Discussion Thread I - 2019-nCov (new coronavirus)

[Tea]

HI everyone!

Thank you very much for participating.

One note - Please only post a tiny snip of an article in its original language. We do not want to infringe on anyone's copyright. Also please - a link back to the original source.

Copyright claims are being used to silence the internet. Let's not give anyone a reason to try to shut us down.

Thanks!

OOh, I wondered about that, I will edit.

[hawkeye]

I’m seeing more and more “soft” (via retired..etc. officials) messaging about the virus significantly spreading beyond China’s borders.

Global spread appears inevitable. So too are the emergence of outbreaks in the U.S.... We shouldn’t have undue panic. But we need to be ready." says former US FDA commissioner
@ScottGottliebMD
of the #coronavirus.

https://mobile.twitter.com/DrEricDin...49062850334720

[hawkeye]

After seeing what is going on in China - I'm having a tough time reconciling this article:

New coronavirus 'not spreading' in the US, CDC says

https://abcnews.go.com/Health/coronavirus-spreading-us-cdc/story?id=68560892

[Laidback Al]

A quick review of the different country threads regarding the 2019-nCoV spread here at FluTrackers seems to indicate that all reported confirmed cases in countries other than China are people who were infected in China before arriving in these other countries. So far, there has been no reported cases of human-to-human transmission outside of China.

[hawkeye]

A quick review of the different country threads regarding the 2019-nCoV spread here at FluTrackers seems to indicate that all reported confirmed cases in countries other than China are people who were infected in China before arriving in these other countries. So far, there has been no reported cases of human-to-human transmission outside of China.

So we have a 4th Gen virus that only spreads within the geographic area of China?

[JimO]

If the incubation period is a week or more, we probably won't see H2H cases outside China for a few more days, at least. Plus, unless serious symptoms develop quickly, cases might not be diagnosed until patients are seriously ill. Assuming the CDC is going to be transparent and not try to control messaging as this unfolds, my guess is that we will likely see confirmed H2H cases in the US within the next week. However, based on the CDC's responses to the 2009 H1N1 outbreak and the ebola outbreak, I believe the CDC will control the release of test results to "avoid panic" and they can do this for the time being since they are the only testing center in the US.

[etudiant]

If the incubation period is a week or more, we probably won't see H2H cases outside China for a few more days, at least. Plus, unless serious symptoms develop quickly, cases might not be diagnosed until patients are seriously ill. Assuming the CDC is going to be transparent and not try to control messaging as this unfolds, my guess is that we will likely see confirmed H2H cases in the US within the next week. However, based on the CDC's responses to the 2009 H1N1 outbreak and the ebola outbreak, I believe the CDC will control the release of test results to "avoid panic" and they can do this for the time being since they are the only testing center in the US.

That is a reasonable assessment. However, the CDC is very much at risk here, at least imho.

The CDC's and the WHO's downplaying the hazards 'to avoid panic' clearly delays the kind of aggressive action that could save the day for the US and others., If largely because of this the epidemic turns out to become as serious here as it already is in China, both these entities will be eviscerated by the politicians and the public.
I do not understand why they are not acting more forcefully, given the unprecedented efforts by the Chinese government.

[hawkeye]

That is a reasonable assessment. However, the CDC is very much at risk here, at least imho.

The CDC's and the WHO's downplaying the hazards 'to avoid panic' clearly delays the kind of aggressive action that could save the day for the US and others., If largely because of this the epidemic turns out to become as serious here as it already is in China, both these entities will be eviscerated by the politicians and the public.
I do not understand why they are not acting more forcefully, given the unprecedented efforts by the Chinese government.

While I'm not a fan of an over zealous government - the fact that the CDC is taking this position when so much is unknown is absolutely incredible (and rather frightening). But, I hope the right..and I hope it stops spreading in China. But hope is not a plan.

[JimO]

I agree with you both. But, some things just won't happen. The Superbowl is in Miami next weekend. If we had epidemic levels in the US, I can't even imagine circumstances under which an event like the Superbowl would be cancelled. There is too much money at stake. Depending on who stands to lose the money, there might even be pressure on the CDC to stand down until after the event.

