A conversation with my friend Brian

The TDVT Hypothesis as explained by Brian:

OK, let me try to grasp this by repeating it back to you in my words.

In order to replicate, a virus moves from host to host. This requires a transmission method (sneezing) which will fail if the host dies or is too ill to socialise: moderate symptoms and a long incubation period are thus ideal.

The virus accomplishes this by being sensitive to temperature. The colder temperatures are in the mouth and nose, which is where transmission through sneezing will happen. To reproduce at higher temperatures, such as the lungs, would incapacitate the host and so prevent transmission.

However, the problem with CV-19 is that it seems not to be sensitive, or as sensitive, to temperature, so getting into more lungs.

The seasonal pattern of respiratory viruses is a consequence of this. As temperatures rise in the air and thus in the mouth and nose, the virus tends not to replicate in any part of the body.

Is that it?

Me:

You have absolutely got it.

Van Loghem

The TDVT Hypothesis

The temperature-dependent viral tropism (TDVT) hypothesis for respiratory viruses is very simple:

      • Viruses refrain from multiplying as fast as they can in order to spread themselves more widely (scientists call this the “trade-off” model)
      • Respiratory viruses do this in a very simple way: they sense temperature. They refrain from developing at normal body temperature, and this allows them to keep out of the lungs, heart, brain etc.  They normally replicate only in the cooler nose and throat, so the host keeps moving around and spreading the virus
      • The seasonal pattern of viruses is a consequence of this. As temperatures rise in the air and thus in the nose and throat, the virus tends not to replicate in any part of the body

For detailed scientific information about respiratory viruses, including discussion of the trade-off model, viral dormancy and much else, see my 2016 paper:

Shaw Stewart, PD.  Seasonality and selective trends in viral acute respiratory tract infections. Medical Hypotheses 2016; 86 104–119.

For a discussion of the strange timing and duration of influenza epidemics, please see

The strange arrivals – and departures – of influenza epidemics in the UK, 1946-1974

Applications to Covid-19

Predicting the seasonality of Covid-19

      • Seasonality of respiratory illness is not mainly driven by changes in the survival rate of viruses outside the body.  If it were, respiratory illness would be rarer in the Tropics than in the summer in temperate regions.
      • We need an explanation of seasonality that fits all the facts.
      • Seasonality seems to be a side-effect the natural temperature-sensitivity of virtually all respiratory viruses
      • CoV-2 may be less temperature-sensitive than typical respiratory viruses, therefore less seasonal
      • Experiments are needed!

Epidemiology of respiratory illness

      • Respiratory illness responds so quickly to changes in ambient temperature that conventional epidemiology can’t give a good description
      • Data often show a “harvesting” mechanism, where temperature changes activate dormant colds and flu
      • Colds and flu frequently appear in the rainy season in the Tropics
      • Explanations based on increased transmission in cold, dry places can’t work in the Tropics!

Covid 19 and the trade-off model

      • Evolution balances the benefits of virulence in parasites (greater rate of shedding) against the disadvantages (shedding for less time, and less dispersal)
      • “Short-sighted selection” increases virulence. “Far-sighted selection” increases transmission.
      • Viruses that jump to new hosts are sometimes extraordinarily virulent. Well-established viruses clearly moderate their virulence.
      • Milder CoV-2 strains that are temperature-sensitive may arise spontaneously in the next few weeks
      • We should be very careful to contain virulent strains that may arise in hospitals and other institutions where transmission can occur at high frequency

A simple model of CoV-2 transmission

      • In institutions where transmission is frequent more virulent strains are favored
      • Their longer incubation periods favor milder strains in the community
      • Lockdown slightly increases the competitive advantage of milder strains
      • We should be very careful to contain virulent strains that may arise in hospitals and other institutions where transmission can occur frequently

The adaptability of respiratory viruses

      • Influenza tends to move from hotter countries to colder ones
      • It seems to take a few months to adapt to a new climate
      • CoV-2 replicated independently in the throat and lungs of a single patient
      • The strain in the throat was derived from the lung one
      • These observations give an indication of how rapidly respiratory viruses can adapt to new environments
      • Experiments are needed ! !

Technical notes on CoV-2 for scientists

      • We should focus on the temperature-sensitivity of RNA secondary structure
      • The “s2m” structure in the 3’ untranslated region is of particular interest
      • The distribution of ACE2 may not be the main driver of viral tropism
      • Influenza has been shown to have a temperature-driven switch, with high temperature favoring transcription over replication

Suggestions for avoiding colds and flu – and Covid-19

      • Observational studies can give us hints
      • Never allow yourself to be chilled; dress warmly
      • Take regular outdoor exercise, dressed warmly
      • If you get a cold, stop exercise, avoid hot (and cold) drinks
      • Stay warm!

 

 

 

 

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