The New Normal?

A COVID-19 patient's lung, scanned using Hierarchical Phase-Contrast Tomography

Should high schools cancel wrestling? Does Sputnik beat Pfizer? What’s the best antigen test? Is the pandemic over? Is health care a right or a privilege? My take on all that, plus mandate madness, Omicron updates, and treatment and vaccine news.

Treatment and prevention news

Band rehearsal at Wenatchee High, Washington State

Antivirals: It seemed likely that, unlike monoclonal antibodies, antiviral drugs such as remdesivir, molnupiravir, and Paxlovid would work fine against Omicron. Now we have a little supportive evidence. Reassuring, even if it’s only in the test tube, not in patients.

Immunoglobulin: After convalescent plasma and monoclonal antibodies a third type of immune therapy has now been tested in a proper trial on 579 patients hospitalized with wild-strain COVID-19: hyperimmune intravenous immunoglobulin containing a broad array of antibodies from the pooled blood of multiple recovered donors. Clever idea, too bad the treatment bombed.

Natural immunity: The CDC has nicely summarized what we know about immunity following infection versus immunity following vaccination: Americans who had COVID-19 3-6 months earlier were 5.5 times more likely to get hospitalized for COVID-19 than people who were fully vaccinated with Pfizer or Moderna 3-6 months earlier. And the superiority of vaccines was even greater during the Delta wave. One UK government study reported previous infection (timing not specified) to be as good as vaccination for preventing Delta, but not Omicron; other UK dataindicate that the protection from Omicron from having had previous COVID-19 may be as low as 19%. 

Brown’s Dr. Ashish Jha tweeted: “You all know the data demonstrating dramatically higher hospitalization rates for unvaccinated folks But one key point often not discussed? Around 60%-70% of unvaccinated adults have already been previously infected Which tells us a lot about infection-induced immunity.”

Ivermectin: Inmates of the Washington County Detention Center in Arkansas are suing the prison and its doctor for lying when they were sick with COVID-19, hiding the fact that the treatment they were getting was high-dose ivermectin.

Paxlovid: Its chief ingredient now has a name: nirmatrelvir. Israel, the first country to try introducing it widely, has encountered substantial logistical problems, but the drug is working as promised for the few patients who’ve received it – 75% improve, mostly within 24 hours. Since many of the high-risk patients who are Paxlovid’s intended target are taking incompatible medications for chronic medical problems (see this list), complicating its use.

Cancel band? The latest CDC guidelines says schools in high-transmission areas – meaning virtualy everywhere – should cancel after-school activities including band, choir, football, and wrestling… They’ve gotten a lot of flak for this, but for once I happen to agree. Kids shouldn’t be wrestling, singing collectively, or spewing viruses out their band instruments, at least not indoors, unless Wenatchee High’s band pods catch on big. About football, I’m agnostic. As with other outdoor team sports, the problem may be less what happens on the field than what happens in the locker rooms.

Return to the world? A British study using stored samples from the early phases of the pandemic has suggested that a few people with mild-moderate disease may remain infectious beyond the canonical 10 days. Their criterion for infectivity is less than sure-fire, and the study is extremely small, so I take this one with a grain of salt and continue to tell patients they can leave self-isolation after 10 days.

 

Vaccine news

The Spallanzani Infectious Disease Hospital in Rome, vials of Sputnik V

Johnson & Johnson: In a study among 461 healthcare workers who had received a single dose of the J&J vaccine, booster doses of any vaccine raised spike protein antibodies well, and neutralizing antibodies less well. Moderna did the best as usual, followed by Pfizer, with J&J itself being the worst. But since antibodies were measured only 4 weeks after the additional dose, this study cannot answer the crucial question, which is how long those antibodies – and the presumed real-life protection – will last. We already know that effectiveness fades faster for primary J&J vaccination than for either of the mRNA vaccines, so I suspect mRNA boosters will hold up longer as well. 

Omicron: After UK studies suggested triple-vaxed adults protected 76% against symptomatic Omicron, US researchers have come up with a quite similar 66%. Alas, that protection fell to about 50% by 10 weeks after the booster, though protection against hospitalization remained a decent 83%. Interestingly, in a small American study of Pfizer vaccinees, a Johnson & Johnson booster induced more and longer-lasting neutralizing antibodies to Omicron than did a third Pfizer shot. Unfortunately Moderna wasn’t tested. The value of a vaccine tailored to Omicron is still under debate.

Moderna rules: In Qatar Moderna shone once again, doing >30% better than Pfizer over a period of 6 months.

