COVID-19: Future’s so bright… I gotta wear shades

A friend of mine says that every news report should come with a warning similar to that for cigarettes: “Warning, this news report contains information that is both addictive and will be harmful to your mental health.” I think the same could be said for announcements by public health professionals. Listen, I get it, public health officials have to thread a very narrow needle. There must be some way to communicate information a little more positively, though. 

So, if you want happy information that is followed by the word “but” (meaning you should only listen to the bad news that comes after the “but”) then turn on the news. 

I, on the other hand, went to the SNL public relations school of Hanz and Franz, which means that I am here to “Pump… *clap*… you up!” 

Editor’s Note: This post is L-O-N-G. Get yourself a snack and a drink and plan to settle in for a while. It’s worth it. I promise.

Good news in younger age ranges

Pfizer sent out a press release on March 31 with results from a small study of their mRNA vaccine in patients 12 through 15 years of age. They were real, and they were spectacular. The study enrolled about 2,200 patients with half getting the mRNA vaccine and half getting placebo. Don’t freak about the small number of patients. There is no biologic, immunologic, or astrologic reason to suspect a different effectiveness or safety profile in 12 year olds versus 16 year olds (who we are already vaccinating). These types of “bridging” studies are very common and are regularly performed (even before the pandemic) when a vaccine already has sufficient data in older age groups. To require a pharmaceutical company to perform a second randomized clinical trial in another 40,000 patients would be a waste of time and money, especially during a pandemic.

Ok, so what did the press release say?

A disclaimer: do not pay too much attention to the big number I’m about to write… Pfizer reported that their vaccine was 100% effective in preventing symptomatic COVID-19 disease in children 12 – 15 years of age. The numbers of patients and disease were small, however, and nothing is 100%. A far better and more realistic way of describing these results is that they fall in line with all the other clinical trial and real-world effectiveness data we have available.

What about the Moderna vaccine?

Moderna is studying their vaccine in younger age groups and I anticipate their results will be very similar. Again, there is no reason why these vaccines should be different; they use the same mRNA in very similar formulations using the same technology.

What does this mean for these darling aliens we call our teenagers?

Expect extension of the current EUA (Emergency Use Authorization) for Pfizer’s vaccine down to 12 years of age within four to six weeks. And Moderna will get the same extension when they release their data in the next couple months. So this means our alien teenagers (that’s redundant) will be getting vaccinated this summer.

What about the vaccines in kids younger than 12 years old?

Both Pfizer and Moderna are studying their vaccine in children all the way down to six months of age. Spoiler alert… we have every reason to expect that these vaccines will be similarly safe and effective in younger children. I’m optimistic those clinical trial results will be available by the end of the year. 

I read in the news “The vaccines are effective, BUT they threaten all of our progress”

Listen, there are thousands of variants because COVID-19 is a virus and mutating (varianting?) is what viruses do. I wrote about the first variant of concern last May and have written before about the U.K. variant as well as the South Africa variant. We now have the Brazil variants, California variants, and even a New York variant. 

Here’s an idea, instead of naming the variants after where they were first discovered, let’s pick some fictional children’s cartoon character we can all agree should be loathed, or at least strongly disliked. For example, I propose that the South Africa variant be called the Caillou variant. And the U.K. variant the Peppa Pig variant.

Are these variants more contagious?

We don’t know that answer for certain. Most of the data that I’ve seen on increased contagiousness of the U.K. variant paints a plausible, but by no means definitive, picture of increased contagiousness. After all there’s no evidence that these variants spread easily through aerosolized transmission.

As an aside, I watched a press conference with CDC Director Walensky several weeks ago where she noted that personal protective measures such as distancing and masks still work and that many of the known U.K. variant cases at that time occurred in individuals who had not been wearing masks. 

You know what is the most contagious COVID-19 variant on the planet? The one you get when you gather in large groups, don’t keep your distance, and don’t wear a mask.

Are these variants more serious or lethal?

I know of no compelling evidence that these variants are inherently more lethal than the first strains of COVID-19. If they are more serious, it doesn’t seem like their lethality is substantially different. And if they are more contagious, you would expect the appearance of increased severity because more people could get infected.

Do the vaccines work against these variants?

We got great news on this front from an April 1 Pfizer press release, but I started writing this section before then, so you’ll have to read a bit more before you get to the mic drop.

I’ll start out with the U.K. variant, which appears to be one of the most common variants. The U.K. variant does not present a threat to vaccine efficacy, certainly not against the mRNA vaccines, and any effect against the J&J vaccine appears to be minimal. We have compelling in vitro data both mRNA vaccines produce antibodies that readily neutralize the U.K. variant. 

In addition, some of the most positive results of mRNA vaccine effectiveness comes from Israel, where according to news reports the U.K. variant accounts for about 80% of cases. As I reported in this blog post, other vaccines do not appear to have substantially reduced effectiveness against the U.K. variant, either.

