Stethoscope On Rome

Paxlovid controversies, vaccines old and new, the red and the blue, unwindings, collateral damage, Boris Johnson, microbiomes, emergencies, RFKs, and comic relief.

Treatment

Paxlovid: University of British Columbia researchers have published a retrospective cohort study finding that only people who are moderately-severely immunosuppressed benefit from treatment with nirmatrelvir-ritonavir, whereas those who are merely elderly or chronically ill have no improvement in rates of hospitalization or death. I’m skeptical, because these findings contradict similar studies from Ontario, Israel, Korea, California, Quebec, and Mass. General Brigham, all of which found Paxlovid effective in vulnerable non-immunosuppressed populations.

Molnupiravir: In mid-November Lagevrio will soon no longer be available from the American government free of charge but will shift to the commercial market, with a “patient assistance program for people who cannot afford the drug.” Given molnupiravir’s inefficacy both in preventing severe disease and in clearing the virus, plus its potential to prolong infection duration, induce mutations transmissible to other people, and breed new variants, it would have been better to withdraw authorization altogether as the European Union already has. Molnupiravir never caught on in the US, with only 1.4 million courses ever used, versus 10 million of Paxlovid.

Paxlovid again: A five-day course has cost the American government $529 ever since the drug came out, though it’s been distributed free of charge to all eligible patients. Paxlovid will move to the commercial market once government warehouses are depleted in mid-December, whereupon Pfizer will triple the price to $1390. But between a patient assistance program, subsidies, and private and public insurance programs, this lifesaving drug should likely remain available without co-pays to the vast majority of Americans who need it.

Fostamatinib (Tavlesse): Approved for a platelet disorder in the US and the EU, Tavlesse also benefits hospitalized patients severely ill with COVID-19, according to an international study presented at a medical meeting. All such reports need to be taken with a grain of salt, pending manuscripts with complete methods and results.

Extracorporeal membrane oxygenation: This costly high-tech intervention, used as a last-ditch treatment in critically ill COVID-19 patients, is valueless and might even worsen prognosis, according to another conference presentation. Same caveat as above.

Tea: You might expect an article titled “Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2” to involve tea-drinking. Nope! The subjects didn’t drink tea but ate a tea-laced candy, and researchers didn’t study COVID-19 but put subjects’ saliva into a test tube together with the SARS-CoV-2 virus.

Clorox: I’ve written about the Grenons, a Florida-based father and three sons who gave Donald Trump the idea of treating COVID-19 by drinking bleach. The gang peddled a deadly “Miracle Mineral Solution” of industrial bleach to thousands of Americans to cure everything from COVID-19 to autism. Now, after more than three years including a period on the lam in Colombia, the DOJ has finally caught up with them, sentencing two to 12 years in prison and the other two to five years.

Vitamin C: Canadian researchers went to the trouble of doing a randomized trial of intravenous vitamin C to treat hospitalized COVID-19 patients. Anybody surprised it didn’t work?

Convalescent plasma: This simple treatment, which I’ve always thought promising, did fairly well in an open-label French/Belgian study of critically ill patients with COVID-19. Of patients given plasma with high antibody titers only 35.4% died, versus 45.0% of patients who received standard care.

Simvastatin: Surprisingly, high doses of this cholesterol-lowering drug barely missed criteria for improved outcomes in critically ill patients with COVID-19. A miss may be as good as a mile, but even being merely 91.9% likely to help seems impressive for such a benign intervention.

Vaccines

Novavax 1: The FDA has approved a Novavax booster reformulated to match the XBB.1.5 spike protein, for anybody over 12 who’s fully vaccinated and has not received an XBB.1.5 mRNA booster from Pfizer or Moderna. During the first week of the US vaccination campaign, before Novavax arrived, about 1.8 million shots went into arms, one million Pfizer and 800,000 Moderna.

Novavax 2: The original Novavax vaccine, was quite effective according to researchers at the Italian equivalent of the CDC, cutting symptomatic Omicron variant COVID-19 in half. The company predicts the updated version will work well against EG.5 and several other current variants, but doesn’t mention either FL.1.5.1 or the hypermutated newcomer BA.2.86.

Novavax 3: Thanks to John Earl for pointing me to a thought-provoking tweet: “My wife stopped by Costco to get the updated monovalent XBB vaccine booster this morning and the pharmacist asked her why is everyone asking for the Novavax booster instead of Pfizer and Moderna.” Two reasons this could be true:

1) Some people (foolishly) don’t want mRNA vaccines on principle. I doubt many current Novavaxers fall in this category, since as of May 2023 more than 800 million mRNA shots had been given in the US, but only about one million Novavax.