Waning efficacy: The numbers are pretty consistent. According to a British study 5 months after the second dose, Pfizer protected only 66% against symptomatic Delta, AstraZeneca by 44%, though both vaccines still worked against severe disease. Effectiveness was even lower in the elderly or chronically ill. A Qatari study found effectiveness against all Beta and Delta variant COVID-19 to fall over 7 months from 90% to just under 50%, while remaining over 90% against more severe outcomes.

Sputnik V: Is Sputnik, not Moderna, the cat’s pyjamas? According to the Russians, yes. First they said neutralizing antibodies against pre-Omicron variants persist after 4 months (true for mRNA vaccines as well). Then they claimed(by press release) that Sputnik remained 80% effective in San Marino after 7 months when Pfizer’s protection fades more (the Russians claim it falls to 23%, misreading a Swedish study. Now they’re saying that a laboratory study from Rome’s Spallanzani Hospital predicts their vaccine will be better against Omicron than Pfizer, inducing twice the number of neutralizing antibodies, and suggest Sputnik be used as a booster after mRNA vaccines. Hmmm… First, this study had serious methodological weaknesses, especially a longer time period after Pfizer vaccination than after Sputnik and lack of adjustment for age and comorbidities. Second, mixing-and-matching experience has been with mRNA boosters after viral vector vaccines, not vice-versa. Third, I continue to harbor doubts about Sputnik’s original efficacy study, whose authors still refuse to provide raw data. Finally, there are sticky quality control issues in Gamaleya’s factories – the WHO is dispatching yet another team to check them out.

Adolescents: A case-control study using the Pfizer vaccine shows it reduced hospitalizations by 94% and ICU admissions by 98% in 12-18-year-olds.

Kids: Pfizer has had a setback in its trial of an ultra-low-dose vaccine (3 µg) for kids under 5: so many toddlers failed to develop a proper antibody response after 2 doses that they are going to try an extra dose. Pfizer somehow thinks it can get Emergency Use Authorization even before the preliminary 3-dose results arrive in March. Moderna is not expecting to see any results from its own kiddie trial until March.

Boosteritis: The Israeli decision to go forward with a 4^th dose without testing it first seems to have been an error – preliminary results say that neither Pfizer nor Moderna gave any additional protection to at-risk healthcare workers. Probably the 500,000 4^th doses that have already gone to elderly Israelis would have better been donated to COVAX. Giving dose after dose of the same mRNA vaccine just doesn’t seem to do the trick.

Incidentally, the World Health Organization seems, at a press conference, to have dropped its ethical objections to vaccine booster campaigns, saying there now are enough doses to cover vulnerable populations in poor countries. Should we read anything into the fact that Tedros Adhahom Ghebreyesus, Mike Ryan, and Soumya Swaminathan, its most prominent officials, were all absent from that particular press conference?

Next generation: Pfizer and BioNTech have begun Phase 1-2 trials of a vaccine aimed at the Omicron variant, with Moderna not far behind. And the same NIAID group that made a plea for universal vaccines last month has already published another one. Once again they set out in detail what they want out of such a vaccine, and once again they say little about how to achieve it.

 

Testing news

Fresh Air Clip

Wearables: Researchers at Yale have come up with a miniature virus detector they call the Fresh Air Clip. It’s not a DYI test, but more like the little gadgets radiologists wear to monitor their radiation exposure over time. You clip it to your clothing, leave it on for several days to accumulate viral particles, then send it to a lab for PCR testing. If SARS-CoV-2 is detected, implying there’s virus in the air you breathe, the protective measures in your environment – a restaurant, say – need to be tightened. The results are even semi-quantitative, not just yes-or-no. It hasn’t hit the market yet, but I’d put this in the category of Very Very Cool.

Thumbs down: The chief message of my last regular post was how poorly rapid tests detect Omicron. The very next morning the full-page headline in the Rome section of Il Messaggero was: “School, false negatives peak,” with subhead “Swabs flop, 20% of children who returned to class Monday learned later they were positive.” Meanwhile, in the US, a study at a professional testing center in San Francisco, which reported that the Abbott BinaxNOW antigen test missed more than a third of PCR-positive infections, is being spun as “A popular at-home test detects most infectious Omicron cases.” 

Rapid tests vary: A study by Swiss researchers found huge variability among 7 antigen tests with current or pending WHO approval. In 4 cases the sensitivity was much lower for Omicron than for Delta, and 2 out of the 3 that detected Omicron less than 40% of the time were made by Western pharma giants Abbott and Roche. The best test, made-in-USA Flowflex, detects Omicron as well as it does Delta, and gives only 11% false negatives. I’ve bought a few myself. 

Caveat emptor: The home test kits being sent out free of charge to American consumers by the Biden administration are from Abbott, iHealth, and Roche. IHealth is unfamiliar, but for the other two, oy. Is this a case of you get what you pay for?