I was under the impression that agencies like the CDC were supposed to engage in risk assessments that involve some predictive element. Sure, the risk might be low in the US today, but we rely on them to anticipate at least the short-term future risk. Both the CDC and the WHO seem to fear being accused of crying wolf far more than they fear underestimating a threat. Even amateurs like myself can see that this virus has a huge potential to be a global threat and yet the WHO seems unwilling to raise the threat level, even with clear evidence that the Chinese government held critical information for weeks before releasing it.

[c3jmp]

One tough aspect is that the cases we've had so far were in China when they caught it. It's not a short flight from China to the US, and transmission in a plane may be be different than folks wandering around in daily life on the ground. I'd expect overseas flights to have a fair number of folks on them. Maybe 10-14 days after the first case popped up in the US. Planning-wise, all the prep stuff for hpai should still be around.

[JimO]

One tough aspect is that the cases we've had so far were in China when they caught it. It's not a short flight from China to the US, and transmission in a plane may be be different than folks wandering around in daily life on the ground. I'd expect overseas flights to have a fair number of folks on them. Maybe 10-14 days after the first case popped up in the US. Planning-wise, all the prep stuff for hpai should still be around.

Great point about time spent on a flight and those contacts might not even end up in the same city as the infected person.

[Okieman]

Folks, we have a highly infectious disease and a "herd" with no immunity. One of the primary goals of the Chinese government and probably most other governments will be to keep the herd from panicking and scattering. They very much need to be able to find and communicate with the contacts of those who have been positively diagnosed with the disease. With this in mind I expect them to say and do any and everything to attempt to keep the herd calm and in one place. In China it appears that due to the Lunar New Year they had to have these quaratines to make that happen. The true death toll may be suppressed or covered up to keep them from panicking and breaking quarantine.

I'm not saying I like this. I still want the truth, but I don't expect to be told the truth.

[JJackson]

So we have a 4th Gen virus that only spreads within the geographic area of China?

hawkeye this is not a great surprise given they have a head start on the rest of us and have only recently started to find extended transmission chains. Our time will come. If the current understanding that there is asymptomatic transmission and mild cases holds then there seems little chance of avoiding a pandemic. The vaccine estimates I have seen seem to range from optimistic to fanciful and none seem likely to be of any use within the pandemic period but may be needed if it becomes an endemic human disease. While a number of candidate small molecule therapeutics have been modeled for the RdRp protein none are likely to be available within a year. If there is a pharmaceutical solution it is likely to be in the form of an off label use of a preexisting drug.

[c3jmp]

Has anyone heard anything about antigenic immunity? If we do the wave thing, it plays in - there wasn't any with H5N1..

[Shiloh]

Source: https://promedmail.org/promed-post/?id=20200126.6918012 (there is more communication regarding the subject via the link)


Published Date: 2020-01-26 21:49:32
Subject: PRO/AH/EDR> Novel coronavirus (19): China (HU) transmission dynamics
Archive Number: 20200126.6918012

PRO/AH/EDR> NOVEL CORONAVIRUS (19): CHINA (HUBEI) TRANSMISSION DYNAMICS
************************************************** *********************
A ProMED-mail post

http://www.promedmail.org

ProMED-mail is a program of the
International Society for Infectious Diseases

http://www.isid.org

In this post:
[1] 2019-nCoV transmission dynamics [letter]
[2] Transmissibility of 2019-nCoV
[3] 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions

*****
[1] 2019-nCoV transmission dynamics [letter]
Date: Sun 26 Jan 2020
From: David Fisman, MD MPH [edited]


I wish to offer the following observations on the epidemiology of 2019-nCoV in Hubei Province, China, over the past few weeks. I hope that the thoughts below will be helpful to others trying to organize and interpret the flood of information that has emerged about this new pathogen.

