High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Treating Heart Inflammation With Interleukin-1 Blockade in a Case of Erdheim–Chester Disease

Pericarditis is an inflammatory heart disease, which may be idiopathic or secondary to autoimmune or auto-inflammatory diseases and often leads to severe or life-threatening complications. Colchicine and non-steroidal anti-inflammatory drugs represent the mainstay of treatment, whereas use of corticosteroids is associated with recurrence of disease flares. While effective and safe anti-inflammatory therapies remain an unmet clinical need, emerging clinical and experimental evidence points at a promising role of inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1). We thus evaluated treatment with the IL-1 receptor antagonist anakinra in a case of extremely severe pericarditis with cardiac tamponade and heart failure secondary to Erdheim–Chester disease (ECD), a rare clonal disorder of macrophages characterized by rampant inflammation and multiorgan involvement. A 62-year-old man was admitted to the Emergency Department with severe pericardial effusion requiring the creation of a pleuro-pericardial window. A whole-body contrast-enhanced computed tomography pointed at a diagnosis of ECD with involvement of the heart and pericardium and of the retroperitoneal space. Over the following days, an echocardiography revealed a closure of the pleuro-pericardial window and a relapse of the pericardial effusion. Treatment with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, was started at a standard subcutaneous dose of 100 mg/day. After 2 days, we observed a dramatic clinical improvement, an abrupt reduction of the inflammatory markers, and a reabsorption of the pericardial effusion. Anakinra was maintained as monotherapy, and the patient remained asymptomatic in the absence of disease flares for the following year. Recent studies point at inhibition of IL-1 activity as an attractive treatment option for patients with refractory idiopathic recurrent pericarditis. Anakinra treatment may also have a role in patients with pericarditis in the setting of systemic inflammatory disorders, such as ECD