Thread by @michaelzlin

A short thread about Guillain-Barré syndrome (=GBS, peripheral paralysis) and J&J vaccines.

Today's ACIP presentation lays out the GBS risk vs benefit ratio in different age groups

cnn.com/2021/07/22/hea…

GBS often happens following infections and, because it is ameliorated by immunsuppressive treatments, appears to be due to antibodies elicited by the infection cross-reacting to some components on peripheral nerves.

J&J (and AZ) COVID-19 vaccines causing GBS may be unsurprising as these are (very limited) virus infections. These vax consist of a replication-defective adenovirus that infects cells to express SARSCoV2 spike (and most likely some leaky adenovirus proteins too)

The GBS following J&J and AZ vaccination occurs 10-22 days after vaccination, which is exactly the time when neutralizing antibodies start being produced and efficacy against SARSCoV2 begins to be measured in clinical trials.
medpagetoday.com/infectiousdise…

The GBS usually presents as bilateral facial paralysis, so in that way is different from most other kinds of GBS which more often affect the limbs.

Biggest risk:benefit is in men <29yo, followed by women 30-49yo, when looking at GBS cases per life saved

Tables from cdc.gov/vaccines/acip/…

But since COVID19 is also a virus infection, and quite a severe one at that, you might wonder, how many cases of GBS due to COVID19 are saved for every case of GBS due to the vaccine?

There were early case reports of COVID19 patients with GBS, but later analyses suggested GBS rates in COVID19 patients were no higher than historical rates (an example of the caution needed in evaluating case reports).

jwatch.org/na53272/2021/0…

That is, COVID19 doesn't seem to increase GBS risk. This might be surprising given common CNS involvement in COVID19, but CNS and PNS are very different environments. So J&J and AZ vax appear to increase risk of GBS in young males without protecting against any GBS from COVID19.

Ad vaccines may carry a small risk of "autoimmune" side effects due to the multiple Ad proteins present. While we knew from earlier Ad vax for Ebola that any side effects would be rare, many times more people have now received Ad vax for COVID19, so very rare effects can pop up.

There's also the vaccine-induced thrombocytopenic thrombosis (VITT) side effect in Ad vax (but rarer for J&J than AZ — maybe because they use different Ad species), which is harder to spot but which also responds to immunsuppressants

The risks of VITT (TTS in the ACIP presentation) after J&J were also noted today. Risk:benefit ratio was highest in 18-49yo females and in 18-29yo males in terms of TTS cases per COVID-19 death

RNA vax have their own side effect of myocarditis. It's about as common as GBS after J&J in women, but 10x more common in men and boys <29yo. Fortunately it's easy to spot as chest pain, and responds to anti-inflammatory drugs.

So where does that leave us? It's complicated but:
1. young men might actually prefer J&J's GBS to the 10x greater rate of myocarditis after RNA vax, but both are easily spotted and treatable, if side effects were the main consideration

2. young women might prefer the RNA vax to avoid worrying about rare GBS or VITT; myocarditis is similar in frequency but easier to spot and treat

3. men and women >50yo might favor the RNA vax as the rate of excess myocarditis is close to 0, and the RNA vax are a bit more effective in preventing breakthrough disease

4. everyone might prefer the RNA vax for better protection against disease since protection is common while side effects are very rare

Like everyone else, I also should emphasize that all three FDA-approved vaccines have been important life-savers. Also, they save many more cases of severe COVID19 that are worse than getting GBS or myocarditis.

Finally preventing 65%-88% of cases that would otherwise occur in the vaccinated is very important as reducing cases indirectly saves lives in the unvaccinated (but CDC wants to focus on the direct prevention of death only so it doesn't have to explain the 12-35% breakthroughs).

Thus we should consider the 1000s of COVID-19 cases saved in the vaccinated for each case of an adverse reaction part of the benefit as well. The above discussion, by ignoring these arguably greater beneficial impacts, thus vastly underestimates the benefits of vaccines.