Efficacy of Covid-19 Vaccines

Now that many of our patients have been vaccinated against Covid-19, they want to know if they could catch it anyway. The answer is yes, of course, but that does not mean that 5% of them will become infected, as some pundits have told them, if they received a 95% effective messenger RNA vaccine. The pundits are not distinguishing between relative and absolute risk.

 In the Pfizer, Moderna, and Johnson and Johnson phase 3 vaccine trials, efficacy was a measure of relative risk, based on the following calculation:

100 x (1- the number of cases of symptomatic COVID per 1000 patient-years of follow-up in the vaccinated group divided by the number of cases per 1000 patient-years in the placebo group).

In the Pfizer trial, for example, there were 3.6 cases of COVID-19 per 1000 person-years in the vaccinated group and 72.9 in the placebo group; plugging those numbers into the equation yields 95.0, the percent efficacy of the Pfizer vaccine. A person who received the vaccine was 19 times (95.0/5.0) less likely to develop symptomatic COVID-19 than a person who received placebo over an identical period of observation.1 Similar calculations generated the 94.1% vaccine efficacy rate in the Moderna trial and the 66.9% rate in the trial of the single-dose, adenovirus-vectored Johnson and Johnson vaccine.

The absolute risk offers a more intuitive sense of the real-life risk, but in these clinical trials the period of observation was not defined. All of the studies were terminated when a predetermined number of cases had been detected.

In the pivotal trial of the Pfizer vaccine, 8 of 18,198 participants (0.044%) who received both doses of the vaccine and 162 of 18,325 who received placebo developed typical symptoms and had a positive PCR test for the virus at least 7 days after the second dose.

In the Moderna phase 3 trial, symptomatic confirmed Covid-19 illness occurred in 11 of the 14,134 fully vaccinated subjects (0.078%) and 185 of the 14,073 who received placebo.2

In the phase 3 trial of the adenovirus-vectored Johnson and Johnson vaccine, among 19,630 participants who received the single dose of the vaccine, there were 116 cases of moderate to severe COVID illness (0.59%), compared to 348 cases among 19,691 who received placebo.3

Of course, neither efficacy percentages nor the numbers of symptomatic cases of COVID-19 convey the most important benefit of these vaccines: all 3 prevented severe disease and death.

In the Pfizer trial, there were 10 cases of severe COVID; 9 of these patients were in the placebo group.

In the Moderna trial, severe disease occurred in 30 participants and one died, all in the placebo group.

And even in the trial of the less efficacious, single-dose Johnson and Johnson vaccine, only 2 vaccinated subjects were hospitalized, compared to 29 in the placebo group; there were 7 deaths, all in South Africa (where the concerning B.1.351 variant was dominant) and all in patients who received placebo.

None of these studies tested the participants for asymptomatic infection. However, weekly PCR testing of vaccinated health care workers in southern California, carried out during a surge of disease in that area, found that only 7 of 4167 tested positive 15 days or longer after vaccination with the second dose of the Pfizer or Moderna vaccine. These participants were younger and presumably more exposed than those in the Pfizer and Moderna clinical trials.4 Other follow-ups of health care workers fully vaccinated with an mRNA vaccine, but with less complete testing, found new infections in 4 of 4069 (Jerusalem) and 4 of 8121 (Texas).5,6

So, for both the vaccinated but still fearful and the vaccine-hesitant who may undervalue the benefit of these vaccines because of something they’ve heard on television or read in the newspaper, we can offer reassurance. Once vaccinated, they are highly unlikely to be infected by the SARS-CoV-2 virus in the ensuing months and, hopefully, years, and if they do become infected, they are almost certain not to have a severe illness or to die.

  1. FP Polack et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383:2603.
  2. LR Baden et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384:403.
  3. FDA authorizes Johnson and Johnson COVID-19 vaccine. Med Lett Drugs Ther 2021; 63:41.
  4. J Keehner et al. SARS-CoV-2 infection after vaccination in health care workers in California. N Engl J Med 2021 March 23 (epub).
  5. S Benenson et al. BNT162b2 Covid-19 vaccine effectiveness among health care workers. N Engl J Med 2021 March 23 (epub).
  6. W Daniel et al. Early evidence of the effect of SARS-CoV-2 vaccine at one medical center. N Engl J Med 2021 March 23 (epub).

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Comments

  1. Michael E Makover, MD says:

    Of those who got COVID after vaccination, how many might have gotten less severe disease but that nevertheless led to long-term problems as seen in some unvaccinated people with mild disease?

  2. Thomas Newton, MD says:

    Not being a statistician, does this mean that the absolute risk after being fully vaccinated with Pfizer is only .04%?

  3. Clifford Dacso, MD says:

    This is a terrific analysis and should be standard reading for residents and students as they seek to understand how to interpret data.

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