Informing emergency care for COVID‐19 patients: The COVID‐19 Emergency Department Quality Improvement Project protocol

Objectives: There is an urgency to support Australian ED clinicians with real‐time tools as the COVID‐19 pandemic evolves. The COVID‐19 Emergency Department (COVED) Quality Improvement Project has commenced and will provide flexible and responsive clinical tools to determine the predictors of key ED‐relevant clinical outcomes. Methods: The COVED Project includes all adult patients presenting to a participating ED and meeting contemporary testing criteria for COVID‐19. The dataset has been embedded in the electronic medical record and the COVED Registry has been developed. Results: Outcomes measured include being COVID‐19 positive and requiring intensive respiratory support. Regression methodology will be used to generate clinical prediction tools. Conclusion: This project will support EDs during this pandemic.     

Coagulopathy in COVID‐19

The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.     

Cardiac injury is associated with inflammation in geriatric COVID‐19 patients

BackgroundGeriatric patients with coronavirus disease (COVID‐19) are at high risk of developing cardiac injury. Identifying the factors that affect high‐sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.MethodsOne hundred and eighty inpatients who were admitted for COVID‐19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.ResultsAge (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin‐2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high‐sensitivity C‐reactive protein (p = 0.001), D‐dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.ConclusionOur results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.     

Incidence and prognosis of cancer associated with bilateral venous thrombosis: a prospective study of 103 patients

Summary.  Background : A strong association between bilateral deep vein thrombosis (DVT) and cancer had been found in one retrospective study. To confirm this finding, consecutive patients with an objective diagnosis of bilateral DVT were followed over 12 months. Patients and methods : One-hundred and three patients, hospitalized for bilateral DVT, were included in the study. Twenty-six patients (25.2%) were already known to have a cancer, 26 (25.2%) had a previous history of venous thromboembolic disease, 44 (42.7%) had a symptomatic pulmonary embolism. The patients were scheduled to be prospectively followed up at 3, 6 and 12 months as outpatients. Information on recurrence, evidence of a new overt cancer and the cause of death were recorded for all patients. Results : A new cancer was diagnosed in 20 (26%) of the 77 patients without known cancer at admission. The risk of cancer was significantly more important in idiopathic thrombosis than in patients with secondary thrombosis (40.5% vs. 12.5%; odds ratio 4.8, 95% confidence interval 1.4, 18.8). Seventy percent of the cancers discovered had already spread. Age, gender, presence of pulmonary embolism, recurrence and location of the thrombosis were not statistically associated with the risk of cancer. The 1-year survival rates of patients with a previously known cancer and patients with a newly discovered cancer were, respectively, 26% and 35% ( P =  0.33). Conclusion : Bilateral DVT is a significant risk indicator of malignancy. Cancer is present in 45% of patients with bilateral DVT and is associated with a poor prognosis.     

COVID‐19 and acute coagulopathy in pregnancy

We present a putative link between maternal COVID‐19 infection in the peripartum period and rapid maternal deterioration with early organ dysfunction and coagulopathy. The current pandemic with SARS‐CoV‐2 has already resulted in high numbers of critically ill patients and deaths in the non‐pregnant population, mainly due to respiratory failure. During viral outbreaks, pregnancy poses a uniquely increased risk to women due to changes to immune function, alongside physiological adaptive alterations, such as increased oxygen consumption and edema of the respiratory tract. The laboratory derangements may be reminiscent of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and thus knowledge of the COVID‐19 relationship is paramount for appropriate diagnosis and management. In addition to routine measurements of D‐dimers, prothrombin time, and platelet count in all patients presenting with COVID‐19 as per International Society on Thrombosis and Haemostasis (ISTH) guidance, monitoring of activated partial thromboplastin time (APTT) and fibrinogen levels should be considered in pregnancy, as highlighted in this report. These investigations in SARS‐CoV‐2‐positive pregnant women are vital, as their derangement may signal a more severe COVID‐19 infection, and may warrant pre‐emptive admission and consideration of delivery to achieve maternal stabilization.     

The De Ritis ratio as prognostic biomarker of in‐hospital mortality in COVID‐19 patients

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID‐19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in‐hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID‐19) admitted to three COVID‐19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91‐1.64 vs 1.67; IQR: 1.38‐1.97, P = .002) whilst there were no significant between‐group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603‐0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan‐Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05‐5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in‐hospital mortality in COVID‐19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.     

Fibrinolysis and COVID‐19: A plasmin paradox

The COVID‐19 pandemic has provided many challenges in the field of thrombosis and hemostasis. Among these is a novel form of coagulopathy that includes exceptionally high levels of D‐dimer. D‐dimer is a marker of poor prognosis, but does this also imply a causal relationship? These spectacularly raised D‐dimer levels may actually signify the failing attempt of the fibrinolytic system to remove fibrin and necrotic tissue from the lung parenchyma, being consumed or overwhelmed in the process. Indeed, recent studies suggest that increasing fibrinolytic activity might offer hope for patients with critical disease and severe respiratory failure. However, the fibrinolytic system can also be harnessed by coronavirus to promote infectivity and where antifibrinolytic measures would also seem appropriate. Hence, there is a clinical paradox where plasmin formation can be either deleterious or beneficial in COVID‐19, but not at the same time. Hence, it all comes down to timing.