Age, Comorbidities, and Mortality Correlation in COVID-19 Patients: A Review

Background: The risk of death due to COVID-19 among hospitalized patients is known to be higher in older adults and those with underlying health conditions. Understanding the percentage of patients who are at increased risk of death due COVID-19 and how this varies between age groups will inform the healthcare community how to evaluate the risk of COVID-19, and better design healthcare and economic policies. Methods: We conducted a literature search for studies published between December 2019 until May 16, 2020 in PubMed, Embase, and Cochrane (CENTRAL). Descriptive statistics were performed. Results: We reviewed 14 studies of which 13 were retrospective and one was prospective. Eleven studies were conducted in Wuhan, China. A grand total of 11,938 COVID-19 confirmed patients were reviewed. Among these patients, 7637 (64%) were males. Our review reported hypertension (41%), diabetes (21%), cardiac diseases (14%), COPD (8%), chronic kidney disease (4%) and cerebrovascular disease (10%) as the most common underlying diseases among patients who died during hospitalization due to COVID-19. The total number of patients died in the hospital was 1744 (15%). Among patients who died in the hospital, 1% patients were 30-39 years, 16% patients were 40-59 years and 83% patients were more than 60 years of age. Conclusions: Older patients with underlying diseases appear to be at higher risk of mortality from COVID-19. Comorbidities are significant predictors of mortality in COVID-19 patients. There is an urgent need to know the epidemiology of the novel virus and characterize its potential impact

Implementing a Clinical Research Program in Long Term Care Facilities: Experiences from the University of Louisville Center Excellence for Research in Infectious Diseases [CERID]

Background: According to the US Census Bureau International Report, in 2015, almost nine percent of the world’s population was aged 65 and over. As the worldwide population ages, there is a need to understand how to best care for those individuals. Developing clinical research programs focusing on long term care (LTC) will be critical to defining best practice. Objectives: The objectives of this manuscript are to: 1) outline the challenges identified in performing clinical research in long term care facilities (LTCF), and 2) offer solutions for future clinical research in the LTC environment based upon our experiences. Methods: A research feasibility study was performed in 14 LTCFs in Louisville, Kentucky during 2018. Research questions involving identification of LTCF residents experiencing diarrhea were used as the basis for determining challenges and abilities to perform research in the LTC environment. Results: Challenges to performing clinical research involving an infectious disease were gathered throughout the twenty-week feasibility assessment period and organized into eight distinct yet inter-related areas. These included: 1) facility recruitment; 2) engagement of facility leadership; 3) engagement of facility personnel; 4) identification of research candidates; 5) consenting processes; 6) management of clinical samples; 7) navigating the medical record systems; and 8) study team workflow. Conclusions: This feasibility assessment found that conducting research in LTCFs was very different in almost every aspect from research conducted in the hospital setting. Results from this feasibility assessment will be used as a basis to determine a more comprehensive population-based incidence of C. difficile infection through the City of Louisville Diarrhea (CLOUD) study

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee