January 31st, 2021

Are We Expecting Too Much from Our COVID-19 Vaccines?

There are no absolutes in life. And nothing is perfect.

Tom Brady isn’t always in the Super Bowl (hard to believe). Serena Williams occasionally exits tennis tournaments in the early rounds. Tom Hanks and Meryl Streep sometimes appear in movies that are stinkers.

I’ve always thought that Frank Lloyd Wright’s Guggenheim Museum in New York fits horribly on Fifth Avenue, and looks like a toilet (not an original thought). Even the Beatles unfortunately released Revolution 9, an interminable abstract sound collage of musical “art” — my vote for their very worst “song”.

So why, then, are we expecting perfection from our COVID-19 vaccines? The vaccines developed in record time and our best chance at controlling the pandemic?

That’s what struck me late last week when we heard the results of two important COVID-19 vaccine studies, one from Novavax, the other from Johnson & Johnson.

Both vaccines worked, but there’s a distinct tone of disappointment in some of the news coverage.

In the Novavax trial, which used a two-shot protein-adjuvant strategy, the vaccine was 90% effective in the United Kingdom, but only 49% effective in South Africa, with most of the vaccine failures in South Africa the result of the B.1.351 variant.

Johnson & Johnson used an adenovirus 26 (Ad26) vector vaccine and one shot. It was only 72 percent effective in preventing COVID-19 in the United States and just 57 percent in South Africa.

(Italics mine, to make a point.)

With the 95% protection in the Pfizer and Moderna studies of mRNA vaccines, the headlines making unfavorable comparisons are understandable.

But there’s a lot to like about these results, even based on the limited information available in the press releases.

Both studies faced a more challenging COVID-19 transmission dynamic than Pfizer and Moderna — with a global surge in cases and emerging variants that are more contagious, potentially of greater disease-causing virulence, and harboring antigenic properties making them more evasive of vaccine protection. We simply don’t know how the Pfizer and Moderna vaccines would perform under similar pressures.

And both vaccines appear to prevent severe disease, a critically important endpoint. (Numbers are small in the Novavax press release, but still in the right direction.) Since it’s highly unlikely we’ll ever be able to eliminate SARS-CoV-2 from the planet, converting it from something that fills our hospitals into a nuisance respiratory virus — causing a mild cold or sore throat — is a welcome trade-off.

Prevention of severe disease is something all of these vaccines appear good at, according to a summary by my Boston ID colleague Dr. Roby Bhattacharyya.

Or, as put quite succinctly by longtime vaccine expert Dr. Paul Offit:

You want to stay out of the hospital, and stay out of the morgue.

More good news — neither vaccine requires the kind of ultra-cold storage of the mRNA vaccines, a huge plus for distribution. And a one-dose strategy could greatly speed getting a larger number of people with at least some protection.

Meanwhile, in related news, reports of COVID-19 vaccine “failures” continue to make headlines, again making me wonder — why are our expectations so high? Did we really expect these vaccines to be perfect? We’re still in the middle of a pandemic, with only a small fraction of the population vaccinated.

Of course, cases of COVID-19 will continue to occur, even after vaccination. They are not 100% effective, even under the best-case scenario of a clinical trial. What we’re hoping for with vaccination is that there will be fewer cases, that they will be less severe, and hopefully less contagious.

I’m highlighting the distinction between “fewer/less” versus “zero” because there’s reason to expect that real-world effectiveness will not match clinical trial efficacy.  We must guard against reports of vaccinated individuals who get COVID-19 as evidence that they don’t work at all.

We don’t know, for example, how they will perform in the frail elderly or the severely immunocompromised — people too infirm to participate in the clinical trials, yet appropriate targets for early immunization. Plus, the variants may make their effectiveness lower than in clinical trials, which is why sequencing of cases that occur after vaccination will be critical.

The true effect on disease incidence must await large, population-based studies — studies we’re likely to see relatively soon, such as these encouraging preliminary data from Israel, which so far has vaccinated a higher proportion of its population than any other country.

