Week of April 18, 2022
This week our family celebrates Passover. And the plagues (or at least one) have been on our minds (and in our bodies). Since last Monday, my wife and I have been COVID positive, thanks to an event we attended where at least 15 out of the 100 participants were infected. We are fortunate to be fully vaccinated/boosted. We are only experiencing minor symptoms and minor inconveniences - like keeping our windows open (for airflow) and everyone in the house masked. Our kids have been negative so far, but the pollen makes us all miserable.
Writing this COVID update while having COVID makes me feel like Sy Sperling, who was "not just the President of the Hair Club for Men, but also a client."
Sadly, I learned Mr. Sperling, whose tagline I quote often, died in the fall of 2020. https://www.washingtonpost.com/local/obituaries/sy-sperling-not-just-the-president-but-also-a-client-of-hair-club-for-men-dies-at-78/2020/02/20/5c876116-5400-11ea-9e47-59804be1dcfb_story.html
He did not have COVID, as far as I can tell.
---- Latest Data
Case rates are starting to rise. Hospitalizations and death rates are still low. Anecdotally, I am aware of even more cases in the last week. I am more concerned that we will see no indication of the magnitude of a 5th wave (BA.2) until hospitalizations start to rise.
CDC Wastewater Surveillance tracker
https://covid.cdc.gov/covid-data-tracker/#wastewater-surveillance
N.Y. Times Tracker
https://www.nytimes.com/interactive/2021/us/covid-cases.html
Country Comparison from FT.com
https://ig.ft.com/coronavirus-chart/?areas=usa&areas=gbr&areas=hkg&areas=chn&areas=jpn&areas=aus&areasRegional=usny&areasRegional=usla&areasRegional=usnv&areasRegional=usar&areasRegional=usks&areasRegional=usmo&cumulative=0&logScale=1&per100K=0&startDate=2021-06-01&values=cases
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I am hearing numerous anecdotes of BA2 infection - often without realizing it. "My allergies are bothering me, I tested and I'm positive" is a common scenario.
The Asthma and Allergy Foundation of America offers this comprehensive chart comparing and contrasting symptoms of COVID, allergies, and flu:
https://www.aafa.org/asthma/asthma-triggers/other-health-conditions/respiratory-infections/covid-19-new-coronavirus.aspx
But the problem is not that simple. Vaccinated individuals often have mild symptoms that are hard to distinguish from allergies, especially early on. Here are the kinds of stories I am hearing from friends and family:
https://twitter.com/watchingdt/status/1513556377121308680
And remember, many people are antigen test negative for 48-72 hours after symptoms start. It is hard to convince people to mask, avoid large gatherings, and test 2-3 times over 2-3 days to be confident they are COVID negative.
Dr. Farzad Mostashari goes through his family's recent round of positive tests. He summarizes the problems with testing, getting antivirals, and knowing when to resume life.
https://twitter.com/Farzad_MD/status/1514572923197173775
Random Medical Realities and Technologies
I want to focus on how physicians know when to try new medications, old medications for new indications, and new technologies. In some ways, this is the modern (and non-surgical) application of the "art of medicine." In other words, what threshold of risk and benefit must be apparent before I, as a physician, try something new? It is not simple.
Amongst the various medications tried for COVID, one has stuck out in my mind. In August 2020, two observational studies, including large numbers of patients in community hospitals in New England, demonstrated lower mortality and intubation rates in patients who received the H2 antacid medication Famotidine (Pepcid).
https://www.mdedge.com/internalmedicine/article/227464/coronavirus-updates/famotidine-associated-benefits-hospitalized
Intriguing but observational data alone is not enough.
In February of 2022, a gastroenterology journal published a randomized, placebo-controlled trial using famotidine for mild to moderate COVID symptoms in outpatients: https://gut.bmj.com/content/71/5/879
It was well designed and demonstrated 3-days of fewer symptoms in patients randomized to the treatment arm. These data were more compelling information but only included a total of 55 patients.
So I began to wonder if there are any proposed mechanisms for famotidine? What is happening at the cellular level? Two articles came up:
https://link.springer.com/article/10.1134/S0022093022010203
and
https://www.researchsquare.com/article/rs-1493296/v1
Both articles demonstrate that famotidine is different from other H2-blockers and seems to decrease inflammation. These data align with the inflammatory markers monitored in the February 2022 randomized trial.
Then I wondered - are there downsides to using high doses of famotidine - can you overdose? The typical amount is 20 to 40 mg per day. The study gave patients 80 mg three times a day for two weeks. While the randomized trial noted no adverse side effects, there are case reports of some transient liver toxicity in the use of famotidine and similar H2 blockers:
https://www.ncbi.nlm.nih.gov/books/NBK548228/
All in all, famotidine is pretty safe.
So, am I ready to recommend famotidine to my patients? No. It would be very comforting to see a larger trial. However, the positive data from observational studies, the data from the randomized trial, a proposed mechanism of action, and the limited risk of complications got my attention. But I am not sure if taking high doses of a drug to shorten symptoms by three days is a reasonable tradeoff. And there have been no further studies on inpatients or more severely ill patients. And, given the modest improvements, I would want to ensure that the patients were not using other medications or supplements that could increase the risk of liver injury. (And confirming medication lists can be tough to do). Thus, while there is enough to keep my interest piqued, I am not yet ready to recommend patients try this. I hope there is more data soon.
Infographics!
The chemistry of dyeing Easter eggs:
https://twitter.com/compoundchem/status/1515416293016576008/photo/1
Things I learned this week
My older son taught me the word contranym - a word or phrase that can have opposite meanings, depending on context.
https://www.dailywritingtips.com/75-contronyms-words-with-contradictory-meanings/
AI language models are increasingly sophisticated and unsettling. The NY Times Magazine covered OpenAI's latest prose-writing algorithm, Generative Pre-Trained Transformer 3 (GPT-3). Maybe I will have it write this email soon.
https://www.nytimes.com/2022/04/15/magazine/ai-language.html
examples
https://openai.com/blog/gpt-3-apps/
and
https://gpt3demo.com/
Clean hands and sharp minds, team
Adam
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