COVID19 update, May 2, 2020 edition: Remdesivir gets FDA approval; detailed German statistics

(1) The top news item of the day is probably that Gilead Scientific’s antiviral drug remdesivir was given FDA Emergency Approval for use in COVID19 patients. Remdesivir is not a “magic bullet”, but it’s a start.

(2) Roger Seheult MD, pulmonologist and medical school instructor, gives a 1.5 hour recap video on what we know about COVID19.

(3) Miscellaneous updates:

  • the Ma`ayanei haYeshua [Wellsprings of Salvation] hospital in Bnei Brak, Israel (a COVID19 hotspot) has deployed an Israeli-developed UV-C room sterilization system. This is of broader relevance than COVID19, and if successful, will prove very helpful in the protracted and increasingly worrying struggle against hospital “superbugs” — bacteria resistant to every known antibiotic. (Such bacteria tend to develop in hospitals and long-term care settings through “Darwinian selection”, as both infections and treatment with aggressive antibiotics are frequent.)
  • Die Welt has a detailed video (in English, with German subtitles) on significant progress with a vaccine in the USA
  • worrisome reports about some peculiar COVID19-like pediatric syndrome noted in earlier updates: these now appear to have been identified as Kawasaki’s disease, which is of uncertain origin but some sort of autoimmune etiology is suspected. Coincidence or new cases triggered by COVID19 infection?
  • disturbing reports of COVID19 “reinfections” in South Korea appear to have been false positives in the test
  • Abbott’s new rapid COVID19 test, which claims 99% accuracy, has been approved for use in Europe.
  • if you give people perverse incentives to cook the books, and don’t balance that out with a deterrent for the act of cooking — well, don’t be surprised if books get cooked. NYC funeral director on candid recording about people who obviously died from otehr causes being coded as COVID19. Mind you, I am sure the un-inflated COVID19 mortality in NYC would be quite bad enough (“thanks” to very high pollution density and the subway as “the mother of all superspreaders”) — but those numbers struck me as anomalously high from the start. (As discussed in previous updates, numbers from Italy and Belgium are inflated for different reasons.)

(4) In contrast, countries like South Korea and Germany have rather more scrupulous reporting standards. I’ve linked previously to the daily Korean CDC reports: here is the detailed daily update (in English) from the Robert Koch-Institute (Germany’s infectious diseases authority, named after the discoverer of the tuberculosis pathogen). A few highlights from the daily report:

  • Only 19% of all cases occurred in persons aged 70 years or older — but these account for 87% of deaths.
  • cases per 100,000 people in age cohorts are fairly homogenous across age cohorts 20-29 through 70-79, climb sharply in the highest age cohorts, and drop steeply for ages 10-19 and especially 0-9.
  • mortality in age cohorts 0-9 and 10-19 are ONE (1) patient each, while age cohorts 20-29 and 30-39 account for just 6 and 14 deceased out of a total of 6,472. Yes, Virginia, ages below forty account for just 0.3% of all dead, and all ages below fifty for just 1%. Fifty-somethings add another 3.2%, sixty-somethings another 9.0%.
  • Their technique of estimating the effective reproductive number R consists of dividing the 4-day moving average of new cases by the one 4 days earlier. At present it is R=0.79, with a 95% confidence interval of 0.66–0.90. Any R value below 1 implies that the epidemic will wither away, while any value over 1 implies slower or faster exponential growth.
  • the report points to a European Union website with all-causes excess mortality graphs. These serve as a useful “sanity check” on COVID19 death reporting criteria for different countries.

COVID19 update, April 28, 2020: drug repurposing; perverse incentives; Neil Ferguson now sees further lockdowns as impractical

(1) “Drug repurposing”: it’s a thing. Basically, if you have an emerging disease and need a remedy right this minute — even if you design a new drug that works well in the test tube, you are still faced with months of Phase 1, 2, and 3 clinical trials.

In contrast, if you can repurpose an existing drug that is already approved for treatment of another condition, you can skip testing whether the drug is safe, what side effects it has, and what is a safe dosage range. (As the old quip goes, nothing is safe at all doses, not even dihydrogen monoxide ;)) All you need to establish is: does it work against the new disease?

So there have been massive efforts to screen databases of approved drugs for molecules that inhibit this, that, or the other enzyme that is a vital part of the viral reproduction cycle. Increasingly, the first step of this is done on the computer, and the most promising candidates are then tested out in vitro, then in “animal models”.

But sometimes scientists stumble serendipitously on something that seems to work. SCIENCE magazine reports on… the H2 antagonist famotidine (sold in the US under the brand name Pepcid), used widely as a heartburn remedy until more recently displaced by proton pump inhibitors such as omeprazole (Prilosec).

