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Overnight in Asia, we hosted a call with professor John Nicholls a clinical professor in pathology at the University of Hong Kong and an expert on coronaviruses. He was a key member of the research team at the University of Hong Kong which isolated and characterized the novel SARS coronavirus in 2003. He’s been studying coronaviruses for 25 years (full bio here). The recording of the call can be found on our website HERE. Below are my notes transcribing the call. The first 30m is worth listening to.
Quick summary: look at the fatality rate outside of Wuhan - it’s below 1%. The correct comparison is not SARS or MERS but a bad cold that kills people who already have other health issues. This virus will burn itself out in May when temperatures rise. Wash your hands.
My notes from the call below:
Q&A Session with Professor Nicholls:
What is the actual scale of the outbreak? How much larger is it compared to the official “confirmed” cases?
People are saying a 2.2 to 2.4% fatality rate total. However recent information is very worthy - if you look at the cases outside of China the mortality rate is <1%. [Only 2 fatalities outside of mainland China].
Two potential reasons 1) either china’s healthcare isn’t as good – that’s probably not the case
2) What is probably right is that just as with SARSthere’s probably much stricter guidelines in mainland China for a case to be considered positive. So the 20,000 cases in China is probably only the severe cases; the folks that actually went to the hospital and got tested.
The Chinese healthcare system is very overwhelmed with all the tests going through. So my thinking is this is actually not as severe a disease as is being suggested. The fatality rate is probably only 0.8%-1%. There’s a vast underreporting of cases in China. Compared to Sars and Mers we are talking about a coronavirus that has a mortality rate of 8 to 10 times less deadly to Sars to Mers. So a correct comparison is not Sars or Mers but a severe cold. Basically, this is a severe form of the cold.
You mentioned a shortage of testing kit can you talk more about that?
There are two ways to detect a virus. 1) Through the genetic material – DNA or RNA or 2) to detect the protein of the virus. The rapid tests used in a doctors’ lab look at the protein. The problem with that is that you need an antibody to pick it up. And it takes 8-12 weeks to make commercial antibodies. So right now for the diagnostics tests, they are using PCR which gives you a turnaround in 1-2 hours. But then you need to run a machine and run 96 runs in 1 hour but then you have to a batch of samples so there’s another delay of 5-6 hours for patient presentation. So that will lead to some problems you can’t turnaround in 5-10m which is what you want when a patient shows up to the emergency room. Because right now you also have influenza going around so what you want is to be able to rule out influenza so you can treat the patients correctly for coronavirus. So that may be why
they missed some of the earlier cases.
Your colleague at HK university estimated that the size of the infected population on Jan 25th was 75K with a doubling time of 6.4 days. So by Feb mid, we would have 150k infected. How accurate do you think these models are and how accurate have they been in the past?
Those figures did not take into account restrictions on travel, quarantine, etc… These reports are likely on the high side. This is not taking into account social distancing. Historically these models have not been all that accurate.
When do you think this thing will peak?
Three things the virus does not like 1) sunlight 2) temperature and 3) humidity. To make you guys really worried. A coronavirus can survive on a stainless steel surface for 36 hours. It hangs around for quite a bit.
Sunlight will cut the virus's ability to grow in half so the half-life will be 2.5 minutes and in the dark, it’s about 13m to 20m. Sunlight is really good at killing viruses. That’s why I believe that Australia and the southern hemisphere will not see any great infection rates because they have lots of sunlight and they are in the middle of summer. And Wuhan and Beijing are still cold which is why there are high infection rates.
In regards to temperature, the virus can remain intact at 4 degrees or 10degrees for a longer period of time. But at 30 degrees then you get inactivation. And High humidity the virus doesn’t like it either. That’s why I think Sars stopped around May and June in 2003 – that’s when there are more sunlight and more humidity. The environment is a crucial factor. The environment will be unfavorable for growth around May. The evidence is to look at the common cold – it’s always during winter. So the natural environment will not be favorable in Asia in about May.
The second factor is that of personal contact. With Sars, once it was discovered that the virus was spread through the fecal-oral route there was much less emphasis on the masks and far more emphasis on disinfection and washing hands. HK has far more cleanliness (than China) and they are very aware of social hygiene. And other countries will be more aware of social hygiene (than China). So in those countries, you should see fewer outbreaks and spread. A couple days ago the fecal-oral route of transmission was confirmed in Shenzhen. In China, most of the latrines are open- there’s more chance of phermites (?) being spread. But in other countries, the sanitation systems tend to closed. My personal view is that this will be a bad cold and it will all be over by May.
