Coronavirus - worldwide spread and control

From the Hammer and Drift article:

I've read something to the effect that antigenic drift is much less common in coronavirus than influenza, so evasion of any previously conferred immunity by new strains due to accumulation of mutations in surface proteins may be possible, but is unlikely. Can you throw any light on this @Jonathan Edwards?

Edited for clarity.

 

1.5 million people in the UK considered “vulnerable” are about to get a letter telling them to isolate. I wonder how many people with ME will get it? Hopefully housebound people with ME will be seen, though the practicalities are more difficult as we all rely on other people!

 

I tried this morning a calculation for the UK, and it came out with 4 years, so if four or ten years, pretty long anyway.

I would disagree, if a great number of hosts die from a pathogen, it´s a sign that the pathogen is not well adapted to the host. (With antibiotics there is a different story, because an underdose which is not lethal for quite a lot of pathogens elects resistance to the adverse enviroment.)

I am not a professionial, but I wonder if this is true, albeit other viruses in asia are said to have been.

For some vaccines there has been now research for 30 years! I guess nobody can estimate how long it would take in the case of corona. Admittedly with a medical it might be a better chance, I don´t know.

Anyhow, when the Europeans entered America a lot of Natives died from the infections the newcomers brought along (which, if I remember rightly, have evolved from contact mainly with pigs). I guess we have a comparable situation now (not up to 50% though, if this is true). It may be that I am stupid, but I don´t see, at least in non-asian countries, a good chance to achieve an eradication. At least in Germany nobody is claiming that, neither a politician nor a virologist (or most of these ones who are asked). At least until now (almost) everybody says that it´s about slowing the spread. Here in Germany it´s allowed to go out, but to meet with only one other person, or with ppl you live together with anyway. Supermarkets and some necessary shops and things like that are open.

Some British people didn´t seem to be able to understand Italian people and their behaviour when it comes to health problems. There obviously are and might be more though.

 

Whether or not that was their aim, it seems to me that it will still be a side effect? Ie by not mass testing people inc healthcare workers, not doing contact tracing, not doing effective social distancing (Infact making things worse eg people crammed onto a smaller number of tubes, people rushing into shops and national parks in greater numbers than ever), AND dragging it out over a long period of time, we are going to see a very large percentage of the population infected?

An MP tweeted this, this morning (scenes like this have been going on for a week now):

https://twitter.com/user/status/1242017365203787776


The lack of mass testing and tracing of any contacts at all, combined with utter lack of PPE and not testing hospital workers, is what is making me think they’re still on the “old” plan. Not the suppression plan. Devi Sridhar, chair of public health at Edinburgh has said this:

https://twitter.com/user/status/1242007338229301249

 

UK - trying to go it alone...
Faisal Islam, BBC

https://twitter.com/user/status/1241797403155496970

 

A tip of the iceberg or not?
I've been searching for studies that might give us a clue of how large the group is that gets the infection but are asymptomatic or who are symptomatic but remain undocumented. The best way would be to test a random sample of the population, but since we don’t have that yet i thought I might highlight some other methods that might give us a rough idea.

1) One method is complex modelling. There’s, for example, this study by Li et al. that was posted here already. The authors looked at the spread of the virus and mobility data and based on those two their model estimates that “86% of all infections were undocumented.” They think that undocumented infections are the infection source for the majority of documented cases.

2) Another method is looking at the secondary attack rate where you zoom in on an affected person, trace all their contacts and then test how many of these were infected. Bi et al. did an analysis of 391 cases and 1,286 of their close contacts. They estimated the household secondary attack rate to be 15%. The interesting thing is that they found that children were as likely to be infected as adults. So that might suggest that the skewed distribution of documented cases in China and Italy are missing a lot of youngsters who had the virus but didn’t get very ill. In the cases that were picked up by their surveillance, 20% were asymptomatic at the time of first clinical assessment and nearly 30% did not have fever. The authors note that “this is consistent with a reasonably high rate of asymptomatic carriage, but less than suggested by some modeling studies.”

The WHO report also commented on this, suggesting that the proportion of truly asymptomatic infections is probably not that high. It writes: “In Wuhan more than 1800 teams of epidemiologists, with a minimum of 5 people/team, are tracing tens of thousands of contacts a day. Between 1% and 5% of contacts were subsequently laboratory confirmed cases of COVID-19. […]The proportion of truly asymptomatic infections is unclear but appears to be relatively rare and does not appear to be a major driver of transmission.”

Bruce Aylward, who leads the WHO mission in China said in March 3 in an interview with VOX: “In Guangdong province, for example, there were 320,000 tests done in people coming to fever clinics, outpatient clinics. And at the peak of the outbreak, 0.47 percent of those tests were positive. People keep saying [the cases are the] tip of the iceberg. But we couldn’t find that. We found there’s a lot of people who are cases, a lot of close contacts — but not a lot of asymptomatic circulation of this virus in the bigger population.”

3) A third method is the data from travellers who returned from affected regions and who got tested, symptomatic or not. Nishiura et al. for example, used information on Japanese nationals that were evacuated from Wuhan, China on chartered flights (n = 566). 4 asymptomatic and 9 symptomatic passengers tested positive forCOVID-19. The asymptomatic ratio was estimated at 30.8%.

4) Finally, there was an outbreak on the Diamond Princess Cruise ship which forms a natural experiment to estimate the spread and fatality of SARS-CoV-2. This is why Ioannidis, the famous scientists, puts so much emphasis on this data even though it’s quite limited in size. 619 of 3700 passengers and crew (17%) tested positive. About half of those patients were asymptomatic, but that might be because they were tested early – they might develop symptoms later on since there’s an incubation period of a couple of days and COVID-19 often develops slowly, many of the asymptomatic. Mizumoto et al. tried to take this into account and estimated the asymptomatic proportion to be 17.9%. This is most likely an underestimation given that the population on board of the cruise ship was substantially older than the general population (most were in their 60s and 70s which are thought to be at higher risk of developing COVID-19) and not everyone on board got tested.

