Silver Bullet Aug 20 - Understanding changes in vaccine protection and the Delta variant
A weekly update on all things COVID-19. News, public health guidance, trends, breakthroughs, and thousands of scientific papers distilled down to what you need to know right now.
Delta shifts vaccine efficacy against infection, but not hospitalization
The emergence of the pandemic prompted an unprecedented global acceleration of scientific research, and with it an extremely high demand for the updated science news about the virus. Scientists and media outlets have increasingly relied on unpublished manuscripts, partial data sets, and even social media posts for clues about the the course of the pandemic and how to fight it. The past two weeks have seen ongoing resurgence of COVID-19 across much of the country, driven by the new Delta variant, a strain of SARS-CoV-2 that transmits much faster than the original strain or previous variants. With that resurgence has come new concerns about how long protection against the virus lasts, whether it protects against Delta, and whether vaccinated people are transmitting the virus. The CDC has recommended that vaccinated people wear masks in areas of substantial or high transmission, and the Biden administration has announced that previously vaccinated people will now be offered an additional booster eight months after their previous inoculation, starting in September.
The scientific evidence for these changes has not always been reported clearly, particularly when it comes to studies that have not been published or peer reviewed. That has left many to fear that vaccines don’t protect them anymore. The evidence still supports vaccines as having very strong protection, but with some additional challenges for the Delta variant. Here are some of the most important new studies for understanding the shifting public health response to the Delta variant.
The Provincetown outbreak
Several of the key recent studies underlying new public health policy have just been released in the CDC’s Morbidity and Mortality Weekly Report. While the MMWR is not a peer-reviewed journal, all of its reports go through a similar process at the CDC known as clearance. The Provincetown outbreak was widely publicized after the CDC issued updated guidelines that vaccinated people should wear masks indoors in public. Shortly after, statements referencing the Provincetown outbreak were issued by public health officials, and the data in the form of powerpoint slides was leaked to The Washington Post. Finally fully published in the MMRW as an Early Release on July 30, the study documents a COVID-19 outbreak associated with summer gatherings in Barnstable County, Massachusetts, among whom about three quarters (76%) were fully vaccinated. This study has been widely taken out of context as evidence that the vaccines either never were effective or have lost their efficacy, in spite of the authors’ note that, “data from this report are insufficient to draw conclusions about the effectiveness of COVID-19 vaccines against SARS-CoV-2, including the Delta variant, during this outbreak.”
The reason that vaccine effectiveness can’t be inferred from a study like this is that to properly calculate vaccine efficacy, you need four numbers. You need the number of vaccinated people who were infected, the overall number of vaccinated people in the pool, the number of unvaccinated infected, and the overall number of unvaccinated in the pool. In pharmaceutical company clinical trials, a known pool of volunteers receive either vaccine or placebo, and then are followed for a period of time, so all of these numbers are known and the number of infections in each group can be compared. The Provincetown outbreak does not include the overall numbers of both vaccinated and unvaccinated that could have been exposed to the virus during that time period.
The report continues, “As population-level vaccination coverage increases, vaccinated persons are likely to represent a larger proportion of COVID-19 cases.” That means rising proportions of breakthrough infections compared to cases in unvaccinated people are to be expected as vaccination rates rise. Taking it to its logical extreme, if 100% of the population is vaccinated, then 100% of infections would be in vaccinated people.
So what is the main significance of this study? The CDC found that vaccinated people with breakthrough infections seemed to have about as much virus in their nasal cavities as unvaccinated infected people. That means if vaccinated people develop infections, even if those infections are mild, they might still be able to spread the virus. More study is needed about whether this is actually happening, but currently experts still believe that the Delta surge is being driven by unvaccinated people. As a precaution, the CDC has recommended universal masking in indoor public settings as a precaution, even for fully vaccinated individuals.
Decreases in vaccine protection
Another study in the MMWR published Aug. 18 details findings from a study of vaccine efficacy in New York residents between May 3 and July 25, 2021. This study groups all vaccines together, and defines full vaccination as beginning 14 days after the final injection. The study found that vaccines were more than 90% effective for preventing hospitalization, even during a period when the Delta variant was prevalent. However, some decline was found in protection against new infection over that time period, from 91.7% to 79.8%. It’s important to keep in mind that prior to the release of clinical trial data by the vaccine manufacturers, the FDA set a minimum standard of 50% efficacy for approval. That means that while it’s encouraging to see numbers of 90% or more, a vaccine that is 79.8% effective still clears the bar by a large margin. In a separate report, the CDC found that protection against being hospitalized with COVID-19 was sustained for 24 weeks, declining only 2% from 86% 2-12 weeks after vaccination, to 84% at 13-24 weeks after vaccination. Lastly, another MMWR study in US nursing homes showed that vaccine protection against infection declined from 75% to 53% between March and August of this year reflecting the shift pre-Delta strains of the virus to a time when Delta was prevalent. (Note: that vaccine efficacy is reduced for older age groups, so starting at 75% is consistent with the baseline efficacy rates from clinical trials.)