Information from a variety of sources suggests that this novel virus is a recombinant betacoronavirus of animal origin that emerged in November or December 2019, likely at the Wuhan Seafood Market. Epidemiological analysis was initiated after recognition of a market-linked pneumonia cluster in late December. Notwithstanding the name of the "Wuhan Seafood Market", the market sells large numbers of live animals, including wild animals, which are kept in close proximity to one another, perhaps facilitating viral recombination. Similar disrupted ecology contributed to the emergence of SARS.

The emergence of many cases of a novel, animal-derived pathogen in a live animal market, over a short time period was suggestive of a point source outbreak with animal-to-human spread, and I'll assume that the initial cluster of approximately 40 cases was largely a result of such transmission, with little human-to-human transmission. However, on [23 Jan 2020], the WHO released the report of its IHR Emergency Committee for nCoV; the report noted that "4th generation transmission" was occurring, and cited internal analyses placing the basic reproduction number (R0) at between 1.4 and 2.5; this report noted that 557 cases (which I'll round up to 600 cases) had been confirmed as of [22 Jan 2020] (ref.1). Several estimates of R0 appeared from independent groups around the same time; these estimates were remarkable in their consistency, ranging from 1.4 to 3.8 (refs. 2-7).

Such consistency despite limited data availability and disparate methods employed for estimation provides a degree of face validity to these estimates. I note that these estimates are likely skewed upwards by the greater recognition of larger case clusters and super-spreader events (there has been at least one 14-case cluster in a hospital), and also by the possibility that later cases are being recognized more completely than earlier cases, all of which would have the tendency of biasing R0 estimates upwards. I'll assume that the lower bound R0 (around 2) is probably about right, and also note that this is consistent with estimates from SARS coronavirus, which shares substantial genetic similarity with nCoV.

What would be the implications of a disease with R0 around 2, with 4 generations of transmission over a period of around a month? This timeline would be consistent with growth in the number of recognized cases from 40 to 600 during that time interval. If nCoV has a generation time of approximately 10 days (similar to that described for SARS), we would have expected the initial 40 cases from late December [2019] to cause 80 secondary cases in early January [2020] (120 total cases); these 80 cases would create 160 incident cases around mid-January [2020] (280 total cases), which would, in turn, create another 320 cases around [22 Jan 2020] (600 total cases).

These numbers fit very nicely to case data available as of [22 Jan 2020], but unfortunately, they are wrong. The abrupt surge in confirmed case counts (to 1423 cases as of [26 Jan 2020]) is not compatible with the growth process described above, certainly not with a SARS-compatible generation time of 6-10 days. Indeed, the authors of the MRC model (ref. 3) noted in one of their earlier reports that the volume of observed exported cases in countries outside China suggested a much larger underlying epidemic than had been reported at that time, and this epidemic may have begun a month prior to the recognition of the market-associated outbreak, consistent with the reported timing of viral emergence based on phylogenetic analyses (ref. 5). The authors of several analyses cited above have incorporated the MRC estimates of under-reporting in order to fit their models (refs. 2, 3, 5). A 2nd line of evidence suggesting undercounting of cases relates to the older age of cases (median 59 years in early reports), and the even older age of fatal cases (averaging around 75 years in the first 17 deaths) as contrasted with a median age of 37 or 38 years in China. Increased age in cases as compared to the population as a whole suggests that younger (likely milder) cases have been under-reported. As such, it would seem likely that at least part of the sudden apparent growth in case counts does not reflect changes in transmission, but rather increasing ascertainment of previously undercounted cases.

Why is R0 so important? As R0 is proportional to duration of infectivity, reducing the infective period of cases would reduce the effective reproduction number. If the effective duration of infectivity is reduced by over 50% for a pathogen with R0 around 2, the average reproduction number would be reduced to less than 1, which should control viral spread over time. It is encouraging that one of the reports cited above suggests that the mean time from symptom onset to isolation has decreased from more than 6 days to less than 1 day as control measures have been implemented (ref. 6). Social distancing measures (like suspension of public gatherings and transportation) and reduced transmission per contact (such as, through the use of personal protective items by healthcare workers) would also result in proportionate reductions in the reproduction number. Precise predictions in the face of substantial uncertainty are not appropriate, but given the large size of the epidemic as of the time of writing, some simple back-of-the-envelope math can demonstrate that large numbers of incident cases should be expected in the coming weeks, even in the face of effective control efforts. Successful control of this outbreak would be expected to take many months (again, as was the case with SARS).

