COVID19 update, April 22, 2020: the two faces of the disease, as explained by a pulmonologist; IL-6 and estrogen explaining gender differences?

(1) I saw a video by pulmonologist Mike Hansen MD that made me go “aha!”. He may be pitching its message a bit too strongly, but was delivered in a highly entertaining manner, and is easy to follow if you have some basic medical knowledge. See the video here. (Something is broken with the YouTube embedding widget that makes WordPress glacially slow to edit on my computer.)

It is almost like the disease has two faces. In the vast majority of patients, there is no involvement of the lower respiratory tract — just upper respiratory and some gastro-intestinal involvement (there are ACE2 receptors there), rarely some cerebral. This disease picture is the (generally) nonlethal one, ranging in severity from mild cold to severe flu without secondary infection. Such patients will get better on their own with nothing more than standard supportive treatment, like you would for a nasty flu at home.

It’s when the infection goes down to the lower part of your lungs that all hell can break loose. Effectively, the inflammation of the alveoli sets off a chain reaction (which he explains in great detail) that can easily blow up into ARDS (acute respiratory distress syndrome) and cytokine storm, and ends up with the patient getting killed by his own immune system. The key is to intervene before this happens.

In his picture, antiviral drugs would be most useful in the early stages — to stop the infection from spreading to the lower lungs — or even for prophylaxis. (However, I’d point out that, especially with remdesivir, there have been “saves” of severely ill patients.) In later stages of the disease, immunosuppressants actually would be more valuable, to rein in the immune system running amok.

The people who say “it’s just a flu” are actually right in 90+% of symptomatic cases. In the remainder it’s almost like what my brother would call the “autoimmune disease from Hell”.

Two other nuggets from the video:

(2) John Campbell keeps coming back to vitamin D and its vital role in the immune system. He points out that, while only 14% of Britons are nonwhite, they constitute nearly one-third of critical COVID19 cases. Socio-economic and cultural factors (e.g., multigenerational families under one roof, like is common in Italy) aside, vitamin D deficiency is much more common at northern latitudes if you have a dark skin type. (Anecdotally, I know that a family acquaintance of Yemenite-Jewish heritage [and hence with very dark skin] who moved to Sweden suffered all sorts of health problems, until UV lamps and vitamin D supplements entered the picture.[*] ) This aspect of the problem is very easy to solve…

Dr. Campbell is a bit dismissive of the estrogen-IL6 hypothesis “since why would there then be a gender difference at post-menopausal age?” Instead, he points out that many immunity-related genes are on the X chromosome, and if you have one defective copy and you’re male, that’s your only copy, while a female would have the 2nd X chromosome… (This is aside from the risk factor of smoking — in countries like China much more prevalent in men than in women.)

In another video (h/t Mrs. Arbel), he backtracks on earlier comments about Greece, and notes they have been more proactive than he thought (canceling school 9 days before the UK, in fact) and are now seeing the fruits thereof, as cases have dwindled. A similar decrease in deaths will lag by several weeks.

(3) Chemical and Engineering News, the house organ of the American Chemical Society, looks at the challenges for Gilead Sciences in scaling up production of remdesivir to the millions of doses range. In the earlier case of Tamiflu, Hoffmann-LaRoche licensed manufacturing from Gilead Sciences — and was able to provide 200 million courses’ worth of Tamiflu in comparatively short order.

(4) Via Instapundit: is there a correlation between universal BCG (Calmette-Guérin) tuberculosis vaccination policy and reduced COVID19 mortality?

(See also https://www.medrxiv.org/content/10.1101/2020.03.24.20042937v1)

I found this database of global BCG policies www.bcgatlas.org (documented here). Let me show a map:

A (ochre) refers to countries with mandatory BCG vaccination, B (purple) to countries who had it as mandatory in the past, and C (orange-red) to countries where it was never mandatory. The blatant difference in mortality between (culturally and ethnically very similar) Portugal and Spain has been ascribed to me by a Portuguese US immigrant to the existence of a parallel private medical system “that actually functions”, unlike the government-only option in Spain; but I wonder whether BCG couldn’t play a role. (TB used to be endemic in Portugal.) Belgium vs. Germany (again, ethnically and culturally quite similar) is another case. However, what about France then?

Israel used to have mandatory BCG until 1982—which implies the older generation (the most at-risk) would see some benefits. (As vaccines go, BCG is a pretty blunt instrument that “trains” the first responders of the immune system, which are not terribly selective.) And indeed, in combination with our young-ish population pyramid and our warm climate (today the mercury hit 90°F), this may go some way towards explaining the comparatively low mortality in Israel.

(5) The NYT has (in part with political ulterior motives) been cheerleading extended lockdowns, so I was surprised to see this article there on the collateral damage of shutting down all “non-emergency” activity at hospitals while bracing for a COVID19 flood. (Archived copy here.)

[…] Early on, as the epidemic loomed, many hospitals took the common-sense step of halting elective surgery. Knee replacements, face lifts and most hernias could wait. So could checkups and routine mammograms.

But some conditions fall into a gray zone of medical risk. While they may not be emergencies, many of these illnesses could become life threatening, or if not quickly treated, leave the patient with permanent disability. Doctors and patients alike are confronted with a worrisome future: How long is too long to postpone medical care or treatment?

Delaying treatment is especially disturbing for people with cancer, in no small part because it seems to contradict years of public health messages urging everyone to find the disease early and treat it as soon as possible. Doctors say they are trying to provide only the most urgently needed cancer care in clinics or hospitals, not just to conserve resources but also to protect cancer patients, who have high odds of becoming severely ill if they contract the coronavirus.

Nearly one in four cancer patients reported delays in their care because of the pandemic, including access to in-person appointments, imaging, surgery and other services, according to a recent survey by the American Cancer Society’s Cancer Action Network.

Tzvia Bader, who leads the company TrialJectory, which helps cancer patients find clinical trials, said frightened patients had been calling to ask her advice about postponements in their treatment.

One woman had undergone surgery for melanoma that had spread to her liver, and was due to begin immunotherapy, but was told it would be delayed for an unknown length of time.

“She says, ‘What’s going to happen to me?’” Ms. Bader said. “This is not improving her chances.”

And some clinical trials, where cancer patients can receive innovative therapies, have been suspended.

“The mortality of cancer has been declining over the last few years, and I’m so terrified we are going backwards,” Ms. Bader said.






[*] As for me, I can’t be outside for more than 30 minutes or so on an Israeli summer day without nasty sunburn 😉 There is a reason the term “redneck” exists in the American South, as does “rooinek” in Afrikaans…