The "Pandemic of the Unvaccinated"
Dr. Walensky's sound bite this past week quickly became the standard catch phrase in the media, and it isn't misleading. Our current COVID-19 infection rate is in the same (but slightly lower) ballpark as last summer, but what isn't in the same ballpark are numbers of hospitalizations, ICU admissions, and deaths, at least not yet. The main difference between this summer and last is the target population: now we are seeing the pandemic being driven by younger (unvaccinated) individuals who are less at risk for the more severe outcomes of COVID-19 infections. Clearly vaccines work, and we now have real-world evidence that demonstrates this. We are still in a race between variants and reaching herd immunity, and each one of those newly-infected individuals might be the one to develop and spread a more troublesome variant that not only has increased infectivity but also increased severity and/or ability to evade vaccine protection.
As a slight aside, yesterday (July 17) I tuned into a regular CDC/IDSA COVID-19 Clinician Call, and this one I thought was particularly useful with explanation of immunity from natural infection versus vaccines and a summary of COVID-19 antibody testing. The key take-home for antibody testing is that it should not be used to infer immunity following vaccination. These tests were only designed to predict likelihood that an individual was previously infected and says nothing about degree of protection. Just say no if a patient requests an antibody test to determine if they are immune. The recording from the July 17 session should be available within a few days.
Ready for Monkey Pox?
Also in the category of history repeating itself, we learned this past week about an individual with monkey pox in Texas, likely picked up in Nigeria. We see sporadic cases of monkey pox in the US, it isn't unexpected. Do you know what to look for to spot a case?
First of all, in spite of the name, don't ask about monkey exposure. Most humans acquire monkey pox from other animal reservoirs, principally rodents, in endemic areas. These areas include Central and West Africa. It can be a difficult diagnosis before the rash appears; the prodrome is nonspecific and consists of fever, malaise, headache, and myalgias. After the 1-3 day prodrome, the rash appears initially as macules and then progresses to papules, vesicles, and pustules. It is very similar to smallpox in that lesions tend to distribute more peripherally. Transmission from infected individuals to other humans most commonly is via droplet spread and likely requires prolonged close contact. Skin lesions themselves also are contagious. Travel history is the key, be sure to ask about that for anyone with a nonspecific febrile illness. Incubation period is about 5-13 days, easily long enough to allow for international travel before symptoms begin.
As the myocarditis is noted after the second dose, this strongly suggests an autoimmune etiology.
Though molecular mimicry is a possibility, I would have expected to see similar cases with the adenoviral platforms ,
As this is unique to the mRNA platforms , I worry that is is triggered by a bystander effect : vaccine translated spike protein peptides presented with MHC-1 antigens by the skeletal muscle cells induce a CD8 effector cell response.
Subsequently self antigens are released by these destroyed skeletal cells , processed and presented by dendritic cells with HLA-2 activating previously present but dormant self antigen T 4 cells.
Note- viral myocarditis is characterized by infiltration of T 4 cells and anti- mitochondrial antibodies as one example, cross react with skeletal and cardiac muscle cells.
More robust T cell responses in younger patients would explain the age pattern seen and myocarditis is more common in males , in general.
If this is the case , it suggests a number of difficulties:
1. This side effect may be characteristic of mRNA platform regardless of disease targeted.
2. There may be a substantial incidence of myocarditis in children < age 12 with these vaccines
3. As an example, in a patient who had myocarditis with COVID-19 vaccine, a MRNA platform influenza vaccine may booster the myocarditis autoimmune reaction.
I would love your option on this theory ?
My great fear is that we will see approval of the COVID-19 mRNA platform vaccines and then see an incidence of myocarditis that shakes public confidence in our vaccine programs .
Those are interesting thoughts, but I had hoped not to get into more myocarditis discussions in the absence of any new evidence. Suffice to say that from my standpoint there are little to no data to support any hypothesis for a mechanism of vaccine-associated myopericarditis. Also, in spite of the intense interest, it's not going to be easy to come to any conclusions very quickly. Remember, Kawasaki Disease has been under intense study for about 50 years and the mechanism is still poorly understood.
Even today the risk of cardiac disease in children is much higher from natural COVID-19 illness, just from MIS-C alone which as we know is a very uncommon condition. The weight of evidence is overwhelmingly in favor of vaccinating children versus not, now matter what adverse outcome one considers. It does bear watching, however, at some point the risk/benefit ratio could change especially if rates of infection go way down.