June 1st, 2021

We’re Allowed to Say that Some COVID-19 Vaccines Are Better than Others, Right?

Centers for Disease Control and Prevention.

Over on the CDC website, an amazing resource, there’s this statement about the COVID-19 vaccines:

The best COVID-19 vaccine is the first one that is available to you. Do not wait for a specific brand.

I certainly agreed with that comment back in late 2020 and early 2021, when demand for vaccines exceeded supply, and we faced record daily case numbers and a race against more transmissible variants, in particular B.1.1.7.

But fast-forward to today, and things COVID-19-wise in the United States have remarkably, wonderfully, changed. (Knocks wood.) Vaccine supply is plentiful. More than half the population has received at least one shot. Cases, hospitalizations, and deaths continue to decline.

Plus, we’ve got a much-expanded database on vaccine effectiveness and safety, in particular with the mRNA vaccines made by Pfizer and Moderna, and an emerging sense of the J&J vaccine as well. Is the CDC’s statement still true?

Let’s take a look at the three vaccines available to us right now, comparing them in various metrics.

Effectiveness. We were appropriately cautious about making cross-study comparisons between results of the Pfizer and Moderna phase 3 studies versus those from the J&J study — different seasons, different variants, different geographic locations, different protocols.

But let’s be blunt — a difference between 95% and 60–70% efficacy in preventing symptomatic disease is pretty large. Plus, now we have many population-based studies of the mRNA vaccines showing 90% or higher effectiveness in clinical practice. Effectiveness studies for the J&J vaccine are just starting to appear, and the data look quite similar to the results from the clinical trial — in other words, around 70% effective.

Safety. Data on the rare — but serious — syndrome of thrombosis with thrombocytopenia (TTS) linked to the J&J vaccine were updated at the latest ACIP meeting on May 12. There have now been 28 cases after nearly 9 million shots. The median age was 40 (range 18–59), with 22 women and 6 men, with the highest risk among women ages 30–39 (roughly 1 case for every 80,000 doses). Again, amazing work by our vaccine safety program in identifying this important safety signal.

The mRNA vaccines, meanwhile, have no confirmed cases of TTS among over 245 million doses administered. Those are extremely reassuring data. Yes, subjective side effects are more common with the mRNA vaccines than with the J&J vaccine, and CDC now is tracking reports of myocarditis among younger people receiving these vaccines — connection still not confirmed — but many of these myocarditis cases have been mild. Meanwhile, some of the TTS cases have led to permanent disability and even death.

Boosters. It’s the question everyone wants to know — when will we need booster shots? From they are inevitable since antibody titers decline to never since cellular immunity is forever, the honest response is that we just don’t know.

But, if antibody titers are a marker for when we’ll need boosters, this modeling study shows a correlation between antibody titers and protection, implying we’ll need them sooner after the J&J vaccine than the mRNA vaccines. Which would not be very surprising with a one-shot approach, would it?

Convenience. Here the J&J vaccine should be the clear winner, requiring only one shot, and also being easy to ship and store. When we first heard of this advantage, many of us assumed this would mean a far greater supply and availability of the J&J vaccine. However, this is currently not the case, at least not yet. Manufacturing of the mRNA vaccines has clearly accelerated, and they are widely available in many diverse locations.

These differences are stark enough that I posted this poll last week:

It seems that most agree with me that the mRNA vaccines are now preferred. If you have a treatment or vaccine that’s both more effective and safer, you don’t need to be a disease modeler to figure out which one is better.

In the comments to this poll, some cited the contrast between where we are currently in the United States, and the situation globally — which remains dire, and still warrants a “first vaccine available” strategy. I cannot stress this point enough.

Others mentioned the importance of patient choice. I acknowledge this is an important consideration for individual cases — someone might need to reach that magic 2-week protected threshold sooner, or not have the time to come back for a second dose. These reasons could be enough to justify going forward with the J&J vaccine preferentially.

However, if someone asked me what COVID-19 vaccine I’d recommend, based on what we know now, my answer would not be “whichever one you prefer” or “whichever one you are offered first” — especially if it were a 35-year-old woman.

It would be an mRNA vaccine.

19 Responses to “We’re Allowed to Say that Some COVID-19 Vaccines Are Better than Others, Right?”

  1. Roberta Carroll says:

    What would you recommend for somebody who has survived documented Covid without sequelae?
    Somebody who has survived Covid and has moderately severe “Long” Covid?

  2. Luis Rico says:

    What about the price? Not a simple matter.

  3. Darko Richter says:

    I just find Dr. Sax’s comments useful, succinct and correct, and in line with what I perceive as common sense based on scientific data.

    • Bruce Oran, D.O. says:

      I think there is also an opportunity to customize and risk-stratify advice. I had a young female patient the other day who wanted to take the J&J vaccine just to be “over with Covid”. I advised against it as she is of child-bearing age, currently on birth control pills thus already at some thrombotic risk. Though the likelihood is small, should she have a significant complication, it might as well have been 100%. I advised the mRNA vaccine and she agreed.

