Wednesday, July 21, 2021

Sitting In Limbo

 

Features Sitting In Limbo



Treatment news

Natural immunity: A rare bright spot in the gloomy recent COVID-19 news. Laboratory research in France examining neutralizing antibodies against the Wuhan original and the Alpha variant suggests survivors stay immune for a solid 12 months. And one-year followup of Italians infected early in the pandemic says immunity is long-lasting in the real world as well as in the lab: of 1,579 people with positive SARS-CoV-2 swabs last spring – a third of them asymptomatic – only 5 were reinfected over the course of the following year. Control had 15 times more infections. Both studies were pre-Delta, though, making them less relevant nowadays.

Azithromycin: A recently published UK trial says this antibiotic does nothing to help COVID-19 outpatients. I’m puzzled that anybody bothered to study it.

Heparin: In a Canadian study among 465 moderately ill hospitalized patients, anticoagulation reduced the risk of reaching a composite primary endpoint from 21.9% to 16.2% and the risk of death from 7.6% to 1.8%, but neither effect reached statistical significance. I doubt anyone will stop anticoagulating hospitalized patients on the basis of these results.

Ivermectin: In my last post I blasted a recent so-called meta-analysis, and the papers it was based on, as junk. Now one of its chief sources has been retracted for data fabrication and ethical concerns. The meta-analysis itself was retracted, then unretracted – Open Forum Infectious Diseases has now officially published it after 6 months of hemming and hawing.

Remdesivir: A study in Norway found that neither remdesivir or hydroxychloroquine did any good for patients hospitalized with COVID-19: no effect on symptoms, no effect on viral load. For hydroxychloroquine that’s no surprise, but the dismal remdesivir results suggest the World Health Organization’s thumbs down and the German agnosticism may be smarter than the American and European thumbs up.

Lilly’s monoclonals: It’s been a roller-coaster. Last September good: hospitalizations fell by 72% if high-risk outpatients received bamlanivimab, leading rapidly to authorization for emergency use. April 2021 bad – bamlanivimab had lost its punch against the Alpha variant – then good again when a bamlanivimab-etesevimab combo stepped in. In June bad – the FDA withdrew emergency authorization altogether, over low efficacy against Beta and Gamma. Now good…? The main Phase 3 study has finally been published, reporting the combination decreases hospitalizations by 70% when given early to high-risk outpatients. The study was unfortunately performed long before Delta rode into town – yet another COVID-19 study published too late to be really useful. Laboratory studies, at least, suggest that etesevimab (though not bamlanivimab) may be effective in Delta-infected patients.

Sotrovimab: This new monoclonal antibody, made by GlazoSmithKline-Vir and authorized in the US and Europe just a couple of months ago, is coming up roses. It’s active against Beta, Gamma, and Delta, and may soon be available as a convenient intramuscular injection.

Germany’s bottom line: The German health authorities have brought out updated guidelines for hospitalized COVID-19 patients. Dexamethasone and anticoagulants unequivocally yes. Tocilizumab maybe, in highly selected patients. Monoclonal antibodies maybe, in early disease. Remdesivir no recommendation for or against; baricitinib insufficient evidence; azithromycin, ivermectin, and vitamin D no. This jibes with my own reading of the data and confirms that nothing new and exciting has come along.

 

Vaccine news



Reithera: This made-in-Italy vaccine dropped out of sight months ago when it had so-so Phase 1 results (details in this blog post) and couldn’t get Phase 3 trials funded. Now it’s trying to make a comeback, claiming better results. (Consider running Enrico Bucci’s excellent commentary through Google Translate.) To be honest, I don't think the world needs another adenovirus vector vaccine. We've had enough trouble with AstraZeneca and Johnson & Johnson, between modest efficacy and rare but serious side effects. Countries who can afford Pfizer and Moderna should stick with them, hopefully retooled to cover variants.

AstraZeneca: Italy is rightly having a hard time convincing people 60-79, the only eligible age group at the moment, to take the Oxford vaccine. The Lazio region announced it won't order any new supplies. The government then raised them one, putting both adenovirus vaccines on hold for a month. Another mess: the AstraZeneca original, Vaxzevria, is approved in the EU but the Indian knockoff, Covishield, the chief source for the Covax initiative, is not. Which means many people from poorer countries are being blocked from entering the EU or obtaining the coveted Green Pass

Clotting problems: AstraZeneca and Johnson & Johnson think they might be able to come up with a fix. I frankly doubt they’ll succeed – and given the rarity of this dread complication I don’t see how they could possibly tell whether the retrofit worked without giving millions more shots. Probably only developing countries desperate for doses will let their people be guinea pigs.