 

The new normal

Is the pandemic nearly over and the SARS-CoV-2 virus about to become endemic and tame, like its cold-causing cousins? If you believe the modelling guru Chris Murray and some other experts, yes. I too was hopeful in early December: “Omicron may turn out to be not the variant from hell but the variant from heaven.” The WHO Europe director, Hans Kluge, agreed on January 22^nd: "It's plausible that the region is moving towards a kind of pandemic endgame." But his boss backed him up only in part, saying maybe “Countries can end the acute phase of the pandemic this year,” but calling it “dangerous” to assume the endgame is near and emphasizing that “Conditions are ideal for more variants to emerge.” Other WHO scientists think the next variant is likely to be more transmissible than Omicron, even better at escaping prior immunity, and perhaps more rather than less severe. 

With others, more others, and still others, I’m no longer as optimistic as I was. Omicron is only heavenly if we assume that 1) nearly everybody is going to get infected, 2) by far most infections will be mild, 3) even asymptomatic or barely-symptomatic infections will protect forever against present and future variants.

A major study did once suggest that asymptomatic or mild infections would bring durable immunity, but that was so early in the pandemic that follow-up was less than 5 months and variants of concern didn’t exist. It’s now thought that mild illness gives briefer immunity – anti-spike antibodies fall by half every month, and neutralizing antibodies disappear entirely over a year. One interesting report found antibody-producing cells in patients’ bone marrow as long as 11 months after mild COVID-19, prompting some to enthuse: “If You’ve Had COVID You’re Likely PROTECTED FOR LIFE…” But that was all wild-strain COVID-19, and both an editorialist and the paper’s top author have pointed out that those bone marrow antibodies are unlikely to neutralize variants. 

True, most people with mild infections are largely protected against reinfection for 4-6 months, but that’s not very long, and according to CDC research in Brazil and Kentucky, some reinfections occur even earlier. I agree with the reporter who called the idea that Omicron will end the pandemic “a mass delusion.”

The only Omicron data relevant to reinfection come from one tiny study saying anti-Delta antibodies rose somewhat in people who had caught Omicron after previously having Delta. And there are already real-world hints that Omicron infections don’t even protect completely against re-infection with Omicron, much less against other variants. Deltamight even make a comeback once the Omicron surge blows over.

Anthony Fauci has commented with his usual caution: “It is an open question as to whether or not Omicron is going to be the live virus vaccination that everyone is hoping for.”

Six former scientific advisors to Joe Biden made a huge splash by publishing an alternative playbook in a series of opinion pieces in JAMA, suggesting ways to achieve the new normal and relieve stress on the health system. Most of their recommendations are uncontroversial: free and easy access to face masks, testing, and therapies, and of course universal vaccination. They also remind us of crucial but neglected mitigation measures such as ventilation and air filtering. And they particularly emphasize rebuilding the public health infrastructure: centralized reporting of positive swabs, widespread monitoring of wastewater and air, more viral sequencing, better surveillance of vaccine effects, etc.

 

MAGA mandate madness 

Meatpacking plants, 1906 and 2016

In the United States, attempts to mandate vaccination or for that matter any mitigation measure has met fierce resistance. The US Supreme Court has been to some extent a force for good, letting mandates for health workers stand in New York State and Maine without a religious exemption. Justices Gorsuch, Alito, and Thomas dissented in the New York case, with Gorsuch penning a personal diatribe saying religious exemptions had to be permitted because the vaccines were tested on cells that may have been derived from abortions. At the risk of sounding like a broken record,so were Benadryl, Sudafed, Tylenol, Tums, Preparation H, albuterol, aspirin, ibuprofen, Pepto Bismol, Lipitor, Senokot, Maalox, Ex-Lax, Benadryl, Sudafed, Preparation H, Claritin, Prilosec, Zoloft, Humira, and Regeneron’s RegenCov. I challenge Justice Gorsuch to find an anti-abortion claimant who has rejected any of those medications on religious grounds.

But that pro-mandate run ended when the battleground moved from the state to the federal realm. The Court did approve a vaccine mandate for healthcare workers in settings (the vast majority) that receive Medicare or Medicaid funding. But when 26 Republican-leaning US states, backed by major corporate lobbyists, challenged the Occupational Safety and Health Administration “vaccine mandate” for companies with more than 100 employees, SCOTUS ruled in their favor on technical grounds: “although Congress has indisputably given OSHA the power to regulate occupational dangers, it has not given that agency the power to regulate public health more broadly.” Note that the OSHA regulation was not a vaccine mandate but a testing and masking mandate, with exemptions for workers who are vaccinated. This decision hobbles the functioning of a major government agency that’s attempting to fulfill its mission – nearly 300workers have died from COVID-19 in the meatpacking industry alone. The regulation has been withdrawn, but OSHA hopes to create a permanent Healthcare Standard to protect workers against COVID-19 that can pass SCOTUS scrutiny.