“The virus was killing as many as one out of five patients older than 80 [in Wuhan]. Patients of all ages with hypertension and chronic obstructive pulmonary disease were faring poorly. Callahan and his Chinese colleagues got curious about why many of the survivors tended to be poor. “Why are these elderly peasants not dying?” he asks.

In reviewing 6212 COVID-19 patient records, the doctors noticed that many survivors had been suffering from chronic heartburn and were on famotidine rather than more-expensive omeprazole (Prilosec), the medicine of choice both in the United States and among wealthier Chinese. Hospitalized COVID-19 patients on famotidine appeared to be dying at a rate of about 14% compared with 27% for those not on the drug, although the analysis was crude and the result was not statistically significant.

But that was enough for Callahan to pursue the issue back home. […]

“Anecdotal evidence has encouraged the Northwell researchers. After speaking to Tracey, David Tuveson, director of the Cold Spring Harbor Laboratory Cancer Center, recommended famotidine to his 44-year-old sister, an engineer with New York City hospitals. She had tested positive for COVID-19 and developed a fever. Her lips became dark blue from hypoxia. She took her first megadose of oral famotidine on 28 March. The next morning, her fever broke and her oxygen saturation returned to a normal range. Five sick co-workers, including three with confirmed COVID-19, also showed dramatic improvements after taking over-the-counter versions of the drug, according a spreadsheet of case histories Tuveson shared with Science. Many COVID-19 patients recover with simple symptom-relieving medications, but Tuveson credits the heartburn drug. “I would say that was a penicillin effect,” he says.”

“After an email chain about Tuveson’s experience spread widely among doctors, Timothy Wang, head of gastroenterology at Columbia University Medical Center, saw more hints of famotidine’s promise in his own retrospective review of records from 1620 hospitalized COVID-19 patients. Last week, he shared the results with Tracey and Callahan, and he added them as a co-authors on a paper now under review at the Annals of Internal Medicine. All three researchers emphasize, though, that the real test is the trial now underway. “We still don’t know if it will work or not,” Tracey says.”

I am definitely looking forward to the results of that trial.

(2) I have heard the claim made that US hospitals have a financial incentive to code a patient as COVID19. Given the complexity of the US health insurance market (and governmental players in it), it struck me as “plausible, but verify”. Turns out: yes, Virginia. (The article notes that notoriously left-biased Snopes agrees with them.)

In our own system, there is no financial incentive to do so as it all comes out of the same insurance pool (divided among the four authorized HMOs by enrollment, not actual costs). Whatever downsides our socialized-with-private-options medical system may have, a perverse incentive to code a non-COVID19 patient as COVID19 is not one of them. As a result, we have “only” 208 COVID19 deceased at the time of writing, according to the Ministry of Health’s daily update.

A source in Belgium’s medical community told me that pathologists massively write COVID19 as the cause of death “if the patient has even been near a COVID19 case”, even if the actual cause is heart attack, stroke,… This appears to be one reason for the anomalously high per-capita COVID19 mortality in Belgium (the highest in the world, and far in excess of next-door Germany which uses much stricter criteria). When all-cause mortalities were compared year over year, an excess mortality was found that is comparable to neighboring countries.

(3) In this interview with Imperial College modeler Neil Ferguson (yes, the one with the “two million million will die” model, that later got revised drastically downward) he seems to take a more nuanced position than some of his acolytes, sees continued lockdown as unrealistic “and causing excess mortality from other causes” (!), expects a second wave (he’s not alone in that), and favors a South Korean-style test, track & trace approach. Defends himself as “as a nation, we acted in time to prevent a breakdown of medical services”. For balance, I offer a video on the same channel by his Swedish critic Prof. Johan Giesecke. The interviewer is fairly tough on both: nice to see some actual journalism.

(4) in John Campbell’s daily update, about 16 minutes in, John Campbell discussed “pediatric inflammation syndrome” in the UK. Is it COVID19 or some unidentified viral pathogen? Abdominal pain, GI symptoms more annoying than anything else, cardiac involvement more worrisome. “Let’s hope that comes to nothing, but would seem to be expedient to have a higher index of suspicion [of abdominal pain in children].”

He also thinks Canada is starting to look good.

(5) Miscellaneous updates (h/t Mrs. Arbel):

Today, Israel marks Yom HaZikaron, or Memorial Day, for its fallen soldiers. Tonight (days on the Jewish calendar run sundown to sundown) it will transition into Yom HaAtzmaut or Independence Day — the former to remind us of those who paid the ultimate price for the latter.