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In this post, we answer your questions about how effective the vaccines we have against SARS-CoV-2 are in the real world and what the implications are for our behavior if we’ve been fully vaccinated. As usual, if you’re less interested in how we got to our conclusions than you are in the conclusions themselves, feel free to skip to the BOTTOM LINE in each section and the CONCLUSION at the end.

Question: How effective are the vaccines in the real world?

Answer: Extraordinarily effective.

The SIREN study is a prospective study of healthcare workers in the U.K. age 18 and older that compared rates of COVID-19 infection, both symptomatic and asymptomatic, in subjects who were immunized and those who were not. There were 23,324 subjects from 104 sites in England. 8,203 (35 percent) of the subjects were considered the “positive cohort,” meaning they’d had the infection in the past, and 15,121 (65 percent) of the subjects were considered the “negative cohort,” meaning they’d not had the infection in the past. By the date the analysis was stopped, Feb 5, 2021, 89 percent of the subjects had been vaccinated, 94 percent with the Pfizer vaccine. When the rates of infections were analyzed, they found that a single dose of the Pfizer vaccine had a 70 percent effectiveness (that is, reduction of infection risk in real-world circumstances) 21 days after the first dose and an 85 percent effectiveness (again, reduction of infection risk in real-world circumstances) 7 days after the second dose. These effectiveness rates were for both symptomatic and asymptomatic infections.

Another study looked at prospective cohorts of health care personnel, first responders, and other essential and frontline workers in eight U.S. locations from December 14, 2020–March 13, 2021. From the paper: “The CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19–associated illness. Estimated mRNA vaccine effectiveness (both Pfizer and Moderna were considered together) for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization.” As the authors of the study concluded: “These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions.”

Another study called the HEROES-RECOVER trial started in July 2020 and also included health care personnel, first responders, and other essential and frontline workers. From the paper: “Active surveillance for symptoms consistent with COVID-19–associated illness (defined as fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle aches, or loss of smell or taste) occurred through weekly text messages, e-mails, and direct participant or medical record reports. Participants self-collected a midturbinate nasal swab weekly, regardless of COVID-19–associated illness symptom status and collected an additional nasal swab and saliva specimen at the onset of COVID-19–associated illness.” 3,950 subjects were included in the study. The analysis found that “estimated adjusted vaccine effectiveness of full immunization was 90%; vaccine effectiveness of partial immunization was 80%.” Again, these estimates were for both symptomatic and asymptomatic infections.

Finally, another study of the real-world effectiveness of the mRNA vaccines looked at 49,220 subjects who were vaccinated and found an effectiveness of over 96 percent for both Pfizer and Moderna.

A CNN article was skeptical of this data, arguing that “real-world studies of the Pfizer-BioNTech and Moderna vaccines show they are only 90% protective against the coronavirus, not 95% as reported in clinical trials. Translated into reality, that means for every million fully vaccinated people who fly, some 100,000 could still become infected.” Importantly, this is not what 90 percent effectiveness means! Ninety percent effectiveness means the vaccines reduce the rate of infection by 90%. To calculate a person’s absolute risk of getting infected after having been vaccinated, you have to start with the base rate of infection, which is different in different contexts. It would be true that “for every million fully vaccinated people who fly, some 100,000 could still become infected” if the base rate of infection for those million people was 100 percent. Yet the highest rate of infection we’ve seen in published contact tracing studies was around 30 percent (for spouses of infected people). This means that post-vaccination rates of COVID-19 infection in the vaccinated population are at most 90 percent less than 30 percent, or 3 percent. And that only if everyone who’s been vaccinated has an infected spouse.

In fact, the CDC reported that, as of April 20, 2021, out of 87 million fully vaccinated people there were only 7,157 breakthrough infections (0.008 percent), only 498 hospitalizations (0.0006 percent) related to COVID-19, and only 88 deaths (0.0001 percent) related to COVID-19.

BOTTOM LINE: The mRNA vaccines are extraordinarily effective at preventing both symptomatic and asymptomatic infection and therefore at preventing transmission of SARS-CoV-2. Most importantly, if you’re fully vaccinated, your risk of dying from COVID-19 is 0.0001 percent.

WHAT ABOUT THE VARIANTS?

Question: Do the vaccines work against the variants?

Answer: Yes.

Numerous studies, like this one looking at the B.1.526 variant circulating in New York, have shown that antibodies from immunized subjects are present in high enough concentrations to neutralize variants in the lab. Even more significantly, a follow-up of the Phase 3 Pfizer study showed that the effectiveness of its vaccine in the real world to be 100 percent against the B.1.351 variant in South Africa. The same study found “vaccine effectiveness was at least 97% against symptomatic COVID-19 cases [involving the B.1.1.7 variant], hospitalizations, severe and critical hospitalizations, and deaths. Furthermore, the analysis found vaccine effectiveness of 94% against asymptomatic SARS-CoV-2 infections.” Neutralizing antibodies created by vaccination with the Moderna vaccine work against the B1.1.7 and B.1.526 variants in lab studies as well.

Could some variants dramatically evade the vaccines and cause severe disease and increased risk of death? It’s certainly possible, which is why getting as many people vaccinated as quickly as possible (to reduce the likelihood of such mutations occurring) is so important. But as variant strains are now widely circulating, we’re seeing in the real-world studies on vaccine effectiveness that this hasn’t happened to any significant degree. Remember also that measuring antibody titers against the SARS-CoV-2 virus is just one way to gauge the immune system’s preparedness to fight off COVID-19 and ignores an entire separate arm of the immune system, cellular immunity, which includes T-cells.

BOTTOM LINE: The vaccines appear to be effective against the variants currently in circulation (more data to come).

CONCLUSION: Given the incredible effectiveness of the vaccines at preventing both symptomatic and asymptomatic disease, and therefore disease transmission, and given that the rates of death from COVID-19 in vaccinated people is 0.0001 percent among all vaccinated people in the U.S. (an analysis that also included the J&J vaccine), if you’ve been vaccinated, we consider it reasonably safe to dine indoors, travel, and gather with even unvaccinated people. Living in the world has, of course, never been risk-free. Yet we can now say that with the advent of effective vaccines against SARS-CoV-2, the risk of living as you did before the pandemic has returned to what it was before the pandemic.

1. Coronavirus February 2020—Part 1 What We Know So Far
2. Coronavirus March 2020—Part 2 Measures to Protect Yourself
3. Supporting Employee Health During the Coronavirus Pandemic
4. Coronavirus March 2020—Part 3 Symptoms and Risks
5. Coronavirus March 2020—Part 4 The Truth about Hydroxychloroquine
6. Coronavirus April 2020—Part 5 The Real Risk of Death
7. Coronavirus April 2020—Part 6 Evaluating Diagnostic Tests
8. Coronavirus April 2020—Part 7 The Accuracy of Our Antibody Test
9. Coronavirus May 2020—Part 8 How to Reopen a Business Safely
10. Coronavirus August 2020—Part 9 Masks, Vaccines, and Rapid Testing
11. Coronavirus December 2020—Part 10 Should You Get the Pfizer Vaccine?
12. Coronavirus December 2020—Part 11 Should You Get the Moderna Vaccine?
13. Coronavirus April 2021—Part 12 Should You Get the Johnson & Johnson Vaccine?

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