Late Pulmonary Embolism after COVID-19 Pneumonia despite Adequate Rivaroxaban Treatment.

INTRODUCTION: SARS-CoV-2 infection may predispose patients to thrombotic disease. Patients with COVID-19 pneumonia who are receiving non-vitamin K antagonists or direct oral anticoagulants for chronic disease are usually switched to heparin treatment during hospitalization. However, information about the most appropriate antithrombotic therapy after the acute infection phase is lacking. CASE DESCRIPTION: We report the case of a patient with chronic atrial fibrillation who was recently hospitalized for severe COVID-19 pneumonia. Four weeks after discharge he experienced an episode of an acute pulmonary embolism while on rivaroxaban therapy with adequate drug plasma levels, and in the absence of strong predisposing risk factors. CONCLUSION: This case highlights the risk of thrombotic complications after COVID-19 infection, raises some concern about their underlying mechanisms, and supports the use of effective anti-thrombotic therapy. LEARNING POINTS: COVID-19 infection is associated with frequent thrombotic events.A pro-coagulative status could be triggered by the persistent inflammatory phase of the infection despite anticoagulation.Adequate antithrombotic therapy is necessary for the prevention of acute and later thrombotic complications and needs close monitoring.

Pulmonary embolism in patients with COVID-19 pneumonia on adequate oral anticoagulation.

Thrombotic complications are common in patients with severe COVID-19 pneumonia with important consequences on the diagnostic and therapeutic management. We report a consecutive series of five patients on long-term oral anticoagulation therapy who presented to our hospital for severe COVID-19 pneumonia associated with segmental acute pulmonary embolism despite adherence to therapy and with an adequate anticoagulant range at the time of the event. Four patients were receiving a direct oral anticoagulant (two with edoxaban, one with rivaroxaban and one with apixaban) and one patient a vitamin K antagonist. No significant thrombotic risk factors, active cancer, or detectable venous thromboembolism were present. In all cases, elevated d-dimer and fibrinogen levels with a parallel rise in markers of inflammation were documented. The combination of these findings seems to support the hypothesis that considers the local vascular damage determined by severe viral infection as the main trigger of thrombi detected in the lungs, rather than emboli from peripheral veins.

Coronary artery disease in patients hospitalised with Coronavirus disease 2019 (COVID-19) infection.

OBJECTIVE: Among patients with Coronavirus disease 2019 (COVID-19), coronary artery disease (CAD) has been identified as a high-risk condition. We aimed to assess the clinical outcomes and mortality among patients with COVID-19 according to CAD status. METHODS: We retrospectively analysed data from patients with COVID-19 admitted to the Cremona Hospital (Lombardy region, Italy) between February and March 2020. The primary outcome was all-cause mortality. CAD was defined as a history of prior myocardial infarction (MI), prior percutaneous coronary intervention (PCI), prior coronary artery bypass grafting (CABG) or CAD that was being medically treated. RESULTS: Of 1252 consecutive patients with COVID-19, 124 (9.9%) had concomitant CAD. Patients with CAD were older and had a higher prevalence of comorbidities compared with those without CAD. Although patients with CAD had a higher risk of all-cause mortality than patients without CAD (HR 3.01, 95% CI 2.27 to 3.99), this difference was no longer significant in the adjusted model (HR 1.14, 95% CI 0.79 to 1.63). Results were consistent among patients with prior MI (adjusted HR (aHR) 0.87, 95% CI 0.54 to 1.41), prior PCI (aHR 1.10, 95% CI 0.75 to 1.62), prior CABG (aHR 0.91, 95% CI 0.45 to 1.82), or CAD medically treated (aHR 0.84, 95% CI 0.29 to 2.44). Multivariable analysis showed that age (aHR per 5 year increase 1.62, 95% CI 1.53 to 1.72) and female sex (aHR 0.63, 95% CI 0.49 to 0.82) were the only two independent correlates of mortality. CONCLUSION: Patients with COVID-19 and CAD have an exceedingly higher risk of mortality, which is mainly attributable to the burden of comorbidities rather than to a direct effect of CAD per se.

Effects on QT interval of hydroxychloroquine associated with ritonavir/darunavir or azithromycin in patients with SARS-CoV-2 infection.

INTRODUCTION: Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc). OBJECTIVE: To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals. METHODS: At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group). RESULTS: A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia. CONCLUSION: Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.