How about the South Africa variant?

Here’s another statement the evidence clearly supports: the AstraZeneca (AZ) vaccine is ineffective against the South Africa variant. I have not written much about the AZ vaccine. I may write more in the future, but for now I will stick to one piece of evidence. 

There was a small but well designed randomized clinical trial published in the New England Journal of Medicine with negative results about the AZ vaccine versus the South Africa variant. 

This conclusion appears to be unique to the AZ vaccine, however. The J&J vaccine clinical trial showed effectiveness against the South Africa variant, albeit possibly lower than that seen against the UK or other variants. 

What is most interesting is that all of the AZ vaccine recipients who later were infected with the South Africa variant did not have neutralizing antibodies against the variant. This was the first clinical data I was aware of showing a correlation between lack of neutralizing antibodies and lack of protection. 

What about the mRNA vaccines and the South Africa variant?

Up until April 1 we only had evidence that the mRNA vaccines produce neutralizing antibodies against the South Africa variant but not any evidence clearly showing effectiveness in preventing disease. But in the April 1 press release that I mentioned above, Pfizer released data on actual protection against disease caused by the South Africa variant. 

In Pfizer’s original clinical trial, Pfizer enrolled 800 patients in South Africa. In that admittedly small subpopulation there were nine cases of COVID-19 disease, and six of those nine cases were caused by the South Africa variant. More importantly, all nine of the cases of COVID-19 disease in the population of 800 patients occurred in those who received placebo. There were zero cases of COVID-19 disease in vaccinated patients. 

Does this “prove” that Pfizer’s vaccine is protective against the South Africa variant? Not necessarily, but… (yes that means I want you to pay attention to what comes after the “but”) this very compelling evidence is about as good as we could hope for; we’re not going to have a clinical trial of 40,000 South Africans after all. 

Does this mean that Pfizer’s vaccine is 100% effective against the South Africa variant? No, but…(yes, that means I want you to pay attention to what comes after the “but”) I am very confident that the vaccine effectiveness of the mRNA vaccines (yes, I believe these results can be extrapolated to the Moderna vaccine) against the South Africa variant will be very high and not materially different than that seen against the original COVID-19 strain.

I saw in the news “The vaccines are effective, BUT we don’t know how long they’ll last.”

Well we don’t know how long they last, but the available evidence predicts a very durable immune response (fancy words for the vaccines will last a long time). 

In the April 1 press release Pfizer released final results of their clinical trial that followed patients for six months. Those results demonstrated approximately 91% effectiveness against symptomatic COVID-19 disease over those six months. There were a total of 927 cases of COVID-19 disease (850 in placebo recipients, 77 in vaccine recipients) in a study of over 44,000 patients, so I expect the confidence intervals to be narrow. 

Don’t look at that 91% number and think it’s different from the 95% number Pfizer reported back in November. It’s the same clinical trial over a longer observation period so the numbers were never going to be identical. Plus, those two percentages are not substantially different. We know that the Pfizer vaccine is highly effective for at least six months. (And the Moderna vaccine will look similar.) 

Most important, however, we have ample evidence that the immunologic response created by all the vaccines (not just the mRNA vaccines by Pfizer and Moderna) is exactly what needs to occur for a very long-lasting response.

How long-lasting? 

There is a good likelihood that the effectiveness produced by these vaccines will last for several years or longer. Besides, even if occasional boosters are necessary, they are not likely to be a substantial challenge, not after all the production, distribution, and administration experience we’re getting right now.

So to summarize where we are…

Pardon me for repeating some of this summary, but we are in a time of truly extraordinary medical advancement and not enough people are giving it the love it deserves.

We have two mRNA vaccines that are 90% protective in both clinical trials and real-world studies against both infection and disease, reducing both the spread of the virus and people getting sick from the virus. And these vaccines reduce the risk of severe disease, hospitalization, mechanical ventilation, and death, making the risk for any one patient exceedingly low.

These vaccines are more effective than we thought possible for a non-live vaccine administered in the muscle, targeting a virus that replicates in the respiratory tract. 

These mRNA vaccines are also very safe with more real-world safety data in a shorter amount of time than any other vaccine in history, except maybe the polio vaccine. 

But wait, there’s more! These vaccines are also safe and effective in adolescents, and we’ll have similar data in young children by the end of the year. 

But wait, there’s even more, uh, morer… The mRNA vaccines are even effective against the most concerning variants yet identified.

But wait, there’s even morer and morer… The J&J vaccine may look just as good as the mRNA vaccines once we get additional data. And we’re likely to get EUAs for vaccines by both Novavax and maybe even GlaxoSmithKline.

This is a gob smacking, jaw dropping, astounding, remarkable, dumbfounding, breathtaking, bewildering, shocking, not to mention really darn good achievement of historic proportions.

I have no “but” after all that vaccine awesomeness.  

Stay safe, and go make some lemonade.

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