Monthly Archives: March 2020

The Corona Princess: Learning from a petri dish cruise (i)

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Q. Was it a mistake to quarantine the passengers aboard the Diamond Princess in Japan?

A. The original statement, which is not unreasonable, was that the best thing to do with these people was to keep them safely quarantined in an infection-control manner on the ship. As it turned out, that was very ineffective in preventing spread on the ship. So the quarantine process failed. I mean, I’d like to sugarcoat it and try to be diplomatic about it, but it failed. I mean, there were people getting infected on that ship. So something went awry in the process of quarantining on that ship. I don’t know what it was, but a lot of people got infected on that ship. (Dr. A Fauci, Feb 17, 2020)

This is part of an interview of Dr. Anthony Fauci, the coronavirus point person we’ve been seeing so much of lately. Fauci has been the director of the National Institute of Allergy and Infectious Diseases since all the way back to 1984! You might find his surprise surprising. Even before getting our recent cram course on coronavirus transmission, tales of cruises being hit with viral outbreaks are familiar enough. The horror stories from passengers on the floating petri dish were well known by this Feb 17 interview. Even if everything had gone as planned, the quarantine was really only for the (approximately 3700) passengers because the 1000 or so crew members still had to run the ship, as well as cook and deliver food to the passenger’s cabins. Moreover, the ventilation systems on cruise ships can’t filter out particles smaller than 5000 or 1000 nanometers.[1]

“If the coronavirus is about the same size as SARS [severe acute respiratory syndrome], which is 120 nanometers in diameter, then the air conditioning system would be carrying the virus to every cabin,” according to Purdue researcher, Qingyan Chen, who specializes in how air particles spread in different passenger crafts. (His estimate was correct: the coronavirus is 120 nanometers.) Halfway through the quarantine, after passenger complaints, they began circulating only fresh air–which would have been preferable from the start. By then, however, it is too late: the ventilation system is already likely filled with the virus, says Chen.[2] Arthur Caplan, the bioethicist who is famous for issuing rulings on such matters, declares that

“Boats are notorious places for being incubators for viruses. It’s only morally justified to keep people on the boat if there are no other options.”

Admittedly, it is hard to see an alternative option to accommodate so many passengers for a 2 week quarantine on land, and there was the possible danger of any infections spreading to the local population in Japan. So, by his assessment, it may be considered morally justified.

The upshot: As of 19 March 2020, at least 712 out of the 3,711 passengers and crew had tested positive for covid-19; 9 of those who were on board have died from the disease (all over the age of 70). As I was writing this, I noted a new CDC report on the Diamond Princess as well as other cruise ships; they state 9 deaths.[3] A table on the distribution of ages of passengers on the Diamond Princess is in Note [4].

So how did the Diamond Princess cruise ship become a floating petri dish for the coronavirus from Feb 4-Feb 20?

The Quarantine

It was their last night of a 2-week luxury cruise aboard the Diamond Princess in Japan (Feb 3) when the captain came on the intercom. He announced: a passenger on this ship who disembarked in Hong Kong 9 days ago (Jan 25) has tested positive for the coronovirus. (He was on board for 5 days.) Everyone will have to stay on board an extra day to be examined by the Japanese health authorities. A new slate of activities was arranged to occupy passengers during the day of health screening–later mostly dropped. But on the evening of February 3, things continued on the ship more or less as before the intercom message.

“The response aboard the Diamond Princess reflected concern, but not a major one. The buffets remained open as usual. Onboard celebrations, opera performances and goodbye parties continued”. (NYT, March 8)

The next day, as health officials went door to door to screen passengers, guests still circulated on board, lined up for buffets, and used communal spaces. But then, the following morning (Feb 5), as guests were heading to breakfast, the captain came over the intercom again. He announced that 10 people had tested positive for the coronavirus and would be taken off the ship. Everyone else would now have to be quarantined in their cabins for 14 days. The second day of the quarantine (Feb 6) it was announced that 20 people more had tested positive, then on day three, 41 more, then 64 more, and on and on. By the end of the quarantine on February 19 at least 621 on the ship had tested positive for the virus.