People talk about the vaccine and this is the big problem that people get from movies. Where in the movie they come out with a vaccine and then three days later it’s all over the world and everybody is saved. In reality, this does not happen because for a vaccine you need to go through clinical trials – is it safe and will it work. The last thing you want to do is rush a vaccine too early. If you get any severe reactions, then the anti-vaxxer will just say “I told you so”. You are talking about a working vaccine in 1 to 2 years.
With SARS, in 6 months the virus was all gone and it pretty much never came back. SARS pretty much found a sweet spot of the perfect environment to develop and hasn’t come back. So no pharmaceutical company will spend millions and millions to develop a vaccine for something which may never come back. It’s Hollywood to think that vaccines will save the world. The social conditions are what will control the virus – the cleaning of hands, isolating sick people, etc…
What do we know about the transmission rate? It’s been estimated at around 2.2 to 2.68. What percent of the patients are transmitting while being asymptomatic?
This is a big problem when you talk about asymptomatic that means you have a good diagnostic test- where you can say they are asymptomatic (which we don’t have with this virus).
We actually looked at this with MERS where people were saying it had a high fatality. We went to Camel abattoirs and took serums from the abattoir workers and found that quite a few had low infections with no symptoms. This is what should have been done at the initial stages of the seafood market. But to do that you need a good diagnostic test. A good diagnostic test is necessary to determine the transmission rate. Now we have normal human airways and we can now look at how long it takes the virus to replicate in that environment. And that will be very useful to determine those who are asymptomatic carriers.
Any sense of whether the estimates of the reproductive number the Ro of 2.5 or 2.7. Do you think that is high or low? What does that mean?
Measles were about 10-15 and influenza is just below 2. I think it’s about 2.2 as it’s being transmitted within the community.
Have we seen any super spreaders? We saw that with Sars and Mers.
There’s talk about that but the epidemiologists are still overwhelmed so no clear answer. But I don’t think there are any super spreaders.
What is the percentage of people transmitting the virus while being asymptomatic?
Unlike SARS, patients were symptomatic at about day 5, some of these cases may be asymptomatic until about day 7. That’s based on the first publications. Asymptomatic is probably the first 5 days.
There’s a paper published looking a familial cluster with a boy who was shedding the virus and he was asymptomatic.
That’s something about kids and we saw this with Sars. Very few kids had very severe disease. We are trying to determine if this is a virus that we call low (unintelligible) kind of inducer or high (unintelligible) kind of inducer. SARS is high [unintelligible] kind of inducer. This means that when it infects the lower part of the lung, the body develops a very severe reaction against it and leads to lots of inflation and scarring. In SARS what we found is that after the first 10 to 15 days it wasn’t the virus killing the patients it was the body’s reaction.
We are doing testing on this now. Is this virus in the MERS or SARS kind picture or is this the other type of virus which is a milder coronavirus like the NL63 or the 229. I think this will be a mild (unintelligible) kind inducer.
Case fatality is about 2.5% or so? Do you expect this to change over time? And are you seeing any difference among the young population and older population in terms of mortality rate?
SARS went really for people in their 30 or 50 years. And MERS on the other hand basically is if you have co-morbidity – try and find somebody in the middle east who does not smoke or does not have high blood pressure etc... The data coming out of China seems to indicate that it’s those with co-morbidity are most at risk. For seasonal influenza that’s also what we find. It’s the people with the co-morbidity that have the increased mortality rate. Having said that there’s a guy in the Philippines who died in his mid-30.
I think this looks more like seasonal influenza where those who die have to co-morbidity. Now that we have better case-control definitions outside of mainland China, we will get a true assessment of the fatality rate. I would now put it at about 0.8% to 1%. When you look at all the death reports – separate out the deaths from mainland China and outside China.
The mortality rate in China – is much higher? Why?
It's related to the environment. In high-income countries, you don’t have as high a population density, higher level of environmental control and hygiene. In Indonesia – it’s unlikely to spread much as it’s very hot and humid. Would this virus move to Africa? I think that’s unlikely – too hot there’s not a lot of travel there.. Europe – possibility higher transmission but environmental care is higher.
