Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: Initial report of the international RISC-19-ICU prospective observational cohort

Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods: Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings: As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5À21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80À148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3¢2, 95% CI [1¢7À6¢0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0¢35, 0¢34), CRP, creatinine, troponin, D-dimer, lactate, neutrophil count, P/Fratio diverged within the first seven days (p<0¢01). On a multivariable Cox proportional-hazard regression model at admission, creatinine, D-dimer, lactate, potassium, P/F-ratio, alveolar-arterial gradient, and ischemic heart disease were independently associated with ICU-mortality. Interpretation: The European RISC-19-ICU cohort demonstrates a moderate mortality of 24% in critically ill patients with COVID-19. Despite high ARDS severity, mechanical ventilation incidence was low and associated with more rescue therapies. In contrast to risk factors in hospitalized patients reported in other studies, the main mortality predictors in these critically ill patients were markers of oxygenation deficit, renal and microvascular dysfunction, and coagulatory activation. Elevated risk of bloodstream infections underscores the need to exercise caution with off-label therapies.

Prevalence and Associated Risk Factors of Mortality Among COVID-19 Patients: A Meta-Analysis

“…Among the included studies, 26 studies were conducted in China [10][11][12][13] [77]. The sample size of the included studies varied from 16 to 51,633 patients and the mean age of the included patients varied from 41 years to 85.5 years.…”

Assessing the Elevation of Cardiac Biomarkers and the Severity of COVID-19 Infection: A Meta-analysis

“…Various comorbidities were assessed and compared between two groups, except Medetalibeyoglu et al and Zheng et al studies which did not assess comorbidities of the subjects (12,13). The comorbidities that were more significantly common in the severe groups included cardiovascular diseases (i.e., coronary artery disease, heart failure) in ten studies (14-24), hypertension in nine studies (14, 16-19, 21, 22, 24, 25), chronic respiratory diseases in nine studies (17,19,20,(23)(24)(25)(26)(27)(28), diabetes mellitus in seven studies (11,16,18,21,22,25,29), cerebrovascular diseases in five studies (15,16,18,21,24), chronic kidney disease in four studies (18,(22)(23)(24), cancer in one study (25), and immunosuppression in one study (17). Four studies did not find significant association between the infection severity and the patients' comorbidities (30)(31)(32)(33).…”

Sixty-Day Mortality Among 520 Italian Hospitalized COVID-19 Patients According to the Adopted Ventilatory Strategy in the Context of an Integrated Multidisciplinary Clinical Organization: A Population-Based Cohort Study

“…Moreover, a study based on the RISC-19-ICU registry reported an ICU mortality of 9.5% (8/84), 25.0% (3/12), and 31.4% (86/274) among patients undergoing oxygen therapy, NIV, and IMV, respectively. 9 Again, the mortalities reported in previous studies are likely to have underestimated the 60-day mortality. However, the mortality reported in the NIV and IMV groups in our study is lower than the mortality in the Italian study and similar to the mortality from the RISC-19-ICU registry.…”

“…Second, information regarding the respiratory management of COVID-19 patients has been mainly elicited from the setting of ICUs. 4 , 8 , 9 , 11 Thus, the number of hospitalized COVID-19 patients treated with oxygen supplementation and NIV has been markedly underreported, leading to inaccurate information regarding the overall use of the different respiratory supports and the outcomes. Third, most previous reports included a percentage of patients still admitted at the ICU at the end of the follow-up, ranging from 2.3% 8 to 71%, 2 and this may have led to different degrees of inaccuracy in estimating ICU mortality.…”