Summary Background Understanding the level and characteristics of protection of past SARS-CoV-2 infection against subsequent reinfection, symptomatic COVID-19 disease, and severe disease is essential to predict the potential future burden of disease, to design policies that restrict travel or access to places where there is a high risk of transmission, and to inform options about when to receive vaccine doses. Our objective was to systematically synthesize studies to estimate protection against past infections by variant and, where data allow, by time since infection. Methods In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception to September 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with prior SARS-CoV-2 infection compared to those without prior infection. We meta-analyzed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate pooled estimates of protection. Risk of bias assessment was assessed using the National Institutes of Health quality assessment tools. The systematic review was PRISMA compliant and registered with PROSPERO (number CRD42022303850). Results A total of 65 studies from 19 different countries were identified. Our meta-analyses showed that protection against past infections and any symptomatic disease was high for the ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. The combined efficacy against reinfection with the omicron BA.1 variant was 45.3% (95% uncertainty interval [UI] 17.3–76.1) and 44.0% (26.5–65, 0) against omicron BA.1 symptomatic disease. The mean combined efficacy was greater than 78% against severe disease (hospitalization and death) for all variants, including omicron BA.1. Protection against reinfection by ancestral, alpha, and delta variants decreased over time but remained at 78.6% (49.8–93.6) at 40 weeks. Protection against reinfection by omicron BA. 1 variant decreased more rapidly and was estimated to be 36.1% (24.4–51.3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, at 90.2% (69.7–97.5) for the ancestral, alpha, and delta variants, and 88.9% (84.5) for the ancestral, alpha, and delta variants. .7–90· 9) for omicron BA.1 at 40 weeks. Interpretation The protection of past infections against reinfection by pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and decreased more rapidly over time than protection against previous variants. Protection against severe disease was high for all variants. Immunity conferred by past infection should be weighed alongside protection from vaccination when assessing the future burden of COVID-19 disease, providing guidance on when people should be vaccinated, and designing policies that require vaccination of workers or restrict vaccination. access, based on immune status, to environments where the risk of transmission is high, such as travel and high-occupancy indoor environments. Money Bill and Melinda Gates Foundation, J Stanton, T Gillespie and J and E Nordstrom. |
Comments
The largest review and meta-analysis assessing the extent of protection after COVID-19 infection by variant and how long-lasting that protection is against different variants, including 65 studies from 19 countries.
For people who have been infected with COVID-19 at least once before, natural immunity against severe disease (hospitalization and death) was strong and long-lasting for all variants (88% or more at 10 months post-infection ).
Previous infection with pre-Omicron variants provided substantially reduced natural immune protection against reinfection with Omicron BA.1 (36% at 10 months post-infection).
The researchers say we should recognize natural immunity in people who have recently been infected with COVID-19, but caution that their findings should not discourage vaccination because it is the safest way to acquire immunity.
For someone previously infected with COVID-19, their risk of hospitalization or death is 88% lower for at least 10 months compared to those who had not been previously infected, according to a systematic review and meta-analysis published in The Lancet .
The analysis also suggests that the level and duration of protection against reinfection, symptomatic disease, and severe disease are at least equal to those provided by two doses of the mRNA vaccines (Moderna, Pfizer-BioNtech) for Ancestral, Alpha , Delta and Omicron. Variants BA.1. The study did not include data on infection of Omicron XBB and its sublineages.
" Vaccination is the safest way to acquire immunity, while the acquisition of natural immunity must be weighed against the risks of severe disease and death associated with initial infection," says senior author Dr. Stephen Lim of the Institute. of Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine, USA.
As IHME co-author Dr. Caroline Stein explains: “Vaccines continue to be important for everyone to protect high-risk populations, such as people over 60 years of age and people with comorbidities. This also includes populations that have not previously been infected and unvaccinated groups, as well as those who were infected or received their last vaccine dose more than six months ago. “Decision makers should take into account both natural immunity and vaccination status to get a complete picture of an individual’s immunity profile.”
