article ID: 8792640. https://doi.org/10.1155/2019/8792640
[304]
Gold, L.I., Eggleton, P., Sweetwyne, M.T., Van Duyn, L.B., Greives, M.R., Naylor, S.-M., Michalak, M. and Murphy-Ullrich, J.E. (2009) Calreticulin: Non-Endoplamic Reticulum Functions in Physiology and Disease. FASEB, 24, 665-683. https://doi.org/10.1096/fj.09-145482
[305]
Andersson, U., Ottestad, W. and Tracey, K.J. (2020) Extracellular HMGB1: A Therapeutic Target in Severe Pulmonary Inflammation Including COVID-19? Molecular Medicine, 26, 42. https://doi.org/10.1186/s10020-020-00172-4
[306]
Derer, A., Deloch, L., Rubner, Y., et al. (2015) Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses—Pre-Clinical Evidence and Ongoing Clinical Applications. Frontiers in Immunology, 6, 505. https://doi.org/10.3389/fimmu.2015.00505
[307]
Stagg, A.J. and Knight, S.C. (2001) Antigen-Presenting Cells. http://labs.icb.ufmg.br/lbcd/pages2/bernardo/Bernardo/Artigos/Antigen-presenting%20Cells.pdf https://doi.org/10.1038/npg.els.0000903
Holtmeier, W. and Kabelitz, D. (2005) γ δ T Cells Link Innate and Adaptive Immune Responses, Mechanisms of Epithelial Defense. Chemical Immunology and Allergy, 86, 151-183. https://doi.org/10.1159/000086659
[310]
Coronavirus and the Cytoskeleton, Cytoskeleton, Inc. https://www.cytoskeleton.com/coronavirus-newsletter
[311]
Simpson, C. and Yamauchi, Y. (2020) Microtubules in Influenza Virus Entry and Egress. Viruses, 12, 117-136. https://doi.org/10.3390/v12010117
[312]
Lv, X., Li, Z., Guan, J., Hu, S., Zhang, J., Lan, Y., Zhao, K., Lu, H., Song, D., He, H., Gao, F. and Hea, W. (2019) Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin a5b1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement to Promote Its Invasion of N2a Cells. Journal of Virology, 93, e01736-18. https://doi.org/10.1128/JVI.01736-18
[313]
Rüdiger, A.-T., Mayrhofer, P., Ma-Lauer, Y., Pohlentz, G., Muthing, J., Brunn, von A. and Schwegmann-Wessels, C. (2016) Tubulins Interact with Porcine and Human S Proteins of the Genus Alphacoronavirus and Support Successful Assembly and Release of Infectious Viral Particles. Virology, 497, 185-197. https://doi.org/10.1016/j.virol.2016.07.022
[314]
Ward, B.M. (Yu2011) The Taking of the Cytoskeleton One Two Three: How Viruses Utilize the Cytoskeleton during Egress. Virology, 411, 244-250. https://doi.org/10.1016/j.virol.2010.12.024
[315]
Vincze, Gy., Szigeti, Gy.P. and Szasz, A. (2016) Reorganization of the Cytoskeleton. Journal of Advances in Biology, 9, 1872-1882. https://cirworld.com/index.php/jab/article/view/4059
[316]
Vincze, Gy. and Szasz, A. (2015) Reorganization of Actin Filaments and Microtubules by Outside Electric Field. Journal of Advances in Biology, 8, 1514-1518.
[317]
Marchetti, M. (2020) COVID-19-Driven Endothelial Damage: Complement, HIF-1, and ABL2 Are Potential Pathways of Damage and Targets for Cure. Annals of Hematology, 99, 1701-1707. https://doi.org/10.1007/s00277-020-04138-8
[318]
Whyte, M.K.B. and Walmsley, S.R. (2014) The Regulation of Pulmonary Inflammation by the Hypoxia-Inducible Factor-Hydroxylase Oxygen-Sensing Pathway. Annals of the American Thoracic Society, 11, S271-S276. https://doi.org/10.1513/AnnalsATS.201403-108AW
[319]
Zhang, R., Wu, Y., Zhao, M., et al. (2009) Role of HIF-1alpha in the Regulation ACE and ACE2 Expression in Hypoxic Human Pulmonary Artery Smooth Muscle Cells. American Journal of Physiology—Lung Cellular and Molecular Physiology, 297, L631-L640. https://doi.org/10.1152/ajplung.90415.2008
[320]
Arias-Reyes, C., Zubieta-DeUrioste, N., Poma-Machicao, L., et al. (2020) Does the Pathogenesis of SAR-CoV-2 Virus Decrease at High-Altitude? Respiratory Physiology & Neurobiology, 22, Article ID: 103443. https://doi.org/10.1016/j.resp.2020.103443
[321]
Joyce, K.E., Weaver, S.R. and Lucas, S.J.E. (2020) Geographic Components of SARS-CoV-2 Expansion: A Hypothesis. Journal of Applied Physiology, 129, 257-262. https://doi.org/10.1152/japplphysiol.00362.2020
[322]
Afsar, B., Kanbay, M. and Afsar, R.E. (2020) Hypoxia Inducible Factor-1 Protects against COVID-19: A Hypothesis. Medical Hypotheses, 143, Article ID: 109857. https://doi.org/10.1016/j.mehy.2020.109857
[323]
Rubio-Casillas, A. (2020) Does SARS CoV 2 Virus Induce Hypoxia to Increase Its Replication?
[324]
Kim, W., Kim, M.S., Kim, H.J., et al. (2017) Role of HIF-1α in Response of Tumors to a Combination of Hyperthermia and Radiation in Vivo. International Journal of Hyperthermia, 34, 276-283. https://doi.org/10.1080/02656736.2017.1335440
[325]
Mathivanan, S., Devesa, I., Changeux, J.-P., et al. (2016) Bradykinin Induces TRPV1 Exocytotic Recruitment in Peptidergic Nociceptors. Frontiers in Pharmacology, 7, 178. https://doi.org/10.3389/fphar.2016.00178
[326]
Jia, Y. and Lee, L.-Y. (2007) Role of TRPV Antagonists in Respiratory Diseases. Biochimica et Biophysica Acta, 1772, 915-927. https://doi.org/10.1016/j.bbadis.2007.01.013
[327]
Dietrich, A. (2019) Modulators of Transient Receptor Potential (TRP) Channels as Therapeutic Options for Lung Disease. Pharmaceuticals, 12, 23. https://doi.org/10.3390/ph12010023
[328]
Kuebler, W.M., Jordt, S.-E. and Liedtke, W.B. (2020) Urgent Reconsideration of Lung Edema as a Preventable Outcome in COVID-19: Inhibition of TRPV4 Represents a Promising and Feasible Approach. American Journal of Physiology—Lung Cellular and Molecular Physiology, 318, L1239-L1243. https://doi.org/10.1152/ajplung.00161.2020
[329]
Lee, S.-Y., Kim, J.-H., Han, Y.-H., et al. (2018) The Effect of Modulated Electro-Hyperthermia on Temperature and Blood Flow in Human Cervical Carcinoma. International Journal of Hyperthermia. https://doi.org/10.1080/02656736.2018.1423709
[330]
Batawi, S., Tarazan, N., Al-Raddadi, R., et al. (2019) Quality of Life Reported by Survivors after Hospitalization for Middle East Respiratory Syndrome (MERS). Health and Quality of Life Outcomes, 17, 101. https://doi.org/10.1186/s12955-019-1165-2
[331]
Ngai, J.C., Ko, F.W., Ng, S.S., To, K.W., Tong, M. and Hui, D.S. (2010) The Long-Term Impact of Severe Acute Respiratory Syndrome on Pulmonary Function, Exercise Capacity and Health Status. Respirology, 15, 543-550. https://doi.org/10.1111/j.1440-1843.2010.01720.x
[332]
Gurkan, O.U., O’Donnell, C., Brower, R., et al. (2003) Differential Effects of Mechanical Ventilatory Strategy on Lung Injury and Systemic Organ Inflammation in Mice. American Journal of Physiology—Lung Cellular and Molecular Physiology, 285, L710-L718. https://doi.org/10.1152/ajplung.00044.2003
[333]
Kalluri, R. and Weinberg, R.A. (2009) The Basics of Epithelial-Mesenchymal Transition. Journal of Clinical Investigation, 119, 1420-1428. https://doi.org/10.1172/JCI39104
[334]
Lee, K.A. and Nelson, C.M. (2012) New Insights into the Regulation of Epithelial-Mesenchymal Transition and Tissue Fibrosis. International Review of Cell and Molecular Biology, 294, 171-221. https://doi.org/10.1016/B978-0-12-394305-7.00004-5
[335]
Cabrera-Benítez, N.E., Parotto, M., Post, M., et al. (2012) Mechanical Stress Induces Lung Fibrosis by Epithelial-Mesenchymal Transition. Critical Care Medicine, 40, 510-517. https://doi.org/10.1097/CCM.0b013e31822f09d7
[336]
Hill, C., Jones, M.G., Davies, D.E., et al. (2019) Epithelial-Mesenchymal Transition Contributes to Pulmonary Fibrosis via Aberrant Epithelial/Fibroblastic Cross-Talk. Journal of Lung Health and Diseases, 3, 31-35. https://doi.org/10.29245/2689-999X/2019/2.1149
[337]
Szasz, O., Szigeti, Gy.P., Szasz, A. and Benyo, Z. (2018) Role of Electrical Forces in Angiogenesis. Open Journal of Biophysics, 8, 49-67. https://doi.org/10.4236/ojbiphy.2018.82005
[338]
Ballerini, M., Baronzio, G.F., Capito, G., Szasz, O. and Cassutti, V. (2013) Androtherm Application for the Peyronie’s Disease. Conference Papers in Medicine, 2013, Article ID: 962349. http://www.hindawi.com/archive/2013/962349 https://doi.org/10.1155/2013/962349
[339]
Hegyi, G., Molnar, I., Mate, A. and Petrovics, G. (2017) Targeted Radiofrequency Treatment—Oncothermia Application in Non Oncological Diseases as Special Physiotherapy to Delay the Progressive Development. Clinical Practice, 14, 73-77. https://doi.org/10.4172/clinical-practice.100098
[340]
Jeung, T.-S., Ma, S.-Y., Choi, J., et al. (2015) Results of Oncothermia Combined with Operation, Chemotherapy and Radiation Therapy for Primary, Recurrent and Metastatic Sarcoma. Case Reports in Clinical Medicine, 4, 157-168. http://www.scirp.org/journal/PaperInformation.aspx?PaperID=56280 https://doi.org/10.4236/crcm.2015.45033
[341]
DaSilva, R.M.V., Barichello, P.A., Medeiros, M.L., et al. (2013) Effect of Capacitive Radiofrequency on the Fibrosis of Patients with Cellulitis. Dermatology Research and Practice, 2013, Article ID: 715829. https://doi.org/10.1155/2013/715829
[342]
de Araujo, A.R., Soares, V.P.C., da Silva, F.S., et al. (2014) Radiofrequency for the Treatment of Skin Laxity: Mith or Truth. Anais Brasileiros de Dermatologia, 90, 707-721. https://doi.org/10.1590/abd1806-4841.20153605
[343]
Hagiwarra, S., Iwasasa, H., Matsumoto, S., et al. (2007) Association between Heat Stress Protein 70 Induction and Decreased Pulmonary Fibrosis in an Animal Model of Acute Lung Injury. Lung, 185, 287-293. https://doi.org/10.1007/s00408-007-9018-x
[344]
Ren, Y., Huo, W., Qi, R.-Q., et al. (2015) Intensive Local Thermotherapy Cleared Extensive Viral Warts in a Patient with Systemic Lupus Erythematosus. International Journal of Hyperthermia, 31, 5-7. https://doi.org/10.3109/02656736.2014.993339
[345]
Li, X., Zhang, C., Hong, Y., et al. (2012) Local Hyperthermia Treatment of Extensive Viral Warts in Darier Disease: A Case Report and Literature Review. International Journal of Hyperthermia, 28, 451-455. https://doi.org/10.3109/02656736.2012.677929
[346]
Fischer, H., Schwarzer, C. and Illek, B. (2003) Vitamin C Controls the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel. PNAS, 101, 3691-3696. https://doi.org/10.1073/pnas.0308393100
[347]
Ou, J., Zhu, X., Zhang, H., et al. (2020) A Retrospective Study of Gemcitabine and Carboplatin with or without Intravenous Vitamin C on Patients with Advanced Triple-Negative Breast Cancer. Integrative Cancer Therapies, 19, 1-7. https://doi.org/10.1177/1534735419895591
[348]
Szasz, O., Szigeti, Gy.P. and Szasz, A.M. (2017) Electrokinetics of Temperature for Development and Treatment of Effusions. Advances in Bioscience and Biotechnology, 8, 434-449. https://doi.org/10.4236/abb.2017.811032
[349]
Szasz, A., Vincze, Gy., Szigeti, Gy. and Szasz, O. (2017) Internal Charge Redistribution and Currents in Cancerous Lesions. Journal of Advances in Biology, 10, 2061-2079. http://cirworld.com/index.php/jab/article/view/6328/6283
[350]
Akdis, M., Sokolowska, M., O’Mahony, L., et al. (2020) Immune Response to SARS-CoV-2 and Mechanisms of Immunopathological Changes in COVID-19. Allergy, 75, 1564-1581. https://doi.org/10.1111/all.14364
[351]
Rokni, M., Ghasemi, V. and Tavakoli, Z. (2020) Immune Responses and Pathogenesis of SARS-CoV-2 during an Outbreak in Iran: Comparison with SARS and MERS. Reviews in Medical Virology, 30, e2107. https://doi.org/10.1002/rmv.2107
[352]
Minnaar, C.A., Kotzen, J.A., Ayeni, O.A., et al. (2020) Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients. Frontiers in Oncology, 10, 1-8. https://doi.org/10.3389/fonc.2020.00376
[353]
Krenacs, T., Meggyeshazi, N., Forika, G., et al. (2020) Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models. International Journal of Molecular Sciences, 21, 6270. https://doi.org/10.3390/ijms21176270
[354]
Patents on Tumor-Vaccination. a) EP 2703001 A1, Europe (2014) http://www.google.com/patents/EP2703001A1?cl=en; b) US 2015/0217099 A1, USA (2015) http://www.freepatentsonline.com/20150217099.pdf; c) 2013 307 344, Australia (2016) http://www.ipaustralia.com.au/applicant/xax-kft/patents/AU2013307344/; d) KR 10-1714281, South Korea (2017) https://patents.google.com/patent/KR101714281B1/en e) CA 2,879,739, Canada (2017) http://www.google.com/patents/CA2879739C?cl=en.
[355]
Lopez-Collazo, E., Avendano-Ortiz, J., Martin-Quiros, A., et al. (2020) Immune Response and COVID-19: A Mirror Image of Sepsis. International Journal of Biological Sciences, 16, 2479-2489. https://doi.org/10.7150/ijbs.48400
[356]
Bootman, M., Golding, J. and Male, D.K. (2020) How Does the Human Body Fight a Viral Infection? Open Learn. https://www.open.edu/openlearn/science-maths-technology/biology/how-does-the- human-body-fight-viral-infection
[357]
Garcia, L.F. (2020) Immune Response, Inflammation, and the Clinical Spectrum of COVID-19. Frontiers in Immunology, 11, 1441. https://doi.org/10.3389/fimmu.2020.01441
[358]
Fu, L., Wang, B., Yuan, T., et al. (2020) Clinical Characteristics of Coronavirus Disease 2019 (COVID-19) in China: A Systematic Review and Meta-Analysis. Journal of Infection, 80, 656-665. https://doi.org/10.1016/j.jinf.2020.03.041
[359]
Mehta, P., McAuley, D., Brown, M., et al. (2020) COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression. The Lancet, 395, 1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0
[360]
Shahabinezhad, F., Mosaddeghi, P., Negahdaripour, M., et al. (2020) Therapeutic Approaches for Covid-19 Based on the Dynamics of Interferon-Mediated Immune Responses. https://doi.org/10.20944/preprints202003.0206.v1
[361]
Matched Antigen Pairs of SARS-CoV-2 Serology Test Development. Creative Diagnostics. https://www.creative-diagnostics.com/news-matched-antigen-pair-for-sars-cov-2-serology-test-development-86.htm
[362]
Chakravarthy, K.V. (2012) Investigating the Adaptive Immune Response in Influenza and Secondary Bacterial Pneumonia and Nanoparticle Based Therapeutic Delivery. PhD Dissertation, Department of Microbiology and Immunology, State University of New York, Buffalo. https://www.researchgate.net/publication/258694611_Investigating_the _adaptive_immune_response_in_influenza_and_secondary_bacterial_pneumonia _and_nanoparticle_based_therapeutic_delivery
[363]
Long, Q.-X., Liu, B.-Z., Deng, H.-J., et al. (2020) Antibody Responses to SARS-CoV-2 in Patients with COVID-19. Nature Medicine, 26, 845-848. https://doi.org/10.1038/s41591-020-0897-1
[364]
Zhang, W., Du, R.-H., Li, B., et al. (2020) Molecular and Serological Investigation of 2019-nCoV Infected Patients: Implication of Multiple Shedding Routes. Emerging Microbes & Infections, 9, 386-389. https://doi.org/10.1080/22221751.2020.1729071
[365]
Zhao, J., Yuan, Q., Wang, H., et al. (2020) Antibody Responses to SARS-CoV-2 in Patients of Novel Coronavirus Disease 2019. Clinical Infectious Diseases, ciaa344. https://doi.org/10.1093/cid/ciaa344
[366]
Guo, L., Ren, L., Yang, S., et al. (2020) Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clinical Infectious Diseases, ciaa310.
[367]
Liu, L., Liu, W., Zeng, Y., et al. (2020) A Preliminary Study on Serological 1 Assay for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in 238 Admitted Hospital Patients. Microbes and Infection, 22, 206-211. https://doi.org/10.1016/j.micinf.2020.05.008
[368]
Sethuraman, N., Jeremiah, S.S. and Ryo, A. (2020) Interpreting Diagnostic Tests for SARS-CoV-2. JAMA, 323, 2249-2251. https://doi.org/10.1001/jama.2020.8259
[369]
Chen, J., Lau, Y.F., Lamirande, E.W., Paddock, C.D., Bartlett, J.H., Zaki, S.R. and Subbarao, K. (2010) Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection. Journal of Virology, 84, 1289-1301. https://doi.org/10.1128/JVI.01281-09
[370]
Liu, A., Wang, W., Zhao, X., et al. (2020) Disappearance of Antibodies to SARS-CoV-2 in a Covid-19 Patient after Recovery. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2020.07.009
[371]
Mo, H., Zeng, G., Ren, X., et al. (2006) Longitudinal Profile of Antibodies against SARS-Coronavirus in SARS Patients and Their Clinical Significance. Respirology, 11, 49-53. https://doi.org/10.1111/j.1440-1843.2006.00783.x
[372]
Fan, E., Beitler, J.R., Brochard, L., et al. (2020) COVID-19-Associated Acute Respiratory Distress Syndrome: Is a Different Approach to Management Warranted? The Lancet Respiratory Medicine, 8, 816-821. https://doi.org/10.1016/S2213-2600(20)30304-0
[373]
Vargas, M., Sutherasan, Y., Gregoretti, C., et al. (2020) PEEP Role in ICU and Operating Room: From Pathophysiology to Clinical Practice. The Scientific World Journal, 2014, Article ID: 852356. https://doi.org/10.1155/2014/852356
[374]
Ranieri, M.V., Macia, L., Fiore, T., et al. (1995) Cardiorespiratory Effects of Positive End-Expiratory Pressure during Progressive Tidal Volume Reduction (Permissive Hypercapnia) in Patients with Acute Respiratory Distress Syndrome. Anesthesiology, 83, 710-720. https://doi.org/10.1097/00000542-199510000-00010
[375]
Zhu, N., Zhang, D., Wang, W., et al. (2020) A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine, 382, 727-733. https://doi.org/10.1056/NEJMoa2001017
[376]
Tsolaki, V., Siempos, I., Magira, E., et al. (2020) PEEP Levels in COVID-19 Pneumonia. Critical Care, 24, 303. https://doi.org/10.1186/s13054-020-03049-4
[377]
Walkey, A.J., Del Sorbo, L., Hodgson, C.L., et al. (2017) Higher PEEP versus Lower PEEP Strategies for Patients with Acute Respiratory Distress Syndrome. Annals of the American Thoracic Society, 14, S297-S303. https://doi.org/10.1513/AnnalsATS.201704-338OT
[378]
Roesthuis, L., van den Berg, M. and van der Hoeven (2020) Advanced Respiratory Monitoring in COVID-19 Patient: Use Less PEEP. Critical Care, 24, 230. https://doi.org/10.1186/s13054-020-02953-z
[379]
Marini, J.J. and Gattinoni, L. (2020) Management of COVID-19 Respiratory Distress. JAMA, 323, 2329-2330. https://doi.org/10.1001/jama.2020.6825
[380]
Vashist, R. and Duggal, A. (2020) Respiratory Failure in Patients Infected with SARS-CoV-2. CCJM. https://doi.org/10.3949/ccjm.87a.ccc025
[381]
Reed, J. and Hutchinson, S. (2020) Coronavirus: Warning Thousands Could Be Left with Lung Damage. BBC News. https://www.bbc.com/news/health-53065340
[382]
George, P.M., Wells, A.U. and Jenkins, R.G. (2020) Pulmonary Fibrosis and COVID-19: The Potential Role for Antifibrotic Therapy. The Lancet Respiratory Medicine, 8, 807-815. https://doi.org/10.1016/S2213-2600(20)30225-3
[383]
Davido, B., Seang, S., Tubiana, R. and de Truchis, P. (2020) Post-COVID-19 Chronic Symptoms: A Post-Infectious Entity? Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2020.09.001
[384]
Arnold, D.T., Hamilton, F.W., Milne, A., Morley, A., Viner, J., Attwood, M., Noel, A., Gunning, S., Hatrick, J., Hamilton, S., Elvers, K.T., Hyams, C., Bibby, A., Moran, E., Adamali, H., Dodd, J., Maskell, N.A. and Barratt, S. (2020) Patient Outcomes after Hospitalisation with COVID-19 and Implications for Follow-Up; Results from a Prospective UK Cohort. https://doi.org/10.1101/2020.08.12.20173526
[385]
Puntmann, V.O., Carerj, M.L., Wieters, I., et al. (2020) Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered from Coronavirus Disease 2019 (COVID-19). JAMA Cardiology, 5, 1265-1273. https://doi.org/10.1001/jamacardio.2020.3557
[386]
Greenhalgh, T., Knight, M., A’Court, C., Buxton, M. and Husain, L. (2020) Management of Post-Acute Covid-19 in Primary Care. BMJ, 370, m3026. https://doi.org/10.1136/bmj.m3026
[387]
Yelin, D., Wirtheim, E., Vetter, P., Kalil, A.C., Bruchfeld, J., Runold, M., Guaraldi, G., Mussini, C., Gudiol, C., Pujol, M., Bandera, A., Scudeller, L., Paul, M., Kaiser, L. and Leibovici, L. (2020) Long-Term Consequences of COVID-19: Research Needs. The Lancet/Infection, 20, 1115-1117. https://doi.org/10.1016/S1473-3099(20)30701-5
[388]
Gousseff, M., Penot, P., Gallay, L., et al. (2020) Clinical Recurrences of COVID-19 Symptoms after Recovery: Viral Relapse, Reinfection or Inflammatory Rebound? Journal of Infection, 81, 816-846. https://doi.org/10.1016/j.jinf.2020.06.073
[389]
Matricardi, P.M., Dal Negro, R.W. and Nisini, R. (2020) The First, Holistic Model for COVID19: Implications for Prevention, Diagnosis, and Public Health Measures. Pediatric Allergy and Immunology, 1-17. https://doi.org/10.1111/pai.13271
[390]
Szasz, A. and Szasz, O. (2020) Time-Fractal Modulation of Modulated Electro-Hyperthermia (mEHT). In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars, Newcastle upon Tyne, Ch. 17, 377-415.
[391]
Cunha, L., Szigeti, K., Mathé, D. and Metello, L.F. (2014) The Role of Molecular Imaging in Modern Drug Development. Drug Discovery Today, 19, 936-948. https://doi.org/10.1016/j.drudis.2014.01.003
[392]
Szigeti, K., Szabó, T., Korom, C., Czibak, I., Horváth, I., Veres, D.S., Gyöngyi, Z., Karlinger, K., Bergmann, R., Pócsik, M., Budán, F. and Máthé, D. (2016) Radiomics-Based Differentiation of Lung Disease Models Generated by Polluted Air Based on X-Ray Computed Tomography Data. BMC Medical Imaging, 16, 14. https://doi.org/10.1186/s12880-016-0118-z
[393]
Szasz, A. (2014) Oncothermia: Complex Therapy by EM and Fractal Physiology. 31th URSI General Assembly and Scientific Symposium (URSI GASS), Beijing, 20 October 2014, 1-4. https://doi.org/10.1109/URSIGASS.2014.6930100
[394]
Szasz, O., Vincze, G., Szigeti, G.P., Benyo, Z. and Szasz, A. (2018) An Allometric Approach of Tumor-Angiogenesis. Medical Hypothesis, 116, 74-78. https://doi.org/10.1016/j.mehy.2018.03.015
[395]
Hegyi, G., Vincze, Gy. and Szasz, A. (2020) Thermodynamic Description of Living Homeostasis. In: George, T.F., Ed., New Insights into Physical Science, Vol. 1, Book Publisher International, London, Chapter 10, 1-13. http://www.bookpi.org/bookstore/product/new-insights-into-physical-science-vol-1
[396]
Szasz, A., Iluri, N. and Szasz, O. (2013) Local Hyperthermia in Oncology—To Choose or Not to Choose? In: Huilgol, N., Ed., Hyperthermia, InTech, London, Ch. 1, 1-82. https://doi.org/10.5772/52208
