The TDVT hypothesis: Frequently Asked Questions

1. What’s a concise description of  Temperature-Dependent Viral Tropism (TDVT)?

• • Natural selection tends to favor viruses that don’t immobilize their hosts.
  • Endemic respiratory viruses accomplish this by replicating only at temperatures below normal body temperature. In this way they normally confine themselves to the nose and throat, and avoid the lungs.

2. How does TDVT give rise to winter seasonality**?

• • When air temperature falls as autumn arrives, the temperature in the nose and throat also falls.
  • This makes any respiratory viruses that are present more active.
  • When air temperature rises as spring arrives, the temperature in the nose and throat also rises.
  • This makes any respiratory viruses that are present less active.

**This is the simple version.  See below for full answer.

3. Which viruses have winter seasonality?

Remarkably, all the common respiratory viruses show winter seasonality. This includes completely unrelated families such as those that replicate in the cell nucleus, those that replicate in the cell cytoplasm, DNA, RNA, positive-sense, negative-sense, icosahedral, irregular, encapsulated and unencapsulated viruses.

The only respiratory virus that seems to show summer seasonality is parainfluenza type 3, which is not very common.

Viruses that are mainly not spread via the mouth, nose and throat, such as polio and rabies, often show summer seasonality.

4. Can you get a respiratory infection without getting a fever or the symptoms of a cold?

A set of papers, which should have been game-changing, were published in 2019 by a group of scientists in New York City. They showed that coronavirus, RSV, parainfluenza, rhinovirus and adenovirus infections were completely asymptomatic in 70 – 80% of cases. Metapneumovirus and influenza infections were asymptomatic in 30 – 50% of cases.

5. What’s the most popular mainstream explanation of winter seasonality of colds and flu among scientists?

It’s that respiratory viruses survive outside the body (in the air and on surfaces) for longer in the cold dry conditions of winter.

6. What are the main problems with that explanation of seasonality?

The main problems are:

• • The same viruses that cause infections during the winter months in e.g. the USA and Europe, thrive year-round in the Tropics. Therefore absolute temperature (as opposed to temperature change, which is what matters) seems not to be the main driver of seasonality.
  • In tropical locations that have rainy seasons such as Singapore, India and Northern Brazil, colds and flu arrive during the rainy season. Therefore low humidity does not seem to be one of the main drivers of respiratory illness.
  • Rhinovirus survives in aerosols for longer in humid conditions. Rhinovirus also has autumn and winter seasonality, so, again, low humidity doesn’t seem to be an important driver.
  • Respiratory illnesses sometimes simultaneously arrive across wide geographical regions, often starting less than a week after temperatures drop. This response is too fast to be explained by changes in the rate of transmission of respiratory viruses.
  • In, for example, the UK, colds and flu don’t follow dry weather.  They do follow cold weather.  There are many examples of this. 

7. How can I avoid getting a viral respiratory infection?

• • Regular outdoor exercise sufficient to cause sweating has been shown to be correlated with a reduced chance of dying of a respiratory illness. Dress warmly, and exercise regularly in cold conditions such as at night. (Don’t overdo it for the first few days!)
  • Standing still outside is correlated with an increased chance of dying of a respiratory illness. If you have to wait at a bus-stop in cold weather, wear an anorak, hat and gloves and move around!

8. Can vitamin D supplements reduce the risk of severe viral respiratory tract illness?

Clearly sunshine has important health benefits – why else would people whose ancestors lived in northern regions of the world have pale skin?

We also know that severe cases of Covid-19 are correlated with vitamin D deficiency.

However:

1. 1. We don’t know for certain whether severe outcomes are caused by lack of vitamin D or lack of sunshine. Although lack of sunshine is correlated with increased cancer incidence, the VITAL Cancer Study did NOT find that vitamin D reduced cancer. So vitamin D supplements may not help – real sunshine may be needed.
   2. Colds and flu often increase a few days after ambient temperature drops – see the figure below, for example. This is too fast to be caused by vitamin D deficiency.
   3. Moreover (in e.g. Europe) sunshine isn’t followed in one or two weeks by decreased colds and flu. Warmer weather is – see figure:

9. Does the hypothesis have implications for stopping a respiratory infection from turning nasty?

I’ve made practical suggestions here: Suggestions for avoiding respiratory bugs

Briefly, if you get a cold:

• • Keep constantly warm. I’d have a small heater in the bedroom at night.
  • No hot drinks. Luke-warm tea and coffee are fine.
  • No chilled drinks.
  • Don’t overheat yourself with steam inhalation, saunas or very hot baths.
  • The pain of a sore throat is a sign that your body is dealing with the infection.

10. Where are these virus particles when they cause asymptomatic infections? Are they inside or outside cells? Could they for example stick on cilia of ciliated cells? Where can they hide?

We don’t know.  We’d like to find out.

11.  What are the other explanations of seasonality?  Are they irrelevant?

• • We crowd together more in winter and open the windows less.
  • The virus survives outside the body for longer in winter (see above).
  • The immune defences in the respiratory tract are weaker in the winter or when we’re chilled.

These are all important mechanisms that can change the course of epidemics.  They’re just not the MAIN driver of the winter seasonality of respiratory illness.

