Pills, Pivots, and Pronouns

 

COVID beds in a Chinese hospital lobby

New oral COVID-19 meds, mask wars, Floridian science, social media screwing up, countries collide, medium COVID, and a fab new conspiracy theory.

 

Treatment

Molnupiravir: A PANORAMIC study manuscript I’ve discussed in preprint form has now been published, reiterating both that the drug does nothing to prevent hospitalization or death, and that it shortens the duration of symptoms from 15 days to 10. The symptom results are suspicious because of the combination of self-reported symptoms and an open-label study design: people randomized to molnupiravir knew they were taking it, and people who were randomized to usual care knew they were in a drug study and weren’t getting the drug. A virology substudy is reported in more detail than in the preprint, with viral loads significantly lower in the molnupiravir group at 5 and 7 days, but significantly higher at 14 days. Make of that what you will.

Zinc: In September CDC recommended against using zinc to treat COVID-19, based on two negative trials. A new randomized, controlled Tunisian study is more promising, though to be taken with a grain of salt. At 30 days, 10.4% of zinc recipients and 16.7% of placebo recipients were dead or or in the ICU. Seems a bit too good to be true, and the placebo group included more diabetics and fewer received anticoagulants, creating bias. But I guess zinc is at least unlikely to cause serious harm.

Paxlovid in China: Until recently Paxlovid was available in China only for VIPs who obtained it through back channels, but now Pfizer has authorized Zhejiang Huahai to produce it in and for mainland China. The drug could already be accessed through selected hospitals, and should now be widely available. In one ill-advised early distribution effort the drug was offered online to anyone with a positive COVID-19 test – it sold out in 30 minutes.

Paxlovid in the West: It’s still enormously underused even though well over 90% of recent COVID-19 deaths, at least in the US, occur among people over 50, in whom Paxlovid has been shown to prevent deterioration.

Azvudine: This anti-HIV drug has now been authorized in China based on a report that it hastened symptom resolution in 10 (ten!) COVID-19 patients, and on a larger supposed study that I haven’t been able to track down. Another trial is still enrolling patients. The efficacy claim has been disputed, and there are no data regarding disease progression. China’s huge current surge in COVID-19 may reveal rapidly how this drug works in the real world.

VV116: Chinese researchers have also developed a second anti-COVID-19 pill, a derivative of the intravenous antiviral remdesivir. In a noninferiority study performed during the Omicron era it prevented disease progression just as effectively as Paxlovid, with none of the nearly 400 high-risk outpatients in either group becoming severely ill within 28 days. VV116 also seemed to provide some symptom relief, though that finding is flawed by an odd single-blind design: patients but not researchers knew which drug they were taking. Paxlovid gave somewhat more side effects overall, perhaps in part because some patients were taking incompatible medications. But VV116 only rarely gave the taste disturbances so common with Paxlovid, and caused less insomnia; muscle pain was rare in both groups. Strangely, the same Chinese authorities who approved azvudine have not yet authorized VV116, despite stronger evidence in its favor.

Upamostat: It’s a big month for oral antivirals. A randomized, placebo-controlled pilot study on upamostat, a protease inhibitor like Paxlovid, found patients on active drug to get well faster and go downhill less often. The study predated Omicron, however, so the larger trial the authors promise will be particularly crucial.

Omicron subvariants: In a laboratory study, Japanese researchers found that molnupiravir may work against BQ1.1 but not XBB, with remdesivir and current monoclonal antibodies good against neither. Paxlovid should work against both newcomers, though. That’s a relief. 

Long COVID: Researchers from Yale have reported that out of 12 long COVID patients with cognitive problems given a combination of one new drug, guanfacine, and one old one, N-acetylcysteine, 8 improved. Two of the 8 had to stop because of dizziness. Fatigue and confusion are described as other common guanfacine side effects, with chest pain and shortness of breath only somewhat less common. I wouldn’t prescribe this cocktail to anyone for brain fog on the basis of this anecdotal evidence, especially not when it may well worsen other long COVID symptoms.

Long COVID again: British researchers have performed a double-blind, placebo-controlled trial finding more improvement in fatigue and general well-being among long COVID patients who took an herbal concoction plus a probiotic than among patients who took the probiotic alone, without significant side effects. Only 112 patients had had symptoms for longer than 30 days, and I’m not fully convinced, but what the hell – these herbs look pretty harmless, and I’ve already written two prescriptions. Thanks to Mayah Kadish for the tip.

 

Prevention

A death from COVID-19

Mask don’t mask: With US hospitalizations for respiratory infections soaring, the CDC is again suggesting people wear masks, effective against all 3 viruses, in public indoor spaces. Los Angeles and Sacramento may soon reinstitute a mandate. New York City health authorities are strongly urging New Yorkers to wear high-quality masks in indoor public spaces and crowded outdoor settings, but have stopped short of a mandate except in healthcare facilities. I think Italy should have reinstituted a mask mandate months ago, but at least now the existing mandate in medical facilities and nursing homes, which was set to expire at the end of 2022, has been extended through April; more generalized mask mandates may be revived if cases and deaths continue to rise.

Mask versus mask: A randomized trial in 4 countries found fairly similar rates of COVID-19 among healthcare workers treating COVID-19 patients whether they used surgical masks or N95/KN95 masks at work. Does this mean both kinds of masks are just as good. Nope!!! The catch, as Leana Wen points out in the Washington Post, is that most of those healthcare workers were enrolled when rates of Omicron were very high in their communities. If both mask groups were highly exposed to the virus when they were off work, their rates of infection would be expected to be similar whatever masks they wore on the job. In Canada, the one country where community rates were low in the study period, infections were 3 times higher for surgical masks.

Flu shots: This year’s influenza vaccine, unlike last year’s, is a good match for the viral strains that are circulating. Get yours!

Zombies: According to one preprinted manuscript cited in the New York Times, the SARS-CoV-2 virus can stay alive in dead bodies for as long as 13 days. That phenomenon is unlikely to cause many COVID-19 cases but families, medical examiners, and funeral parlors should be aware.

 

Vaccines 

Floridian science: Ron DeSantis and his sidekick Joseph Ladapo have officially declared war on mRNA COVID-19 vaccines, launching a so-called study of vaccine side effects, especially myocarditis, and even calling for a grand jury to investigate “the development, promotion, and distribution of vaccines purported to prevent COVID-19 infection, symptoms, and transmission.” “Purported”? It is easy to calculate, between earlier estimates and recent figures, that 350,000 Americans have died unnecessarily by remaining unvaccinated, with perhaps as many as 3 million lives saved by vaccines in the US alone.

Real science: But the way to refute disinformation from the right is not with misinformation from the left. On the December 14^th Alex Wagner show Dr. Vin Gupta rightly criticized DeSantis for politicizing vaccines. But when he said post-vaccine myocarditis is both extremely rare and always mild he was unfortunately wrong. Among male vaccinees between about 15 and 25 the incidence after a second dose of an mRNA vaccine, especially Moderna’s, may be as high as one in 5,000 or even 2,500. For this reason many countries are giving them only one dose or postponing the second one. Most myocarditis cases are mild, but some require intensive care and a handful of deaths have been reported. Careful analysis of one Israeli study, which also reported a death, suggests that teenaged boys may run more risk of being hospitalized due to vaccines than they do from COVID-19. 

Bivalents: The latest study from the CDC finds that updated vaccines decrease the risk of hospitalization for COVID-19 by 38% in people whose latest booster was 5-7 months earlier, and by 45% if it was 11+ months earlier. To be honest, these numbers seem more plausible than those of a previous CDC study, which claimed increased protection against infection of about 50% over the protection from previous boosters. I say “more plausible” partly because in all previous studies COVID-19 vaccines have done much better against severe outcomes than they do against infection. Another encouraging report says the bivalent Moderna booster will likely work against the BA.2.75 subvariant, even without including its spike protein.

Blame vaccines? An opinion piece in the Wall Street Journal asks “Are Vaccines Fueling New Covid Variants?” As far as I can tell – the article is behind a paywall but I’ve gotten more information from one that isn’t – it’s all about an article rushed into Nature in pre-final form. The complexity of its science goes a bit over my head, but Peer Reviewer 2 seems skeptical of the vaccines-fuel-variants interpretation. This study does further document the extreme resistance of recent Omicron subvariants to neutralization by existing antibodies. It also suggests prioritizing development of a pan-coronavirus vaccine, long the Holy Grail of COVID-19 vaccines; such efforts have thus far gotten nowhere.

 

The state of the pandemic

The winter surge that started in Europe has now hit the US, with hospital admissions doubling in two months despite most Americans’ relative protection from severe illness by vaccines and/or previous infections. The apparent decline in Italy is not because severe cases have fallen but because COVID-19 wards are saturated.

Wastewater surveillance in the US suggested a huge surge dipped around mid-December, but lags in reporting make the apparent improvement suspect. Italy is so far behind on this metric that its December 22^nd bulletin only reached September.

The Biden administration is finding ways to combat the pandemic despite the lack of funding from Congress, by making testing, vaccines, and treatments more readily available. In New York City, where cases have been rising for months and 6 times as many people are hospitalized as in the spring, elderly or disabled residents can now be vaccinated at home, and Walgreens will home-deliver Paxlovid free of charge.

Then there’s China, which like Italy has quietly stopped publishing daily pandemic updates. The statistics they do report are if anything even less credible than earlier in the pandemic, with only 12 (twelve!) deaths reported between December 1^st and 29^th, while funeral homes and crematoria were working overtime. Half the passengers on a recent China-to-Milan flight tested positive on arrival! As we know street demonstrations forced China to scrap its no-COVID policy. Disaster will follow if it does not start vaccinating its elderly – ideally with mRNA vaccines, but at least with Sinovac and Sinopharm. Only 60% of older Chinese have received even one booster, though those home-grown vaccines are near-useless without them. Chinese authorities have pivoted from exaggerating the dangers of COVID-19 to underrating them, for instance claiming 90% of Omicron cases are asymptomatic or nearly so. This makes it less likely they will undertake the vitally necessary vaccination campaign. China’s pandemic surge is decimating hospital staffs and bringing shortages of ventilators, oxygen tanks, and intensive care beds. Note that in China a death is counted as COVID-19-related only if it involves respiratory failure, with doctors being pressured not to report even those. Modeling studies are predicting one to two million COVID-19 deaths in China in 2023, and on the ground it’s total confusion. Here’s one joke said to be viral on Chinese social media: 

“Three men who don’t know one another sit in a prison cell. Each explains why he was arrested:
“I opposed Covid testing.”
“I supported Covid testing.”
“I conducted Covid testing.”

 

Crow for breakfast

I need to eat some crow. After I’ve said repeatedly that Palovid had been proven ineffective in people under 65, anAmerican study during the winter-spring Omicron wave may have proved me wrong. In adjusted analyses Paxlovid cut the hospitalization rate over 2 weeks by 45% among patients over 50. And, in stark contrast with that Israeli studyI’ve cited, results were if anything marginally better among patients ages 50-65 than among the elderly, a discrepancy the authors never mention. Two subgroups responded better to the drug: the few who were not fully vaccinated and the many who were obese. People of color were less than half as likely to have received Paxlovid as white patients, reflecting systemic racism in the US healthcare system.

 

Pick your model

American: The House Select Subcommittee on the Coronavirus Crisis’s final report highlighted the poor outcomes in the US during the first two years of the pandemic, rightly slamming both the inadequacies of the American healthcare nonsystem and the criminal mishandling by the Trump administration. 

British: The UK, which dropped all COVID-19 restrictions last spring, has been running somewhat lower excess mortality than Italy or the US. But it’s had rather more cases lately than the US, though fewer than Italy. Cumulative COVID-19 deaths are remarkably similar in all 3 countries. They’d surely be lower if everybody were masking in indoor public spaces and getting regular boosters. I'm a bit shocked to see that both the US and the UK seem to have stopped reporting booster administrations just when the updated shots came out.

Swedish: A retired historian called David T. Beito claims research proves that Sweden did great during the pandemic despite never shutting down: “We have new compelling evidence that Sweden's covid policy (no lockdowns, no mask mandates, no school closures) was right all along. According to a new OECD study, Sweden had the lowest rate of cumulative excess deaths for all the countries surveyed, lower than much touted New Zealand, and lower than its Scandinavian neighbors, each of which briefly locked down.” I can’t find that OECD study, but I do see 3 problems with Beito’s statement: one is that though the government never called for a formal lockdown the Swedes, no fools, largely invented one for themselves. The second is that the cumulative number of confirmed COVID-19 deaths per million as of January 4^th was 878 in Norway, 1337 in Denmark, 1432 in Finland, and 2069 in Sweden. None hold a candle to the USA (3238) or Italy (3128), and all are much worse off than New Zealand (450). The third is that excess mortality was vastly higher in Sweden than in its neighbors until a year ago, when high infection and vaccination rates began flattening out the difference. 

 

After the ball is over

A giant US Veterans Administration study shows a striking increase in new vascular disease during the year after acute COVID-19, among patients who survive the first 30 days. As compared with VA patients without COVID-19, the increased risk of stroke was 52%, atrial fibrillation 71%, myocarditis 438%, myocardial infarction 63%, heart failure 72%, cardiac arrest 145%, and pulmonary embolism 193%. All were much more common among patients sick enough to need hospitalization. An earlier VA study was severely marred by being limited to people who had sought medical assistance; I can’t figure out whether that’s true of this one as well.