2) Others think Novavax gives fewer side effects. True! In the original Novavax trial about 28% had fatigue after the first dose, and 25% headache. Compare that to 40-50% for both with Pfizer and Moderna. Modernareports similar rates for the latest version: fatigue in 44%, headache in 34%.

There is even, to my surprise, some evidence for pro-Novavax claims made in response to that tweet by “Hugh Wouldathunkit”: mucosal immunity and longer duration of protection. Having had a severe reaction to my first Pfizer shot, I may personally go for Novavax whenever it hits Rome.

Italy: The XBB.1.5-targeted vaccine arrived on October 2, intended for administration in GP offices and pharmacies. There should also be websites for making appointments, but getting your hands on a dose may not be easy. Healthcare workers and nursing home residents were immediately eligible, followed two weeks later by people over 80, medically fragile, pregnant, or nursing. At the end of October the floodgates theoretically opened to all comers, provided they’re six months after their latest vaccine or bout of COVID-19 (three months would have been more reasonable). But in Rome there are no doses available at all, as my local pharmacist confirms; my one 84-year-old patient who succeeded in getting vaccinated lives far outside town. I am also concerned that the solo product around now is Pfizer-BioNTech, the one tested only in mice. Moderna and Novavax are theoretically available but actually nowhere to be found.

Side effects: After getting an mRNA COVID-19 vaccine most people have a sore arm for a day or two, but some have much stronger reactions. According to an American study a more severe reaction – chills, fever, headache, fatigue, general malaise – predicts higher antibody levels against SARS-CoV-2 even six months later. So a severe side effects may possibly foretell better protection.

Pulmonary damage: There have been claims on social media that mRNA vaccines can damage the lungs. True, but extremely rare. Interstitial lung disease related to mRNA vaccines has been reported in a total of eleven individualsout of more than 5.5 billion people worldwide who have received at least one dose of vaccine, mostly Pfizer or Moderna.

Two-in-one: Moderna has come up with an influenza/COVID-19 vaccine in a single syringe, and calls preliminary results in human beings promising, with elicited antibody levels similar to those following standalone flu or COVID-19 jabs, and side effects similar to the original Spikevax. Novavax has developed a similar product, with initial trials underway. I don’t approve, since an FDA study found that combining the two vaccines – even one in each arm – carries a risk of stroke, especially in the very elderly. That study tested last year’s bivalent product, but there’s no reason to expect the XBB.1.5 vaccines to be different. I suggest leaving a couple of weeks between COVID-19 and influenza vaccines, especially if you are over 65.

Nasal sprays: Sprays such as nitric oxide, Iota-carrageenan, and proprietary agents have been touted as protection or treatment for COVID-19. Some clinical trials are ongoing, while the FDA seeks injunctions against other manufacturers for false medical claims.

Timing: How quickly does vaccine efficacy fade over time? New analyses of the principal Moderna trial, described at a major medical meeting, suggest that – surprisingly – a booster dose was more effective in preventing Omicron COVID-19 if it was given 13 months after the primary series than if the gap was only 8 months. So an annual booster strategy (as the US plans) may be as valid as the more frequent jabs suggested for high-risk individuals by the World Health Organization. The usual caveats for conference presentations apply.

Pregnancy: Pregnant women, who are at risk for severe outcomes, should be prioritized for COVID-19 vaccination. Now a study by Canadian researchers reports that vaccination during pregnancy also prevents severe illness, ICU admission, and death among newborns. Nevertheless, pregnant women in the US, Canada, and Italy are being vaccinated at lower rates than nonpregnant women. One possibly related phenomenon in the US is a rise in both maternal and infant mortality.

Menstruation: Getting an mRNA COVID-19 vaccine can change a woman’s next menstrual period, though probably no more than getting sick with COVID-19. Estimates of frequency range from 7.3% to 42%, not counting wild and easily debunked assertions that 66% of postmenopausal women bleed after being vaccinated. Conspiracy theorist Naomi Wolf goes way out in left field, claiming that simply being near vaccinated people, or being in rooms where they had been, could cause bleeding and cramping.

Long vax: Does a prolonged, long COVID-like reaction to vaccination exist? Articles in venues such as Forbes and even Science claim the concept is gaining acceptance, but the evidence remains weak. A small case series of nerve-related symptoms was preprinted in May 2022 but never published, which always raises doubts. One study did report a slight increase in POTS, a common long COVID symptom, following vaccination, and there are a few case reports. I don’t think it adds up to much.

