Updates on the Wuhan Corona Virus, nCoV2019

To make new information on this viral story easier to find, I’m adding updates with the most recent at the top.

As a reminder, I’m neither an epidemiologist nor a public-health expert, but I study microbial populations from a basic-science perspective. So I have a pretty good sense of what the experts are saying, what is reliable within the stated limits of uncertainty and assumptions, and so on. However, keep in mind that this is a rapidly developing situation, so the “facts” (data and interpretations) may change quickly.

UPDATE 11:05 am (Feb 4): It’s now reported by expert Helen Branswell that the traveler from Wuhan who infected co-workers in Germany was not entirely asymptomatic, contrary to the Lancet paper. [See New Info from 5:00 pm on Jan 29 below for discussion of that paper.] Still, her symptoms were not obvious to others, and with the potential for hidden transmission chains, that seems pretty important. Moreover, that same paper reported that first German who was infected had a very high viral load in his sputum even after he seemed to have recovered, again suggesting the potential for hidden transmissions.

NEWS 10:30 am (Feb 4): Several new cases in Hong Kong do not have recent travel history to mainland China, nor other obvious connections to travelers. According to Chuang Shuk-kwan, head of the Centre for Health Protection’s communicable disease branch: “It is highly probably the four cases were infected locally, so there could be invisible chains of infection happening within communities … We do not rule out a large spread [of the virus] in the future.”

NEWS 10:20 am (Feb 4): There are some reports of travel-related nCoV2019 cases that do not involve travel to or from China. According to this tweet, a Korean may have been infected in Thailand, and a Malaysian in Singapore.

UPDATE 9:45 am (Feb 4): Richard Neher updates his informative graphs showing growth in cumulative numbers of nCoV2019 cases reported in Hubei (province where Wuhan is located) and elsewhere in China, as well as reported death rates and international travel cases. As Neher notes, there’s much we still don’t know well at all, such as the mortality rate. [See the Update from 6:20 pm on Feb 1 below for some of the complicated issues surrounding even a seemingly simple concept like the death rate.] While it is now clear that many cases are mild, there are also many cases that have not caused death (at least yet), but where the patients are critically ill. To my mind, a huge unknown is whether we will see other hotspots of this coronavirus in China (see News just below) and elsewhere, especially in areas with less developed medical systems and public-health infrastructure, in the weeks and months ahead.

NEWS 11:00 pm (Feb 3):  China closes off another large city, Wenzhou, according to The Straits Times. An east coast city with 9 million residents, Wenzhou is some distance from Wuhan. Only one resident per household can leave home every second day to shop for necessities. Schools are closed until March, and most businesses are shut for two weeks.

UPDATE 10:30 pm (Feb 3):  CDC updated its test results for “people under invesigation” (PUI) — that is, possible cases of nCoV2019 infection. The cumulative totals include 11 positives and 167 negatives, for an overall proportion of 6.2% positive tests. That’s up a bit from the previous report at 5%, although I think the new data includes two secondary infections of spouses.  So not much change. The backlog of pending cases is currently 82, down from 121 in the previous report. With the travel restrictions in place, I would guess that the number of new PUI cases would continue to decline … at least for a while. But we now enter a period of great uncertainty, as the outbreak spreads in China and into other countries.  From the NY Times:

  • “It’s very, very transmissible, and it almost certainly is going to be a pandemic,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease. “But will it be catastrophic? I don’t know.”
  • It is “increasingly unlikely that the virus can be contained,” said Dr. Thomas R. Frieden, a former director of the Centers for Disease Control and Prevention who now runs Resolve to Save Lives, a nonprofit devoted to fighting epidemics. “It is therefore likely that it will spread, as flu and other organisms do, but we still don’t know how far, wide or deadly it will be.”

UPDATE 6:20 pm (Feb 1):  Epidemiologist Maia Majumder (@maiamajumder) provides a clear and concise explanation of the different ways of measuring and describing the “deadliness” of infectious diseases. As importantly, she explains why the different estimates change over time. In the case of the population mortality rate, that will tend to increase as an outbreak grows in size, before eventually reversing course once an outbreak has been brought under control. By contrast, the case fatality rate (CFR) reflects the fraction of diagnosed infections that cause death. This latter rate is subject to an early spike because the earliest cases are often the most severe. Also, increased awareness and testing of less severe cases tends to increase over time. Both of these factors mean the CFR typically declines as an outbreak progresses. On the other hand, many serious cases (as reported for nCoV2019 by Chinese health authorities) have not yet resolved. In short, the CFR remains poorly understood at this time. Then, too, there are some people who get an infection, including the nCoV2019 virus, but with no or minimal symptoms, and so they are not diagnosed, These subclinical cases can be discovered later on when populations are surveyed serologically, allowing a further, lower estimate of the fraction of total infections (those discovered later as well as those discovered clinically) that cause death. Dr. Majumder also reminds us that different subpopulations (such as those with chronic diseases) may face different risks.

