Past COVID-19 Infection Plus Vaccination Confers Most Future Disease Protection

Previous COVID-19 infection and hybrid immunity both provided individuals with greater protection against hospitalization and severe disease from the omicron variant than vaccination alone, with hybrid immunity offering the greatest amount of protection. These were among systematic review and meta-regression findings published in The Lancet Infectious Diseases.

Investigators conducted a systematic review and meta-regression to characterize the duration and magnitude of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity (ie, previous infection combined with previous vaccination) against infection and severe disease caused by the omicron variant.

The reviewers searched the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, Embase, ClinicalTrials.gov, Web of Science, MEDLINE, and Europe PubMed Central from January 2020 through May 2022 for cohort, cross-sectional, and case-control studies. The investigators sought studies that assessed outcomes regarding:

• the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against reinfection and hospital admission or severe disease;
• the relative protective effectiveness of hybrid immunity vs previous vaccination alone;
• the relative protective effectiveness of hybrid immunity vs previous infection alone; and
• the relative protective effectiveness of hybrid immunity with more vs fewer vaccine doses.

Studies that did not report evidence of previously confirmed SARS-CoV-2 cases or did not report time between the index infection and reinfection were excluded.

In the meta-regression analysis, investigators included 15 studies reporting the protective effectiveness of hybrid immunity and 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection.

With respect to previous infection, the data included 97 estimates — 70 with serious risk of bias and 27 with moderate risk of bias; the effectiveness of previous infection against severe disease or hospital admission at 12 months was 74.6% (95% CI, 63.1-83.5%) and the effectiveness of previous infection against reinfection at 12 months was 24.7% (95% CI, 16.4-35.5%).

With respect to hybrid immunity, the data included 153 estimates — 75 with serious risk of bias and 78 with moderate risk of bias. The effectiveness of hybrid immunity against severe disease or hospital admission at 12 months was 97.4% (95% CI, 91.4-99.2%) with primary series vaccination. Effectiveness at 6 months with the first booster vaccination after the most recent infection or vaccination was 95.3% (95% CI, 81.9-98.9%). Effectiveness at 12 months of hybrid immunity following primary series vaccination against reinfection was 41.8% (95% CI, 31.5-52.8%). Effectiveness at 6 months of hybrid immunity following first booster vaccination was 46.5% (95% CI, 36.0-57.3%).

Further analyses showed that the independent protective effects at 6 months of previous infection alone, first vaccine booster, and primary vaccine series were as follows: 80.1% for previous infection alone (95% CI, 70.3-87.2%), 76.7% for first booster vaccination alone (95% CI, 72.5-80.4%), and 64.6% for the primary series alone (95% CI, 54.5-73.6%).

The most common reason for increased risk of bias included incomplete adjustment for confounding factors and not reporting an a-priori protocol to enable ruling out reporting bias.

Review limitations include uncertainty of unmeasured biases, unaccounted for sequence of timing between vaccination and previous infection, scarcity of data, uncertainty of relative proportions of individuals vaccinated by each product, vaccine effectiveness data taken from another systematic review, and examination of protection conferred by pre-omicron SARS-CoV-2 variants only.

“Both previous infection alone and previous infection combined with previous vaccination (ie, hybrid immunity) conferred rapidly waning protection against SARS-CoV-2 infection with the omicron variant, but high and sustained protection against hospital admission or severe disease due to the omicron variant,” the investigators concluded. “Previous infection was found to provide higher protection against reinfection and more sustained protection against hospital admission or severe disease than vaccination alone,” the reviewers noted. They further added that individuals with hybrid immunity maintained the highest magnitude and durability of protection against all outcomes, reinforcing the significance of vaccination among previously infected individuals.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Pulmonology Advisor