key: cord-0758875-35ljrfj8
authors: Case, Robert; Ramaniuk, Aliaksandr; Martin, Pamela; Simpson, Paul J.; Harden, Christopher; Ataya, Ali
title: Systemic Capillary Leak Syndrome secondary to Covid-19
date: 2020-07-03
journal: Chest
DOI: 10.1016/j.chest.2020.06.049
sha: 73d29de9ffce9a4752b9cdcd86d97c7a02e9bde6
doc_id: 758875
cord_uid: 35ljrfj8

Abstract Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia and subsequent organ failure. The condition may be idiopathic or secondary to an underlying cause, which can include viral infections. Here we describe a patient with acute COVID-19 infection who presented with hemoconcentration, shock and hypoalbuminemia. The patient subsequently developed rhabdomyolysis and compartment syndrome of all four extremities requiring fasciotomies. This is the first reported case of systemic capillary leak syndrome associated with COVID-19 infection. This case adds to the evolving spectrum of inflammatory effects associated with this viral infection.

Systemic capillary leak syndrome (SCLS) is a rare disorder characterized by severe hypotension, hemoconcentration, and hypoalbuminemia due to extravasation of plasma and proteins into the interstitial space as a result of endothelial dysfunction. 1, 2 Systemic capillary leak syndrome may be idiopathic or secondary to an underlying cause. Viral infections have been reported to be a cause for secondary capillary leak syndrome. 3 We report a case of systemic capillary leak syndrome in a patient who presented to our institution with COVID-19 pneumonia and developed profound shock.

A 63-year-old male with a past medical history of systemic hypertension presented to our facility with symptoms of fevers, chills, nonproductive cough and epigastric pain for three days. Laboratory examination revealed a lactic acidosis of 4.9 mmol/L, serum creatinine of 2.34 mg/dl, hemoglobin of 21.6 g/dl, hematocrit of 65.6%, serum protein of 6.4 g/dl and albumin of 3.5 g/dl, and normal liver enzymes. Testing for SARS-COV-2 was positive. Despite volume crystalloid resuscitation, and broad spectrum antibiotics, he rapidly deteriorated and required initiation of vasopressors, intubation, and mechanical ventilation. Computed tomography scan of the chest and abdomen showed scant peripheral ground glass infiltrates but was unrevealing for a cause for his abdominal pain or source of septic shock.

On echocardiogram, bilateral ventricular function was normal; there was a pericardial effusion without signs of tamponade.

Over the next few hours, despite ongoing resuscitation, vasopressor requirement increased, lactic acid rose to >20 mmol/L, and serum protein and albumin dropped to <3.0 g/dl and <1.5 g/dL respectively. His 

Idiopathic Capillary Leak Syndrome was first described by Clarkson in 1960. 1 The syndrome is characterized by episodic hypotension, edema, hemoconcentration, and hypoalbuminemia due to extravasation of fluid and proteins from the intracellular space into the interstitial space. The exact cause of the hyperpermeability is not clear, though it is believed to be the result of a cytokine-mediated response leading to apoptosis of the endothelium. 1,2 Patients with idiopathic SCLS often report a preceding trigger, which is often reported as a flu-like syndrome, prior to developing an episode with acute presentation of hypotension. The acute phase of SCLS is referred to as the 'acute leak phase', during which patients present with hypotension and may have hemoconcentration due to loss of intravascular volume. This phase may last up to three days. A recovery phase may follow with return of fluid into the vascular space with subsequent diuresis. 5 Hemoconcentration is a potential diagnostic clue for SCLS and may help to differentiate the condition from other causes of shock. 6 In a series of nearly 30 patients at the Mayo Clinic, rhabdomyolysis occurred in 36% of cases and compartment syndrome in 20%. 6 A drop in albumin by more than 2 g/dL was associated with a higher likelihood of developing rhabdomyolysis in that case series. The case we described had similar features with an initial hematocrit of 64%, a drop of albumin more than 2 g/dL and subsequent rhabdomyolysis that required fasciotomy of all extremities. Secondary SCLS is a diagnosis of exclusion. In our case, other causes of shock were not apparent based on advanced imaging. Despite having areas of ground glass change on the chest CT, the patient was not reporting dyspnea and was on room air up until his shock-state precipitously worsened a few hours after admission.

Secondary SCLS has been associated with underlying causes such as hematological malignancies, medical treatments such as therapeutic growth factors or chemotherapies, and viral infections. 7 Considering how the condition can mimic other common causes of shock in the intensive care unit, it is possible that the condition is under recognized. The spectrum of disease associated with the newly described COVID-19 virus continues to evolve. The virus has been associated with overproduction of pro-inflammatory cytokines that may lead to multiorgan failure, referred to as a cytokine storm. 8 It has also been associated with development multisystem inflammatory syndrome in children (MIS-C) with features of vasculitis. 9 To date, there have been no reports of systemic capillary leak syndrome secondary to COVID-19 infection. This case adds to our evolving understanding of the varied presentations of the inflammatory response associated with COVID-19 infection.

Cyclical edema and shock due to increased capillary permeability

Narrative review: the systemic capillary leak syndrome

Severe capillary leak syndrome with cardiac arrest triggered by influenza virus infection

The systemic capillary leak syndrome: a case series of 28 patients from a European registry

Idiopathic systemic capillary leak syndrome (SCLS): case report and systemic review of cases reported in the last 16 years

Idiopathic systemic capillary leak syndrome (Clarkson's disease): the Mayo Clinic experience

Idiopathic and secondary capillary leak syndromes: A systematic review of the literature

The pathogenesis and treatment of the 'Cytokine Storm' in COVID-19

Kawasaki-like disease: emerging complication during the COVID-19 pandemic