12. How can scientists test the hypothesis?

It would be very interesting to run controlled studies in hospitals or in the community: Proposals for simple RCTs based on the Temperature-Dependent Viral Tropism hypothesis

I have also suggested that wet-lab work should look at how temperature changes up and down can trigger the various steps of the life-cycle of common viruses such as coronavirus and influenza.

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The points above are all covered in the movie: https://youtu.be/l_jmqGvdeBY?t=43

That’s the simple explanation, written for the busy Executive.  Those who REALLY want to understand, should read on:

Longer answers for intellectuals:

1. **So you gave us the short answer above.  Why DOES the TDVT mechanism give rise to winter seasonality?

The answer I gave above is absolutely correct, but there’s more to it. We have to explain why there’s very often an epidemic of colds and flu in October.  Why should these virions be activated suddenly when the temperature has only fallen by a few degrees and is no lower than it was in, say, May?

• • During hot summer weather, viral strains with reduced temperature-sensitivity are selected – because only less temperature-sensitive (ts) strains are active enough to transmit themselves effectively in summer.
  • When ambient temperature drops in the autumn, the temperature in the nose and throat also falls and the respiratory viruses that are present become more active and we get sick.
  • In winter, on the other hand, the most virulent strains immobilize their hosts, so the more ts (therefore less virulent) strains tend to be transmitted.
  • When ambient temperature rises in the spring, these more ts viruses become less active and the number of colds is reduced.
  • The net result is more colds and flu in winter, fewer in summer.

(Note that in winter all strains replicate efficiently.  However the milder strains have the advantage for a different reason: they don’t immobilize us.)

2. Can the adaptation of viral strains to the seasons be shown in a simple schematic diagram?

Imagine that there are just two strains: a “spring” strain that is more TS and less pathogenic; and an “autumn” strain that is less TS and more pathogenic.

The spring strain doesn’t survive the summer well because it doesn’t replicate well in the high temperatures.  In winter, both strains replicate efficiently, but the milder strains have the advantage for a different reason: they don’t immobilize us.

In reality there are many strains, with different degrees of temperature-sensitivity.  And bear in mind that all strains are mutating, so low TS strains can give rise to high TS strains, and vice versa.

3. Virus replication is engendered by colder temperatures. So when the ambient temperature drops this causes temperature in the nose and throat (where the viruses reside) to also drop. This causes the virus to begin replicating more.

How does this lead the viruses to then migrate to the lower respiratory tract (where temperature is higher and thus replication lower?), wouldn’t the selection pressure cause the viruses to stay in the colder upper tract?

The virus sometimes migrates to the lungs IN SPITE OF its initial temperature-sensitivity.

Bear in mind that the virus is mutating all the time. Scientists usually focus on and report only the mutations that give changes in protein sequence, not on the “silent” mutations that affect only RNA sequences. These mutations in untranslated regions of the viral genome may well control temperature-sensitivity.

The temperature-sensitivity of any respiratory virus strain (yes there are many strains IMO, including many CoV-2 strains) is the result of the selective pressures that it has recently been subject to. A strain coming out of a community in lockdown might well be more temp-sensitive than say a strain coming from a hospital or care home that has just been overwhelmed by the virus, and where transmission takes place even when people are sick in bed – not the case in the community.

Moreover the virus keeps adjusting its temp-sensitivity throughout the year, and as it moves around the world. It does this because it has to, in order to be transmitted. In particular, if it is inadequately active at higher temperatures, it won’t be transmitted in the Tropics, or in eg the UK during the summer months.

It seems to take most resp-virs two or three months to adjust their temp-sensitivity. (I say this because by the end of the summer they are clearly more virulent.)

This suggests that viruses should be more likely to move from the Tropics to temperate regions than in the other direction, and this is indeed what is observed.

So what probably happens is, if you get an infection in your nose and throat, and, if you’re unlucky because this strain was relatively less temp-sensitive than is normal – maybe it came from a care-home – or if you’re unlucky because one or a few viral genomes mutate to less temp-sensitive forms, and end up in the lungs – you can get a serious infection.

4. What happens if a serious infection develops in the lungs?

Once a respiratory virus takes hold in warm tissue, all bets are off. (1) The target area of lung tissue is huge compared to the area of the nose and throat. (2) Huge numbers of viruses are now replicating in warm tissue, and subject to mutation. (3) They can now spread to other parts of the body including the heart, brain lining, toes, kidneys, liver etc. This is roughly what happens with HIV – the virus mutates until it overcomes the body’s defenses, one might almost say by accident (because the mutations don’t help HIV to transmit itself). In HIV it takes a long time – around 10 years.

5. Why is cold air protective if the body is warm, but not if the body is cold?

The temperature of the respiratory tract is influenced by the air coming in and out not the core body temperature no? Is this because when the body is cold, the body diverts blood away from the extremities to the core organs?

You’ve got it. Yes the temperature of the cells lining the respiratory tract is mainly controlled by the air coming in and out – this is physics. And the diversion of the blood flow was shown by an American doctor called Mudd in 1918. When you’re chilled, blood flow is diverted from the skin and also from the nose and throat. The body needs to conserve heat, or your brain will cease to work properly. We don’t know exactly how or why, but lack of blood flow to the nose and throat presumably interferes with the local immune response.

Part of the point here is that if you take exercise in cold air EVERY DAY you’re having a daily clear-out. On the other hand, if you live and work indoors for weeks, then one day you stand at the bus-stop and become chilled, your immune defenses may need to deal with huge numbers of active virus particles all at once.