The report said that overall case and hospitalization rates were the highest among those who were unvaccinated without a prior COVID-19 diagnosis. Before the delta variant became predominant in June, vaccination was conferring better benefits than even vaccination plus a prior infection: Both case rates and hospitalization rates were lower for the vaccination-only group.
After delta, that changed.
“By early October, persons who survived a previous infection had lower case rates than persons who were vaccinated alone,” the report said, noting that this was “a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning.”
Some of the data show even greater protection for the vaccinated-plus-prior-infection (the “hybrid immunity” folks) than the unvaccinated-but-infected. For one week, ending Oct. 3, case rates for unvaccinated-but-infected were 29-fold lower in California and 15-fold lower in New York, compared with unvaccinated-never-infected. But rates among vaccinated-plus-infected were 33-fold and 20-fold lower, respectively. (The vaccinated-never-infected group had only 6-fold and 5-fold lower case rates.)
The CDC stressed that vaccination was the “safer” way to get immunity: “Although the epidemiology of COVID-19 might change as new variants emerge, vaccination remains the safest strategy for averting future SARS-CoV-2 infections, hospitalizations, long-term sequelae, and death.”
It also noted that other studies have similarly found vaccination was better than prior infection pre-delta, but after delta, that changed.
“Similar to the early period of this study, two previous U.S. studies found more protection from vaccination than from previous infection during periods before Delta predominance,” the report said. “As was observed in the present study after July, recent international studies have also demonstrated increased protection in persons with previous infection, with or without vaccination, relative to vaccination alone.”
There was a similar pattern for hospitalization rates in California. Those rates were “always highest among unvaccinated persons without a previous COVID-19 diagnosis,” the report said. But during Oct. 3 through 16, after delta became predominant, those who had a prior diagnosis, both those vaccinated and those not, had lower hospitalization rates than vaccinated people without a previous infection.
This is all good news for those who had a prior infection — at least when it comes to the delta variant. But, again, the study didn’t assess omicron, or the impact of booster vaccine doses, because those largely came after the study period. It was late September when the CDC first recommended booster doses for older Americans and certain other groups, concerning the Pfizer/BioNTech vaccine, and late November when the agency said all adults should get booster doses. The CDC says either the Pfizer or Moderna mRNA vaccines are “preferred” for boosters.
What We Know About Immunity and Omicron
Given that Paul mentioned the omicron variant, which made up an estimated 99.9% of the U.S. cases for the week ending Jan. 22, we asked his office what research showed for natural versus vaccination immunity for omicron. “Research often lags a few months and the only available, reliable data is from October,” spokesperson Kelsey Cooper said, adding that “all studies from beginning of pandemic show long lasting immunity from previous COVID infection.”
But we do have some early research on omicron, and it doesn’t show natural immunity having an advantage against this variant.
Balazs’ research has found that “people who had received the booster who had no signs of ever having been infected before actually were making even better antibodies than people who were naturally infected or naturally infected and then got two doses of an mRNA vaccine,” he told us. “So getting three doses of an mRNA vaccine seems to be even better than natural immunity” or natural immunity with the primary vaccination series. The researchers didn’t study a prior infection plus three doses of an mRNA vaccine.
“Whether it’s against the original Wuhan strain or against delta, either of those, having three vaccines, three mRNA shots is better than having two plus getting infected. And it’s definitely better than just getting infected on its own,” Balazs said. But for omicron, the third booster dose “broadened the type of immunity that you had” so that the antibodies “could recognize omicron where they couldn’t really recognize it before the boost.”
Dr. Wilfredo F. Garcia-Beltran, also with the Ragon Institute and a research fellow in pathology at Massachusetts General Hospital, told us in an email that “vaccinated individuals have higher levels of neutralizing antibodies than individuals that had prior infection alone (without vaccination). In fact, we often see that prior infection, especially mild infection, results in very low levels of neutralizing antibodies, while vaccines produce high levels of neutralizing antibodies in pretty much anyone with a normal immune system.”
Balazs, Garcia-Beltran and other researchers, primarily affiliated with the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, published results in the journal Cell on Dec. 23 of research on blood samples from more than 200 vaccine recipients, finding that those who had an mRNA booster “exhibited potent neutralization of Omicron” that was only moderately lower than for the original virus.
The limitation is that this research is done in a lab, using samples from patients and seeing how antibodies block pseudoviruses. The “gold standard,” Balazs told us, is clinical evidence, but that, too, is showing people who received booster doses had lower rates of hospitalization. “So I think what we’ve seen in our dish is definitely backed up by what’s happening clinically.”
A CDC study released Jan. 21 and using data from 10 states found vaccine effectiveness against COVID-19-association hospitalizations when omicron was predominant increased from 57% at six months or more after a second mRNA dose to 90% at least 14 days after the third dose. Two other CDC studies, one published in JAMA, also found lower case rates among vaccinated-and-boosted individuals, compared with the unvaccinated and those with only primary vaccinations.
Another peer-reviewed paper, published in the New England Journal of Medicine on Dec. 30, by Rockefeller University researchers, found “low or undetectable” levels of neutralizing antibodies against omicron in samples from those with two-dose vaccinations or recovery from COVID-19 without vaccination. But for those who got three doses of an mRNA vaccine or had COVID-19 and then were vaccinated, neutralizing antibodies were “substantial.” Plasma specimens were used from 47 people.
“What some are missing is that 3rd (booster) shots don’t simply restore immunity that has waned since the 2nd,” Paul Bieniasz, a virologist who co-led the study, said on Twitter. “Rather, they expand and broaden the antibodies and memory cells, likely giving a degree of protection against variants you NEVER previously had.”
As for what immunity one can expect after recovering from an omicron infection, that research is even more preliminary.
A study from South Africa — not yet peer-reviewed — evaluated plasma from 15 people, both vaccinated and unvaccinated, who had been infected with omicron. Researchers found antibody neutralization increased from soon after symptom onset to about two weeks later against both omicron and delta.
“The researchers also show that vaccinated participants were able to mount a better neutralising response against Delta, while the response in unvaccinated participants was more variable,” a Dec. 28 announcement on the results by Africa Health Research Institute said.
Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, has said that when people are reinfected with COVID-19 it mostly involves a different variant from the original infection. At a Jan. 21 White House briefing, he said “it is unlikely that if you mount a good immune response — at least over a period of several months — it is extremely unlikely that you will be reinfected with the same variant.”
“As for the next variant,” Bhattacharya told us, “it’s tough to know what will come next. It could be more similar to the original than to Omicron, or vice versa, or something substantially different than either one (hopefully not!).”
Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.