Adding to the stress, “we quickly learned that our tests were part of an initial batch of 273 samples and that the first 10 cases reported on day one were only from the first 31 samples that had been processed” from the passengers with highest risk. (U.S. passenger, Spencer Fehrenbacher, interviewed on the ship)

As the number of infected ballooned, passengers were not always informed right away; some took to counting ambulances lined up outside to find out how many new cases would be announced at some point. I wonder if the passengers were told that the very first person to test positive was a crew member responsible for preparing food. In fact, by February 9, around 20 of the crew members tested positive, 15 of which were workers preparing food. Crew members lived in close quarters, shared rooms and continued to eat their meals together buffet-style. They had no choice but to keep running the ship as best as they could.

“Feverish passengers were left in their rooms for days without being tested for the virus. Health officials and even some medical professionals worked on board without full protective gear. [Several got infected.] Sick crew members slept in cabins with roommates who continued their duties across the ship, undercutting the quarantine”. (NYT Feb 22)

Passengers in cabins without windows (and later, others) were allowed to walk on deck, six feet apart, for a short time daily. Unfortunately, presumed infection-free “green zones” were not rigidly separated from potentially contaminated “red zones”, and people walked back and forth between them. Gay Courter, a writer from the U.S. who, as it happens, situated one of her murder mysteries on a cruise ship, told Time “It feels like I’m in a bad movie. I tell myself, ‘Wake up, wake up, this isn’t really happening.’” (Time, Feb 11). This is the same bad movie we are all in now, except our horror tale has gotten much worse than on Feb 10.

At some point, I think Feb 10, the ship became the largest concentration of Covid-19 cases outside China, which is why you’ll notice the Diamond Princess has own category in the data compiled by the World Health Organization (Worldometer).

In a Science Today article, a Japanese infectious disease specialist regretted the patchwork way in which passenger testing was done:

Japan has missed a chance to answer important epidemiological questions about the new virus and the illness it causes. For instance, a rigorous investigation that tested all passengers at the start of the quarantine and followed them through to the end could have provided information on when infections occurred and answered questions about transmission, the course of the illness, and the behavior of the virus.

(They were only able to test people in stages.) A similar paucity of testing in the U.S. robs us from crucial information for understanding and controlling the coronavirus. However, there is a fair amount being gleaned from the Diamond Princess, as you can see in the references below. (Please share additional references in the comments.) More is bound to follow.

Estimates from the Diamond Princess

“Data from the Diamond Princess cruise ship outbreak provides a unique snapshot of the true mortality and symptomatology of the disease, given that everyone on board was tested, regardless of symptoms”–or at least virtually all. [link] The estimates (from the Diamond Princess) I’ve seen are based on those from the London School of Hygiene and Tropical Medicine, in a paper still in preprint form,”Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship”.

Adjusting for delay from confirmation-to-death, we estimated case and infection fatality ratios (CFR, IFR) for COVID-19 on the Diamond Princess ship as 2.3% (0.75%-5.3%) [among symptomatic] and 1.2% (0.38-2.7%) [all cases]. Comparing deaths onboard with expected deaths based on naive CFR estimates using China data, we estimate IFR and CFR in China to be 0.5% (95% CI: 0.2-1.2%) and 1.1% (95% CI: 0.3-2.4%) respectively. (PDF)

(For definitions and computations, see the article.) These are lower than the numbers we are often hearing. They used their lower fatality estimates to adjust (down) the estimates from China data. The paper lists a number of caveats.[5] I hope readers will have a look at it (it’s just a few pages) and share their thoughts in the comments. (Their estimates are in sync with an article by Fauci et al., to come out this week in NEJM; but whatever the numbers turn out to be, we know our healthcare system, in many places, is being overloaded. [6])

