Hybrid immunity from a COVID-19 infection plus a vaccine provided an immune boost against symptomatic disease, as well as severe outcomes, Brazilian researchers found.
Among people who survived a COVID infection from Feb. 24, 2020 to Nov. 11, 2021, vaccine effectiveness against symptomatic disease at least 14 days after series completion was 44.0% (95% CI 31.5-54.2) for Johnson & Johnson's vaccine and 64.8% (95% CI 54.9-72.4) after two doses of Pfizer's vaccine, reported Julio Croda, MD, PhD, of Universidade Federal de Mato Grosso do Sul in Brazil, and colleagues.
Moreover, vaccine effectiveness against COVID-related hospitalization or death was 57.7% (95% CI -2.6 to 82.5) for Johnson & Johnson's vaccine, and 89.7% (95% CI 54.3-97.7) for Pfizer's, the authors wrote in Lancet Infectious Diseases.
While four COVID vaccines in total were evaluated (including AstraZeneca's vaccine and CoronaVac), only Johnson & Johnson's and Pfizer's are authorized for use in the U.S.
"There has been ongoing public debate about whether previously infected individuals need to be vaccinated," said Croda in a statement. "Our results suggest that vaccine benefits far outweigh any potential risk and support the case for vaccination, including the full vaccine series, among individuals with prior SARS-CoV-2 infection."
However, the authors noted that this analysis was done prior to the emergence of the Omicron variant.
Using national data, Croda and team identified 30,910 people (5.4% of the total 213,457 individuals who tested positive for COVID at least 90 days after the start of the vaccination program) who had a subsequent positive test "consistent with reinfection"; 22,566 were matched with 68,426 controls who tested negative.
Median age of the matched population was 36, and about 60% were women. Median time between first infection and a subsequent positive test was 216 to 223 days. About 65% of cases and 57% of controls were unvaccinated. Overall, 39,717 people were vaccinated -- about 80% were vaccinated with either AstraZeneca's vaccine or CoronaVac, 15% were vaccinated with Pfizer's vaccine, and 2% with Johnson & Johnson's.
Of the four examined vaccines, only Pfizer's vaccine showed a significant increase in effectiveness against symptomatic disease when given 180 days after the first infection versus 91 to 180 days (70.7% vs 35.3%, P=0.011).
An accompanying editorial by Pramod Kumar Garg, MBBS, MD, and Ramachandran Thiruvengadam, MD, of the Translational Health Science and Technology Institute in Faridabad, India, noted that the vaccine effectiveness estimates in this study are "generally lower than those in naive populations reported earlier," but added that these "estimates were for additional protection provided by vaccination over and above that offered by immunity resulting from natural infection."
This study "challenges the concept of population-level herd immunity through natural infection alone" and suggests that "vaccinating individuals who were previously infected provides further protection, particularly against severe disease," they noted.
"Understanding the duration and effectiveness of immunity for those vaccinated with a previous COVID-19 diagnosis becomes increasingly important as ... surges in new cases ... occur as a result of more transmissible variants," Croda said in a statement. "Further research on the need for vaccination for those with a previous COVID-19 infection is a vital step to pandemic policy intervention."
Even Sweden Finds Hybrid Immunity Is Best
A second study in Lancet Infectious Diseases found the lowest number of reinfections and hospitalizations among those with hybrid immunity.
Two-dose vaccination plus prior immunity resulted in a 66% lower risk of COVID reinfection versus infection alone (adjusted HR 0.34, 95% CI 0.31-0.39, P<0.001), with a non-significant trend towards attenuation after 9 months (P=0.07), reported Peter Nordström, MD, PhD, of Umeå University in Sweden, and colleagues.
In addition, two-dose hybrid immunity was linked with a significantly lower risk of COVID hospitalization compared with infection alone (aHR 0.10, 95% CI 0.04-0.22, P<0.001).
One dose of vaccine had similar results, albeit on a smaller scale. Hybrid immunity with one-dose vaccination resulted in a 58% lower risk of reinfection (aHR 0.42, 95% CI 0.38-0.47, P<0.001), with significant attenuation after 9 months. One-dose hybrid immunity also resulted in a lower risk of hospitalization (aHR 0.06, 95% CI 0.03-0.12, P<0.001).
Nordström and team examined data from Swedish nationwide registries, looking at infections from March 20, 2020 to Oct. 4, 2021, and hospitalizations with COVID from March 30, 2020 to Sept. 5, 2021. Cohort 1 included 2,039,106 unvaccinated individuals with prior infection who were matched with unvaccinated individuals without prior infection. Cohort 2 included 2,962,318 individuals with prior infection and one vaccine dose and cohort 3 included 567,810 individuals with prior infection and two vaccine doses, both matched to individuals with "natural immunity." Median age in all cohorts was 38 to 40.
Compared with unvaccinated individuals without infection, prior infection was associated with a 95% lower risk of reinfection at 3 months and a 87% lower risk of COVID hospitalization for up to 20 months of follow-up, the authors said.
During a mean follow-up of 66 days, 438 people with two-dose hybrid immunity were reinfected with COVID versus 808 with natural immunity. After a median follow-up of 52 days, there were 639 reinfections among those with one-dose hybrid immunity versus 1,662 reinfections in those with natural immunity.
Due to Omicron plus varying recommendations for boosters, hybrid immunity may result from "vaccination followed by infection," rather than vice-versa, noted Hyon-Xhi Tan, PhD, and Jennifer A. Juno, PhD, of the University of Melbourne in Australia, in an accompanying editorial.
However, they cited research that indicated that regardless of the order of infection and vaccination, "the quantity, quality, and breadth of the humoral immune response were vastly improved."
"This finding further supports the notion that infection histories should be an important consideration in determining whether individuals are protected against SARS-CoV-2," Tan and Juno wrote.
Disclosures
Cerqueira-Silva and colleagues were supported by the Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.
Co-authors disclosed support from the Fazer o Bem Faz Bem programme from JBS, Bristol Myers Squibb, Regeneron, Serimmune, and Tata Medical Devices.
Croda and several co-authors are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria (ChAdOx1 nCoV-19 vaccine) in Brazil through a full technology transfer agreement with AstraZeneca.
Garg and Thiruvengadam disclosed no conflicts of interest.
Nordström and colleagues disclosed no conflicts of interest.
Tan and Juno disclosed no conflicts of interest.
Primary Source
The Lancet Infectious Diseases
Secondary Source
The Lancet Infectious Diseases
Source Reference: Garg PK, Ramachandran T "Effectiveness of SARS-CoV-2 vaccines in the post-natural infection world" Lancet Infect Dis 2022; DOI: 10.1016/S1473-3099(22)00207-9.
Additional Source
The Lancet Infectious Diseases
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