Johnson & Johnson: A study of antibody titers and cellular immune responses in a handful of Phase 3 trial volunteers 8 months after vaccination revealed that immunity had hardly faded at all. But, as usual, that’s immunity against early strains only.

Mix-n-match: Findings of heightened antibody responses, including against the vaccine-resistent Beta variant, when Pfizer or Moderna are given on top of AstraZeneca, have now been published. The top World Health Organization scientist has nonetheless taken a strong stand against this approach, calling it a “dangerous trend.” Given that neither France nor Germany, where they’ve been mixing and matching for months, have experienced explosions of breakthrough cases, I can’t agree.

Mind the gap: Canada’s 16-week gap between vaccine doses, the longest in the world, was promulgated on March 3rd. Three months later most provinces cut that in half, and just 2 weeks ago several started giving their second doses after only 4 weeks. Canada luckily ducked the Delta variant during the months when most vaccinees had only a single dose (one is useless against Delta).

Pfizer: Pregnant women were excluded from clinical trials, but a case-control study among 15,060 pregnant Israelis now allows us to estimate real-world effectiveness at 78% in preventing clinical COVID-19 during pregnancy – perhaps only 45% at preventing hospitalization (too few cases to be sure). Vaccinated and unvaccinated women had identical pregnancy outcomes, from preeclampsia to birth weight. …Also, the Phase 3 trial showing strong immune stimulation and 100% efficacy among adolescents has now been published.

Belfast, Northern Ireland


New frontiers in vaccine hesitancy: Hostility toward COVID-19 vaccination is so intense in some mainly Republican parts of the United States that people don’t dare do it for fear of being ostracized by friends and relations. In Howell County, Missouri, where 81.4% voted Trump vs. 17.3% Biden, only 23% of people have had even one dose and cases are soaring. One local clinic made an astonishing offer, immediately shared on the Health Department’s Facebook page: “Choosing to get vaccinated has been put in a strange light. For some getting a vaccine may mean losing friendships . . . if you are afraid of walking into a public area where you might be seen getting your vaccine, we will work to accommodate even more of a private setting for you to receive your vaccine.” Meanwhile, on the bribe front, we have Canada offering kids ice cream, and lotteries that promise guns in West Virginia, herrings in Holland, cows in Thailand, and gold bars in Hong Kong. Different strokes for different folks. 

On the bright side, even Steve Scalise (influential Republican congressman) and Sean Hannity (influential Fox News personality) have abandoned their anti-vaccine stances and are urging their followers to get the jab.

 

The state of the virus

US cases county by county last week


Every state in the USA is now seeing an upswing in cases, with hospitals and ICUs starting to fill up in ArkansasMississippi, and Alabama, joining already hard-hit Missouri.

Everybody’s concerned about breakthrough cases of SARS-CoV-2 infections in vaccinated people. Should they be? Not very, I think, at least not so far. In California, 10,430 breakthrough cases were identified between January 1 and July 7 among 20.4 million fully vaccinated individuals. A total of 1,472,970 cases were diagnosed in that half-year, so only 0.7% were in people who had been fully vaccinated. Put another way, as of July 12th only 5,492 of 159 million fully vaccinated Americans had needed to be hospitalized for COVID-19. 

Still more COVID-19 infections among the Yankees. But don’t let that shake our faith in vaccines: some of the cases were unvaccinated, we don’t know whether the vaccinated ones had any symptoms, and all the vaccinated Yanks had the less effective Johnson & Johnson product.

With COVID-19 hospitalizations surging among the unvaccinated, Los Angeles has had to reinstate the indoor mask mandate that had been dropped only weeks earlier. In San Francisco and many other counties it’s merely a recommendation, not a mandate, at least for now. 

Indonesia has now become the pandemic’s global epicenter, with more daily cases than Brazil or India, as the Delta variant sweeps across Java and Bali toward points east. Local experts believe the real number of daily cases is 5 or 6 times the official 60,000. Hospitals are overwhelmed, lacking beds, oxygen, and staffing. Only 15% of the population has received any vaccine, usually the relatively ineffective Sinovac (dozens of fully vaccinated doctors have died).