Another study takes the daily reports of infections on the Diamond Princes to attempt to evaluate the impact of the quarantine, as imperfect as it was, in comparison to a counterfactual situation where nothing was done, including not removing infected people from the ship. They estimate nearly 80%, rather than 17% would have been infected. [link]

We found that the reproductive number [R0] of COVID-19 in the cruise ship situation of 3,700 persons confined to a limited space was around 4 times higher than in the epicenter in Wuhan, where was estimated to have a mean of 3.7.[7]

The interventions that included the removal of all persons with confirmed COVID-19 disease combined with the quarantine of all passengers substantially reduced the anticipated number of new COVID-19 cases compared to a scenario without any interventions (17% attack rate with intervention versus 79% without intervention) … However, the main conclusion from our modelling is that evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew members from getting infected.” [link]

Only 76, rather than 621 would have been infected, they estimate. [8]

Conclusions: The cruise ship conditions clearly amplified an already highly transmissible disease. The public health measures prevented more than 2000 additional cases compared to no interventions. However, evacuating all passengers and crew early on in the outbreak would have prevented many more passengers and crew from infection.

These studies and models are of interest, although I’m in no position to evaluate them. Please share your thoughts and information, and point out any errors you find. I will indicate updates in the title of this post.

Optimism

I leave off with the remark of one of the U.S. passengers interviewed while still on the Diamond Princess:

“Being knee deep in the middle of a crisis leaves a person with two options — optimism or pessimism. The former gives a person strength, and the latter gives rise to fear.” (link)

He, like the others who were evacuated, faced an additional 2 weeks of quarantine.[9] He has since returned home and remains infection free.

*****

 

[1] As a noteworthy aside, Fauci was able to assure the interviewer that the “danger of getting coronavirus now is just minusculely low” (in the U.S. on Feb. 17). What a difference 2 weeks can make.

[2] In a 2015 paper, Chen and colleagues found a cruise ship’s ventilation spread particles from cabin to cabin. They found that 1 infected person typically led to more than 40 cases a week later on a 2000 passenger cruise. By contrast, the coronavirus, with a reproductive rate of 2 cases per infected person, would only lead to 3 new cases during that time. Planes rely on high-strength air filters and are designed to circulate air within cabin sections.

[3] In a March 23 CDC report: Among 3,711 Diamond Princess passengers and crew, 712 (19.2%) had positive test results for SARS-CoV-2. Of these, 331 (46.5%) were asymptomatic at the time of testing. Among 381 symptomatic patients, 37 (9.7%) required intensive care, and nine (1.3%) died (8).

They found coronavirus in Diamond Princess cabins 17 days after passengers disembarked (prior to cleaning).

[4] A table from the Japanese National Institute of Infectious Diseases (NIID) (Source LINK):

[5]

“There were some limitations to our analysis. Cruise ship passengers may have a different health status to the general population of their home countries, due to health requirements to embark on a multi-week holiday, or differences related to socio-economic status or comorbidities. Deaths only occurred in individuals 70 years or older, so we were not able to generate age-specific cCFRs; the fatality risk may also be influenced by differences in healthcare between countries”.

[6] In a March 26 article by Fauci and others, Covid-19 — Navigating the Uncharted, we read:

“If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%.”

[7] R0 may be viewed as the expected number of cases generated directly by 1 case in a susceptible population.

[8] The number in the most recent report is 712, but that would be after the quarantine ended on Feb 19.

[9] I read today that one of the U. S. evacuated passengers just entered a clinical trial on remdesivir. This would be over a month since the end of the first quarantine.

