Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

OBJECTIVE: To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms. DESIGN: Prospective, open-label, multicentre, stratified, randomised clinical trial. SETTING: Five hospitals in UK and India, from September 2020 to May 2021. PARTICIPANTS: Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset. INTERVENTION: Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care. PRIMARY OUTCOMES: The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days. RESULTS: Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047). CONCLUSION: Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients. TRIAL REGISTRATION NUMBERS: EudraCT Number: 2020-002952-18, NCT05007678.

Influences of the COVID-19 pandemic on admissions and clinical outcomes in mental health disorders and self-poisoning: Age- and sex-specific analysis.

We measured rates of hospital admissions for mental health disorders and self-poisoning during the pandemic in patients without COVID-19, compared to those admitted before the pandemic. Data were collected from 01/04/2019 to 31/03/2021, including the pandemic period from 01/03/2020. There were 10 173 (47.7% men) from the pre-pandemic and 11 019 (47.5% men) from the pandemic periods; mean age = 68.3 year. During the pandemic, admission rates for mental health disorders and self-poisoning were higher for any given age and sex. Self-poisoning was increased with toxic substances, sedatives and psychotropic drugs, but reduced with nonopioid analgesics. Patients admitted with mental health disorders had lower readmission rates within 28 days during the pandemic, but did not differ in other outcomes. Outcomes from self-poisoning did not change between the two study periods.

Does the length of stay in hospital affect healthcare outcomes of patients without COVID-19 who were admitted during the pandemic? A retrospective monocentric study.

Uncertainties remain if changes to hospital care during the coronavirus disease (COVID-19) pandemic had an adverse impact on the care-quality of non-COVID-19 patients. We examined the association of hospital length of stay (LOS) with healthcare quality indicators in patients admitted with general medical conditions (non-COVID-19). In this retrospective monocentric study at a National Health Service hospital (Surrey), data were collected from 1st April 2019 to 31st March 2021, including the pandemic from 1st March 2020. Primary admissions, in-hospital mortality, post-discharge readmission and mortality were compared between the pre-pandemic (reference group) and pandemic period, according to LOS categories. There were 10,173 (47.7% men) from the pre-pandemic and 11,019 (47.5% men) from the pandemic period; mean (SD) age 68.3 year (20.0) and 68.3 year (19.6), respectively. During the pandemic, primary admission rates for acute cardiac conditions, pulmonary embolism, cerebrovascular accident and malignancy were higher, whilst admission rates for respiratory diseases and common age-related infections, and in-hospital mortality rates were lower. Amongst 19,721 survivors, sex distribution and underlying health status did not significantly differ between admissions before the pandemic and during wave-1 and wave-2 of the pandemic. Readmission rates did not differ between pre-pandemic and pandemic groups within the LOS categories of < 7 and 7-14 days, but were lower for the pandemic group who stayed > 14 days. For patients who died within seven days of admission, in-hospital mortality rates were lower in patients admitted during the pandemic. Mortality rates within 30 days of discharge did not differ between pre-pandemic and pandemic groups, irrespective of the initial hospital LOS. Despite higher rates of admission for serious conditions during the pandemic, in-hospital mortality was lower. Discharge time was similar to that for patients admitted before the pandemic, except it was earlier during the pandemic for those who stayed > 14 days, There were no group differences in quality-care outcomes.

High LACE index scores are associated with disproportionate excess deaths in hospital amongst patients with COVID-19.

Risk factors for COVID-19-related outcomes have been variably reported. We used the standardised LACE index to examine admissions and in-hospital mortality associated with COVID-19. Data were collected in the pre-pandemic period (01-04-2019 to 29-02-2020) from 10,173 patients (47.7% men: mean age ± standard deviation = 68.3 years ± 20.0) and in the pandemic period (01-03-2019 to 31-03-2021) from 12,434 patients. With the latter, 10,982 were without COVID-19 (47.4% men: mean age = 68.3 years ± 19.6) and 1452 with COVID-19 (58.5% men: mean age = 67.0 years ± 18.4). Admissions and mortality were compared between pre-pandemic and pandemic patients, according to LACE index. Admission rates rose disproportionately with higher LACE indices amongst the COVID-19 group. Mortality rates amongst the pre-pandemic, pandemic non-COVID-19 and COVID-19 groups with LACE index scores < 4 were 0.7%, 0.5%, 0%; for scores 4-9 were 5.0%, 3.7%, 8.9%; and for scores ≥ 10 were: 24.2%, 20.4%, 43.4%, respectively. The area under the curve receiver operating characteristic for predicting mortality by LACE index was 76% for COVID-19 and 77% for all non-COVID-19 patients. The risk of age and sex-adjusted mortality did not differ from the pre-pandemic group for COVID-19 patients with LACE index scores < 4. However, risk increased drastically for scores from 4 to 9: odds ratio = 3.74 (95% confidence interval = 2.63-5.32), and for scores ≥ 10: odds ratio = 4.02 (95% confidence interval = 3.38-4.77). In conclusion, patients with LACE index scores ≥ 4 have disproportionally greater risk of COVID-19 hospital admissions and deaths, in support of previous studies in patients without COVID-19. However, of importance, our data also emphasise their increased risk in patients with COVID-19. Because the LACE index has a good predictive power of mortality, it should be considered for routine use to identify high-risk COVID-19 patients.

