A pair of studies published yesterday in JAMA show that COVID-19 vaccines offer good protection against severe illness and death, but with one finding waning effectiveness against milder disease, Omicron infection, and hospitalization after a few months—even in previously infected and boosted participants.
Less effective against Omicron infection
University of North Carolina researchers led a study of the state's 10.6 million residents from Mar 2, 2020, to Jun 3, 2022, comparing outcomes among those who completed a primary COVID-19 vaccine series versus those who remained unvaccinated.
The median age was 39 years, 51.3% were female, 71.5% were White, 9.9% were Hispanic, and 67% were vaccinated by the end of the study. A total of 2,771,364 infections occurred, with a hospitalization rate of 6.3% and a death rate of 1.4%.
Seven months after the first of the two doses in the primary series, estimated two-dose vaccine effectiveness (VE) of the Pfizer/BioNTech vaccine was 54.3% against infection, 85.8% against hospitalization, and 89.6% against death. Five months later, its estimated VE was 37.5% against infection, 58.8% against hospitalization, and 75.2% against death.
Estimated VE of the Moderna vaccine at 7 months was 69.2% against infection, 89.8% against hospitalization, and 93.0% against death after two doses. Five months later, its estimated VE was 47.2% against infection, 64.7% against hospitalization, and 69.6% against death.
For the Johnson & Johnson (J&J) vaccine—whose primary series is just one dose—estimated VE 7 months after that dose was 60.2% against infection, 69.7% against hospitalization, and 76.7% against death. Five months later, its estimated VE was 50.7% against infection, 56.3% against hospitalization, and 73.6% against death.
Estimated effectiveness of the six common combinations of primary and booster vaccines against infection, compared with the primary series alone, peaked at about 2 to 4 weeks post-booster then began to wane. VE against hospitalization and death after a booster was lower for people who received them before Sep 22, 2021, than for those who received them after. And VE against Omicron infection was lower than for previous strains but stayed strong against severe outcomes.
VE of a third dose of Pfizer vaccine received from Sep 22 to Nov 30, 2021, against infection after 1 month was 66.8%, while it was 61.2% for December recipients. Those who received the booster in the earlier period saw a VE of 39.3% after 3 months, while VE was 16.2% for December recipients.
Receipt of a Moderna booster after a Pfizer primary series in December 2021 resulted in a VE of 68.4% after 1 month and 40.5% after 3 months, while VE among those who received a third dose of Moderna was 62.1% after 1 month and 14.7% after 3 months. VE after receipt of a Pfizer booster in December 2021 after a Moderna primary series was 66.1% after 1 month and 27.0% after 3 months.
For participants who received the first dose of Pfizer vaccine in April 2021 or May 2021 and the third dose from Sep 22 to Nov 30, 2021, VE of the booster relative to no vaccination against infection was 79.9% at 1 month and 40.5% at 5 months.
A previous COVID-19 infection conferred about 86.5% protection against future infection, 96.2% against hospitalization, and 94.5% against death after 4 months. At 8 months, those figures were 75.8%, 95.2%, and 94.4%, and at 12 months, they were 62.2%, 91.0%, and 89.5%. But protection waned over time, especially against severe infection, and a risk of Omicron reinfection was noted after 4 months.
"The findings from this study suggest that the estimated effectiveness of all 3 vaccines was high, especially against hospitalization and death, although the effectiveness decreased over time," the authors wrote. "After the emergence of the Omicron variant, the estimated vaccine effectiveness was lower against infection, but estimated effectiveness against hospitalization and death remained high."
Need for enhanced surveillance
In a related commentary, Mark Tenforde, MD, PhD, and colleagues from the Centers for Disease Control and Prevention COVID-19 Response Team, said that while vaccines offer less protection against Omicron infection, "even modest protection against SARS-CoV-2 infection may provide important benefits by reducing surges that can overwhelm health care systems, keeping schools and workplaces open, and protecting vulnerable populations at risk for severe outcomes."
Previous infection alone is associated with a lower risk of COVID-19 reinfection, but Tenforde and colleagues said that vaccination also prevents ongoing transmission and confers the additional benefits of less severe illness and a lower risk of long COVID.
The group called for enhanced disease surveillance systems that integrate genomic sequencing, COVID-19 test results, and detailed clinical data to help parse the association between reinfections and vaccine waning and immune evasion and outcomes.
"Strong and overlapping surveillance and research platforms are needed to ensure timely understanding of the strengths and weaknesses of these and other new vaccine preparations; to understand how effective COVID-19 vaccines are against new variants; and to provide direction for future policy considerations, such as preferential recommendations for certain people such as those with immunocompromising or other complex medical conditions and timing of booster doses," they concluded.
Low rate of COVID pneumonia, death
In the second study, a team led by San Francisco Veterans Affairs (VA) Medical Center researchers evaluated the incidence of severe COVID-19 after primary vaccination and booster doses of the Pfizer, Moderna, and J&J vaccines.
The researchers followed more than 1.6 million VA patients from Jul 1, 2021, to May 30, 2022, after they had completed a primary vaccine series and received a booster dose. The study period spanned both the Delta and Omicron waves. A total of 68.4% of participants were 65 years or older, 8.2% were women, 70.4% had high-risk underlying conditions, and 9.6% had impaired immune systems.
During follow-up, 125.0 per 10,000 people had breakthrough COVID-19 reinfection, 8.9 per 10,000 were hospitalized for COVID-19 pneumonia or died, and 3.4 per 10,000 were hospitalized with severe pneumonia or died.
Among high-risk patients, the rate of hospitalization with COVID-19 pneumonia or death was 1.9 per 10,000 people aged 65 years and older, 6.7 per 10,000 among those with high-risk chronic conditions, and 39.6 per 10,000 among those with impaired immune systems.
"There was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster" with any of the three vaccines, the authors wrote. "The 24-week observation period occurred while a series of SARS-CoV-2 variants were predominant in the US, including the Delta variant and the Omicron BA.1, BA.2, and BA.2.12.1 variants, suggesting that boosters continued to provide protection against severe illness despite viral evolution."