 

Omicron tidbits – see also overviews from the WHO and Dr. Eric Topol

"COVID parties" in Italy, USA, UK

The Age of Omicron: Italy is finally there, at 96% of cases, though some regions still have Delta rates as high as 17%. In the United States, virtually all new cases are Omicron.

Covid parties: Some Italians deliberately try to contract COVID-19 so they can get a Super Green Pass: “Wanted: COVID-19 positive girl to kiss.” One Tuscan restaurant is supposedly offering exposure to the virus alongside your truffles, at a price of €150. Dr. Paul Offit says that’s “all the rage” in the US too. Unfortunately some of those suckers are going to wind up dead, especially since most are likely to be unvaccinated – like the 30-year-old Texan and the 57-year-old Czech folksinger who died after deliberately exposing themselves to the virus. 

Transmissibility: Omicron spreads more readily than Delta but it’s not quite as contagious as it seemed at first, spreading to only 25%-35% (rarely 50%) more vaccinated household contacts than Delta; unvaccinated contacts catch both variants at equal rates. At first that rapid spread was attributed to a higher viral load, but recent data from Switzerland and the US say that if anything it’s Delta patients who carry more virus in the nose. Omicron’s rapid multiplication in bronchial tissue may also not be relevant. The heightened transmissibility is now thought to be due mostly to immune escape: many more people are vulnerable hosts, no longer well protected by previous COVID-19 or vaccination. 

Severity: Portuguese researchers say that during December patients diagnosed with Omicron were one-quarter as likely to need hospitalization as those with Delta, and none of 6581 Omicron patients died. But not all reports are that rosy. In Denmark the risk of hospitalization was only a third lower overall with Omicron than with Delta, only half even in people who were boosted. And high recent death rates in countries like the US, Italy, France, and Greece confirm that Omicron may not be as benign as it was cracked up to be.

Self-isolation: Omicron’s shorter incubation period bred hope that patients would remain infectious more briefly – one of the CDC’s excuses for cutting self-isolation from 10 days to 5, a policy unfortunately being imitated by some Italian regions. It turns out, though, that Omicron infections are barely shorter than Delta (10 vs. 11 days average), with fully a third of Omicron cases remaining infectious for 6-11 days.

 

Healthcare system? What healthcare system?

As Sarah Kliff tweeted, “Only in the United States could the government run a public health campaign centered on fears of large, unexpected medical bills.” The richest country on the planet, with the highest medical spending per capita and some of the world’s best hospitals, notoriously has the worst health outcomes of any developed nation. That’s what happens when medical care is run for profit, not for health – check out this excellent commentary from out in left wing.

Of the 7 nations with no mandated sick leave, only one is a developed country: the United States. Ten percent of all employed Americans, one in 4 who work in the private sector, and half of workers earning less than $15 an hour have no sick leave at all, and those who do have only an average of 7 days. If so many working-age Americans can’t afford to take time off to quarantine, self-isolate, or get vaccinated, workplace exposures are guaranteed.

Duration of paid medical leave around the world

Not everybody has suffered from the COVID-19 pandemic. American health insurance companies, for instance, are making a killing. No sign they’re planning to reduce premiums, though, and they’re not rushing to send customers the rebates required by the Affordable Care Act. 

Big Pharma’s happy too, with Pfizer + Moderna making $1000 every second. Yes, I said every second.

KFF polling on the Affordable Care Act since its inception

But there are tiny silver linings for the rest of us: Oklahoma, Nebraska, Montana, Missouri, and Arkansas expanding Medicaid, more approval of the Affordable Care Act, and more support for a public option in healthcare insurance – though the backing of “Medicare for All” holds steady at 55%.

Will COVID-19 be the straw that finally breaks the back of the already broken American medical non-system and drives it to join the rest of the civilized world in making health care a right as fundamental as water, schools, and highways?

What killed 'em?

 

The number of death certificates in the US citing COVID-19 as the cause of death is far less than the real number. Coroners say one reason is that they take the word of families for the cause of death of people who die at home, and many such families, especially in red states, prefer to say the person died of Alzheimer’s, heart attack, diabetes, whatever. Admitting their relative had died of COVID-19 would apparently be a personal insult to Donald Trump.

But then – contrariwise – you have families who try to falsely have COVID-19 added to the death certificate, or obtain a forged one, so as to be eligible for the up to $9000 offered by FEMA in funeral assistance!