At this stage it’s a really bad cold which can cause problems in people. People are talking about the “lethal virus” but seasonal influenza can cause deaths in elderly but we don’t call that “lethal influenza”
There’s news reports that antivirals are being used and that it’s working what are your thoughts on that?
With SARS it didn’t seem to work at all with the commercially available antivirals. But there seem to be good effects with the case in Washington with the Gilead agent. And it sounds like China will be using it.
Interferon works and it has quite a bit of benefit.
The problem with the antivirals – because the virus has different ways of replicating within the cell, finding a nice common target has been difficult. But the Gilead agent appears to me to be very promising. We now have the virus growing in our labs/cultures so we can now test it to see what will work and not work.
Would the opening of the hospitals in China change anything? What we found with SARS in HK was that a contributing factor to the spread was the overwhelming of the HK healthcare system. Hospitals and doctors were overwhelmed. When China built these Wuhan hospitals – it’s to take the workload off the staff which is likely exhausted.
In HK with SARS, we found quite a lot of infection of healthcare workers as they are close and doing invasive procedures. But this time around there is not much evidence of the healthcare workers getting sick or dying (but maybe China is not reporting it) so this may suggest that I think it is not being spread by close aerosol contact but more by the fecal-oral route or with droplets. So it will not be as contagious within hospitals. So getting the two hospitals built it will take a lot of the workload off the other hospitals so it should be a big benefit.
The recovery rate now higher than the death rate? Thoughts on that? What we found is that in HK with SARS we didn’t know how long to treat a patient for. Now in China, they are using the SARS model but treating patients for shorter time periods so that they don’t get the secondary problems that they did with Sars. Getting actual data on recovery from the mainland is still a bit of a challenge.
I’d consider a patient recovered if he’s been discharged. The problem is that with SARS, there were quite a bit of people where the steroid was very beneficial to treat the acute stage and we didn’t know how long the virus would live for so we kept them on the steroids for a long period of time and they came out with all sorts of secondary problems due to the immunosuppression.
I haven’t seen any data on the quality of life of those who have been discharged.
Evidence of E-coli?
Secondary infection are most likely the cause of deaths of the patients in the Philippines and HK.
What does it mean for a patient to have recovered?
That means the patient has been discharged from the hospital. That’s the criteria for Hong Kong. But there’s no good data or guidelines on this.
What is the probability that this will be contained and eradicated or will it be endemic in the human population?
If it is like SARS it will not be endemic. It most likely will be a hit and run just like SARS. People talk about mutation but what we found with SARS was that there was no mutation and we have been tracking MERS and we have not seen any severe mutation. This is unlike the common coronavirus which when they replicate they don’t have a ”spell check” so they mutate. So if this virus follows the same path as SARS or MERS it won’t mutate. This will not be endemic. I think it will burn itself out in about 6 months.
Does mortality rate or fatality rate typically increase over time? That was apparently the case with SARS.
With SARS we didn’t know how long the virus was alive for. So with SARS in the later stages, people were not dying of SARS but of the complications of SARS which is why the mortality rate increased. But now people are much more aware of the dangers of over immunosuppression. So the death rate shouldn’t be more severe. Especially with the new hospitals being established which should take some of the workloads off of the healthcare workers from Wuhan.
If we look at the serious cases being reported it’s about 13% of the total cases being reported. If we assume a 50% mortality rate for severe cases than we are looking at a mortality rate of 5-6%. Is that a fair assumption?
In Hubei, the milder cases are not making it to the hospital. Because they are so overwhelmed that milder cases are being sent away. So that’s why it’s important not to look at the mortality rate in Wuhan but to look at the mortality rate in Shanghai or Shenzhen or outside of Wuhan. It’s very important to dissect it out.
Would it be too early to make a conclusion outside of Wuhan? It’s still really early days outside of Wuhan? Are we making an assumption with very little data and very early data?
That’s all the data we have to work with. When you are dealing with an epidemic at the early stages – there’s such a variable. But now for a political reason, people are far more aware of the virus so it won’t be as epidemic as it was early on. There are far more awareness and controlled environment and changes in social behavior. Which I’m not sure is taken into account in the models. So it should spread far.
Bloomberg also has detailed a story on China buying out a patent on Gilead drug for CoNv which still under trial.
The Gilead drug is being rushed into human trials - no guarantees
In any case, the situation was never raised to the pandemic level.
Broadly it is emerging it's over on Corona faster than SARS.
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