COMMENT 1:15 pm (Feb 1): There’s plenty of reasons to be worried about this nCoV2019 outbreak, especially if you’re in the most affected areas of China. Hopefully, journalists, scientists, clinicians, and everyone else on social media can communicate and amplify the relevant facts and uncertainties, and avoid sloppy thinking and conspiracy theories.

UPDATE 1:10 pm (Feb 1):  Boom. Trevor Bedford demolishes the claim that the nCoV2019 genome contains bits of HIV sequence, and thereby destroys the conspiracy theory that this corona virus was a bioengineered strain.

UPDATE 12:20 pm (Feb 1): Using his knowledge as an infectious disease specialist combined with common sense, Adam Lauring dismantles the assertion that people might become reinfected with nCoV2019. That’s not to say it’s impossible, but it’s extremely unlikely given such closely related strains (just a few mutations different), and there’s no way of testing that yet. Perhaps something was lost in translation, and the original work only meant to say that nCoV2019 infections increased one’s risk of other secondary infections?

NEW INFO 11:20 am (Feb 1): Simple graphs can reveal a lot. Biophysicist Richard Neher plotted the number of nCoV2019 cases in Hubei and the rest of China over time. Note the log-transformed scale, so a linear trend corresponds to exponential growth. Neher notes some slight decline in the rate of increase, which could mean either that the number of new cases is decelerating (which would be good news) or that the testing capacity is limited and becoming saturated (not good news). Daniel Falush weighed in, suggesting that the number of deaths—alas, not subject to testing limits—would be a better indicator, and he thought that would show signs of slowing. So Neher produced a plot of those data. And yikes: There’s no hint of any slowing, with the number of fatalities doubling about every 3 days. Here’s a screen shot of Neher’s plot:

Corona virus fatalities trajectory from Richard Neher

UPDATE 6:30 pm (Jan 31):  CDC has updated data on the numbers of positive, negative, and pending cases for “patients under investigation.” The proportion of positive tests continues to drop, which is good news:  It’s now 6/120 = 5.0% of the tests of potential nCoV2019 cases in the US that have proven to be positive to date, down from 6.8% a few days ago and 13.5% before that. However, the number of pending (unresolved) cases has continued to increase and now stands at 121.

AN IDEA 11:45 am (Jan 31): For biology teachers at multiple levels (including high school, undergrad, and graduate), this on-going corona virus outbreak could provide valuable information and timely data for teaching core concepts like R0, transmission chains, genomes, phylogenies & more. Students could even analyze and/or interpret new incoming data themselves to draw their own inferences. To see what I mean, check out the superb multi-slide presentation of important concepts, data, and inferences based on the first 42 sequenced genomes of the virus produced and made freely available by the @nextstrain team.

NEW ANALYSIS 10:15 am (Jan 31): The ever-clever Trevor Bedford (say that 10 times fast!) has a twitter thread explaining his new analysis for estimating the probability distribution of the number of new mutations in the viral genome per transmission from one person to another. It relies on knowing the time course of infections and transmissions, as well as the mutation rate, but these parameters are reasonably bounded and becoming better estimated over time. One can also do the inverse analysis to estimate the number of intermediate infections in a transmission chain, which could be useful for epidemiological tracking and investigation.

NEW INFO 10:00 am (Jan 31): New clinical and epidemiologically relevant information on secondary infections in Germany reported in New England Journal of Medicine. h/t @HelenBranswell, who highlights that Patient 1 had “recovered” enough to go to work, but when tested had “a high viral load of 10^8 [100,000,000] copies per milliliter in his sputum.” If this situation is common, it would seem to present a new set of serious challenges.

UPDATE 7:00 pm (Jan 30):The number of international-travel cases continues to increase exponentially, as shown in graph produced by Trevor Bedford. Note the logarithmic y-axis, so a straight line corresponds to exponential growth. With more travel restrictions in place, we would expect that to slow down, even if the epidemic within Wuhan, or China more broadly, continues. So Trevor says he will try to track these data as a function of airplane passengers.

NEW INFO 1:20 pm (Jan 30): First case of transmission within US reported by CDC. Involves a husband and wife, so no evidence of any community-wide spread here in the US to date.

UPDATE 1:00 pm (Jan 30): The @nextstrain team has updated their excellent multi-slide presentation of important inferences based on the first 42 sequenced genomes of the virus. These data continue to point to a single recent origin of the outbreak, with rapid expansion from there. As I noted yesterday, there appear to be clusters of travelers that share one or two mutations, presumably derived from the same intermediate source in the chains of transmissions. These cases, if investigated epidemiologically, might provide valuable clues about the transmission dynamics.