Meanwhile, let’s stop expecting perfection, carefully review the emerging research, and focus on getting as many people vaccinated as fast as possible.

And enjoy this amazing medley as a Revolution 9 palate cleanser.


9 Responses to “Are We Expecting Too Much from Our COVID-19 Vaccines?”

  1. Alex Crawley says:

    Great commentary!

    So far these are the best infographics I’ve seen on educating patients on covid vaccines:

    Both are from the University of Waterloo in Canada.

    Has anyone else seen other useful tools yet?

  2. Kimon Zachary says:

    Johnson & Johnson used moderate-to-severe disease, not just any symptomatic disease, as the primary endpoint, making the comparison to the mRNA vaccines appear even more unfavorable (and do we think the Variants of Concern really impacted the US data?). However, the comparison seems a bit unfair, given the single dose regimen. I eagerly await the actual data and hope they are robust with regards to hospitalizations and severe disease. I also wish they had started their two dose trial sooner.

    If the single dose J&J gets FDA EUA, it will be a challenge to determine who should get it instead of two doses of one of the mRNA products. There will be perceived inequities. Maybe keep the mRNA timeline as is, and offer J&J to groups otherwise not yet eligible?

  3. Emilio Fumero says:

    Great analysis PAul. We should not forget that influenza vaccine when the virus swift could only bring as low as 35-40% efficacy and still is undeniable the impact on overall year influenza pandemic. Covid-19 vaccine achievements are definitively great successes. best

  4. Luiz Augusto M. Fonseca says:

    Great analysis! We need vaccines and to vaccinate the most people we can, all over the planet. All vaccines so far seem to be good enough for this task-even CoronaVac, the virus-inactivated vaccine from Chinese Sinovac that is currently being given in some Brazilian states.
    And there is a simple way of having an idea of the exposure intensity of the samples involved in each vaccine trial: just measuring coronavirus disease incidence rates in the placebo arm. for Example, incidence rates in Pfizer’s trial placebo arm was roughly half that of Oxford/AstraZeneca trial and one-fourth that of CoronaVac.

  5. Bernhard Lämmle says:

    Dear Dr. Sax
    your comment is excellent and to the point (as always). Thank you very much for putting things into perspective
    Bernhard Lämmle, Switzerland

  6. Sandy. Kimmel, M.D. says:

    I agree that it’s hard to compare the efficacy of different vaccines. After all, the efficacy of the Pfizer Covid-19 vaccine is at best 52% after the first dose. I am not an I.D. expert but understand that J&J is planning a study with a second dose (booster) of their vaccine two months after the first. Am I correct?

  7. David Charkes M.D. says:

    I am 89, my wife 88. We stay at home except for grocery shopping twice a week, curbside dinner pickups once or twice a week. Our children visit us every few weeks, all wearing masks. We live in a
    retirement community where others do the same. So far only one person of 630 has become infected, and survived. We are scheduled for vaccination in about 6 weeks. Will it make a difference for us? I doubt it – For those who are young(er) and live in crowded inner city housing the story is different. That’s where action (including vaccination) is important to get the RR below unity.

  8. Sean Gartner says:

    Fantastic article. Great drive home message “It’s good to avoid the hospital and morgue”, and all these vaccines will do that, and will bring us closer to ending things.

    Also as a proud Canadian and fan of Walk off the Earth, here is another unique video they made years ago


  9. Robert Beckhardt M.D. says:

    It’s marvelous that we have technologies emerging that will enhance the chances of defeating the virus. It’s unnerving that all the effort, talent and expenditure to create vaccines is not universally rewarded with the public’s unanimous and unequivocal embrace of the simplest behaviors to add very significantly to the chances that control will occur sooner than later so fewer will succumb to the disease. The blame for this, well beyond any reasonable doubt whatsoever is the willingness of many in the political class to promote an incompetent, self-serving leadership whose reckless disregard of science will surely kill more people, lead to more distrust of scientific rigor and take years to repair.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

Biography | Disclosures | Summaries

Learn more about HIV and ID Observations.