FDA is About to Approve Covid-19 Vaccines for Young Children… But Should It?

 I’m not in the best of moods today, having woken up with a raging fever, chills, muscle aches, and a feeling like the inside of my skull was being lit up by a blowtorch. Yes, I finally got my case of Covid-19, almost certainly from a 100% outdoor school performance. Go figure. I’ll say to whomever thought it was funny calling this #Omicold (yeah, I’m looking at you, Marty Makary): my patients and I disagree. However, with a brief Tylenol-induced respite from my misery, what better subject matter to discuss than the pending approval of the Covid vaccines for young children? It’s the ideal topic for a doctor in a seriously grumpy mood.

I’ll say the obvious part first: we physicians are supposed to be excited about every vaccine approval, because all vaccines are wonderful, and only bad doctors complain about any vaccine. Let’s be real, though; a vaccine with zero (or negative) effectiveness and a high rate of side effects is a loser, and a vaccine with near-total effectiveness and few side effects is a clear winner. Every vaccine is on a spectrum, and we should not approve examples of the former, and we should strongly endorse the latter, especially if the disease in question is severe. The billion dollar question is: where do the Pfizer and Moderna vaccines for young children fall on this spectrum?

Starting with Pfizer, readers might recall that their vaccine project for 6 months to 5 years has been a bit of a dumpster fire. The 2-5 year olds failed in their immunobridging tests for the 2 shot series (the antibody response was below that for young adults in their initial studies); as I discussed at the time, likely the tiny 3mcg dose was just too small. After some serious hemming, hawing, and misdirection, the FDA ultimately asked Pfizer to add a 3rd shot some 8 weeks after the primary series was given. This went better; immunobridging was positive, and the listless vaccine efficacy from the 2 shot series appears to be better.

But “better” is by no means “great”. Some media outlets are claiming “80% efficacy” for the vaccine, but this is irresponsible, especially with the study’s sample size being so tiny.

Put mildly, I would be very surprised that further reporting after more cases have accrued will bring anything like 80% efficacy. Of course, we also have good reason to expect from virtually every real world data set we have on the subject, that whatever the initial efficacy against Omicron infection, it will rapidly wane within months.

Moderna had a less convoluted road to data submission. Their trial of a 2-shot series, at the much higher dose of 25 mcg for 6 month to 6 year olds, unsurprisingly met their immunobridging endpoint on the first try. Of course, creating an immune response that rivals that of an effective vaccine, and actually being an effective vaccine, can be two different things. When it came to actual efficacy, the numbers were rather humbling, at around a 40% reduction in infections. This was below the 50% threshold proposed by the FDA prior to the approval of the adult vaccines, an inconsistency not lost on some observers. To be fair, though, these numbers are similar to the real world data we have on the mRNA vaccines’ initial two-shot series in adults against Omicron infections. In a large UK study, initial effectiveness was in the 65-75% range, but that dropped to 8-15% after 25 weeks.

All in all, it begs the question: what are we doing here? Short of boosting every 3-4 months, these vaccines make minimal inroads into reducing transmission. In the words of the World Health Organization, from their primer on the Moderna vaccine:

We don’t know if vaccines reduce the risk of long Covid, and what little real world evidence we do have is not very promising. It would be nice to know that severe disease in high risk children will be reduced via vaccination. This seems extremely likely to be the case, but the one cause for concern has to be the size of the dose chosen by Pfizer. Three micrograms seemed like a low dose when initial efficacy and immunobridging reports came out, and with Moderna using a 25mcg dose in this age group with less-than-stellar results, it seems even more likely now.

Due to the small size of the Pfizer trial for young kids, despite a very expanded criteria for “severe disease” (including rapid heart rate, elevated breathing rate, etc.), there were too few cases of serious illness to draw conclusions. Six cases of severe disease were in the Pfizer group, none after the 3rd shot, however, and only one was likely truly caused by Covid, and the same can be said of the two cases in the placebo group.

