Durability of protection from original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes among adults in the United States — September 2022–August 2023

ABSTRACT

Objective

To evaluate the durability of protection provided by original monovalent and bivalent COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

Design

Multicenter case-control design with prospective enrollment

Setting

26 hospitals in 20 US states

Participants

Adults aged ≥18 years admitted to hospital with COVID-19-like illness from 8 September 2022 to 31 August 2023

Main outcome measures

The main outcomes were absolute and relative vaccine effectiveness of original monovalent and bivalent COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes, including advanced respiratory support (defined as receipt of high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation [IMV]) and IMV or death. Vaccine effectiveness was estimated using multivariable logistic regression, in which the odds of vaccination (versus being unvaccinated or receiving original monovalent vaccination only) were compared between COVID-19 case patients and control-patients. Bivalent vaccine effectiveness analyses were stratified by time since dose receipt.

Results

Among 7028 adults without immunocompromising conditions, 2924 (41.6%) were COVID-19 case patients and 4104 (58.4%) were control patients. Compared to unvaccinated patients, absolute vaccine effectiveness against COVID-19-associated hospitalization was 6% (-7% to 17%) for original monovalent doses only (median time since last dose [IQR] = 421 days [304–571]), 52% (39% to 61%) for a bivalent dose received 7–89 days earlier, and 13% (-10% to 31%) for a bivalent dose received 90–179 days earlier. Absolute vaccine effectiveness against COVID-19-associated advanced respiratory support was 31% (15% to 45%) for original monovalent doses only, 66% (47% to 78%) for a bivalent dose received 7–89 days earlier, and 33% (-1% to 55%) for a bivalent dose received 90–179 days earlier. Absolute vaccine effectiveness against COVID-19-associated IMV or death was 51% (34% to 63%) for original monovalent doses only, 61% (35% to 77%) for a bivalent dose received 7–89 days earlier, and 50% (11% to 71%) for a bivalent dose received 90–179 days earlier.

Conclusion

When compared to original monovalent vaccination only, bivalent COVID-19 vaccination provided additional protection against COVID-19-associated hospitalization and certain severe in-hospital outcomes within 3 months of dose receipt. By 3-6 months, protection from a bivalent dose declined to a level similar to that remaining from original monovalent vaccination only. Although no protection remained from original monovalent vaccination against COVID-19-associated hospitalization, it provided durable protection against severe in-hospital outcomes >1 year after receipt of the last dose, particularly against IMV or death.

SUMMARY BOX

What is already known on this topic

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  On September 1, 2022, bivalent mRNA COVID-19 vaccination was recommended for US adults who had completed at least an original monovalent COVID-19 primary series.

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  Early estimates of bivalent vaccine effectiveness are available for the period soon after dose receipt; however fewer data exist on their durability of protection and effectiveness against severe outcomes.

What this study adds

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  When compared to original monovalent vaccination only, bivalent mRNA COVID-19 vaccination provided additional protection against COVID-19-associated hospitalization and certain severe in-hospital outcomes within 3 months of dose receipt. By 3-6 months, protection from a bivalent dose declined to a level similar to that remaining from original monovalent vaccination only.

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  Although no protection remained from original monovalent vaccination against COVID-19-associated hospitalization, it provided durable protection against severe in-hospital outcomes >1 year after receipt of the last dose, particularly against invasive mechanical ventilation or death.