Proposals for simple RCTs based on the Temperature-Dependent Viral Tropism hypothesis

Option 1: pilot trial of constant external warming, and the maintenance of constant pharyngeal temperature, in hospitalized COVID-19 patients.

Study Description

The purpose of this study is to determine whether maintaining constant warm ambient temperature, and avoiding both hot and chilled drinks, improves the outcome for COVID-19 patients in a hospital setting.

Inclusion Criteria: hospitalized patients who have been diagnosed with Covid-19.

The experimental arm will receive the following treatment:

1. 1. Keep ambient temperature absolutely constant, day and night.
  2. Keep the patient warm enough to cause mild sweating, and don’t let them become chilled even for a minute.
  3. Eliminate all chilled drinks, ice cream, etc.
  4. (Counterintuitively) also avoid all hot drinks, soup, casseroles etc.
  5. Tea, coffee, soft drinks, soup etc. are acceptable but should be served at 27 – 37°C.

The control arm will receive treatment based on previously-used recommendations.

Outcome measures:

1. 1. Mortality (time frame: 28 days)
  2. Measures of the progression of COVID-19 such as viral load, serology, immunological markers etc.

Option 2: pilot trial of advice to maintain constant external warming, and constant pharyngeal temperature, in patients diagnosed with COVID-19 in the community.

Study Description

The purpose of this study is to test the effectiveness of advice to maintain constant warm ambient temperature, and to avoid both hot and chilled drinks, for improving the outcome for COVID-19 patients in the community.

Inclusion Criteria: individuals in the community who have been diagnosed with Covid-19.

The experimental arm will receive verbal and written advice to follow the 5 points above. This advice will include using heating in the sickroom during both the day and night.

The control arm will receive advice based on previously-used recommendations.

Outcome measures:

1. 1. Hospitalization (time frame: 20 days)
  2. Measures of the progression of COVID-19 such as viral load, serology, immunological markers etc.

Both proposals are based on the Temperature-Dependent Viral Tropism (TDVT) hypothesis, which proposes that the seasonality and pathogenicity of virtually all viral respiratory illnesses are determined by the viruses’ natural biochemical temperature-sensitivity. For more information click here.

References:

Shaw Stewart PD, Bach JL. Temperature dependent viral tropism: understanding viral seasonality and pathogenicity as applied to the avoidance and treatment of endemic viral respiratory illnesses. Reviews in Medical Virology. 2021 May 3:e2241. https://doi.org/10.1002/rmv.2241

Shaw Stewart, Patrick D. “Seasonality and selective trends in viral acute respiratory tract infections.” Medical hypotheses 86 (2016): 104-119.

Eccles, Ronald. “Why is temperature sensitivity important for the success of common respiratory viruses?” Reviews in Medical Virology (2020): e02153.

Figures

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1. – Graph II from van Loghem’s report on the epidemiology of respiratory illnesses in the Netherlands in the winter of 1925/26. I have superimposed ambient temperature at five Dutch weather stations (colored lines) with the temperature scale inverted (lowest temperatures at the top). From Van Loghem JJ. J Hyg 1928; 28(01):33–54.
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2. – Hope-Simpson’s record of feverish respiratory illnesses in his medical practice in Cirencester, UK, compared with notifications of such diseases in Prague, Czechoslovakia 1969–74. From Hope-Simpson RE. J Hyg 1981; 86(01):35–47.
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3. – The viruses that caused respiratory tract infections in hospitalized children in Mainz, Germany, which has an oceanic climate, 2000 – 2008. The four most frequent pathogens were, in order, rhinovirus (RV), respiratory syncytial virus (RSV), influenza A (IVA), and adenovirus (AV). From Du Prel JB et al. Clin Infect Dis 2009; 49(6):861–8.
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4. – The viruses that caused respiratory tract infections in hospitalized children in Buenos Aires, Argentina, which has humid subtropical climate, 1998 – 2003. The four most frequent pathogens were, in order, respiratory syncytial virus, influenza A, adenovirus, and parainfluenza. From Viegas M et al. J Infection 2004; 49(3):222–8.
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5. – The viruses that caused respiratory tract infections in hospitalized children in Singapore, which has a tropical climate, 1990-94. The four most frequent pathogens were, in order, respiratory syncytial virus, parainfluenza, influenza A and adenovirus. Chew FT et al. Epidemiol Infect 1998; 121 (01):121–8.
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6. – The Eurowinter Group analyzed the climate and the measures taken to protect individuals from cold in eight European regions, ranging from northern Finland to Athens. The table shows the regression coefficients (R) and their significance (p), for cause-specific indices of respiratory disease-related mortality on personal cold-exposure factors standardized at 7°C mean daily temperature. I have added labels to the plot on the right, drawing attention to some points that I found interesting. The most dangerous activities are at the top left of the plot, with the most protective at the bottom left. Activities that don’t affect the chance of dying from respiratory illness are on the right or at the middle level. Donaldson G et al. (The Eurowinter Group). Lancet 1997; 349:1341–6.
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7. – During sporting competitions people tend to crowd together in bars and at home to watch the events. The figure above shows that during the 2014 FIFA World Cup, in 18 countries in the Northern Hemisphere, there was no increase in the number of Google searches for terms related to colds and flu. It seems safe to conclude that the peaks that can be seen in winter in every country are not driven by crowding. (Notice the epidemics of colds in early autumn 2014. Autumn epidemics quite often appear when the temperature dips at the end of summer.)
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8. – Humidity: a fashionable explanation of influenza seasonality. In the last few years it has been suggested that flu seasonality is the result of the greater stability of flu virions (virus particles) in cold, dry conditions. (This comes under M2 in my categorization.) There are two major problems here: first, we have to account for the much higher levels of influenza during the rainy season in the tropics compared to other times of the year. For example, in Fortaleza (northern Brazil) influenza almost disappears outside the rainy season. Second, we would have to believe that the seasonality of influenza was driven by a different mechanism to that of many other respiratory viruses. A dozen studies, shown above, have been carried out where virus aerosols were created in rotating drums (the rotation stops the virions from settling) and the stability of virions was measured in air of different humidities. The results showed that several respiratory viruses (including influenza virus) are indeed more stable in dry air, but several others, including rhinovirus and adenovirus, are much more stable in moist air!
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Option 1: pilot trial of constant external warming, and the maintenance of constant pharyngeal temperature, in hospitalized COVID-19 patients.

Option 2: pilot trial of advice to maintain constant external warming, and constant pharyngeal temperature, in patients diagnosed with COVID-19 in the community.

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