My concern is for the next age group up: the 6-11 year olds who received a 10mcg dose. A New York State pre-print showed a rather striking drop in effectiveness between 11 year olds and 12 year olds (who receive 30mcg doses) in the Omicron era, and a more concerning drop in protection versus hospitalization as well:

Yes, I worry about confounders in real world data of this sort, but that hard drop from age 12 to 11 is striking.

While we have no real world data on severe disease on lower doses with Moderna, since they are only going through the approval process this week for ages 6-11 at 50mcg, that 25mcg dose for 6 months to 6 years would seem ample. It does bring me to ruminate on our assumption that Moderna and Pfizer are essentially equal microgram-for-microgram. Those with long memories might recall that Pfizer bailed out of a 30mcg dose in their ages 5-11 Phase 1 trial due to every single kid getting a fever; and yet 50mcg of Moderna does fine in this same age group? Either Moderna’s thermometer is broken, or some brilliant vaccinologist needs to explain to us how these doses really compare.

On the subject of fever, the kids in the Moderna trial had a rate of fever over 100.4 degrees in the 15-20% range; in the Pfizer trial, that stood at 5-7% (and was barely higher than the placebo group, a sure sign that Pfizer’s thermometer works really well). I looked through the reports on adverse events until my eyes hurt — which, granted, does not take much today — and did not see anything worthy of concern. I truly think these vaccines are quite safe, despite the fact that both trials were too small to pick up rare adverse reactions in the 1 in 5,000 or 1 in 10,000 range.

So why the hesitation? I stand by what I wrote in February:

Hence the value of knowing the effectiveness of the vaccines we recommend. I favor the EUA for these vaccines in this population, mostly because I believe in choice, and the parents of high risk children with health concerns like obesity, neurodevelopmental disorders, and compromised immune systems, are anxious for a vaccine, any safe vaccine, that might help protect their children from Covid-19. However, it strikes me as quite possible that these vaccines will have minimal value for normal risk kids, and especially the majority of U.S. children who have already had a Covid infection. We simply lack the data to evaluate that concern.

This could have been avoided. The FDA — which has its long arm in the execution of all these trials — could have insisted on longer term, larger trials with enough early reporting of data to get an approval by now (or sooner) for high risk groups. When the dust settled, we might have known if “long covid” or severe disease could be prevented, and in which subgroups. That we will probably never have this data is a failure of governmental oversight.

I will end on this note, although it is not one that the “Covid Minimizers” will appreciate: Omicron is a serious problem. Yes, it may have been reduced to flu-like mortality by vaccines and infections:

However, like most Americans, I only get a symptomatic case of the flu every decade or so. I don’t hang out in bars much, and, for reasons which I cannot grasp, am not invited to a lot of parties. Getting this sick from an outdoor gathering of maybe 50 people? This wave-after-wave BA.2>BA.2.12.1>BA.4&BA.5 pattern happening in the once-friendly seasons of late spring and early summer is distressing. What #Omicold might not do in terms of disease severity, it can accomplish with sheer contagion; and Omicron sub-variants are only getting better at transmission and immune evasion.

That’s probably the best justification for pushing out these vaccines now; even a small edge against infection and hospitalization or death can make a difference on a societal level of suffering and hospital strain. I just wish that the FDA, Pfizer, and Moderna had conducted these trials in such a way as to allow us physicians a real plan. Maybe Moderna for high risk kids who shouldn’t wait another 8 weeks for decent protection? Pfizer for parents worried about side effects who don’t mind a 3-shot series? (Although it’s rather clear that Moderna will be a 3-shot series eventually.)

The greatest failure in a time when so many kids have had Covid has been the lack of reporting clinical outcomes in previously infected children. If we’re to believe that 75% (and rising) of children have had Covid, this needs to be the primary outcome group in all these trials.