Anyone on Twitter can check out an excellent compendium of articles documenting various kinds of immune dysfunction during the months after COVID-19.

A year ago I described an autopsy study that found SARS-CoV-2 virus scattered throughout the body even 7 months after death. It has now been published in Nature, with added emphasis on the presence of viral RNA in the brain in 10 of the 11 cases where it was sought. In one case the researchers actually succeeded in culturing the virus from the brain. This might help explain the cognitive aspects of long COVID.

An excellent article by Benjamin Mazer, MD, maintains (rightly, in my opinion) that the biggest reason to avoid catching COVID-19 is the “medium COVID” affecting one of every ten COVID-19 patients, with symptoms like fatigue, headache, and brain fog dragging on for 4-12 weeks. It does usually blow over eventually, with only a small percentage developing devastating forms of long COVID. But 4-12 weeks is a good chunk out of anyone’s life.

 

The sour smell of musk

I wouldn’t ordinarily offer the new owner of Twitter any publicity, but here goes: “Effective November 23, 2022, Twitter is no longer enforcing the COVID-19 misleading information policy.” Apparently 11,000 accounts had been suspended based on that policy. What’s your bet as to how many Mr. M. will bring back? Check here. He’s already reactivated the Twitter accounts of two prominent antivax physicians, while temporarily cancelling the accounts of journalists from such dubious publications as the New York Times, the Washington Post, and CNN. 

On December 11 Musk took it one step further. Dig the gratuitous transphobia and the 1.2 million “Likes”:

Other social media don’t necessarily do any better despite trying harder. TikTok claims to have removed more than 250,000 videos for COVID-19 disinformation, but researchers have found that if you search TikTok for “hydroxychloroquine” the second result claims to tell you how to cook it up in your kitchen. If you search on “covid vaccine,” TikTok thinks you probably want “covid vaccine injury” or “covid vaccine warning.” Don’t Be Evil Google at least suggests “walk-in covid vaccine” and “types of covid vaccines.”And typing “mRNA vaccine” into TikTok brings up 5 videos with false claims in the first 10 results. 

 

Triple whammy

For the first time since the pandemic began, hospitalizations for influenza in the US are matching, or even overtaking, hospitalizations for COVID-19. This is due to an early arrival of the flu season combined with a particularly virulent viral strain. If you add in respiratory syncytial virus (RSV), which mostly affects children, you have a triple threat. So should we be worrying as much about the flu as we do about COVID-19? I don’t think so. For one thing, though hospitalizations are about even, with COVID-19 you’re much more likely to wind up in the intensive care unit or dead. For another, influenza is a seasonal disease. So the rise in hospital admissions is unlikely to continue with the same vertiginous slope, and the admissions will fade away in 2 or 3 months. COVID-19, on the contrary, may just be beginning a long roll.

 

Here comes the crunch

I’ve warned about terrible consequences of the failure of Congressional Republicans to extend pandemic funding, and now they may be landing. The 30 million Americans who are still uninsured despite the Affordable Care Act will start having to pay out of pocket for COVID-19-related medical visits, tests, vaccines, and treatment. For the time being Paxlovid remains distributed gratis, but to get a prescription you need to pay for a doctor’s visit, and that free supply is set to run out. The situation is particularly dire in the 12 mostly red states that still refuse to expand Medicaid. The poor are already much more likely to die from COVID-19, not just in the US but even in the UK despite its universal National Health Service. When impoverished uninsured people start having to pay for vaccines, they’re not going to get vaccinated. And if they get sick and need Paxlovid they’re not going to get it. Let’s not even talk about what happens if they get so sick they need to be hospitalized. So the pandemic gap between rich and poor is about to get a lot worse. When the hell is the United States going to join the rest of the civilized world and make access to health care as much a human right as access to weapons of war?

 

My new favorite conspiracy theory

Love this one. A September 5^th 2022 Facebook post that accumulated 650 likes and 254 shares claims science has proven that wearing a face mask makes you more “slave like” and obedient. The idea is that masks block your breathing and tell you that “a powerful and master force must already be in play.... threatening you,” which triggers the nervous system to assume a mode of obedience and compliance. Thusly, “our world misleaders psychologically manipulate the public into the darkest era this world will ever know.”