Surveillance of pneumococcal serotypes in adults hospitalised with acute lower respiratory tract infection in Bristol, UK.

INTRODUCTION: Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. METHODS: A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). RESULTS: Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DISCUSSION: Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

Relative vaccine effectiveness of mRNA COVID-19 boosters in people aged at least 75 years during the spring-summer (monovalent vaccine) and autumn-winter (bivalent vaccine) booster campaigns: a prospective test negative case-control study, United Kingdom, 2022.

BackgroundUnderstanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is a public health priority. A precise analysis of the rVE of monovalent and bivalent boosters given during the 2022 spring-summer and autumn-winter campaigns, respectively, in a defined population remains of interest.AimWe assessed rVE against hospitalisation for the spring-summer (fourth vs third monovalent mRNA vaccine doses) and autumn-winter (fifth BA.1/ancestral bivalent vs fourth monovalent mRNA vaccine dose) boosters.MethodsWe performed a prospective single-centre test-negative design case-control study in ≥ 75-year-old people hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, sex, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation.ResultsWe included 682 controls and 182 cases in the spring-summer booster analysis and 572 controls and 152 cases in the autumn-winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed 46.6% rVE (95% confidence interval (CI): 13.9-67.1) vs those not fully boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had 46.7% rVE (95% CI: 18.0-65.1), compared with a fourth monovalent mRNA COVID-19 vaccine dose.ConclusionsBoth fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offered similar protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support immunisation programmes in several European countries that advised the use of BA.1/ancestral bivalent booster doses.

Effectiveness of BNT162b2 COVID-19 vaccination in prevention of hospitalisations and severe disease in adults with SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant between June 2021 and July 2022: A prospective test negative case-control study.

Background: Whilst other studies have reported the effectiveness of mRNA vaccination against hospitalisation, including emergency department or intensive care admission, few have assessed effectiveness against other more clinically robust indices of COVID-19 severity. Methods: A prospective single-centre test-negative design case-control study of adults hospitalised with COVID-19 disease or other acute respiratory disease between 1 June 2021 and 20 July 2022. We assessed VE (vaccine effectiveness) against hospitalisation, length of stay [LOS] >3 days, WHO COVID Score >5 and supplementary oxygen FiO2 (fraction inspired oxygen) >28%, conducting regression analyses controlling for age, gender, index of multiple deprivation, Charlson comorbidity index, time, and community infection prevalence. Findings: 935 controls and 546 cases were hospitalised during the Delta period, with 721 controls and 372 cases hospitalised during the Omicron study period. Two-dose BNT162b2 was associated with VE 82.5% [95% confidence interval 76.2%-87.2%] against hospitalisation following Delta infection, 63.3% [26.9-81.8%], 58.5% [24.8-77.3%], and 51.5% [16.7-72.1%] against LOS >3 days, WHO COVID Score >5, and requirement for FiO2 >28% respectively. Three-dose BNT162b2 protection against hospitalisation with Omicron infection was 30.9% [5.9-49.3%], with sensitivity analyses ranging from 28.8-72.6%. Protection against LOS >3 days, WHO COVID Score >5 and requirement for FiO2 >28% was 56.1% [20.6-76.5%], 58.8% [31.2-75.8%], and 41.5% [-0.4-66.3%], respectively. In the UK, BNT162b2 was prioritised for high-risk individuals and those aged >75 years. In the latter group we found a higher estimate of VE against hospitalisation of 47.2% [16.8-66.6%]. Interpretation: BNT162b2 vaccination results in risk reductions for hospitalisation and multiple patient outcomes following Delta and Omicron COVID-19 infection, particularly in older adults. BNT162b2 remains effective against severe SARS-CoV-2 disease. Funding: AvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer.

Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study.

BACKGROUND: On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age. METHODS: This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557. FINDINGS: Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5-90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4-94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0-92·5). INTERPRETATION: One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years. FUNDING: Pfizer.