Since January 2021, several studies and reviews have reported the effectiveness of past COVID-19 infections in reducing the risk of reinfection and how immunity wanes over time. But none have comprehensively evaluated how long protection will last after natural infection and how long-lasting that protection will be against different variants.
To provide more evidence, the researchers conducted a review and meta-analysis of all previous studies that compared the risk reduction of COVID-19 among unvaccinated people against SARS-CoV-2 reinfection with unvaccinated people without a previous infection. until September 2022.
It included 65 studies from 19 countries [2] and evaluates the efficacy of past infections by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. Studies that examined natural immunity in combination with vaccination (i.e., hybrid immunity) were excluded from the analyses.
Immunity fades over time
Analysis of data from 21 studies reporting time from infection with a pre-Omicron variant estimated that protection against reinfection with a pre-Omicron variant was about 85% per month, declining to about 79%. % at 10 months. The protection of a pre-Omicron variant infection against reinfection with the Omicron BA.1 variant was lower (74% at 1 month) and decreased more rapidly to 36% around 10 months.
However, analysis of five studies reporting serious illness (hospitalization and death) found that protection remained universally high over 10 months: 90% for Ancestral, Alpha, and Delta, and 88% for Omicron BA.1.
Six studies evaluating protection against Omicron sublineages specifically (BA.2 and BA.4/BA.5) suggested significantly reduced protection when the previous infection was a pre-Omicron variant. But when the previous infection was Omicron, the protection remained at a higher level.
"The weaker intervariant immunity with the Omicron variant and its sublineages reflects the mutations they have that make them escape from the built-up immunity more easily than other variants," says IHME co-author Dr. Hasan Nassereldine. “The limited data we have on the natural immunity protection of the Omicron variant and its sublineages underscore the importance of continued evaluation, particularly as they are estimated to have infected 46% of the world’s population between November 2021 and June 2022. needs more research. “It was also necessary to assess natural immunity from emerging variants and examine the protection provided by combinations of vaccination and natural infection.”
The researchers point out some limitations of their study, cautioning that the number of studies examining the Omicron BA.1 variant and its sublineages and the number from Africa was generally limited. Furthermore, only limited data were available beyond 10 months after initial infection. They also note that some information, such as previous infection status and hospital admissions, was measured differently or incompletely, and could bias the estimate of protection.
In a linked comment, Professor Cheryl Cohen, National Institute of Communicable Diseases, South Africa, who was not involved in the study, says: “The high and sustained levels of protection conferred by prior infection against severe disease have important implications for COVID-19. . 19 vaccine policy. As of September 2021, the global seroprevalence of SARS oV-2 was estimated at 59%, with substantial variation in the proportion of immunity induced by infection or vaccination in different settings. Seroprevalence in Africa was estimated at 87% in December 2021, largely as a result of infection. High levels of immunity are an important contributor to the lower levels of severity seen with infection caused by emerging Omicron subvariants.
Implications of all available evidence
Our findings confirm that past infection offers significantly less protection against reinfection by the omicron BA.1 variant compared to previous variants, highlighting the high immune escape characteristics of this variant. Our finding that the level of protection against past infections per variant and over time is equivalent to that provided by two-dose mRNA vaccines has important implications for guidance regarding the timing of vaccine doses, including boosters .
This finding also has important implications for designing policies that restrict access to travel or locations or require vaccination of workers. It supports the idea that those with a documented infection should be treated similarly to those who have been fully vaccinated with high-quality vaccines. This was implemented, for example, as part of the EU COVID certificate, but not in countries like the US. The paucity of data on the protection provided by past infections of the BA.1 omicron variant and its sublineages (BA.2 , BA.4 and BA.5) highlights the importance of continuous evaluation, particularly considering that approximately 46% of the world’s population was infected by the omicron variant between November 15, 2021 and June 1, 2022.
The study was funded by the Bill and Melinda Gates Foundation, J. Stanton, T. Gillespie, and J. and E. Nordstrom. The study team included researchers from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine, USA.