 

Delta blues



People infected with the Delta variant seem to have a viral load 1000 times higher than those with the original Wuhan strain, helping to explain why it’s so contagious. But there’s mounting evidence that the effectiveness of mRNA vaccines in preventing it is closer to the 88-89% observed in Canada and the UK than to the 64% hinted at by Israel (see my last post). In Rome’s Lazio region, fewer than 10% of Delta cases had been fully vaccinated. In California, as I just pointed out, virtually all cases are among the unvaccinated. And in Israel itself they are backtracking on lifting pandemic mitigation measures, saying “We may have lifted some of the restrictions much too early” – suggesting that they think the apparent decrease in vaccine effectiveness may be related to over-hasty normalization.

We already knew Delta might be more virulent as well as more contagious; now it seems the vaccine-resistant Beta variant may be as well.

A French group has done careful evaluation of neutralizing antibodies against various SARS-CoV-2 variants. People who had had COVID-19 a year earlier still had plenty against Alpha, but few against Beta or Delta. Blood samples from people fully vaccinated with either Pfizer or AstraZeneca were similarly worse at knocking out those two variants; we already knew a single dose was useless. Another laboratory study found both Pfizer and Moderna to score high against Delta, Delta plus, and Lambda, while Johnson & Johnson flunked out against all 3 variants. A third group claims the opposite – we’ll see what happens in the real world… Fortunately some monoclonal antibody products are still effective against Delta: etesivimab (part of the Lilly cocktail), GlazoSmithKline-Vir’s sotrovimab, and both casirivimab and imdevimab (the two elements of Regeneron’s REGEN-COV).

On beyond Delta we now have Kappa (similarly born in India) and Lambda (which first showed up in Peru). Neither of them seems particularly contagious, vicious, or resistant to vaccines and therapies, though, so the World Health Organization is still calling them Variants of Interest rather than Variants of Concern.

 

Green Pass skulduggery

Phony Green Pass


The EU Digital COVID Certificate (“European Green Pass”) is a reality – I’ve proudly carried mine in wallet and cellphone for 3 weeks. They’re needed to travel within Europe, to go to a soccer game in Italy – and, in France, to enter a restaurant, café, intercity train, hospital, or movie theater. The day after this last stroke of brilliance was announced, 1.3 million vaccine-shy citoyens and citoyennes signed up for the shot. Italy is about to follow suit for nightclubs, restaurants, and concerts. Supposedly in September you’ll need a Green Pass even to get on a Rome bus – how the hell do they think they can enforce that?

What happens when you require a Green Pass to eat indoors...


There are 3 ways to qualify for a Green Pass: get vaccinated (good for 9 months), get COVID-19 (good for 6 months), or have a negative swab (good for 3 days). But, as the Italians say, “fatta la legge, trovato l’inganno,” as soon as they pass a law someone will find a way around it. For a mere $150 in cryptocurrency you can get a fake Green Pass whose QR code will pass muster at the airport. And it’s not only those anarchic Italians, the dutiful Germans are at it too. The Italian police are busily shutting down the “dark web” sites that deal in conterfeit passes, threatening buyers and sellers alike with 6 years in prison. Knowing how widespread the phenomenon is in the US, I was surprised to read a few days ago that a homeopathic “doctor” was the very first American charged with distributing false vaccination cards.

But the heartland of bogus vaccination certificates is Russia, where the irresistible force of vaccine mandates – for everyone from teachers to barflies to women needing Pap smears – is about to slam up against the immovable object of baked-in vaccine refusal. One month ago there were 500 domain names selling fake vaccination certificates… a mere 18.5% of Russians have had even one dose.

 

Scandal variations 

Yangon, Myanmar, hoping to refill oxygen cannisters


An outbreak at the US Embassy in Kabul supposedly reached 159 people, causing deaths and medical evacuations, even though the embassy had received its vaccine supply two months earlier. How many people are there at that embassy, anyway? 

There’s a raging surge in Myanmar, fueled by its common border with India – the Delta variant’s home town – and a stumbling vaccination campaign. The military leaders who seized power in February have been doing what they can to make things worse: denying oxygen to private clinics and charities while stockpiling it in army hospitals, firing live ammunition into crowds lined up to buy oxygen, vaccinating soldiers before the elderly.

Until now Australia has done a great job in keeping the spread of the virus down, by tracing contacts and by sealing its borders at the drop of a hat. At this moment some 34,000 citizens are trapped abroad by closed borders. But its vaccination campaign still hasn’t taken off. Between supply shortages, no-vaxxism, and old-fashioned inefficiency, only 6% of its population was fully vaccinated as of July 2nd (compare 32% in Italy, 47% in the US…). I start to suspect an ideological component to the failure, that deep down the Australian authorities believed they had the pandemic so well under control that they didn’t need vaccinations. 