I’m sure that VRBAC will recommend these vaccines to the FDA on Wednesday; and that ACIP will endorse to the CDC soon after, and kids will have access to both vaccines within weeks. The public health community will celebrate these approvals unabashedly. But this doctor will continue to be grumpy at the slipshod nature of the trial data Pfizer and Moderna were allowed to collect, and the vacuum in knowledge we’ll need to work around as we advise our patients.

https://doctorbuzz.substack.com/p/the-fda-is-about-to-approve-covid

Beyond Kavanaugh, Dozens of Incidents Targeting Pro-Lifers Nationwide

 An armed would-be assassin’s alleged attempt on the life of Supreme Court Justice Brett Kavanaugh last week is part of a wave of violence, arson, vandalism, and intimidation targeting pro-life groups and government officials since the leak last month of a draft Supreme Court opinion that would overturn Roe v. Wade.

There have been more than three dozen such incidents directed at crisis pregnancy centers and churches in at least 20 states and Washington, D.C., according to a tally maintained by LifeNews.com, an anti-abortion site.

These include:

• The firebombing of a pro-life pregnancy center in suburban Buffalo on June 7
• An arson attack including Molotov cocktails against the headquarters of the pro-life Wisconsin Family Action center in Madison on May 8
• Graffiti with the threat, "If abortion isn't safe then you aren't either," spray-painted on the walls of centers in Washington state
• Extensive graffiti spray-painted on small rural evangelical churches in the Deep South, where some of the deacons protested their congregations were apolitical

A loosely organized group known as Jane's Revenge claimed responsibility for several of the attacks, including the apparent arson in Wisconsin and Buffalo. The group, which sometimes attaches the Antifa "A" symbol to its pronouncements, has called for a "night of rage" over the pending Supreme Court decision, on a website called The Anarchist Library.

Above, graffiti threat at Wisconsin Family Action. Below, the attackers' "call to action."

Another group, Ruth Sent Us – its name evoking the late liberal Justice Ruth Bader Ginsburg – has published the home addresses of conservative Supreme Court justices on Twitter. While not claiming responsibility for the disturbed gunman arrested near Kavanaugh's house, it informed followers where his children and the children of Justice Amy Coney Barrett attend school.

Justice Amy Coney Barrett: Extremists publicized where her and Justice Kavanaugh's children attend school.

AP

Federal law expressly prohibits “pickets or parades … in or near a building or residence occupied or used by” any judge, and the House passed a bill this week to expand Supreme Court Police protection to justices' families.

The rash of incidents and intimidating behavior is domestic terrorism, said Jim Harden, executive director of CompassCare, a nonprofit that operates the Buffalo pregnancy clinic and two others in upstate New York. Harden and his family relocated Sunday after social media accounts began seeking his home address.

“This is new,” he said. “It was the leak that really sparked this kind of activity.”

CompassCare also described the campaign against it as “abortion terrorism” – expressing heightened fears in a place where a white supremacist terrorist had murdered 10 people just weeks before. FBI agents visited the Buffalo clinic in response to the firebombing, but the organization has heard nothing since from federal authorities. Harden expressed skepticism that they – in contrast with local police – have taken the incident seriously.

“It’s been eerily silent,” Harden said. 

In response to the May 2 leak of the draft opinion overturning Roe, which in 1973 legalized abortion nationally, New York Gov. Kathy Hochul earmarked $35 million in protection funds – but it was to safeguard abortion clinics, which have not been targets of attacks lately.

The Justice Department did not respond to questions from RealClearInvestigations about whether it has classified the multiple incidents as domestic terrorism or assigned a team to an investigation. Jane’s Revenge has claimed responsibility for the arson and vandalism attack on the Madison office of the Wisconsin Family Action center. Madison police also did not respond to multiple requests for comment.

Suburban Buffalo: “Abortion terrorism,” its director says -- followed by an official response of silence.