While average estimates of R0 are helpful, it is also important to note that other betacoronaviruses of public health importance (SARS, MERS) have been notable for the "overdispersion" of their reproductive numbers. Without getting too technical, this means that the average R0 is quite different from the variability in the R0. We actually have a distribution of R0 with a long "tail", which is a mathematical shorthand for superspreader events, where a case infects a large number of individuals. For example, there was at least one SARS superspreader who generated 76 downstream cases. However, with an overdispersed R0 many cases are "dead ends" and will not transmit. The 3 key insights here for the contour of this epidemic are:
1. It is the average R0 that determines whether, and how, the disease can be controlled. By analogy with SARS and MERS, with which nCoV seems to share many characteristics, the spread of this virus should be controllable.

2. Superspreader events are likely (and have already occurred) and are important to outbreak control efforts: they are demoralizing and dangerous to response personnel. They often occur in hospitals during aerosol-generating procedures like intubation. These events make it feel like the battle is being lost. They should be anticipated, and it is important to emphasize that their occurrence will represent a temporary setback which is likely to be overcome.

3. While superspreader events are unwelcome, their occurrence may, in fact, be a salutary sign for the control of this outbreak. An average R0 of, say, 2, with an overdispersed R0 means that many cases are also likely to be "dead ends" epidemiologically. Inasmuch as superspreader events may be more likely to be recognized due to their dramatic nature, an outbreak driven by superspreaders may be more likely to attract the control measures needed to disrupt transmission. By contrast, a more homogeneous outbreak, where each and every case has the potential to create a downstream cascade of cases in the absence of recognition, may be much more difficult to control.

As I note above, this outbreak is in its early weeks and understanding and knowledge will doubtless change. However, analysis of the cases counts, rate of growth of the epidemic, reproduction number estimates, and estimates of likely undercounting that have emerged over the past two weeks can provide a coherent view of the likely early dynamics of this outbreak, and also suggest what the contours of the outbreak may look like if control efforts are successful.

--
David N Fisman, MD MPH FRCP(C)
Professor, Epidemiology
Dalla Lana School of Public Health
University of Toronto
Canada

References
----------
1. World Health Organization. Statement on the meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). Available at https://www.who.int/news-room/detail...us-(2019-ncov). Last accessed 25 Jan 2020. Geneva, Switzerland.
2. Riou J, Althus C. Pattern of early human-to-human transmission of Wuhan 2019-nCoV. Preprint. Available at https://github.com/jriou/wcov/blob/m...cript/ncov.pdf. Last accessed 25 Jan 2020.
3. Imai N, Cori A, Dorigatti I, et al. Report 3: Transmissibility of 2019-nCoV. Available at https://www.imperial.ac.uk/mrc-globa...n-coronavirus/. Last accessed 25 Jan 2020.
4. Majumdar M, Mandl K. Early transmissibility assessment of a novel coronavirus in Wuhan, China. Preprint. Available at https://papers.ssrn.com/sol3/papers....act_id=3524675. Last accessed 25 Jan 2020.
5. Bedford T, Neher R, Hadfield J, et al. Genomic analysis of nCoV spread. Situation report 2020-01-23. Available at https://nextstrain.org/narratives/nc...2020-01-23?n=0. Last accessed 25 Jan 2020.
6. Liu T, Hu J, Lin L, et al. Transmission dynamics of 2019 novel coronavirus (2019-nCoV). bioRxiv 2020.01.25.919787. Available at https://twitter.com/biorxivpreprint/...29332369281024. Last accessed 26 Jan 2020.
7. Read J, Bridgen J, Cummings D, et al. Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions. Note that the authors have stated that the R0 estimates here are overestimates and will be revised downward. medRxiv. 2020. Available at https://www.medrxiv.org/content/10.1....23.20018549v1. Last accessed 26 Jan 2020.