Marty Markary and Vinay Prasad (FDA Chief and CBER Director) released their perspective on COVID-19 vaccination in a NEJM piece today, with an accompanying webcast.

My quick thoughtsnejm.org/doi/full/10.10… First, I think they raise some reasonable points. I support their goal of increasing trust in vaccines. They do point out young children as having higher risk with COVID infections. They see significant antigenic shifts requiring broad booster uptake.

Large study in children and adolescents shows that SARS-CoV-2 infection is linked with long term cardiovascular complications Study is part of the RECOVER consortium with over 1 million kids.
Link to the paper: nature.com/articles/s4146…

Excited to see our paper out on determinants of SARS-COV-2 infection risk.
Nasal ACE2 and TMPRSS2 levels can predict higher risk of COVID-19.
The nasal microbiome can alter ACE2/TMPRSS2 levels, thus potentially modifying infection risk. Elevated ACE2 and TMPRSS2 levels were higher in individuals who went on to be infected. Higher levels were associated with a four times higher odds of future infection. Cases also had more unstable ACE2 and TMPRSS2 levels over time (i.e. potentially longer windows of risk)

Preprint: Higher IgG4 is linked with lower neutralizing Ab & Fc receptor responses. Paper also suggests the Novavax platform may produce higher IgG1/3 and lower IgG4 compared with mRNA COVID vaccines. To illustrate the magnitude:
NVX priming vs. mRNA priming = 49 vs 8,567 ng/mL in IgG4 (the bad one).
Conversely, IgG1 - 3 (the good ones) were similar or higher in the NVX group.

Link: medrxiv.org/content/10.110…

New RCT comparing Moderna bivalent and Novavax (original strain) as a fourth dose. Novavax has:
- lower side effects
- similar cell mediated immunity, lower IgG response
- potentially broader protection vs variants Link to study:

Side effects are a leading cause of vaccine hesitancy. The Novavax reactogenicity shows roughly half the frequency of each symptom, and lower severity. journalofinfection.com/article/S0163-…

Having worked with many EIS officers, I can confirm they are among the best and brightest. They leave high-paying jobs to serve communities, ready to face danger at a moment’s notice. Now, the entire class has been let go. These heroes won’t be there when we need them.

https://twitter.com/Farzad_MD/status/1890587835184324644

One particular memory of mine that highlights the character of an EIS officer. We were on call with an EIS grad while he was in the field. Heard screeching tires and the line went dead. Called his cell, and he picked up and said calmly, "Hi, it's [name]".

Results from PREVENT-19 Novavax pediatric RCT of >1,000 adolescents.
- Vaccine efficacy was 74% (original Wuhan vax vs Delta variant).
- Nearly all infections after vaccination were asymptomatic or very mild.
- Viral load lower in vaccinated, but not statistically significant Notably, this study used twice-weekly swabs to detect asymptomatic infections. Not directly comparable, but Moderna had 39% efficacy vs. asymptomatic infections in adolescents. Ad.26 was lower at 29%.
nejm.org/doi/10.1056/NE…
nejm.org/doi/10.1056/NE…

Recent RCT: Co-administering NVX (COVID) & PCV20 (Pneumococcal) vaccines is as effective as when given separately, with no extra side effects.
This is key, as both diseases are major killers, and PCV may also reduce severe COVID by reducing pneumococcal carriage (🧵on this below) Link to paper: journalofinfection.com/article/S0163-…

Nice coverage from Vox on some of the benefits of the Novavax COVID vaccine: similar effectiveness, fewer side effects, and potentially longer lasting protection. Since concerns about the mRNA platform and side effects are leading causes of vaccine hesitancy, increasing awareness will increase uptake and have societal benefits.
Link to article: vox.com/even-better/39…

Epidemiologists did remarkable work in the early days of COVID-19. Within months, they:
- Accurately predicted the timing of every major wave for the next 3 years.
- Warned SARS-CoV-2 would likely become endemic.
- Identified risk of aerosol transmission.

https://x.com/Daniel_E_Park/status/1865510627965374932?t=ZfA38-edK5Oiwm6hmJ5sJg&s=19

We knew from day 1 that airborne transmission was likely (like SARS-CoV-1).
As confusion w/ masks grew, we saw the urgent need to provide clarity on ventilation (e g. Excerpt from Drs. Prather @kprather88 and Milton, Oct 2020)
science.org/doi/10.1126/sc…
nejm.org/doi/full/10.10…

