Predicting mortality of individual COVID-19 patients: A multicenter Dutch cohort

ObjectiveDevelop and validate models that predict mortality of SARS-CoV-2 infected patients admitted to the hospital. DesignRetrospective cohort study SettingA multicenter cohort across ten Dutch hospitals including patients from February 27 to June 8 2020. ParticipantsSARS-CoV-2 positive patients (age [≥] 18) admitted to the hospital. Main Outcome Measures21-day mortality evaluated by the area under the receiver operatory curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. The predictive value of age was explored by comparison with age-based rules used in practice and by excluding age from analysis. Results2273 patients were included, of whom 516 had died or discharged to palliative care within 21 days after admission. Five feature sets, including premorbid, clinical presentation and laboratory & radiology values, were derived from 80 features. Additionally, an ANOVA-based data-driven feature selection selected the ten features with the highest F-values: age, number of home medications, urea nitrogen, lactate dehydrogenase, albumin, oxygen saturation (%), oxygen saturation is measured on room air, oxygen saturation is measured on oxygen therapy, blood gas pH and history of chronic cardiac disease. A linear logistic regression (LR) and non-linear tree-based gradient boosting (XGB) algorithm fitted the data with an AUC of 0.81 (95% confidence interval 0.77 to 0.85) and 0.82 (0.79 to 0.85), respectively, using the ten selected features. Both models outperformed age-based decision rules used in practice (AUC of 0.69, 0.65 to 0.74 for age > 70). Furthermore, performance remained stable when excluding age as predictor (AUC of 0.78, 0.75 to 0.81) ConclusionBoth models showed excellent performance and had better test characteristics than age-based decision rules, using ten admission features readily available in Dutch hospitals. The models hold promise to aid decision making during a hospital bed shortage.

Cardiovascular risk factors are independently associated with COVID-19 mortality: a prospective cohort study

ObjectivesRecent reports suggest a high prevalence of hypertension and diabetes in COVID-19 patients, but the role of cardiovascular disease (CVD) risk factors in the clinical course of COVID-19 is unknown. We evaluated the time-to-event relationship between hypertension, dyslipidemia, diabetes, and COVID-19 outcomes. DesignWe analyzed data from the prospective Dutch COVID-PREDICT cohort, an ongoing prospective study of patients admitted for COVID-19 infection. SettingPatients from 8 participating hospitals, including two university hospitals from the COVID-PREDICT cohort were included. ParticipantsAdmitted, adult patients with a positive COVID-19 polymerase chain reaction (PCR) or high suspicion based on CT-imaging of the thorax. Patients were followed for major outcomes during hospitalization. CVD risk factors were established via home medication lists and divided in antihypertensives, lipid lowering therapy, and antidiabetics. Primary and secondary outcomes measuresThe primary outcome was mortality during the first 21 days following admission, secondary outcomes consisted of ICU-admission and ICU-mortality. Kaplan-Meier and Cox-regression analyses were used to determine the association with CVD risk factors. ResultsWe included 1604 patients with a mean age of 66{+/-}15 of whom 60.5% were men. Antihypertensives, lipid lowering therapy, and antidiabetics were used by 45%, 34.7%, and 22.1% of patients. After adjustment for age and sex, the presence of [≥]2 risk factors was associated with increased mortality risk (HR 1.52, 95%CI 1.15-2.02), but not with ICU-admission. Moreover, the use of [≥]2 antidiabetics and [≥]2 antihypertensives was associated with mortality independent of age and sex with HRs of respectively 2.09 (95%CI 1.55-2.80) and 1.46 (95%CI 1.11-1.91). ConclusionsThe accumulation of hypertension, dyslipidemia and diabetes leads to a stepwise increased risk for short-term mortality in hospitalized COVID-19 patients independent of age and sex. Further studies investigating how these risk factors disproportionately affect COVID-19 patients are warranted. Strengths and limitations of this studyO_LIWhile previous data reported a high prevalence of CVD risk factors in COVID-19 patients, this study investigated whether diabetes, dyslipidemia and hypertension predict adverse outcomes. C_LIO_LIThis study is limited by the use of medication as surrogate for cardiovascular risk factors C_LIO_LIThe causality of the investigated risk factors remains to be addressed in future studies. C_LI

Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine

ObjectiveTo compare survival of subjects with COVID-19 treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. MethodsWe analysed data of COVID-19 patients treated in 9 hospitals in the Netherlands. Inclusion dates ranged from February 27th 2020, to May 15th, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated subjects with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox-regression with adjustment for age, sex and covariates based on premorbid health, disease severity, and the use of steroids for adult respiratory distress syndrome, including dexamethasone. ResultsAmong 1893 included subjects, 21-day mortality was 23.4% in 1552 subjects treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 17.0% in 341 subjects that were treated in hospitals that did not. In the adjusted Cox-regression models this difference disappeared, with an adjusted hazard ratio of 1.17 (95%CI 0.88-1.55). When stratified by actually received treatment in individual subjects, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95%CI 1.25-2.01) in the full model. ConclusionsAfter adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine, compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in patients with COVID-19.