Beat That Bug!

 

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Lots of encouraging treatment news, for once. Then onward to vaccines, of course, with a variant detour and a Godly coda.

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• Nip it in the bud

The Gout (James Gillray, 1799)

Colchicine: Used to treat gout since the time of the Pharaohs, this drug is claimed to reduce “hospitalizations by 25%, the need for mechanical ventilation by 50%, and deaths by 44%” in high-risk COVID-19 outpatients, as compared with placebo. A preprint of the manuscript reveals that the results are only just barely statistically significant, but it’s big news nonetheless – colchicine is the very first oral medication to show any benefit. My skeptometer reading is for once relatively low, because by now we’re used to finding novel targets for this ancient drug, from pericarditis to canker sores. And after 3500 years there will be no surprise side effects. I’ll prescribe colchicine for my next patient with COVID-19.

Oral or injected corticosteroids – beware: Since a patient told me the other day that friends with COVID-19 get stuffed with steroids by their Italian physicians, I thought I’d reiterate wht a bad idea this is. Dexamethasone and other steroids can be life-saving for patients on respirators, but when given early in the disease these drugs actually increasethe risk of both hospitalization and death.

Inhaled corticosteroids: Steroid asthma inhalers are another story altogether. Patients who start them early are less likely to go downhill and get well faster. according to the preprint of a new study. Ten out of 69 patients given a placebo inhaler eventually needed urgent care, as versus 1 out of 71 who received inhaled budesonide. Inhaled budesonide and similar steroids stay in the airways without being absorbed into the body, so they can’t have the negative effects I just described. My next COVID-19 patients will get this one too.

Bamlanivimab plus etesevimab (Lilly): This combination of monoclonal antibodies has scored a major triumph: a single intravenous infusion given early to high-risk outpatients, already known to decrease viral load, has now been shown to reduce the rate of hospitalization by a rip-roaring 70% compared to placebo. All 10 deaths were in the placebo group. The US Food and Drug Administration promptly approved it for emergency use; Germany has started using American antibody preparations without waiting for European Union authorization. Intravenous administration is still awkward and labor-intensive, though. If only there were a more convenient way of getting monoclonal antibodies into patients…

REGEN-COV (Regeneron): …but maybe there is. The Regeneron antibody cocktail has gotten a new boost from a Phase 3 trial as a preventative for household contacts of COVID-19 patients. Nobody who received the drug became ill, versus 8 in the placebo group. Even more exciting, the drug was given as a simple subcutaneous injection, which makes antibody treatment of outpatients feasible for the first time. If it were available in Italy, I’d give my next COVID-19 patient this one too.

Dimeric lipopeptide: Well glory be. Just when I had given up on these nose drops after November’s preprint, here they come again as a real publication. Unfortunately it’s still the same old data, those same old 6 ferrets… in the intervening 3 months somebody could have started human studies.

Convalescent plasma: The nice Argentine trial I mentioned a couple of months ago has now been properly publishedtoo. Antibody-loaded plasma given very early to elderly patients cut the risk of severe disease in half. This low-tech, inexpensive solution should get widely used in the developing world.

“COVID kits”: In Italy, outpatients are regularly prescribed azithromycin, corticosteroids, and vitamin D. Brazilian docs add ivermectin, hydroxychloroquine, and an anticoagulant …plus or minus a local special: rectally infused ozone, a venerable quack treatment described by the American Food and Drug Administration as “a toxic gas with no known useful medical application.” There’s no good evidence any of this stuff helps, though the NIH has softened upsome on ivermectin, shifting from a “recommend against” stance to “insufficient data to recommend either for or against.”

 

• "Zap it on the wards

Early COVID-19 pneumonia

Solidarity trial: The final results of the World Health Organization megatrial – 11,000 hospitalized patients, 30 countries – have now been published. But we already knew the main findings: hydroxychloroquine, lopinavir, and interferon beta-1a were useless, while remdesivir merely shortened hospitalization by a few days. It’s too bad remdesivir was started relatively late in illness; given earlier it might have worked better. 

Heparin: According to a press release, anticoagulating hospitalized COVID-19 patients improves outcomes. No news – they’ve been hospital routine for months.

Anakinra (Kineret): This cytokine blocker is the latest arthritis drug being repurposed against COVID-19. A poorly-done Italian study claimed it was life-saving.  In a better randomized trial among hospitalized French patients with moderate COVID-19 pneumonia, it did no good at all. The drug might conceivably be useful for sicker patients.

Vitamin D: An excellent Brazilian study has looked at vitamin D in hospitalized patients: it tanked. As I’ve explained in the past, we see low vitamin D levels in people who are frail and generally unhealthy, so they are correlated with all kinds of serious diseases including COVID-19. But correlation does not mean causation, and supplementation with this evergreen panacea fails over and over again in treating anything except flimsy bones. That Brazilian study came out just in the nick of time to ward off a  "crank article:

Mr. Cook bases his article on a preprint so transparently invalid that it was withdrawn within 48 hours. If you click on the link in his article what you find is:

Rescue missions

Advanced COVID-19 pneumonia (same patient as above)