Inpatient COVID-19 Mortality Has Reduced Over Time: Results from an Observational Cohort (preprint)

Introduction: The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes were different in the first and second waves.Methods: The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and January 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.Findings: There were 3,457 COVID-19 admissions, 2,494 hospital discharges and 619 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (25.7% versus 13.2%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.41(0.30, 0.56)p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 1.22(95%CI 0.91, 1.62),p=0.18] or dexamethasone [HR 1.31(95%CI 0.80, 2.14),p=0.29].Interpretation: There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.Funding: None.Conflict of Interest: None declared by authors.Ethical Approval: This project operated under London South East Research Ethics Committee (reference 18/LO/2048) approval granted to the King’s Electronic Records Research Interface (KERRI); specific work on COVID-19 research was reviewed with expert patient input on a virtual committee with Caldicott Guardian oversight.

Incidence and outcomes of healthcare-associated COVID-19 infections: significance of delayed diagnosis and correlation with staff absence (preprint)

BackgroundThe sudden increase in COVID-19 admissions in hospitals during the SARS-CoV2 pandemic of 2020 has led to onward transmissions among vulnerable inpatients. AimsThis study was performed to evaluate the prevalence and clinical outcomes of Healthcare-associated COVID-19 infections (HA-COVID-19) during the 2020 epidemic and study factors which may promote or correlate with its incidence and transmission in a London Teaching Hospital Trust. MethodsElectronic laboratory, patient and staff self-reported sickness records were interrogated for the period 1st March to 18th April 2020. HA-COVID-19 was defined as symptom onset >14d of admission. Test performance of a single combined throat and nose swab (CTNS) for patient placement and the effect of delayed RNA positivity (DRP, defined as >48h delay) on patient outcomes was evaluated. The incidence of staff self-reported COVID-19 sickness absence, hospital bed occupancy, community incidence and DRP was compared HA-COVID-19. The incidence of other significant hospital-acquired bacterial infections (OHAI) was compared to previous years. Results58 HA-COVID-19 (7.1%) cases were identified. As compared to community-acquired cases, significant differences were observed in age (p=0.018), ethnicity (p<0.001) and comorbidity burden (p<0.001) but not in 30d mortality. CTNS negative predictive value was 60.3%. DRP was associated with greater mortality (p=0.034) and 34.5% HA-COVID-19 cases could be traced to delayed diagnosis in CA-COVID-19. Incidence of HA-COVID-19 correlated positively with DRP (R=0.7108) and staff sickness absence (R=0.7815). OHAI rates were similar to previous 2 years. ConclusionEarly diagnosis and isolation of COVID-19 would help reduce transmission. A single CTNS has limited value in segregating patients into positive and negative pathways.

Hospital mortality and resource implications of hospitalisation with COVID-19 in London, UK: a prospective cohort study (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 33 000 cases reported in London by July 6, 2020. Detailed hospital-level information on patient characteristics, outcomes and capacity strain are currently scarce but would guide clinical decision-making and inform prioritisation and planning. MethodsWe aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK. We included adult patients admitted to hospital with laboratory-confirmed COVID-19 and followed them up until hospital discharge or 30 days. Baseline factors that are associated with hospital mortality were identified via semi-parametric and parametric survival analyses. ResultsOur study included 429 patients; 18% of them were admitted to ICU, 52% met criteria for ICU outreach team activation and 61% had treatment limitations placed during their admission. Hospital mortality was 26% and ICU mortality was 34%. Hospital mortality was independently associated with increasing age, male sex, history of chronic kidney disease, increasing baseline C-reactive protein level and dyspnoea at presentation. COVID-19 resulted in substantial ICU and hospital strain, with up to 9 daily ICU admissions and 41 daily hospital admissions, to a peak census of 80 infected patients admitted in ICU and 250 in the hospital. Management of such a surge required extensive reorganisation of critical care services with expansion of ICU capacity from 69 to 129 beds, redeployment of staff from other hospital areas and coordinated hospital-level effort. ConclusionsCOVID-19 is associated with a high burden of mortality for patients treated on the ward and the ICU and required substantial reconfiguration of critical care services. This has significant implications for planning and resource utilization.

A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19 (preprint)

BackgroundPeople of minority ethnic background may be disproportionately affected by severe COVID-19 for reasons that are unclear. We sought to examine the relationship between ethnic background and (1) hospital admission for severe COVID-19; (2) in-hospital mortality. MethodsWe conducted a case-control study of 872 inner city adult residents admitted to hospital with confirmed COVID-19 (cases) and 3,488 matched controls randomly sampled from a primary healthcare database comprising 344,083 people resident in the same region. To examine in-hospital mortality, we conducted a cohort study of 1827 adults consecutively admitted with COVID-19. Data collected included hospital admission for COVID-19, demographics, comorbidities, in-hospital mortality. The primary exposure variable was self-defined ethnicity. ResultsThe 872 cases comprised 48.1% Black, 33.7% White, 12.6% Mixed/Other and 5.6% Asian patients. In conditional logistic regression analyses, Black and Mixed/Other ethnicity were associated with higher admission risk than white (OR 3.12 [95% CI 2.63-3.71] and 2.97 [2.30-3.85] respectively). Adjustment for comorbidities and deprivation modestly attenuated the association (OR 2.28 [1.87-2.79] for Black, 2.66 [2.01-3.52] for Mixed/Other). Asian ethnicity was not associated with higher admission risk (OR 1.20 [0.86-1.66]). In the cohort study of 1827 patients, 455 (28.9%) died over a median (IQR) of 8 (4-16) days. Age and male sex, but not Black (adjusted HR 0.84 [0.63-1.11]) or Mixed/Other ethnicity (adjusted HR 0.69 [0.43-1.10]), were associated with in-hospital mortality. Asian ethnicity was associated with higher in-hospital mortality (adjusted HR 1.54 [0.98-2.41]). ConclusionsBlack and Mixed ethnicity are independently associated with greater admission risk with COVID-19 and may be risk factors for development of severe disease. Comorbidities and socioeconomic factors only partly account for this and additional ethnicity-related factors may play a large role. The impact of COVID-19 may be different in Asians. Funding sourcesBritish Heart Foundation (CH/1999001/11735 and RE/18/2/34213 to AMS); the National Institute for Health Research Biomedical Research Centre (NIHR BRC) at Guys & St Thomas NHS Foundation Trust and Kings College London (IS-BRC-1215-20006); and the NIHR BRC at South London and Maudsley NHS Foundation Trust and Kings College London (IS-BRC-1215-20018).