The Coronavirus Vaccines Are “Home Runs”
The vaccines prevent severe disease, hospitalization, and death.
Preventing severe disease and death is the greatest value of a vaccine and a very personal benefit to each one of us. Achieving herd immunity — that is, stopping or at least greatly diminishing transmission of disease — is also a great value and a benefit for the entire community. On both scores, the three FDA-authorized COVID vaccines deserve to be called “home runs.”
The Pfizer- BioNTech Phase 3 trial enrolled over 43,000 volunteers; half of the volunteers received the vaccine; the other half received a placebo. Over a third of them were at risk for serious disease.
The “primary endpoint” of the study was the number of symptomatic infections that occurred in each group beginning seven days after the second dose of the vaccine. At that point in time, the volunteers were at the peak of their immune response to the vaccine.
The development of mild to moderate symptomatic infection occurred among eight volunteers in the vaccinated group and among 162 volunteers in the placebo group, for an efficacy rate of 95%.
The development of severe infection occurred only once in the vaccinated group compared to nine among the volunteers in the placebo group. There were no deaths. Results of the Pfizer study can be found on the Food and Drug Administration website and reported in the New England Journal of Medicine.
Is there some early protection after receiving just the first dose of the vaccine?
In the Pfizer study, during the 21 days between their first and second doses, 39 volunteers in the vaccinated group developed a symptomatic infection while 82 volunteers in the placebo group did so. That was a 50% efficacy rate after just one dose. The results are better when considering only those infections that occurred beginning two weeks after the first dose, i.e., when immunity from the first dose peaked. From day 14 to 28 there were 6 and 42 symptomatic infections, respectively.
Regarding the Moderna vaccine, just over 30,000 volunteers were enrolled with about fifty percent at risk for severe disease. The primary endpoint was slightly different — symptomatic infections that occurred fourteen days after the second dose.
The FDA data and New England Journal of Medicine indicate the vaccinated group developed eleven infections and the placebo group developed 185 for a 94% efficacy rate. There were no severe infections among the vaccinated volunteers whereas there were thirty including one death in the placebo group. As to infection prevention after the first dose until day 42, seven volunteers in the vaccinated group developed infection compared to 65 infections in the placebo group.
In a new report from the Centers for Disease Control (CDC) on March 29th, in a study of healthcare workers, the first dose of both vaccines was effective at preventing symptomatic infection and also prevented asymptomatic infection.
The Johnson &Johnson vaccine requires only one dose.
The FDA data analysis indicates that the vaccine was 67% effective (116 vaccinated individuals vs 348 cases placebo group) in preventing moderate/severe disease beginning 14 days after vaccination and 66% (66 vs. 193 cases) beginning 28 days after immunization.
The image below shows this graphically. Although the efficacy rate appears less than for the Pfizer and Moderna vaccines, the case definitions were somewhat different and the volunteer groups were from different times and countries. Most importantly, there were no Covid-19 related deaths among the vaccinated group compared to seven among the placebo group. None of the vaccinated group required hospitalization.
These three vaccines have emergency use authorization from the Food and Drug Administration. They are clearly very effective at preventing mild to moderate disease and especially preventing severe disease, hospitalizations, and death.
Two additional vaccines are in the offing that were part of Operation Warp Speed — The Oxford-AstraZeneca vaccine and the Novavax vaccine. The former has been approved in the United Kingdom, the European Union, and by the World Health Organization.
The company has recently released updated data on its US, Peru, and Chile Phase 3 trial. With over 32,000 volunteers, the efficacy rate to prevent mild to moderate disease was 76% and over 85% for those over age 65. None of the vaccinated group required hospitalization and none died. It should shortly be presented to the Food and Drug Administration. The Novavax vaccine is not ready for submission to the FDA; probably in the early spring. It looks promising from early data.
A common question is whether a second dose of the Pfizer or the Moderna vaccine is necessary.
While it is true that both start working rather effectively within about ten days after the first dose, the full effects are not seen until after the second dose. Therefore, for the additional efficacy and possibly longer immunity, the second dose is important and I would advise getting it on schedule if possible.
However, the CDC, although recommending the second dose be given at the prescribed time interval, now indicates that it is acceptable to delay it for a few weeks. The United Kingdom is actively delaying the second dose of the Pfizer-BioNTech and the Oxford-Astra Zeneca vaccines for up to 12 weeks in an effort to use available supplies as first doses for more individuals.
A small study from the Oxford developers indicates that one dose reduces transmission and prevents severe infection during that 12-week window. The government’s decision has met with resistance because no clinical trials have tested this approach. For now, the UK is proceeding.
A related question — if I am given the opportunity to get either the Pfizer or the Moderna now, should I wait for the Johnson & Johnson vaccine since it only requires one shot? My response is simple. Get whatever vaccine is offered now. Do not wait, especially if you are a high-risk person for severe disease. Remember that a coronavirus infection can be deadly.
We hear regularly about variants of the coronavirus. Should you be concerned? Mutations of RNA viruses, including the coronavirus, are very common. Many coronavirus mutations have been detected during this pandemic and there will undoubtedly be more over the months and years to come.
It is important to understand that mutations only develop while the virus is infecting a human host. If the virus is not inside a human cell, it cannot mutate. So, the best defense against mutations is to get everyone or nearly everyone to both take the standard precautions of masking, social distancing, etc. as well as getting vaccinated so that transmission from person to person is markedly curtailed.
The media tends to over-hype negative news and a new study reviewed by the New York Times demonstrates this with Covid-19 reports in the mainstream media. That said, the variant in the United Kingdom has proven to be substantially more transmissible than the original virus but the available vaccines are quite effective against it.
Another concern is the variant in South Africa because in a small study it could not be as well controlled by the Oxford -Astra Zeneca vaccine but that and the other vaccines still give good protection against hospitalization and death.
Here is the good news. These new Covid vaccines, such as the mRNA vaccines of Moderna and Pfizer can be “tweaked” quite easily. Since they are now known to be safe as well as effective making a change in the mRNA to match the genetic sequence in the new variant is a relatively easy task.
An updated vaccine can then be tested in small numbers of volunteers to be sure that it is effective in producing neutralizing antibodies and if so, it should be able to get fairly rapid FDA approval. The technology is different for the AstraZeneca and the Johnson & Johnson vaccines or from the technology used in the Novavax vaccines but in each case alterations can be made reasonably readily and each company is doing so now.
The rollout has not been and still is not perfect (nothing is), but it is time to reflect and appreciate that this accomplishment in less than a year is incredible. No vaccine, let alone three and soon five, has ever before been created, tested, found to be incredibly effective, authorized, and administered as widely in anywhere near as short a time frame. It really can be declared that these vaccines are “home runs” — actually grand slams!