New RCT study shows the "conventional" Novavax COVID vaccine has a similar side effect profile to the routine meningococcal vaccine, and fewer side effects than the mRNA options.
Side effects are a leading cause of COVID vaccine hesitancy. This can help. Both concerns about the mRNA platform and vaccine side effects are leading causes of hesitancy.
Being able to say the NVX vaccine has similar side effects to routine vaccines that most people are familiar with could be a useful tool.
Paper:
sciencedirect.com/science/articl…

"Trust the experts" is generally a wise approach in many facets of life.
But in an era of Internet "experts" and Monday morning quarterbacks, sometimes we forget what expertise actually looks like.
Lessons from chess, pilots, and epidemiologists and applications to COVID, a 🧵 Chess: Do you know chess? Imagine being shown a chess board, with pieces placed as they were mid-game from a tournament 20 years ago, and being asked to recognize the game. Now imagine doing that with all the pieces replaced with identical discs.

Preprint: comparison of mRNA & protein vaccines and neurodegenerative and neuroinflammatory responses to SARS-CoV-2.
Infection causes neurological damage.
Both vaccines generally protective, but among higher-risk mice, only the protein-based vaccine was protective. Caveat that this is a small mouse study, and is a preprint. Link to the paper: biorxiv.org/content/10.110…

More evidence showing the updated JN.1 vaccines are protective against currently dominant strains (KP.3.1.1 and XEC).
Just in case you needed extra motivation to stay up to date on your COVID boosters.
Paper is here: thelancet.com/journals/lanin…
And my earlier thoughts on the preprint:
x.com/Daniel_E_Park/…

People often ask me what the optimal timing of boosters is. That's an incredibly complex question that varies by individual, including location, anticipated future exposure, family or contacts who are at higher risk, and variants. This paper covers a few of these nuances. Link to paper: academic.oup.com/cid/advance-ar…

Another paper from the PICOBOO randomized trial, evaluating second boosters after mRNA priming.
1) novavax is more durable
2) mRNA vaccines have higher antibody responses
3) novavax has fewer side effects
More nuances in this thread
journalofinfection.com/article/S0163-… 1) Durability: Pfizer antibody levels drop around 40% between 1 month to 3 months post vax.
Moderna is less, w/ a 14% drop in younger adults, 26% decline in older adults.
Novavax had only a 3% decline in younger adults and 17% in older adults.

A trio of Novavax preprints, showing 1) remarkable durability >6 months, 2) cross protection against newer variants, and 3) low reactogenicity (side effects), supporting NVX as an excellent booster platform.
medrxiv.org/content/10.110…
medrxiv.org/content/10.110…
medrxiv.org/content/10.110… 1) Antibody levels remained high over 6 months after the first booster, with pre-boost levels before Dose 4 being similar to post-primary antibody levels. This is quite remarkable durability.

Comparison of NVX (Novavax) and BNT (Pfizer) after primary or booster from South Korea through 180 days. NVX primary series offered slight "added protection" against infection (~10%) and severe disease (~35%), while homologous boost findings were mixed.
sciencedirect.com/science/articl… Again, this is one of the few populations that have the adequate sample size to explore this comparison. The 180 day window is helpful at assessing longer term patterns.

Preprint: Pfizer preprint supporting that JN.1 and KP.2 vaccines are similarly effective against currently circulating strains, including KP.3.1.1 and XEC.
And some very interesting info supporting earlier suggestions about conformation of JN.1, KP.2, and KP.3.1.1 The current dominant strains are KP.3.1.1 and XEC (which is gaining steam quickly)
covid.cdc.gov/covid-data-tra…

I closed my Public Health lecture today with this quick thought.

We can't control everything around us, but we can control our actions, we can impact those around us, and we can save and help millions around the world with our work, which is now more important than ever. There are reports a certain vaccine conspiracy theorist may have a role in the next administration. Vaccines have saved 154 million lives over the last 50 years - six lives every minute. Many more live full healthy lives thanks to prevention of chronic/debilitating illness

Large study provides support for many long COVID (LC) findings:
1 Fatigue & neurological symptoms most common
2 Women more likely to have LC
3 Reinfection has milder acute symptoms but more severe LC
4 Vaccination reduces LC risk
5 ⬆️post-COVID infections
thelancet.com/journals/lanwp… For #1, memory loss was a leading LC symptom along with fatigue, and brain fog was in ~15% of respondents.
Brain damage and neurological symptoms following even mild cases of COVID are becoming better understood and characterized

https://x.com/Daniel_E_Park/status/1847257999305273465