Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study

Abstract

The Omicron variant has been associated with reduced vaccine effectiveness (VE) against mild disease with rapid waning. Meanwhile Omicron has also been associated with milder disease. Protection against severe disease has been substantially higher than protection against infection with previous variants. We used a test-negative case-control design to estimate VE against hospitalisation with the Omicron and Delta variants using PCR testing linked to hospital records. We investigated the impact of increasing the specificity and severity of hospitalisation definitions on VE. Among 18-64-year-olds using cases admitted via emergency care, VE after a 3rd dose peaked at 82.4% and dropped to 53.6% by 15+ weeks after the 3rd dose; using all admissions for > = 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% to 67.4%; further restricting to those on oxygen/ventilated/intensive care VE ranged from 97.1% to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% to 76.9%; 91.3% to 85.3% and 95.8% to 86.8%. Here we show that with milder Omicron disease contamination of hospitalisations with incidental cases is likely to reduce VE estimates. VE estimates increase, and waning is reduced, when specific hospitalisation definitions are used.

Fig. 1. Vaccine effectiveness estimates with 95% confidence intervals 7+ days after a 3rd dose against symptomatic disease and different hospitalisation outcomes by age group and variant.

ECDS Emergency Care Dataset—administrative data from emergency departments, SUS Secondary Users Service—administrative data from all secondary care which is coded on discharge, ECDS All all admissions through emergency care. ECDS Resp Coded respiratory SNOMED coded admission through emergency care, SUS All admitted with a respiratory ICD code, SUS Not Primary admitted with a respiratory ICD code not in the primary diagnosis field, SUS Primary admitted with a respiratory ICD code in the primary diagnosis field. 0 days, 1+ days, 2+ days, 3+ days: length of stay, for example, 1+ means at least one overnight stay. Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously testing positive.

Fig. 2. Vaccine effectiveness estimates with 95% confidence intervals against hospitalisations using ECDS by age group and manufacturer (all symptomatic controls, Omicron only).

a 18–64: Two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, b 18–64: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, c 65 and older: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, d 65 and older: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of the test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously tested positive.

Fig. 3. Vaccine effectiveness estimates with 95% confidence intervals against hospitalisations >=2 days and >=2 days and on oxygen/ventilated/on ICU using SUS by age group and manufacturer (all symptomatic controls, Omicron only).

Vaccine effectiveness estimates are adjusted using sex, index of multiple deprivation (quintile), ethnic group, care home residence status (for age 65+), geographic region (NHS region), period (calendar week of the test), health and social care worker status (for age <65), clinical risk group status (for age <65), clinically extremely vulnerable, severely immunosuppressed, and previously tested positive. a 18–64: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, b 18–64: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose, c 65 and older: two doses of ChAdOx1-S with a BNT162b2 or mRNA-1273 third dose, d 65 and older: two doses of BNT162b2 with a BNT162b2 or mRNA-1273 third dose.