Diagnostic and therapeutic considerations in idiopathic systemic capillary leak syndrome: a case report

Background: Systemic capillary leak syndrome (SCLS) is a rare disorder which leads to severe shock. Typically, endothelial dysfunction leads to massive leakage of fluids from the intravascular compartment to the interstitial space, causing hemoconcentration, hypoalbuminemia, hypotension and potential organ failure. The syndrome may be idiopathic or triggered by disease, such as viral infections. The syndrome is often unrecognized and besides resuscitation, no effective treatments are known. Case Description: Here we describe a 46-year-old female with recurrent episodes of shock due to unrecognized SCLS, with the second episode being triggered by an asymptomatic COVID-19 infection. She was, besides resuscitation, treated with high dose vasopressors and intravenous immunoglobulins (IVIG). The case is complicated by compartment syndrome with infected muscle necrosis and eventually amputation of both lower legs. Moreover, the patient still has a chronic kidney insufficiency. In this case report we will discuss pittfalls and potential therapeutic options in SCLS treatment. Conclusions: Vasopressor use may aggravate ischemic complications in a hypovolemic condition and its use should therefore be discouraged in these patients. Cardiac output monitoring should be considered early. The use of IVIG might be beneficial in the acute phase as well as in preventing future episodes of shock. Whether the use of bevacizumab is also of value is yet unclear. © Journal of Emergency and Critical Care Medicine. All rights reserved.

Early dexamethasone treatment does not alter the development of pulmonary fibroproliferation in critically ill COVID-19 patients

Introduction: A subgroup of critically ill COVID-19 patients develops pulmonary fibroproliferation (PF), which is associated with worse outcomes. We explored the kinetics of fibrosis markers and ventilatory parameters prior to and following use of steroids to treat suspected PF. Furthermore, we investigated the effects of early dexamethasone (DEXA) treatment, the current standard-of-care for COVID-19, on the incidence and time to development of PF and clinical outcomes. Methods: We included 191 critically ill COVID-19 patients spanning two treatment cohorts: no DEXA treatment (pre-DEXA cohort, n = 67) and dexamethasone treatment as standard-of-care (DEXA cohort, n = 124). Kinetics of circulating fibrosis markers and ventilatory parameters were analyzed in suspected PF patients prior to and following initiation of steroid therapy as well as in patients in whom PF was not suspected. Furthermore, associations between PF and clinical outcomes were explored. Results: Patients with suspected PF exhibited higher circulating fibrosis markers, lower lung compliance and PaO2/FiO2 ratios, and increased dead space ventilation. Incidence of suspected PF was 28% in the pre-DEXA cohort and 25% in the DEXA cohort (p = 0.61), and time to development of suspected PF was also similar between cohorts (16 [12-21] vs. 19 [14-23] days from ICU admission, p = 0.11). Time on ventilator, LOS in ICU and mortality were significantly higher in suspected PF patients than in no suspected PF patients, with no differences between the cohorts (Fig. 1). Conclusions: Increased circulating fibrosis markers reflect development of PF in critically ill COVID-19 patients, which is associated with prolonged ICU length of stay and high mortality rates. Introduction of dexamethasone as standard-of-care is not associated with altered incidence of PF or improved clinical outcomes in patients with PF. (Figure Presented).

Late Breaking Abstract - Plasma cells and endothelitis in COVID-19 lung pathology

Histopathology is a powerful tool to understand the COVID-19 pathogenesis and come up with rational treatment strategies. We present lung histopathological features of biopsies of fatal COVID-19 cases together with anakinra (Kineret®) 11-1 a and IL-1ß receptor blocking treatment of the disease. Lung biopsy of 8 cases were scored for alveolar, vascular and inflammatory features on a 4-point scale (none-severe) by 3 lung pathologists;consensus scores were used. Anakinra was given in off-label setting to 3 COVID-19 cases receiving ICU treatment including mechanical ventilation. Lung pathology includes 1. Extensive epithelial damage with regenerative metaplasia with co-localization of neutrophils and macrophages, together with organizing pneumonia and scarring, 2. Alveolar edema, hemorrhage, diffuse alveolar damage and a dominant pattern of acute and chronic arterial thrombosis in all cases as manifestations of vascular leakage and its sequelae, and 3. plasma cell orT cell endothelitis of the pulmonary arteries as a characteristic feature to COVID-19 in six out of eight cases, indicating a role for plasma cells (fig.1) orT cells in its vascular pathology. The temporal heterogeneity of both the epithelial damage and repair and the thrombosis and thrombotic arteriopathy within in all cases indicated ongoing disease. The anakinra-treated cases showed a rapid response with extubation in 2-4 days and a drop in fever and inflammatory parameters. We propose that these distinctive features of COVID-19 are initiated through the IL-1 innate immunity pathway and operated by plasma cells. We further provide proof of concept that the IL-1 receptor antagonist anakinra was beneficial in the late and severe stage of COVID-19 disease.