Association Between Risk of VTE and Mortality in Patients with COVID-19 (preprint)

Background: Hospitalized patients with COVID-19 appeared high risk of venous thromboembolism (VTE), which exhibited the predictor of mortality in non-COVID-19 patients. Objectives: We aimed to investigate the association between risk of VTE with 30-day mortality in COVID-19 patients.Methods: In this retrospective cohort study, 1030 consecutive hospitalized patients with COVID-19 were recruited in two hospitals of Wuhan, China. We collected baseline data on demographics, SOFA parameters, and VTE risk assessment models (RAMs) including Padua Prediction Score (PPS), IMPROVE and Caprini RAM. The primary outcome of the study was 30-day mortality. Results: Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk defined by PPS. Similar findings were also observed for risk of VTE defined by IMPROVE and Caprini score. Progressive increases in VTE risk also were associated with higher SOFA score. Our findings showed that the presence of high risk of VTE was independently associated with 30-day mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19, 37.37, 20.60 for PPS, IMPROVE and Caprini RAM, respectively (P< 0.001 for all comparisons). Predictive accuracy of PPS (AUC, 0.900), IMPROVE (AUC, 0.917) or Caprini RAM (AUC, 0.861) as the risk of 30-day mortality was markedly well.Conclusions: The presence of high risk of VTE identifies a group of patients with COVID-19 at higher risk for 30-day mortality. Furthermore, there is higher accuracy of VTE RAMs to predict 30-day mortality in these patients.

Corticosteroid therapy for corona virus disease 2019-related acute respiratory distress syndrome: a cohort study with propensity score analysis (preprint)

Background: The impact of corticosteroid therapy on outcomes of patients with Coronavirus disease-2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. Methods In this single-centre retrospective observational study, patients with ARDS caused by COVID-19 between 24 December 2019 and 24 February 2020 were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. Results A total of 382 patients including 226 (59.2%) patients who received systemic corticosteroids and 156 (40.8%) patients with standard treatment were analyzed. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days (HR, 0.48; 95% CI, 0.25, 0.93; p  = 0.0285). The association remained significantly after adjusting for age, sex, Sequential Organ Failure Assessment score at hospital admission, propensity score of corticosteroid treatment, and comorbidities (HR: 0.51; CI: 0.27, 0.99; p  = 0.0471). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. Conclusion In this clinical practice setting, low-to-moderate dose corticosteroid treatment was associated with reduced risk of death in COVID-19 patients who developed ARDS.

Corticosteroid Therapy of Patients in ICU with Coronavirus Disease 2019(COVID-19): A Single-center, Retrospective, Observational study (preprint)

The authors have withdrawn this preprint due to author disagreement.

Derivation and validation of a prognostic model for predicting in-hospital mortality in patients admitted with COVID-19 in Wuhan, China: the PLANS (Platelet Lymphocyte Age Neutrophil Sex) model (preprint)

OBJECTIVETo develop and validate a prognostic model for in-hospital mortality in COVID-19 patients using routinely collected demographic and clinical characteristics. DESIGNMulticenter, retrospective cohort study. SETTINGJinyintan Hospital, Union Hospital, and Tongji Hosptial in Wuhan, China. PARTICIPANTSA pooled derivation cohort of 1008 COVID-19 patients from Jinyintan Hospital, Union Hospital in Wuhan and an external validation cohort of 1031 patients from Tongji Hospital in Wuhan, China. MAIN OUTCOME MEASURESOutcome of interest was in-hospital mortality, treating discharged alive from hospital as the competing event. Fine-Gray models, using backward elimination for inclusion of predictor variables and allowing non-linear effects of continuous variables, were used to derive a prognostic model for predicting in-hospital mortality among COVID-19 patients. Internal validation was implemented to check model overfitting using bootstrap approach. External validation to a separate hospital was implemented to evaluate the generalizability of the model. RESULTSThe derivation cohort was a case-mix of mild-to-severe hospitalized COVID-19 patients (n=1008, 43.6% females, median age 55). The final model (PLANS), including five predictor variables of platelet count, lymphocyte count, age, neutrophil count, and sex, had an excellent predictive performance (optimism-adjusted C-index: 0.85, 95% CI: 0.83 to 0.87; averaged calibration slope: 0.95, 95% CI: 0.82 to 1.08). Internal validation showed little overfitting. External validation using an independent cohort (n=1031, 47.8% female, median age 63) demonstrated excellent predictive performance (C-index: 0.87, 95% CI: 0.85 to 0.89; calibration slope: 1.02, 95% CI: 0.92 to 1.12). The averaged predicted survival curves were close to the observed survival curves across patients with different risk profiles. CONCLUSIONSThe PLANS model based on the five routinely collected demographic and clinical characteristics (platelet count, lymphocyte count, age, neutrophil count, and sex) showed excellent discriminative and calibration accuracy in predicting in-hospital mortality in COVID-19 patients. This prognostic model would assist clinicians in better triaging patients and allocating healthcare resources to reduce COVID-19 fatality.

Heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (COVID-19) (preprint)

Importance: Heart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated. Objective: To explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later. Design, Setting, and Participants A single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020. Exposures: High levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; -HBDH). Main Outcomes and Measures: Mortality in hospital and days from admission to mortality (survival days). Results: Of 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21~83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission ([≥] 6.126 pg/mL), even within the clinical normal range (0~28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and -HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and -HBDH on admission were associated with higher mortality. Both high LDH and -HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64~-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59~-0.05, P=0.022). Conclusions and Relevance: Heart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury.