key: cord-0942579-hvv5gume authors: Ramirez, Francisco E; Sanchez, Alberto; Pirskanen, Aki T title: Hydrothermotherapy in prevention and treatment of mild to moderate cases of COVID-19 date: 2020-11-16 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110363 sha: 356dbe8342a05499b39e5b680d4f48fc7bb5c02d doc_id: 942579 cord_uid: hvv5gume COVID-19 is a new contagious disease caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is a disease that has reached every continent in the world; it has overloaded the medical system worldwide and it has been declared a pandemic by the World Health Organization. Currently there is no definite treatment for COVID-19. We realize that host immunity is a critical factor in the outcome of coronavirus 2 infection. Here, however, we review the pathophysiology of the disease with a focus on searching for what we can do to combat this new disease. From this, we find that coronavirus is sensitive to heat. We have thus focused on this area of vulnerability of the virus. The emphasis of this hypothesis is on the action of body heat-internal (fever) and external (heat treatment)-in activating the immune system and its antiviral activities, and specifically related to the coronavirus. We hypothesize from this review that heat treatments has the potential to prevent COVID-19 and to decrease the severity of mild and moderate cases of Coronavirus. We propose heat treatments for this uncontrolled worldwide coronavirus pandemic while studies are being done to test the effectiveness of heat treatments in the prevention and treatment of COVID-19. severe acute respiratory syndrome ( 6 ) that may lead to death. 4 The epidemiological history of COVID-19 is that the virus was originally transmitted in Wuhan, China from a meat market that sold animals. The virus enters the nose and throat where the virus finds cells that are rich in a cell surface receptor called angiotensin-converting enzyme 2 (ACE2) ( 7 ) . The virus requires the ACE2 receptor to enter the cell, the same as SARS-CoV-1 ( 8 ). Person to person transmission is the way the infection continued to spread to others ( 9 ). It spreads mainly via respiratory droplets in a manner similar to influenza but non-respiratory virus particles have also been documented in eyes, blood and stool ( 10 ). The most common manifestations of the infection is at the prodromal phase and it can last a week or so. This phase of the disease includes fever, myalgia, dry cough, loss of smell and taste, fatigue and diarrhea. If the immune system can't stop the virus it will continue to attack the body further and develop dyspnea and lymphopenia as it attacks the alveoli in the lungs and other organs. The alveoli are especially vulnerable since they are also rich in ACE2 receptors that allow the virus into the cell ( 11 ). The challenging patients continue to deteriorate and develop acute respiratory distress syndrome and super infections ( 12 ). Even asymptomatic patients after CT studies (computed tomography) show bilateral ground-glass opacities ( 13 ). One third of those infected developed blood clot abnormalities and an increase in D-dimer ( 14 ). This abnormality may explain why diabetic and hypertensives have poor prognosis after contracting COVID-19 since those patients may already have previously damaged blood vessels ( 15 ). The innate immune response seems to be the important factor that determines the outcome of COVID-19 for each individual. An important type of protein that helps regulate the activity of the immune system is the type I interferons (IFNs). These proteins elicit an anti-viral response involving IRF3/IRF7 antiviral pathways ( 16 ). When secreted they stimulate macrophages and natural killer (NK) cells. In the case of viral infections, interferons are secreted by infected cells preparing the body against a possible viral infection. Previous research has documented how SARS-CoV-2 suppresses or delays type I interferons (IFN), specially in the initial infection ( 17 ). It is thought that it suppresses the immune system which may explain why some people don't present with symptoms early in the disease, as interferon is also involved in producing fever (pyrogenic) ( 18 ). A study analyzing the evolution of a mild case of SARS-CoV-2 showed a dramatic decrease of NK cells and monocytes, which seem to be a target of the virus ( 19 ) .Patients with lower response of IFN tend to have poorer prognosis and higher risk of death from coronavirus infections ( 20 ) . People with chronic diseases (cardiovascular disease, hypertension, obesity, diabetes, etc.) seem to be more prone to the infection with the SARS-CoV-2 ( 21 ) possibly due to the fact that SARS-CoV-2 infects also the endothelium and triggers inflammation ( 22 ) . Conversely, children have a strong immune reaction against viral infections ( 23 ) and that may explain why less than 2% of all confirmed COVID-19 infections in the USA are from children even though children are 22% of the entire US population ( 24 ). 6 The pathophysiology of the coronavirus appears daunting but there is much we can do about it. The way to approach this unnerving disease is to understand and select a weak point of the virus and attack its weakness. Coronaviruses are vulnerable to heat, basic pH and acid pH ( 25 ). The virus seems to like lower temperatures as it is more stable at 39.2 o F ( 26 ). We explore the potential effect that fever or artificially induced body heat can have on the infection. The term Hydrothermotherapy come from three Greek words-"Hudor," meaning water, "Thermo," meaning heat, and "Therapeia," meaning healing-Some authors called it hydrotherapy. It is the intelligent application of water in any form, including ice and steam, either internally or externally, for the healing of disease ( 27 ) . Hydrothermotherapy is a unique mechanism that creates an artificial fever in the human body. One benefit of fever in an infection is better survival of the host and another is a shorter duration of the disease ( 28 ). Heat by itself has an antiviral effect. When a container of human cells and rhinovirus was immersed in a 113° F hot water bath, the heat suppressed the multiplication of the virus by 90%, but did not kill the human cells ( 29 ). Infectious agents may trigger fever, which is a defense mechanism ( 30 ). Fever is usually triggered when monocytes meet pathogens and this results in an increase of IL-1 ( 31 ), which is what triggers the fever response since IL-1 is a pyrogen( 32 ). IL-1 is also involved in the activation of the cellular and humoral immune response against the pathogen ( 33 ). Fever promotes migration of leukocytes and neutrophils to the area where the pathogen is ( 34 ) and it activates T Cell function ( 35 ) . Genes involved in the activation of the interleukins have 7 been identified. The most important pathway is the nuclear factor kappa B (NF-kB), which is responsible to activate IL-1, IL-6 and IL-8 and it has an effect on two other pathways-the p53 protein and the heat-shock factor protein 1 (HSF1) ( 36 ). Cautions with the use of saunas have been documented, but they are uncommon. A review of deaths in Finland of people using the sauna from 1990 to 2002 shows that there were less than 2 cases per 100,000 inhabitants, but the conclusion was that the most common cause of deaths in saunas was the use of alcohol and that it should be avoided ( 71 ). The role of saunas per se in death is unknown. A perspective on deaths related to saunas is that the risk of sudden death ( 77 ). The participants were submerged in hot water at 103 o F in order to simulate an artificial fever and test its effect on monocytes and TNF-alpha. In the vitro part of the study it was shown that the receptors CD14 and CD11b, that are helpful in infections, were increased after the water treatment. When the in vivo part of the study took place 3 hours after the hyperthermia the response of monocytes to endotoxins was improved as documented by greater TNF-alfa release. The conclusion of this study was that hydrothermotherapy activates monocytes and prepares them to respond to infections ( 78 ). A separate small study (N=7) was designed to test the effect of hydrothermotherapy followed by a cold application on the immune system. The heat followed by cold therapy significantly increased the number of white blood cells, granulocytes, lymphocytes and monocytes. The researchers concluded that the brief cold following the heat treatment was effective in increasing the white blood cell count, the NK cell activity and the IL-6. Physical exercise before therapy had a synergistic effect on the immune system ( 79 ). Hyperthermia stimulates cytokine release in a similar way as fever ( 80 ),( 81 ). During the Spanish flu pandemic of 1918 ( 82 ) that killed 50 to 100 million people( 83 ) there were health centers known as sanitariums for the treatment of disease and for health education in lifestyle ( 84 ). Hydrothermotherapy was used in sanitariums as a means of assisting the body to combat various types of diseases ( 85 ), ( 86 ). The hydrothermotherapy used in these sanitariums were hot water baths, fomentations, steam baths and wet sheet packs. Mortality from the Spanish flu in the general public hospitals ranged from 13 to 40 percent( 87 ). It was stated that the Army camps offered the best treatment available against the Spanish flu ( 88 ) and the death rate from the pandemic at these hospitals where hydrothermotherapy was not used was 6.7% There are numerous factors that determine the number of cases of COVID-19 in any community or country. Also, this report above is merely a report and not a study of cause and effect. It is of interest to us, however, to note that there is a lower than average number of COVID-19 cases in the two countries that practice regular heat treatments as compared to the average for the other European countries-54.7% in Finland and 63.6% in Estonia as compared to the rest of Europe. Far more important than the lower number of cases is the remarkably lower number of deaths from COVID-19 in Finland (32.1%) and in Estonia (28.3%) as compared to the rest of Europe considered as 100.0%. It would be hard to compare worldwide data with other countries due to limited testing and reporting in other countries ( 93 ) . Nevertheless, the community use of heat treatments is consistent with a lower prevalence and a lower death rate from COVID-19. This report highlights the effectiveness of inactivating the coronavirus by heat, ideally followed by cold to stimulate the immune response. The emphasis is not on the method but on the fact that heat may inactivate the virus. The reality is that any method to heat the body is better than none. And a readily accessible method for the larger portion of the population is more effective than the best method that is accessible to relatively few. Following the model of Finland and Estonia of regular heat treatments followed by cold, we propose the regular use of home hydrothermotherapy as the means of hot and cold treatment of choice during this pandemic. It is a home heat treatment method that uses tools typically available in the homewater, a means for heating water, a large kettle with lid for steam, towels, a container for foot bath, and a chair or stool. A hot shower followed by a cold shower could potentially have some of those benefits. These home tools are accessible to most people worldwide. All the evidence cited above may be reduced to two major conclusions: 1) elevating the body heat weakens the virulence of the virus and/or improves body immunity ( 94 ),( 95 ) and 2) the use of heat treatments (such as steam baths, sauna or hot baths using water 92°f to 104°f) appears to be associated with a lower incidence of viral infections and lower death rates from viral diseases including COVID-19, when applied for 5 to 20 minutes followed by cold (as shown by 14 the Finnish and Estonian populations)( 96 ), ( 97 ) . The application of these modalities does not necessarily require expensive equiment. Constructing a sauna or paying to use it could be an expensive investment but hydrothermotherapy can also be applied with simple equipment such as pails, towels and hot water, things available worldwide. We thus hypothesize that frequent treatments of heat followed by cold are the effective first line approach in the prevention and treatment of mild to moderate coronavirus 2 infections. We further hypothesize that if this approach is followed by large numbers of individuals in each community the impact of coronavirus 2 on the world population will be significantly decreased. CONCLUSION SARS-CoV-2 is a dangerous virus that has caused a world-wide pandemic. This virus, however, is susceptible to elevated body heat and elevated body heat also enhances the immune system. We thus hypothesis that frequent treatments of heat followed by cold are the effective first line approach in the prevention and treatment of mild coronavirus 2 infections. We recommend for all stages of COVID-19 that the most accessible method of hydrothermotherapy interventions should be used. 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