  4. Philip Bolduc says:

    Hi Paul – I wonder if someone vaccinated with the J&J vaccine would benefit from getting a Moderna or Pfizer series. I haven’t heard that this is being studied given the focus on vaccinating as many folks as possible, but now that vaccine supplies are ample throughout the US and as the information in your post becomes more widely known, I expect to get this question from patients. Your thoughts? Thank you – Phil

    • Erika Otter says:

      Public health person here, dutifully got J&J right away when I could, just asked this question when I took my kid to be vaccinated – can I get a dose of Pfizer or Moderna now? They said no, but I would if I could!

  5. julio c melo, md says:

    Dr Sax analysis is based on the available science and i truly trust and enjoy reading his interpretations and recommendations.
    Though not available in USA , the Sputnik V / Sputnik Light and the Chinese Covid 19 vaccine ( dead virus ) are the predominant vaccines in most South American Countries. I am frequently asked my opinion about those vaccines since i have plenty of relatives there. I would like to know Dr Sax opinion of those vaccines, efficacy especially. Many thanks.

    • gerald creager says:

      I recently read a review of clinical results, and while it’s not in front of me right now, I recall the Chinese vaccine reviewed had an efficacy on the order of 62% and had reasonable response to most of the variants of interest. I don’t recall seeing a Sputnik review from what I’d consider a credible trial. Based on that, I suspect Dr Sax would still recommend the more effective mRNA vaccines.

  6. Al Padilla MD says:

    Another, more easily comprehensible way of presenting this is 4-10% “inefficacy” for the mRNA vaccines and 30-40% inefficacy for J&J. Yes, it’s analagous to half-full/half-empty, but only the J&J is anywhere near 50%.

  7. Alan King says:

    Pfizer can now be kept for 30 days in a less stringent freezer or refrigerator, which will significantly reduce the supply line storage complexity of these miraculous vaccines.

  8. DBDavid says:

    Dr Sax, please comment about the myocarditis cases repirted with the Pfizer vaccine in Israel.

    • gerald creager says:

      Time will tell. Perhaps the best starting point on that investigation will be the Big 10’s Cardiac Registry, where they’ve been recording such cases. I’ve not dove into the statistics myself, so I’ve no answer, but I suspect, since we’ve seen inflammatory infiltration into cardiac muscle solely from infection, it will be difficult to attribute myocarditis solely to a vaccine.

  9. Jon Blum says:

    If I understand correctly, there is a trial in progress of a two-dose regimen of the J&J vaccine, Ensemble 2. I don’t know when results will be available, but it would not be surprising if it showed better efficacy than one dose. After all, two doses are better than one for many vaccines (including the mRNA COVID vaccines). The J&J vaccine is approved for a single dose because the company made a strategic decision to do the trial that way. I suspect many J&J recipients will come back for a second dose if a benefit is shown. They will get the second dose later than the trial recipients, but that’s unlikely to be a problem. Some will still want a booster dose of an mRNA vaccine instead due to fear of clots, but it may be a long time before we have evidence for that strategy.

  10. Randall Fisher says:

    I suspect the myocarditis cases are going to end up being causally related. We know that wild-type infection with SARS-CoV-2 also causes myocarditis. It may be that that disease process is largely a post-infectious issue, rather than directly related to viral replication. If so, it stands to reason that the vaccines, which produce at least a somewhat similar immune response to that caused by wild-type infection, might also be expected to cause a milder form of the condition, probably in persons already predisposed to such a problem were they to be infected.

  11. John Blakey says:

    I completely agree with you that there are significant differences in safety and efficacy. I would add, however, that another alternative will soon be available that is arguably better than all of the current shots on both counts. Novavax’s vaccine is protein-based with an adjuvant. Efficacy against the Wuhan strain is higher than both mRNA shots, and it’s also shown strong efficacy against the UK strain. From what limited data is available at this point the safety profile is also excellent, and very likely better than all currently approved shots.

    I write this as someone whose 17-year-old son has developed postural orthostatic tachycardia syndrome (POTS) following the second shot of Pfizer’s vaccine. This is another serious side effect that is being increasingly recognized.

    As a healthcare provider I had little choice but to get the mRNA shot in January. I was hoping the the Novavax vaccine would have been approved months ago and be the one for my kids, but supply shortages, other logistic challenges and potentially politics have delayed the approval. It’s very unfortunate.

  12. Nadim Salomon says:

    Statements of greater effectiveness may lead to more vaccine hesitancy as people in other parts of the world think they are being offered inferior vaccines. Tracking systems for second dose may be difficult to implement in many parts of the world. The JJ vaccine could lead to faster protection against severe disease during COVID surge. Effectiveness in one country is not effectiveness in other countries due to supply and implementation of second dose. Pending head head comparisons, I think first available vaccine and disclosure of know side effects may be good policy.

Leave a Reply

Your email address will not be published. Required fields are marked *

Note: This is a moderated forum. By clicking on the "Submit Comment" button below, you agree to abide by the NEJM Journal Watch Terms of Use.

Our physician bloggers cannot respond to requests for personal medical advice, and recommend patients discuss health issues with their individual physicians.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

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.