ABSTRACT
Background Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥65y) as compared to younger adults (<65y). Methods We included adults (≥18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age ≥65y reduced the probability of meeting syndromic LRTI case definitions, using patients’ symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups. Results Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. After controlling for sex, dementia and comorbidities, age ≥65y significantly reduced the probability of meeting the case definition (aOR=0.67, 95% CI:0.63-0.71). Cases aged ≥65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥85y were characterised by lack of cough but frequent confusion and falls. Conclusions LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.
Subject(s)
Dementia , Pleurisy , Confusion , Fever , Severe Acute Respiratory Syndrome , Respiratory Tract Infections , COVID-19 , Cognition DisordersABSTRACT
Background Understanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is an urgent public health priority. A precise comparison of the rVE of monovalent and bivalent boosters given during the 2022 Spring-Summer and Autumn-Winter campaigns, respectively, in a defined population has not been reported. We therefore 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. Methods A prospective single-centre test-negative design case-control study of [≥]75 year-olds hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, gender, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation. Results 682 controls and 182 cases were included in the Spring-Summer booster analysis; 572 controls and 152 cases for the Autumn-Winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed rVE 46*9% (95% confidence interval [CI] 14*4-67*3) versus those not boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had rVE 46*4% (95%CI 17*5-65), compared to a fourth monovalent mRNA COVID-19 vaccine dose. Interpretation Both fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offer equivalent protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support the current UK immunisation programme that advises the use of bivalent booster doses.
Subject(s)
COVID-19 , Respiratory Tract DiseasesABSTRACT
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults ([≥]18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection. Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
Subject(s)
COVID-19ABSTRACT
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults (≥18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection. Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
Subject(s)
COVID-19ABSTRACT
Background: Concomitant administration of COVID-19 and influenza vaccines would reduce burden on healthcare systems. We assess the safety of concomitant administration. Methods: Adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomised 1:1 to receive concomitant administration of either age-appropriate influenza or placebo alongside second COVID-19 vaccine. Three weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed to six weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted (aTIV) or a cellular or recombinant quadrivalent vaccine (QIVc/QIVr)). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reaction in the seven days after first trial vaccination(s), with a difference of <25% considered non-inferior. Local and unsolicited systemic reactions and humoral responses were also assessed (ISRCTN14391248). Findings: Between 1st April and 26th June 2021, 679 participants were recruited to one of six cohorts: (129 ChAdOx1/QIVc; 139 BNT162b2/QIVc; 146 ChAdOx1/aTIV; 79 BNT162b2/aTIV; 128 ChAdOx1/QIVr; 58 BNT162b2/QIVr). Overall, 340 participants were randomised to concomitant administration of influenza and COVID-19 vaccine and 339 were randomised to placebo and COVID-19 vaccine. Non-inferiority was indicated in four cohorts; ChAdOx1/QIVc: risk difference (influenza vaccine minus placebo) -1·29% (95% confidence interval (CI) ‑14·7%, 12·1%); BNT162b2/QIVc: 6·17% (‑6·27%, 18·6%); BNT162b2/aTIV: -12·9% (‑34·2%, 8·37%); ChAdOx1/QIVr: 2·53% (‑13·3%, 18·3%). In two cohorts the upper limit of the 95%CI exceeded 25%; ChAdOx1/aTIV: 10·3% (‑5·44%, 26·0%) and BNT162b2/QIVr: 6·75% (‑11·8%, 25·3%). Most reactions were mild or moderate. Rates of local and unsolicited systemic reactions were similar between randomised groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. Interpretation: Concomitant vaccination raises no safety concerns and preserves the immune response to both vaccines.Clinical Trial Registration Details: The trial is registered (ISRCTN14391248)Funding Information: The trial is commissioned and funded by the Department of Health and Social Care (DHSC) through the National Institute for Health Research (NIHR). This research was supported by the Vaccine Task Force (VTF) and NIHR Policy Research Programme (PR-R17-0916-22001, NIHR203243).Declaration of Interest: RL reports grants from National Institute for Health Research during the conduct of the trial, and grants from Elizabeth Blackwell Institute, AstraZeneca, Janssen and Valneva outside the submitted work. CR reports grants from National Institute for Health Research, during the conduct of the trial. JSN-V-T reports he is seconded to the Department of Health and Social Care, England. AF reports grants from Pfizer during the conduct of the trial, and grants from Elizabeth Blackwell Institute, Gates Foundation, Sanofi Pasteur, VBI Vaccines, Pfizer, Janssen, GSK, MedImmune, Novavax and Valneva outside the submitted work. Between May 2015 and May 2019 AF was President of the European Society for Paediatric Infectious Diseases which, during this period, received sponsorship from GSK for its annual congress. He currently serves as chief investigator on the Valneva (Covid-19) vaccine phase 1/2 and 2/3 studies .He also serves as co-investigator on the Janssen (Covid-19) vaccine 2 dose phase 3 study. He does advisory work related to vaccines for the UK government, the World Health Organisation and several companies developing vaccines. He also leads clinical trials of vaccines funded by the UK government, charities and vaccine manufacturers. He receives no personal remuneration or benefits in kind for any of this work apart from his salary via the University of Bristol from the Higher Education Funding Council and the NHS. He is a member of the UK Department of Health’s Joint Committee on Vaccination, Chair of the WHO European Technical Advisory Group of Experts in which capacity he attends SAGE. AM reports grants from National Institute for Health Research during the conduct of the trial, and grants from AstraZeneca, Janssen and Valneva outside the submitted work. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers, including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax, Pfizer, Janssen, Medimmune and MCM. The views in this paper are those of its authors and not necessarily those of the DHSC.Ethical Approval Statement: Approvals were received from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number 2021-001124-18) and the South-Central Berkshire Research Ethics Committee (21/SC/0100).