NEW INFO 5:00 pm (Jan 29): I’ve mentioned that we know little about the distribution of outcomes with respect to disease severity. The Lancet (a leading medical journal) has just published a paper analyzing 99 of the early cases in Wuhan, China, that were confiirmed as involving the new nCoV2019 corona virus. These cases involved hospitalization, during a period of considerable stress on the health-care system.  Half of these cases involved patients with other underlying chronic diseases. Nonetheless, about 75% of the patients now have a good prognosis, and about a third have been discharged from the hospital. However, many of the others developed “acute respitory distress syndrome” and 11 of the 99 died. Again, these are atypically severe cases. It’s also very interesting that almost half of all the cases involved individuals who worked at the Wuhan seafood market.  However, the earliest cases appear to not involve that market, which makes this association rather curious.  Also, we still don’t know much about the infections that are less severe for individuals, but which are nonetheless very important for understanding the viral transmission dynamics.

NEW INFO 6:10 pm (Jan 29): From Richard Neher via twitter, a report that 4 Germans who tested postitive after contact with a work-place visitor from Wuhan are apparently asymptomatic. It’s unclear from the short tweet whether the Germans never exhbited any symptoms at all, or only very mild ones, but they are now recovered. This finding supports the conclusion that there are many mild infections (good news), but it also implies that the number of infected people–some of whom might transmit the virus–is quite large (bad news), in line with some of the calculations of the number infected.

NEW INFO 5:20 pm (Jan 29): More nCoV2019 viral genomes have been sequenced from around the world and placed in their phylogenetic context by the @nextstrain team.  I’ve copied a screenshot below that shows the latest version, plotted in terms of mutational distance from the earliest Wuhan samples. It’s very interesting that there are clusters of some of the international-travel cases including (about 2/3 of the way down) the French (2 identical isolates), one from the USA, and a Taiwan case. They all share one mutation that none of the other isolates have. That might not seem like much, but with so few mutations in total (over the whole tree), it strongly suggests that these cases all have some secondary (or later) source in common along the viral transmission chain.  And just above that cluster is another cluster of isolates that all share 2 mutations with an interesting mix of international and non-Wuhan Chinese samples. So there might be some useful epidemiological clues in there, if this information can be coupled with careful studies of patient travel and contacts. 

nCoV2019 nextrstrain phylogram

NEW INFO 12:45 pm (Jan 29): Physicist Dirk Brockmann presents an analysis that uses actual worldwide travel data to estimate the relative probabilities (“import risks”) that travelers from Wuhan enter other countries via specific airports. The results align quite well with where new international cases have been turning up.  [h/t to Richard Neher @richardneher via twitter]

NEW INFO 12:15 pm (Jan 29):  I had read some discussions on the web that the nCoV2019 outbreak might be caused by a “recombinant” virus. This, in turn, led to some conspiracy-type speculation about a virus that escaped from a lab. Recombinants can occur naturally, as well as be made in the lab. So I wondered whether there was good evidence for recombination in these viruses and, if so, whether the recombination pre-dated or post-dated the split between the most closely related bat strain and the Wuhan strain nCoV2019. I turned, once again, to expert Trevor Bedford (@trvrb), since this is a phylogenetically based question. He pointed me to in-depth analyses and discussion of these issues among experts.  First, some genetic recombination has occasionally occurred in these viruses in nature. Second, he sees no evidence of “recombination in the ~50 years since the ancestor of nCoV outbreak viruses split from RaTG13” (i.e., the most closely related corona virus in the data base, which derives from a bat in the year 2013).

NEW INFO 11:00 am (Jan 29):  A bit of good news from CDC. Now 5/73 = 6.8% tests of potential nCoV2019 cases in US have been positive to date. It had been 5/37 = 13.5% at last update. That means no new confirmed positive cases in US. As expected given the spreading infection and expanding concern, the number of pending (unresolved) cases has increased.

NEW INFO 2:00 pm (Jan 27):  On Twitter @afferent_input found monthly data on visitors to US from China. Seasonal data suggest number of travelers in this period might be ~2X higher than my crude estimate, which would reduce the inferred infection proportion and numbers relative to my initial estimates. This factor and the other new info posted [just below] might roughly cancel. Again, all of this information is rough and crudely extrapolated. And none of it bears on critical issues of distribution of severity of infections, etc. 

NEW INFO 1:20 pm (Jan 27):   Here’s another interesting (and concerning) bit of data from the CDC. So far, 37 cases have been investigated.  Of these, 5 have been positive, and 32 negative. However, there are 73 more cases with pending test results in just this first week of CDC data. If the % positive holds in these pending cases, that would triple my estimate of proportion & number infected.  That is, the product (5/37) x 73 suggests that an additional 10 or so infected individuals will be identified as having entered the US in this first week. Again, this is a crude estimate with assumptions, and these potential cases are also presumably in isolation, etc.

Links to my first two posts

Jan 29:  Developing News on the Wuhan Corona Virus, nCoV2019

Jan 27:  Quick-and-Dirty Estimate of Number of nCoV2019 Infections in Wuhan

 

3 Comments

Filed under Education, Science, Uncategorized

3 responses to “Updates on the Wuhan Corona Virus, nCoV2019

  1. Old Engineer

    Thank you for your efforts. In addition to serving the science community you provide a great source of credible info for laymen trying to educate ourselves from credible scientific sources.

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