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.