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REFERENCES:

  • Giwa, A.,  LLB, MD, MBA, FACEP, FAAEM; Desai, A., MD; Duca, A., MD; Translation by: Sabrina Paula Rodera Zorita, MD (2020). “Novel 2019 Coronavirus SARS-CoV-2 (COVID-19): An Updated Overview for Emergency Clinicians – 03-23-20” EBMedicine.net; Pub Med ID: 32207910; (LINK)
  • Japanese National Institute of Infectious Diseases (NIID). “Field Briefing: Diamond Princess COVID-19 Cases, 20 Feb Update” (LINK)
  • Rocklöv, J., Sjödin, H., & Wilder-Smith, A.  “COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures”, Journal of Travel Medicine, (Feb 28, 2020) [link]
  • Russell, T., Hellewell, J.,Jarvis, C., van-Zandvoort, K.Abbott, S.,Ratnayake, R., Flasche, S., Eggo, R. & Kucharski, A. (2020). “Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship.” MedRXIV: The preprint server for the Health Sciences. (March 9, 2020). (PDF)
  • Zheng, L., Chen, Q., Xu, J., & Wu, F. (2016). Evaluation of intervention measures for respiratory disease transmission on cruise ships. Indoor and Built Environment, 25(8), 1267–1278. (First Published online August 28, 2015 ). (PDF)
Categories: covid-19 | 11 Comments

Stephen Senn: Being Just about Adjustment (Guest Post)

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Stephen Senn
Consultant Statistician
Edinburgh

Correcting errors about corrected estimates

Randomised clinical trials are a powerful tool for investigating the effects of treatments. Given appropriate design, conduct and analysis they can deliver good estimates of effects. The key feature is concurrent control. Without concurrent control, randomisation is impossible. Randomisation is necessary, although not sufficient, for effective blinding. It also is an appropriate way to deal with unmeasured predictors, that is to say suspected but unobserved factors that might also affect outcome. It does this by ensuring that, in the absence of any treatment effect, the expected value of variation between and within groups is the same. Furthermore, probabilities regarding the relative variation can be delivered and this is what is necessary for valid inference. Continue reading

Categories: randomization, S. Senn | 6 Comments

My Phil Stat Events at LSE

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I will run a graduate Research Seminar at the LSE on Thursdays from May 21-June 18:

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(See my new blog for specifics (phil-stat-wars.com).
I am co-running a workshop
from 19-20 June, 2020 at LSE (Center for the Philosophy of Natural and Social Sciences CPNSS), with Roman Frigg. Participants include:
Alexander Bird (King’s College London), Mark Burgman (Imperial College London), Daniele Fanelli (LSE), David Hand (Imperial College London), Christian Hennig (University of Bologna), Katrin Hohl (City University London), Daniël Lakens (Eindhoven University of Technology), Deborah Mayo (Virginia Tech), Richard Morey (Cardiff University), Stephen Senn (Edinburgh, Scotland).
If you have a particular Phil Stat event you’d like me to advertise, please send it to me.
Categories: Announcement, Philosophy of Statistics | Leave a comment

Replying to a review of Statistical Inference as Severe Testing by P. Bandyopadhyay

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Notre Dame Philosophical Reviews is a leading forum for publishing reviews of books in philosophy. The philosopher of statistics, Prasanta Bandyopadhyay, published a review of my book Statistical Inference as Severe Testing: How to Get Beyond the Statistics Wars (2018, CUP)(SIST) in this journal, and I very much appreciate his doing so. Here I excerpt from his review, and respond to a cluster of related criticisms in order to avoid some fundamental misunderstandings of my project. Here’s how he begins:

In this book, Deborah G. Mayo (who has the rare distinction of making an impact on some of the most influential statisticians of our time) delves into issues in philosophy of statistics, philosophy of science, and scientific methodology more thoroughly than in her previous writings. Her reconstruction of the history of statistics, seamless weaving of the issues in the foundations of statistics with the development of twentieth-century philosophy of science, and clear presentation that makes the content accessible to a non-specialist audience constitute a remarkable achievement. Mayo has a unique philosophical perspective which she uses in her study of philosophy of science and current statistical practice.[1]

Bandyopadhyay

I regard this as one of the most important philosophy of science books written in the last 25 years. However, as Mayo herself says, nobody should be immune to critical assessment. This review is written in that spirit; in it I will analyze some of the shortcomings of the book.
Continue reading

Categories: Statistical Inference as Severe Testing–Review | Tags: | 24 Comments

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