Clinical Features and Death Risk Factors in COVID-19 Patients with Cancer: A Retrospective Study (preprint)

Purpose: Coronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors.Methods: From February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching analysis, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients were performed. Next, we identified death related risk factors and developed a nomogram for predicting the probability.Results: In 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significant different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed.Conclusion: In COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significant different. NLR and CRP were the risk factors that could predict death outcome.

Development and Validation of a Novel Predictive Nomogram for Disease Progression of COVID-19: A Multicenter Retrospective Cohort Study of 4,086 Cases in China (preprint)

Aim: Coronavirus disease 2019 (COVID-19) has caused an unprecedented healthcare crisis. We aim to develop and validate a nomogram for predicting disease progression based on a large cohort of hospitalized COVID-19 patients. Methods: This is a multicenter retrospective cohort study, with a total of 4,086 hospitalized COVID-19 patients enrolled from two hospitals in Wuhan, China between February 3rd and Apr 10th. Nomogram was developed based on a cohort of 3, 022 patients from one hospital, and externally validated in another cohort of 1,064 patients from the other hospital. The calibration was assessed by a calibration plot and the HL test to evaluate the goodness of fit, and the Area under the ROC Curve (AUROC) as a measure of discriminative ability.Results: Six independent predictors, including age, dyspnea, platelet count, lactate dehydrogenase, D-dimer and cardiovascular disease, were finally identified for construction of the nomogram for predicting disease progression of COVID-19 patients during hospitalization. The AUROC was 0.877 and 0.817 for development cohort and validation cohort, respectively. The calibration plots AND Hosmer-Lemeshow test showed optimal agreement between nomogram prediction and actual observation. The decision curve analysis showed the performance of the nomograms were better than all univariable models, and had greater net benefit. Next, a predictive nomogram for disease severity on admission was formulated and the six independent factors used were similar to that of the nomogram for disease progression, which indicates that those factors play important roles in determining disease severity and the risk of disease progression. Conclusion: In the current study, a nomogram was developed based on generally readily available variables at hospital admission to help predict disease progression of COVID-19.

Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment (preprint)

Background Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.

Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation (preprint)

An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.