The reds and the blues

Between January 2019 and December 2021 Americans who trusted medical scientists to work for the public good fell from 87% to 78%. But there was a sharp political divide: Democrats held steady at 87%-90%, while Republicans fell from 88% to 66%. A more recent poll, in May 2023, found trust in scientists overall dropping to 59% from 86% in January 2019. With another striking partisan divide: Republicans went from 82% to 56%, Democrats from 91% to 82%.

As of September 2023 89% of Democrats and 58% of Republicans were vaccinated against COVID-19. This gap is the main reason Republicans have died of COVID-19 at far greater rates than Democrats.

Winding and unwinding

As of November 1, 2023, the number of people kicked off Medicaid hit an estimated 10,046,000, about 11% of those who were on the rolls in January, with many fewer transferring to Obamacare than would be entitled. That number, which includes nearly two million children, is expected to double in the next six months. A computer glitch caused half a million people, mostly children, to be purged so wrongfully that the federal government is demanding they be reinstated.

The extra Medicaid protections added during the pandemic aren’t all that’s being “unwound.” About 70,000 childcare providers will also soon lose their American Rescue Plan funding, imperiling care for more than 3 million kids.

Then there’s the increased child tax credit payments that cut child poverty drastically between 2019 (14.4%) and 2021(5.2%). That program ended in December 2021, and child poverty leapt back to 12.4%. Overall 12.4% of all Americans were living in poverty in 2022, versus 7.8% in 2021. As the Washington Post Editorial Board says, it’s a damn shame Joe Manchin and his Republican pals kept this great program from becoming permanent.

Shockingly, the Social Security Administration has been dunning disability pensioners for many thousands of dollars – contrary to stated SSA policy – because the COVID relief payments deposited in all Americans’ bank accounts pushed their assets over an eligibility threshold that hasn’t been adjusted for inflation in decades.

I know I sound like a broken record, but when will the US join the rest of the civilized world in providing health care to everybody? California is taking baby steps. Vermont tried and gave up. Colorado, Nevada, and Washington have at least passed a public option. A somewhat peculiar proposal for universal “basic” coverage has been featured in the New York Times. Even the American Medical Association, the doctors’ group that helped sink one health reform after another, may be reconsidering its objection to a single-payer system. And, marvelously, the American Academy of Pediatrics now recommends automatically enrolling all U.S. infants at birth in public health coverage lasting until age 26.

Two billion people worldwide face severe financial hardship due to healthcare costs. Among high-income countries, Malta, the US, and particularly Switzerland have the highest out-of-pocket costs. Even some countries with universal healthcare, such as Italy and the UK, have relatively high out-of-pocket averages due to burgeoning privatization.

Long COVID

Paxlovid: A major Veterans Administration study found Paxlovid to substantially decrease the risk of developing long COVID. But since the VA patient population skews older and male many have doubted the same holds true more generally. Now a study reported at a “late-breaking abstract session” at a medical meeting – making it even more dubious than other conference presentations – suggests that adults over 50 are protected, but that teenagers who received the drug actually had more long-lasting symptoms. Remember, adolescents don’t often get COVID-19 in the first place, and rarely have preexisting conditions or immunosuppression severe enough to qualify for Paxlovid. I can’t access the abstract itself, much less a manuscript, so have no idea whether there’s any there there.

Serotonin: A small study claiming that low serotonin levels are at the root of long COVID made it into the New York Times in mid-October. If that were true, SSRI antidepressants should be extremely useful. One review article had lots of speculation but no evidence. Randomized trials are testing fluvoxamine (Luvox) and vortioxetine (Trintellix, Brintellix); the latter trial has supposedly been completed, but I can’t locate any results. The only other relevant research I’ve found is a methodologically weak Italian study finding that vortioxetine can help treat depressive episodes that occur after COVID-19. Why shouldn’t it? Depression is depression.

Collateral damage

A study by Seattle-based researchers found that out-of-hospital cardiac arrests rose by 19% during the pandemic but treatment success fell. In 2018-2019 17.2% of patients survived with decent brain function, in 2020-2021 only 13.7%. The poor outcomes were related less to acute COVID-19 than to factors such as slower response to 911 calls and fewer bystander-witnessed events (see: lockdowns).

Pulmonary embolism may be another disease that is more deadly in the presence of SARS-CoV-2 infection, with 19.8% of infected patients dying, versus only 7.1% of patients with PE alone. This is from a medical conference presentation, so the usual caveats apply.

COVID-19 during pregnancy might cause situs inversus, where internal organs such as the heart are on the wrong side of the body, according to Chinese researchers who noted a fourfold jump in this rare condition during the unspeakable surge that infected an estimated 82% of China’s population after the zero-COVID policy was scrapped last December.