I don't really know what to make of all of this. I suspect there are reasons to think that asymptomatic or undocumented COVID-19 cases with mild symptoms contribute substantially to the spread of the virus, making it very contagious and hard to control. There was this letter recently in the New England that noted:

"The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV." ​

If I understand correctly, the first SARS-coronavirus was also quite contagious but people mainly started to infect others when they were having notable symptoms. That makes it easier to contain it cause you know who to isolate. It could be that the main difference with this second SARS-coronavirus is that people often spread it even when they are not notably symptomatic. That's why we all have to isolate.

On the other hand, the estimates of the asymptomatic proportion aren't that big and based on what Aylward saw in China it doesn't seem like there's a tip of the iceberg situation. That might explain why China and other Asian countries were quite successful in reducing the spread of the virus.

Anyone knows of any other methods or studies that estimated the asymptomatic or undocumented proportion of people infected with SARS-CoV-2?

 

Thanks. I think CNN meant for just Wuhan. Reporting on this pandemic leaves many things to be desired. It has been incredibly politicized here in the US.


WHO figures, March 22, data as of March 21 - total confirmed new cases - China 82

https://www.who.int/docs/default-so...0322-sitrep-62-covid-19.pdf?sfvrsn=f7764c46_2

WHO daily situation reports

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

 

I don’t know if you’ve seen this before or if it’s been posted here before:

Iceland is doing a mass testing program, including testing asymptomatic cases,

So far, Of 1800 non symptomatic people that they tested, 1% had the corona virus.

https://www.buzzfeed.com/albertonardelli/coronavirus-testing-iceland?bfsource=relatedmanual

 

I'm assuming that you must have winced when you saw "(thousands of lines of undocumented C)", especially 13 year old undocumented code?

Do we know if it's worth the effort? Is it accurate (as much as these things can be)? I can't say I have much faith in it. Surely there must be other modelling teams out there.

 

Not a lot. The point in the article is valid.

I think flu has a reservoir outside humans (maybe ducks) that allows it to mutate and reinfect populations. Covid19 probably only has a reservoir in some animal we do not normally meet. Vallance said something about Covid maybe becoming an annual thing once we have herd immunity. No way is that a sensible solution.

 

From what I can glean from the recent paper on immunodeficiency this list is actually of the wrong conditions. Immunodeficiency does not seem to be a big problem. Chest problems, diabetes and heart disease seem to be the issue. It looks as if the risk is associated with a hypersensitivity reaction in lung that poor cardiorespiratory physiology cannot cope with. Diabetes is an interesting one. Diabetes is associated with damage to small blood vessels with leakage. Maybe that aggravates pulmonary inflammatory oedema.

I personally see no particular reason to think PWME are at special risk.

 

The people getting letters are ones considered "extremely vulnerable". Long term disabled are classed as just vulnerable and that is where we fit in. Our vulnerability is more likely to be a long term exacerbation of our ME rather than an increased risk of death from covid-19.

No one else will be considering that so we will have to take extreme precautions ourselves. I don't know if there is a way of getting on to a register for priority for food and medicines but that is what we need most, especially those of us who are alone and bed bound.

 

Thanks @lunarainbows, very helpful!

I found this report by the government of Iceland which says: "deCode has published the results of a total of 5 571 tests. Those have yielded 48 positive results (0.86%) indicating that the prevalence of the virus is modest among the general population."

I think figures around 1% are quite high. Iceland has a population of approximately 350.000, so 1% would mean 3500 people are infected with the virus. Yet thus far Iceland has only around 500 confirmed cases. So that would mean that only 1 in 7 were picked up! That would mean that the fatality rate would be much lower if the virus were to spread among the general population than what the current CFR estimates are suggesting. On the other hand, some of those who were missed might develop symptoms later on and thus eventually get picked up by the normal testing procedure (which tests persons because they developed COVID-19 symptoms). Given that the spread of the virus is exponential, a lot of cases were probably infected quite recently, so this might substantially muddle the figures. One should probably wait 7-10 days after the 1% figure in the general population was determined to compare it to the number of cases that was picked up with the normal testing procedure that are being used in most countries.

I sometimes find it difficult to determine if it's bad news that the virus has spread further among the general population than expected (because that would mean it might be more difficult to contain) or good news (because that would mean it's less deadly than currently estimated).

EDIT: another relevant statistic. South-Korea has proportionally tested the most. They have performed 338036 tests of which 8961 (2.6%) tested positive. So I'm assuming that's an upper limit of how far the virus has spread there since persons with COVID-19 symptoms or those with close contact to cases are probably much more likely to get tested.

 

I'm not sure about this yet - couldn't it be that this is just a consequence of older people have more of these comorbidities and that age is the main factor in determining a bad outcome? I think that thus far none of the published papers or documents have persuasively looked at both factors at the same time. See: https://www.s4me.info/threads/the-b...-vaccines-treatments.14022/page-3#post-246160

(I've sent this question to the podcast This Week In Virology - hope they will discuss the topic there).

 

I'm sure I won't, just as I never get invited for a flu jab. I'm hoping that they'll publish the contents of the letter so that we can all see it.

 

I think I may be in the vulnerable group, judging by the list, due to severe asthma (defined as taking inhaled steroids + another inhaler, which I do take, plus also another medication), so I’ll post it if I get it.