Brazilian President Jair Bolsenaro is accused of making irregular deals to acquire tens of millions of doses of India’s unproven Covaxin vaccine. As Brazil’s Supreme Court authorizes a criminal investigation into his conduct, some think the scandal will bring down his government (here’s hoping!). Brazilians have an astonishingly original array of nutty beliefs about COVID-19: they’re still enthusiastic about hydroxychloroquine, especially inhaled. Some think face masks cause cancer, people are being buried alive to inflate COVID-19 statistics, and vaccination breeds homosexuality. And here I thought the kings of conspiracy theory lived in North America.

Thousands of unwitting Indians went for COVID-19 vaccinations, paid, and received shots of salt water instead. Fourteen doctors have been arrested. 

 

Hauling COVID-19 along





study from Norway found that 52% of adults under age 30, especially women, were still suffering symptoms 6 months after mild COVID-19. Thirty percent were still fatigued, 26% sleepy, 13% short of breath; 23% had trouble finding words and 18% had memory problems. Older patients were even worse off, but all these figures far outpace the 10% rate generally cited.

An international survey of nearly 4,000 COVID-19 survivors, mostly under age 60 and almost none hospitalized, was even more troubling. Six months after falling ill 77.7% complained of fatigue, 72.2% of exercise intolerance, and 55.4% said they couldn’t think straight. Most had not returned to a full work schedule, and 22.4% were still off work. A separate sober assessment of the cognitive aspects of long COVID concludes that physicians have little to offer.

A 12-year-old with long COVID


Fortunately this often devastating syndrome, which can occasionally strike children as well as adults, is starting to be recognized as a “public health disaster in the making.” Hopefully the billion dollars being funneled into long COVID research by the National Institutes of Health, along with smaller investments in the UKSwedenGermany, and elsewhere, will eventually yield results.

But there’s also encouraging news: long COVID is virtually unheard of after breakthrough infections in the fully vaccinated. Get your shots, people!

 

Limbo


On the one hand we have mass pandemic burnout, the coronavirus conflagration reducing dreams to ashes…

Doctors and nurses are leaving the medical field in droves. In July 2020 12% of American doctors had either already closed their practices or planned to do so by the end of the year, and 72% said their income had dropped. Primary care providers are particularly likely to be fleeing. And 25% of all United States physicians said they were contemplating early retirement, while another 12% hoped to at least stop seeing patients. Even worse in the UK, where 32% of National Health Service doctors are would-be pensioners.

Doctors are unlikely to starve if they retire early. Unfortunately the same can’t be said for millions of others, notably teachersairline employees, and people of color in general. Most of the working-class Americans who retired in 2020 did so involuntarily.

Then there’s dancers and actors, more than half of whom were unemployed in July-September 2020. Gigging musicians were wiped out financially, and even a steady job was little protection – New York Philharmonic players accepted a 25% paycut for two years, and may never get back to their prepandemic salaries. I’ve read articles claiming the pandemic has boosted creativity, that people work better together on Zoom than in person, etc. For managerial types that could be, but for the performing world it’s blather. 

Igor Levit playing one of his daily lockdown concerts


Artists have scrambled to find ways to cope and survive, creatively and financially, with some success. But for one Igor Levit, who broadcast extraordinary piano concerts from his Berlin living room, dozens more feel their worlds have been thrown into disarray, their senses deranged, “past their prime.” In one British study half the composers and writers found themselves unable to do creative work during lockdowns, with a third of arts workers spending no time at all practicing or reflecting; 15% felt a lack of motivation or focus (“everything seems pointless and I feel forgotten,” “hard to feel motivated to do anything”);  many artists in Australia felt “sure the recovery couldn’t heal them,” or “parts of their lives would be damaged forever.” One survey of nearly 3000 musicians found that 35% (!) had sought professional counseling during the pandemic – but most found they couldn’t afford it. 


There’s a flip side, though, people who found the pandemic the perfect moment to trash their careers or transform their lives for the better. Radio host Brian Lehrer invited job quitters to call in when he faced an unexpectedly empty quarter of an hour. Callers included a teacher who’s turning himself into a real estate agent. A non-profit’s CEO going back to school to become a social worker. A working stiff who went over to online trading, and struck gold. A home health aide and assistant librarian who’s become a fulltime actor. And just this week, the Washington Post published a remarkable series of interviews with people who during the pandemic had started an art studio, founded a consulting firm, moved to Paris, built a house with their own hands, run successfully their school board, or gotten gender-affirming top surgery. Even the economic recovery is peppered with cheerful “I quits.” Call it the YOLO principle, You Only Live Once.

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