Inter-rater Variability in the Evaluation of Lung Ultrasound on Videos Acquired from COVID-19 Patients (preprint)

Lung ultrasound (LUS) allows the detection of a series of manifestations of COVID-19 such as B lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the impact of performing the test in the longitudinal or transverse orientation. 33 physicians with advanced experience in LUS, independently evaluated ultrasound videos previously acquired with the ULTRACOV system of 20 patients with confirmed COVID-19. In each patient, 24 videos of 3 seconds were acquired (using 12 positions with the probe in longitudinal and transverse orientations). Physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), only a fair IRR for the presence of individual B lines (κ = 0.36) and for confluent B lines occupying <50% (κ = 0.26), and a moderate IRR in consolidations and B-lines >50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR in LUS of COVID-19 patients may benefit from more standardization of the clinical protocols.

Optimal thromboprophylaxis strategies in non-critically ill patients with COVID-19 pneumonia. The PROTHROMCOVID Randomized Controlled Trial. (preprint)

Background : Hospitalized patients with COVID-19 are at increased risk for thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. Objective: To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. Design, setting, and participants : Randomized controlled, multicenter trial (PROTHROMCOVID) enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Interventions: Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) doses of tinzaparin during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. Measurements: The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Results : Of the 311 subjects randomized, 300 were included in the analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]. The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (P= 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Conclusions: In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to increase benefit regarding the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death. Trial Registration ClinicalTrials.gov Identifier (NCT04730856). Funding: This independent research initiative was supported by Leo-Pharma; Tinzaparin was provided by Leo Pharma.

Association between prior cardiometabolic therapy and in-hospital mortality in very old patients with type 2 diabetes mellitus hospitalized due to COVID-19. A nationwide observational study in Spain (preprint)

Background Advanced age and diabetes are both associated with poor prognosis in COVID-19. However, the effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well-known. This work aims to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥ 80 years with type 2 diabetes mellitus hospitalized for COVID-19.Methods We conducted a nationwide, multicenter, retrospective, observational study in patients ≥ 80 years with type 2 diabetes mellitus and COVID-19 hospitalized in 160 Spanish hospitals between March 1 and May 29, 2020 who were included in the SEMI-COVID-19 Registry. The primary outcome measure was in-hospital mortality. A multivariate logistic regression analysis were performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality. The regression analysis values were expressed as adjusted odds ratios (AOR) with a 95% confidence interval (CI). In order to select the variables, the forward selection Wald statistic was used. Discrimination of the fitted logistic model was assessed via a receiver operating characteristic (ROC) curve. The Hosmer-Lemeshow test for logistic regression was used to determine the model’s goodness of fit.Results Of the 2,763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (AOR 0.502, 95% CI 0.309–0.815, p = 0.005) and angiotensin receptor blockers (AOR 0.454, 95% CI 0.274–0.759, p = 0.003) were independent protectors against in-hospital mortality whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95% CI 1.092–2.842, p = 0.020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins showed neutral association with in-hospital mortality. The model showed an area under the curve of 0.788.Conclusions We found important differences between cardiometabolic drugs and in-hospital mortality in older patients with type 2 diabetes mellitus hospitalized for COVID-19. Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers may reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors and statins seem to have a neutral effect; and acetylsalicylic acid may be associated with excess mortality.

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry. (preprint)

Aim: To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods: Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results: As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p=0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.219, 95%CI 0.069-0.693, p=0.01). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions: Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality.

The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals. (preprint)

ObjectivesA decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with severe SARS-CoV-2 (COVID-19), but there is no knowledge of the potential role of their recovery in these patients prognosis. This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. DesignThis work is a multicentre, retrospective, cohort study of 9,644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicines SEMI-COVID-19 Registry. SettingThis study examined patients hospitalised in 147 hospitals throughout Spain. ParticipantsThis work analysed 9,644 patients (57.12% male) out of a cohort of 12,826 patients [≥]18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020. Main outcome measuresThe main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death and then multivariate analysis was carried out to control for potential confounders. ResultsAn increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs 22.6% in non-recoverers, OR 0.234 [95% CI, 0.154 to 0.354]) and lower complication rates, especially regarding to development of acute respiratory distress syndrome (8% vs 20.1%, p=0.000) and ICU admission (5.4% vs 10.8%, p=0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor. ConclusionEosinophil recovery in patients with COVID-19 is a reliable marker of a good prognosis that is independent of prior treatment. This finding could be used to guide discharge decisions.