A different study published Aug. 12 in the peer-reviewed New England Journal of Medicine found that efficacy against symptomatic disease of the first dose of the Pfizer-BioNTech vaccine or the AstraZeneca vaccine was decreased against Delta compared to the Alpha variant (B.1.1.7). Both vaccines were about 30.7% effective against Delta after the first dose, compared to 48.7% efficacy against Alpha after one dose. (These vaccines were not approved for just one dose, however.) For the Pfizer vaccine, efficacy after two doses was 93.7% for Alpha, and 88.0% for Delta. Two doses of the AstraZeneca vaccine were 74.5% effective against Alpha and 67.0% effective against Delta. This study did not distinguish between hospitalizations and infections.
Comparing Pfizer and Moderna
A study published on the preprint server Medrxiv compared efficacy of the Moderna and Pfizer vaccines to each other between Dec. 1 2020 and July 29, 2021. In this retrospective, observational study, they found that while both vaccines strongly reduced the risk of SARS-CoV-2 infection and severe disease, people vaccinated with the Moderna vaccine were about half as likely to have breakthrough infections as those vaccinated with the Pfizer vaccine. The differences, if borne out, could be due to a 3-fold higher concentration of mRNA in the Moderna shot compared to Pfizer, or differences in the lipid nanoparticle technology used by each company. Another study from Denmark (also a preprint not yet peer reviewed) comparing the two vaccines shows Moderna somewhat stronger for preventing infections.
In summary, these recent studies consistently show that vaccines—all of them—remain strongly protective against severe Covid-19 disease and hospitalization. However, they also show that effectiveness against becoming infected (with mild symptoms or no symptoms) seems to be dropping. If true, that means we could see more breakthrough infections resulting in vaccinated people potentially becoming spreaders of the virus. Notably, we don’t seem to have studies addressing asymptomatic infections among vaccinated people. (And if you’ve seen any, please send them to me.) One of the leading theories as to why vaccinated people might still be vulnerable to infection is that the virus infects the nasopharyngeal space (the back of your nasal cavity) initially, a place the vaccine-generated antibodies don’t reach easily, because it is on the surface of your body—albeit a cavity surface—and vaccine antibodies circulate in the blood. So while potentially having very strong immune protection against infection in the lungs and other parts exposed to antibodies in the blood stream, the vaccine may still allow the virus to replicate (possibly for only a short time) in the nose and throat. All of this is just theory and requires more research to confirm.
MMR and Tdap vaccines offer immunity to SARS-CoV-2
Testing of T cells from people who have had COVID-19 showed that showed that people who had been previously immunized with MMR (measles/mumps/rubella) or Tdap (tetanus/diptheria/pertussis) vaccines had T cell responses to SARS-CoV-2. Additionally, researchers found that identical T cell receptors were found in patients exposed to SARS-CoV-2, MMR, and Tdap antigens, suggesting some overlap in binding of the different pathogens. Prior vaccination with MMR or Tdap was correlated with reduced COVID-19 severity.
New drug could be a game-changer
A drug based on a common protein on the surface of certain cells is showing promising results in a Phase 2 clinical trial in 90 patients hospitalized with COVID-19 in Greece. Ninety-three percent of patients treated with the drug were discharged in five days or less. In this study and the previous Phase 1 trial, no significant side effects were observed. The drug emulates CD24, a common surface antigen in cells that may contribute to the “cytokine storm” phenomenon believed to contribute to severe disease with SARS-CoV-2 infection.
Surprise vaccine protection for organ transplant recipients
Organ transplant recipients take powerful drugs to suppress the immune system and prevent rejection of their donated organs. That immune suppression has made vaccination against Covid-19 challenging, and at the same time puts them at high risk from the virus. Now researchers at the University of California San Diego have found that fully vaccinated organ transplant recipients seem to have protection from Covid-19 compared to unvaccinated transplant recipients in spite of their weakened immune systems. In this retrospective study, the vaccinated group had an 80% reduction in symptomatic Covid-19 compared to the unvaccinated group.
Iceland has been a vaccination success. Why is it seeing a coronavirus surge? by Reis Thebault, The Washington Post
Why the U.S. Delta wave could be far less deadly, by Amanda DAmbrosio, MedPage Today
This is really scary: kids struggle with long Covid, by Pam Belluck, The New York Times