Comparison of characteristics and outcomes of patients admitted to hospital with COVID-19 during wave 1 and wave 2 of the current pandemic.

In this study of patients admitted with COVID-19, we examined differences between the two waves in patient characteristics and outcomes. Data were collected from the first COVID-19 admission to the end of study (01/03/2020-31/03/2021). Data were adjusted for age and sex and presented as odds ratios (OR) with 95% confidence intervals (CI). Among 12,471 admissions, 1452 (11.6%) patients were diagnosed with COVID-19. On admission, the mean (± SD) age of patients with other causes was 68.3 years (± 19.8) and those with COVID-19 in wave 1 was 69.4 years (± 18.0) and wave 2 was 66.2 years (± 18.4). Corresponding ages at discharge were 67.5 years (± 19.7), 63.9 years (± 18.0) and 62.4 years (± 18.0). The highest proportion of total admissions was among the oldest group (≥ 80 years) in wave 1 (35.0%). When compared with patients admitted with other causes, those admitted with COVID-19 in wave 1 and in wave 2 were more frequent in the 40-59 year band: 20.8, 24.6 and 30.0%; consisted of more male patients: 47.5, 57.6 and 58.8%; and a high LACE (Length of stay, Acuity of admission, Comorbidity and Emergency department visits) index (score ≥ 10): 39.4, 61.3 and 50.3%. Compared to wave-2 patients, those admitted in wave 1 had greater risk of death in hospital: OR = 1.58 (1.18-2.12) and within 30 days of discharge: OR = 2.91 (1.40-6.04). Survivors of COVID-19 in wave 1 stayed longer in hospital (median = 6.5 days; interquartile range = 2.9-12.0) as compared to survivors from wave 2 (4.5 days; interquartile range = 1.9-8.7). Patient characteristics differed significantly between the two waves of COVID-19 pandemic. There was an improvement in outcomes in wave 2, including shorter length of stay in hospital and reduction of mortality.

Prolonged QT predicts prognosis in COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc). METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19. RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C-reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre-COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID-19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre-COVID vs COVID, p < 0.01). Multivariate Cox-regression analysis revealed age, C-reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]). CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

SARS-CoV-2 antibody seroprevalence in NHS healthcare workers in a large double-sited UK hospital.

We determined the seroprevalence of SARS-CoV-2 antibodies in NHS healthcare workers (HCWs) in a cross-sectional study from a large general hospital located in a double-sited rural and semi-rural area. The sample size of 3,119 HCWs (mean age 43±13) consisted of 75.2% women, 61.1% White individuals and predominantly (62.4%) asymptomatic individuals. Seroprevalence of SARS-CoV-2 antibodies was 19.7%. Determinants of seropositivity were preceding symptomatic infection and non-White ethnicity. Regardless of staff role or sex, multivariate regression analysis revealed that non-White HCWs were three times (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.53-3.86, P<0.001) more likely to have antibodies than White staff, and seven times (OR 7.10, 95% CI 5.72-8.87, P<0.001) more likely if there was a history of preceding symptoms. We report relatively high rates of seropositivity in all NHS healthcare workers. Non-White symptomatic HCWs were significantly more likely to be seropositive than their colleagues, independent of age, sex or staff role.

COVID-19 outcomes in UK centre within highest health and wealth band: a prospective cohort study.

OBJECTIVES: To describe the characteristics and outcomes of hospitalised patients with COVID-19 from UK in the highest decile of health and gross regional products per capita. DESIGN: Prospective cohort study. SETTING: Recruited all adult inpatients with laboratory-confirmed COVID-19 symptoms admitted to a single Surrey centre between March and April 2020. Extensive demographic details were documented. OUTCOME MEASURE: COVID-19 status of alive/dead and intensive care unit (ICU) status of yes/no. PARTICIPANTS: Patients with COVID-19 from Surrey centre UK (n=429). RESULTS: 429 adult inpatients (mean age 70±18 years; men 56.4%) were included in this study, of whom, 19.1% required admission to ICU and 31.9% died. Adverse outcomes were associated with age (OR with each decade of years: 1.78, 95% CI 1.53 to 2.11, p<0.001 for mortality); male gender (OR=1.08, 95% CI 0.72 to 1.63, p=0.72, present in 70.7%, of admissions to ICU versus 53% of other cases, p=0.004); cardiac disease (OR=3.43, 95% CI 2.10 to 5.63, p<0.001), diabetes mellitus (OR=2.37, 95% CI 1.09 to 5.17, p=0.028) and dementia (OR=5.06, 95% CI 2.79 to 9.44, p<0.001). There was no significant impact of ethnicity or body mass index on disease outcome. CONCLUSIONS: Despite reports of worse outcomes in deprived regions, we show similar complication and mortality rates due to COVID-19 in an affluent and high life expectancy region.