Most comprehensive study to date provides evidence on natural immunity protection by COVID-19 variant and how protection fades over time


  • The largest review and meta-analysis evaluating the extent of protection after infection with COVID-19 by variant and the extent to which this protection persists against different variants, including 65 studies from 19 countries.
  • For people who had had COVID-19 at least once before, natural immunity against severe disease (hospitalization and death) was strong and long-lasting for all variants (88% or greater at 10 months after infection).
  • Previous infection with pre-Omicron variants provided significantly reduced natural immunity protection against reinfection with Omicron BA.1 (36% 10 months after infection).
  • The researchers say we should learn about natural immunity in people who have recently contracted COVID-19, but they caution that their findings should not discourage vaccination because it is the safest way to gain immunity.

For someone previously infected with COVID-19, the risk of being hospitalized or dying is 88% lower for at least 10 months compared to those without previously infection, according to a systematic review and meta-analysis published in scalpel.

Image by Gerd Altmann from Pixabay

The analysis also indicates that the level and duration of protection against reinfection, symptomatic disease, and severe disease are at least equal to that provided by two doses of mRNA vaccines (Moderna and Pfizer-BioNtech), progenitor, alpha, delta, and Omicron. BA.1 variants. The study did not include data on infection from Omicron XBB and its progenitors.

says lead author Dr Stephen Lim of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine, USA.

As Dr. Caroline Stein, co-author at IHME, explained: “Vaccines remain important for everyone in order to protect high-risk populations such as those over 60 years of age with comorbidities. This also includes previously uninfected populations and non-infected populations. Immunized, as well as those who were infected or received their last vaccine dose more than six months ago. Decision makers must take both natural immunity and vaccination status into account to get a complete picture of an individual’s immunity profile.”

Since January 2021, several studies and reviews have reported the effectiveness of previous COVID-19 infection in reducing the risk of reinfection and how immunity wanes over time. However, none of them comprehensively evaluated the length of protection after natural infection and the extent of this protection against different variants.

To provide more evidence, the researchers conducted a review and meta-analysis of all previous studies that compared reduced risk of contracting COVID-19 among unvaccinated individuals against re-infection with SARS-CoV-2 in unvaccinated individuals without prior infection. Until September 2022.

They included 65 studies from 19 countries and evaluated the effectiveness of prior infection by outcome (infection, symptomatic, severe disease), variable, and time since infection. Studies examining natural immunity in combination with vaccination (i.e., hybrid immunity) were excluded from the analyses.

Immunity wanes over time

Analysis of data from 21 studies reporting time since infection from the pre-Omicron variant estimated that protection against re-infection from the pre-Omicron variant was about 85% at 1 month – this decreased to about 79% at 10 months. Protection from infection by the Omicron variant pre-infection against reinfection of the Omicron BA.1 variant was lower (74% at 1 month) and decreased more rapidly to 36% at about 10 months.

However, an analysis of five studies reporting severe disease (hospitalization and death) found that protection remained universally high for 10 months: 90% for grandparents, alpha and delta, and 88% for omicrons BA.1.

Six studies evaluating protection against specifically Omicron subspecies (BA.2 and BA.4/BA.5) suggested significantly reduced protection when previous infection was a pre-Omicron variant. But when the previous infection was Omicron, the protection was kept at a higher level.

“Weaker cross immunity with the Omicron variant and its sub-strains reflects mutations that they have that cause them to escape accumulated immunity more easily than other variants,” says Dr. Hassan Nasiruddin, co-author at IHME. “The limited data we have on the natural protection of immunity from the Omicron variant and its sub-lineages underscore the importance of continued evaluation, especially since it is estimated to have infected 46% of the global population between November 2021 and June 2022. Further research is also needed to assess immunogenicity. Naturalization of emerging variants and an examination of the protection afforded by natural infection and vaccination combinations”.

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The researchers note some limitations of their study, and caution that the number of studies examining the Omicron BA.1 variant and its subspecies and the number from Africa was generally limited. In addition, only limited data were available 10 months after the initial infection. They also noted 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 related commentary, Professor Cheryl Cohen, National Institute of Infectious Diseases, South Africa, who was not involved in the study, says, “Sustained high levels of protection provided by past infection against severe disease have important implications for COVID-19 vaccine policy. By September 2021, The global seroprevalence of SARS oV-2 was estimated to be 59%, with significant variability in the percentage of immunity resulting from infection or vaccination in different settings.The seroprevalence rate in Africa was estimated to be 87% in December 2021, largely due to infection. High levels of immunity are an important factor in the lower levels of severity observed with infection caused by emerging sub-variants of Omicron.As the epidemiology of SARS-CoV-2 shifts to more stable circulation patterns in the context of high levels of immunity, studies of the burden and cost of SARS infection are needed -CoV-2 and acute disease risk groups to guide rational vaccination policy and decisions about prioritization in relation to other vaccine-preventable diseases.”

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