Review finds hybrid immunity provides best protection against Omicron

Man getting COVID vaccine

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A review and meta-regression of 26 studies shows that hybrid SARS-CoV-2 immunity provides the highest level of protection against the Omicron variant, researchers reported yesterday in The Lancet Infectious Diseases.

The authors say the finding of the study, the first to estimate the durability of protection conferred by hybrid immunity—the antibody response developed through a combination of SARS-CoV-2 infection and vaccination—could provide guidance on vaccine timing at both the individual and public health level.

Hybrid immunity highly protective against severe outcomes

Of the 26 studies reviewed by a team led by researchers from the University of Toronto and the World Health Organization, 11 reported on the protective effectiveness of previous infection, and 15 reported on protection from hybrid immunity; 7 reported on both. The studies looked at protection against reinfection, hospitalization, and severe disease caused by Omicron.

The effectiveness of previous infection against hospital admission or severe disease at 12 months was 74.6% (95% confidence interval [CI], 63.1% to 85.3%], with effectiveness against reinfection waning to 24.7% (95% CI, 16.4% to 35.5%) at 12 months. For hybrid immunity, protection against hospital admission or severe disease was 97.4% (95% CI, 91.4% to 99.2%) at 12 months with primary series vaccination and 95.3% (95% CI, 81.9% to 98.9%) at 6 months with the first booster shot. The effectiveness of hybrid immunity against reinfection waned to 41.8% (95% CI, 31.5% to 52.8%) at 12 months, and to 46.5% (95% CI, 36.0% to 57.3%) following the first booster shot at 6 months.

Further analysis of the 7 studies that reported on both types of protection showed that hybrid immunity conferred a significant gain in protection compared with previous infection alone—whether subjects with hybrid immunity had received the partial primary vaccine series, the full vaccine series, or the first booster shot.

The authors say the findings indicate that the protection conferred by previous infection should not detract from the need for vaccination, because infection-induced immunity wanes rapidly and vaccines increase the durability of protection. In addition, they suggest the results can be used to tailor guidance on the number and timing of SARS-CoV-2 vaccinations.

'Substantial durability' of hybrid immunity

"Our findings make clear the substantial durability of hybrid immunity and could help inform the timing and prioritisation of vaccination programmes in populations with high rates of past infection," the study authors wrote. "Policy makers can use these findings to project population protection from local vaccination and seroprevalence rates, helping to inform the use and timing of COVID-19 vaccination as an important public health tool."

They add that further analysis is needed to determine effectiveness of hybrid immunity against hospitalization or severe disease over a longer duration.

A first-generation vaccine is still an excellent option when offered as a primary series in areas with a high rate of previous infection.

In an accompanying commentary, researchers with Brazil's Universidad Federal de Bahia say the findings demonstrate that the focus of first-generation vaccines should be prevention of severe disease.

"For this purpose, a first-generation vaccine is still an excellent option when offered as a primary series in areas with a high rate of previous infection, or with boosters, if a low infection rate has been observed," they wrote.

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