{"id":9981,"date":"2021-01-31T13:28:40","date_gmt":"2021-01-31T18:28:40","guid":{"rendered":"https:\/\/blogs.nejm.org\/hiv-id-observations\/?p=9981"},"modified":"2021-01-31T20:56:41","modified_gmt":"2021-02-01T01:56:41","slug":"are-we-expecting-too-much-from-our-covid-19-vaccines","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/are-we-expecting-too-much-from-our-covid-19-vaccines\/2021\/01\/31\/","title":{"rendered":"Are We Expecting Too Much from Our COVID-19 Vaccines?"},"content":{"rendered":"
\"\"<\/a>

Photo by Wolfgang Hasselmann<\/a> on Unsplash.<\/a><\/p><\/div>\n

There are no absolutes in life. And nothing is perfect.<\/p>\n

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.<\/p>\n

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<\/a>, an interminable abstract sound collage of musical “art” — my vote for their very worst “song”.<\/p>\n

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?<\/p>\n

That’s what struck me late last week when we heard the results of two important COVID-19 vaccine studies, one from Novavax<\/a>, the other from\u00a0Johnson & Johnson<\/a>.<\/p>\n

Both vaccines worked, but there’s a\u00a0distinct tone of disappointment in some of the news coverage.<\/a><\/p>\n

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

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

(Italics mine, to make a point.)<\/p>\n

\n
\n
\n
\n
\n

With the 95% protection in the Pfizer and Moderna studies of mRNA vaccines, the headlines making unfavorable comparisons are understandable.<\/p>\n

But there’s a lot to like about these results, even based on the limited information available in the press releases.<\/p>\n

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.<\/p>\n

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.<\/p>\n

https:\/\/twitter.com\/VirusesImmunity\/status\/1355149007220310019?s=20<\/p>\n

Prevention of severe disease is something all<\/em> of these vaccines appear good at, according to a summary<\/a> by my Boston ID colleague Dr. Roby Bhattacharyya.<\/p>\n

Or, as put quite succinctly<\/a> by longtime vaccine expert Dr. Paul Offit:<\/p>\n

You want to stay out of the hospital, and stay out of the morgue.<\/p><\/blockquote>\n

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.<\/p>\n

Meanwhile, in related news, reports of COVID-19 vaccine “failures” continue to make headlines<\/a>, 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.<\/p>\n

Of course, cases of COVID-19 will continue to occur, even after vaccination.<\/em> 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.<\/p>\n

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.\u00a0 We must guard against reports of vaccinated individuals who get COVID-19 as evidence that they don’t work at all.<\/p>\n

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.<\/p>\n

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<\/a>, which so far has vaccinated a higher proportion of its population than any other country.<\/p>\n

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

And enjoy this amazing medley as a Revolution 9 palate cleanser.<\/p>\n