Phylogenetic Trees - What they Can (and Can't) Tell us About COVID-19 (May 22)
Some of the most intriguing mysteries of the epidemic can be investigated by creating phylogenetic trees - genetic family trees of the virus. IDM's Jeremy Martinson and HUGEN and BIOST's Eleanor Feingold talk about how these trees are created and what we can and cannot learn from them.
- Where did the virus come from?
- How did it spread?
- How long has it been in the U.S.?
- And, is there really a "turbo-charged" strain that is more infectious than the rest?
Watch on YouTube or click below
Additional Q and A from the 5/22 seminar
joint responses from both Martinson and Feingold
1. Recombination effect on phylogenetic tree analysis?
Genetic recombination would have the effect of lengthening the branches of the tree, and increasing the overall level of diversity because you are bringing in variation that did not arise within that viral lineage. That being said, in the case of SARS-CoV-2 in 2020, we have some pretty good measures of the dates at which the virus samples were collected, and a recombination event may stand out, as that virus would be more different from the contemporaries. There are other ways of displaying sequence information that would indicate recombination events if there was a lot of sequence diversity, but there really isn’t that much in SARS-CoV-2 – at least, no more than you would expect from a coronavirus.
2. So, since phylogeny can't tell us the efficiency of transmission, can it still be used to identify genetic factors that relate to transmission in the population? I understand that phylogeny is used in disease transmission dynamics to some extent.
If a recombinant virus has a selective advantage that would increase its transmissibility then you might see its increase in populations where it was present. Such selective advantages are hard to detect in sequence data unless you have a large representative sample, though, and even then the selective effect has to be high.
3. The bottom line question is where SARS-CoV-2 originated from. Can you tell us?
Other than a transmission event from an animal host to a human, in the vicinity of Wuhan, China, not really. We have not found any animal viruses that are close enough to the human one to be sure it is the culprit.
4. Are there mutational hotspots in virus genome? If so, similar mutational pattern cannot necessarily be used to tracking the virus?
If you look at the distribution of mutations across the SARS-CoV-2 genome (you can do that at nextstrain.org) you don’t see a real hotspot. You do see a few sites spread across the genome that mutate more often than others. If you look within a country, you can track the appearance of these mutations over time, and there is enough background variation to be able to tell if some mutations have arisen more than once.
5. Is there a relationship of the mutational burden in COVID-19 and the infectivity/fatality rate? Are the differences in mortality rate between countries solely due to burden on healthcare system, available resources and the age and concomitant diseases of patients?
There has been some discussion about the impact of one variant, called D614G, on viral load, but there is little widespread evidence that any of these mutations alter the lethality of the virus. Much of the difference in mortality is due to external factors, such as age and pre-existing conditions. Inequalities in access to healthcare probably plays a role too, and there is some emerging evidence that human genetic variation may be important.
6. Do all human coronaviruses bind to the ACE2 receptor or just SARS-CoV and SARS-CoV2
No – in fact, MERS-CoV binds to a different receptor, called hDPP4. Some of the coronaviruses that cause mild symptoms – the “common cold” – use ACE2, but others use different receptors.
7. The Washington group found no association of D614G with hospitalization, ICU. Are you aware of this study?
Yes, that and other studies have shown little or no association with disease severity, and only a slight association with viral load.
8. In other words could there be natural selection for less virulence?
That is possible, but there is little or no evidence that it has happened yet.
9. We know that viruses like SARS-CoV-2 undergo recombination. Is that effect taken into account when building these evolutionary
See the answer to question #1. The trees displayed by nextstrain do not take recombination into account as far as we know.
10. Should everyone then be tested so that more data can be obtained to see if there is a mutation that is not as serious?
Broader testing is absolutely critical as a surveillance tool. A secondary advantage might be discovery of features such as differentially serious mutations.
11. Is it theoretically possible to predict when a pandemic like this will happen again in the future?
It is hard to predict the specific location and time of any future outbreak, but if you talk to virologists about the likelihood of any future pandemic, they have been saying for years that they are most worried about two viruses: coronaviruses, and novel influenza virus strains.
12. Would be able to help make a vaccine against other coronaviruses like common cold?
That has been tried many times, with little success. The most successful studies have produced antibodies to the common cold when people received a vaccine, but those antibody responses do not persist for long enough to give lifelong protection.
13. Do you believe that the decision in China to stop selling live animals in their markets can slow down a next pandemic?
We think it will reduce, but not eliminate, the risk of another transfer from animals to humans.
For further reading, consider this Nature article mentioned during the webinar, which addresses some of these same questions.
CONVERSATIONS ABOUT COVID-19 | PITT PUBLIC HEALTH SEMINAR SERIES
Each Friday this May and June, Pitt Public Health experts will have a conversation about different aspects of the COVID-19 pandemic and then address questions from the seminar attendees. The goal of the COVID-19 seminar series is to provide our school community, alumni, and the public with credible information about the virus and the associated health impacts.