Pandemic recovery is one thing for the rich, another for the poor. In Manhattan, a poster child for income inequality, the richest fifth of households earned over 50 times more in 2022 than the poorest fifth.

Murders in the US fell by 6% in 2022, but the huge surge in the first year of the pandemic left a lasting mark, with 25% more homicides in 2022 than in 2019. And the number of children shot to death increased by 12%. Crimes against property have been soaring, with a million cars stolen in 2022 and that figure poised to double in 2023.

State of the pandemic

On July 22^nd there were 728 COVID-19 patients in Italian hospitals, on October 27^th 3,657, more than 5 times as many. That’s lower than in previous surges, which hit 35,000, but here in Rome, at least, everybody knows someone who’s sick. There has been less of a peak in the United States, with hospitalizations only tripling, then trailing offsince mid-September. At last call Sweden had about as many hospitalized patients per capita as the United States, Italy had 50% more, Canada more than double, England nearly double, Japan triple, and Holland fewer than half as many. Many Western European countries seem to have quit providing data months ago.

Johnsonthink

I’ve already covered the part of the UK’s COVID-19 inquiry where the chief concern of the health ministry was said to be the adequate provision of body bags.

But the worst was yet to come. Now we hear from the British government’s chief scientific advisor at the time that Boris Johnson, the Prime Minister at the height of the pandemic, was “obsessed with older people accepting their fate and letting the young get on with life and the economy going,” and that he believed, “Covid is just nature’s way of dealing with old people,” and “I think we should let the old people get it and protect others.” One of his texts begins: “I must say I have been slightly rocked by some of the data on covid fatalities. The median age is 82 – 81 for men 85 for women. That is above life expectancy. So get COVID and live longer.” Good God.

COVID-19 miscellany

Characteristics of the intestinal bacteria, specifically low microbiome diversity, may be a risk factor for severe disease in people infected with SARS-CoV-2. Another conference presentation, to be taken with the usual grain of salt. The effect largely resulted from patients harboring Staphylococcus Aureus in their mouth and gut, a germ which if inhaled into the lungs can cause a particularly virulent pneumonia.

We've long said that COVID-19 patients’ viral load, thus infectiousness, is highest on the day before and the day of symptom onset. This may have changed now, between Omicron and widespread immunity, with viral load peakingabout three days after symptoms begin. Two important implications: a negative antigen test early on is even less reliable than before, and you likely stay infectious longer.

A research letter in JAMA Pediatrics found the average duration of infectivity in children with Omicron to be three days after the first positive swab. Adults remain contagious somewhat longer, for an average of five days. That means fully half of adults can infect others after five days have passed, contradicting CDC advice; about one in four patients is still infectious at eight days, and a few even longer. When I had COVID-19 myself a year ago, I remained antigen-swab positive, thus likely infectious, for two full weeks.

Emergencies

The head of Rome’s medical society has admitted that emergency calls to Italy’s 911 often don’t get answered for 20 minutes, long waits for ambulances are the norm (few vehicles, scanty personnel), and that once an ambulance gets you to a hospital the Emergency Room is often so packed they won’t allow you into the waiting room. I thought emergency services were bad when I was finalizing my memoir 6 years ago, but I see they’ve worsened with time.

It’s not much better in the US. Living in notoriously inefficient Italy I’ve always imagined American ambulances arrived near-instantaneously, but in reality the average time nationwide before a 911 call is even answered is seven minutes. Another nationwide study says the time between when a 911 call is made and an ambulance shows up averages seven minutes in cities, eight in suburbs, and 14.5 in rural areas. Should that be added to the abovementioned seven minutes?

All the way with RFK

Robert Francis Kennedy, Jr.’s novaxx conspiracy theories have been drifting into antisemitism. The New York Postobtained this from a private gathering: “Covid-19 is targeted to attack Caucasians and Black people. The people who are most immune are Ashkenazi Jews and Chinese.” For Jews, actually, the opposite is true. Apparently at the same gathering he said the United States had “put hundreds of millions of dollars into ethnically targeted microbes,” which is what “those labs in the Ukraine are about: they’re collecting Russian DNA. They’re collecting Chinese DNA so we can target people by race.”

He’s not alone. An Oxford University study early on found nearly one in five Brits believed, at least to some extent, that Jews created the coronavirus pandemic for financial gain. In the meantime, legal attacks on the US government’s ability to combat health disinformation, and even on the right of researchers to study it, have been making shocking headway.

Comic relief