COVID and venous thrombosis: systematic review of literature.

INTRODUCTION: We aimed to review the prevalence, the risk factors and the outcomes of venous thrombosis (VT) in patients hospitalized for COronaVirus Disease 19 (COVID-19). EVIDENCE ACQUISITION: Electronic bibliographic databases were searched using the words "COVID venous thrombosis". The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. EVIDENCE SYNTHESIS: The search of the literature retrieved 877 results. After assessment of full texts, 69 papers were included in the qualitative analysis and 23 of them in the quantitative evaluation. The analyzed studies included a total of 106,838 patients hospitalized for COVID-19 from January to December 2020. The pooled reported prevalence rate of VT was in median 16.7% (IQR 5.8-30%), being higher in ICU patients (60.8-85.4%). VT events were reported in about 75% of cases in the popliteal and calf veins. Signs and symptoms were present in 6.1% of cases. At quantitative evaluation, older age, D-dimer and obesity increased the odds to experience a VT (OR=3.54, 95% CI 0.65-6.43, P=0.01; OR=956.86, 95% CI 225.67-1668.05, P=0.01; OR=1.42, 95% CI 1.01-1.99, P=0.03 respectively). Female sex seemed to be protective against the odds of VT (OR=0.77, 95% CI 0.63-0.93, P=0.007). CONCLUSIONS: Among patients hospitalized for COVID-19, VT is a relatively common finding, with higher prevalence rates in ICU patients. VT occurs mostly in the distal regions of the lower limb and is asymptomatic in most cases. Older age, obesity and higher D-dimer values on admission increased the odds of VT, while female sex was protective against the odds of VT.

Biomarkers Predict In-Hospital Major Adverse Cardiac Events in COVID-19 Patients: A Multicenter International Study.

BACKGROUND: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19. METHODS: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE). RESULTS: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan-Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001). CONCLUSIONS: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial.

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) exhibit high thrombotic risk. The evidence on a potential independent prognostic role of antiplatelet treatment in those patients is limited. The aim of the study was to evaluate the prognostic impact of pre-admission low-dose acetylsalicylic acid (ASA) in a wide series of hospitalized patients with COVID-19. METHODS: This cohort study included 984 COVID-19 patients stratified according to ASA intake before hospitalization: ASA+ (n = 253) and ASA- (n = 731). Patients were included in ASA+ group if they received it daily in the 7 days before admission. 213 (83%) were on ASA 100 mg daily. Primary endpoint was a composite of in-hospital death and/or need for respiratory support upgrade, secondary endpoints were in-hospital death and need for respiratory support upgrade. RESULTS: Mean age was 72 [62; 81] with 69% of male patients. ASA+ patients were significantly older, with higher prevalence of comorbidities. No significant differences regarding the degree of respiratory dysfunction were observed. At 30-day Kaplan-Meier analysis, ASA+ patients had higher survival free from the primary endpoint and need for respiratory support upgrade, conversely in-hospital death did not significantly differ between groups. At multivariate analysis ASA intake was independently associated with a lower probability of reaching primary endpoint (HR 0.697, 95% C.I. 0.525-0.924; p = 0.012). CONCLUSIONS: In COVID-19 patients undergoing hospitalization, pre-admission treatment with ASA is associated with better in-hospital outcome, mainly driven by less respiratory support upgrade.

Sudden rupture of small aneurysm of the radial artery in a patient with COVID-19 pneumonia.

In patients with COVID-19, even small radial aneurysm may suddenly rupture.

Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. METHOD: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). RESULTS: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. CONCLUSIONS: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with acute and chronic aortic conditions.

OBJECTIVES: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures. METHODS: Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared. RESULTS: No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89-1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded (<12 h 32% vs > 12 h 68% in 2020, < 12 h 34% vs > 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76-0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (-40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02). CONCLUSIONS: There was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly. Patients with acute aortic syndromes presented despite COVID-19 and were managed according to current guidelines. Further analysis is required to prove that deferral of elective cases had no impact on premature mortality.

Non-Overt Coagulopathy in Non-ICU Patients with Mild to Moderate COVID-19 Pneumonia.

INTRODUCTION: Aim of the study is to assess the occurrence of early stage coagulopathy and disseminated intravascular coagulation (DIC) in patients with mild to moderate respiratory distress secondary to SARS-CoV-2 infection. MATERIALS AND METHODS: Data of patients hospitalized from 18 March 2020 to 20 April 2020 were retrospectively reviewed. Two scores for the screening of coagulopathy (SIC and non-overt DIC scores) were calculated. The occurrence of thrombotic complication, death, and worsening respiratory function requiring non-invasive ventilation (NIV) or admission to ICU were recorded, and these outcomes were correlated with the results of each score. Chi-square test, receiver-operating characteristic curve, and logistic regression analysis were used as appropriate. p Values < 0.05 were considered statistically significant. RESULTS: Data of 32 patients were analyzed. Overt-DIC was diagnosed in two patients (6.2%), while 26 (81.2%) met the criteria for non-overt DIC. Non-overt DIC score values ≥4 significantly correlated with the need of NIV/ICU (p = 0.02) and with the occurrence of thrombotic complications (p = 0.04). A score ≥4 was the optimal cut-off value, performing better than SIC score (p = 0.0018). Values ≥4 in patients with thrombotic complications were predictive of death (p = 0.03). CONCLUSIONS: Overt DIC occurred in 6.2% of non-ICU patients hospitalized for a mild to moderate COVID-19 respiratory distress, while 81.2% fulfilled the criteria for non-overt DIC. The non-overt DIC score performed better than the SIC score in predicting the need of NIV/ICU and the occurrence of thrombotic complications, as well as in predicting mortality in patients with thrombotic complications, with a score ≥4 being detected as the optimal cut-off.