AP

There have been no arrests made in connection with any of the incidents, which began after Politico published the leaked draft opinion by conservative Justice Samuel Alito declaring that “Roe was egregiously wrong from the start.” 

Harden compared the law enforcement response to the CompassCare attacks to the silence surrounding the person who may have leaked the draft opinion.

“There doesn’t appear to be anything going on in either case,” Harden said. 

Chief Justice John Roberts said he had ordered an internal investigation that might identify the leaker, who presumably comes from a very small circle of people who would have had access to draft opinions.

Agreeing with Harden was Rebecca Anderson of 40 Days for Life, an anti-abortion group headquartered in Texas that has worked with an organization also targeted by Jane’s Revenge vandals: a Lynnwood, Washington, crisis pregnancy center called NextStep.

"I don't think these acts of violence are being taken seriously as elected officials aren't publicly condemning them," she said. "The lack of response from the Justice Department leads one to believe that they pick and choose what qualifies as domestic terrorism based on politics. Our concern is that this will embolden abortion supporters to commit more violence against those who support life."

In contrast, several anti-abortion figures told RealClearInvestigations, local police have been exemplary in their response and attitude.

“The police came immediately, and the DC Metro Police have been outstanding,” said Janet Durig, executive director of the Capital Pregnancy Center, which saw its front door splashed with red paint and the threatening graffiti tag left by Jane’s Revenge vandals, “If abortion isn’t safe then you aren’t either.” 

“The local authorities are taking this very seriously and are investigating,” Harden said. “We had cameras trained at all the points of entry so there is videotape evidence.” Still, there has been no indication that local authorities have made any progress in their investigations.

The available evidence may be thin. Cameras did capture the vandals at NextStep in Lynnwood, Washington, but the assailant was bundled up like an Antifa extremist and nearly impossible to identify, according to NextStep Executive Director Heather Vasquez. “You could tell it was a woman,” she said.

The attacks on pro-life centers don’t square with an emphasis in major news outlets on the potential for attacks on abortion providers, which do not appear to have proliferated in the past several weeks.

“Abortion clinics are secured like fortresses,” a USA Today headline blared a week after the Politico story. “Advocates fear Roe ruling could spur new attacks.”

Reports about the spate of incidents involving anti-abortion centers by both CNN and the Washington Post have stressed that violence occurs on “both sides” of the abortion debate.

Planned Parenthood said late Tuesday that "we condemn violence and hatred in all forms” in a statement to RCI that emphasized "acts of violence, vandalism, and intimidation from anti-abortion activists and politicians" aimed at the organization's "health center staff and patients."

The pro-choice National Abortion Federation claimed in a 2020 report that abortion providers receive hundreds of death threats and thousands of “hate emails” and harassing phone calls each year. There has been one deadly incident at an abortion clinic since 2010 – the 2015 attack on a Planned Parenthood facility in Colorado Springs that left three dead.  

The anti-abortion movement does not have an equivalent database regarding threats received by pregnancy centers and religious organizations. In 2012, a left-wing activist entered the Family Research Council’s Washington, D.C. headquarters and shot and wounded a security guard.

While violence and intimidation have long characterized the abortion debate, Jane’s Revenge has promised to escalate the conflict. In its self-titled “First Communique” published after the Wisconsin attack, it declared:

We have run thin on patience and mercy for those who seek to strip us of what little autonomy we have left. As you continue to bomb clinics and assassinate doctors with impunity, so too shall we adopt increasingly extreme tactics to maintain freedom over our own bodies. We are forced to adopt the minimum military requirement for a political struggle. Again, this was only a warning. Next time the infrastructure of the enslavers will not survive. Medical imperialism will not face a passive enemy. Wisconsin is the first flashpoint, but we are all over the US, and we will issue no further warnings.

https://www.realclearinvestigations.com/articles/2022/06/15/beyond_the_kavanaugh_scare_dozens_of_incidents_targeting_pro-lifers_nationwide_837247.html