Fatal Exacerbations of Systemic Capillary Leak Syndrome Complicating Coronavirus Disease

Cheung, Patricia C; Eisch, A. Robin; Maleque, Noble; Polly, Derek M.; Auld, Sara C.; Druey, Kirk M.

doi:10.3201/eid2710.211155

Cited by 29 publications

(30 citation statements)

References 27 publications

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“…Studies have reported acute respiratory failure caused by pulmonary capillary leak syndrome (CLS) after SARS-CoV-2 infection ( Bahloul et al., 2021 ). A study showed that in mild to moderate COVID-19, patients with known or suspected systemic capillary leak syndrome (SCLS) may have an increased risk of disease emergencies ( Cheung et al., 2021 ). Under normal physiological conditions, water and electrolytes can enter the interstitial space through the capillary barrier due to changes in the osmotic balance, while substances with slightly larger molecular masses such as albumin cannot.…”

Section: Pathophysiology Of Long Covid Thrombotic Complicationsmentioning

confidence: 99%

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation

Wang

Jing

et al. 2022

Front. Cell. Infect. Microbiol.

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Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.

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Section: Pathophysiology Of Long Covid Thrombotic Complicationsmentioning

confidence: 99%

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation

Wang

Jing

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Various components in the blood, including macromolecules (mainly albumin and globulin), enter the alveolar cavity. This fluid in the alveolar cavity then induces aggravated dyspnea ( 35 – 37 ). The alveolar liquid evaporates under airflow action, leaving behind plasma proteins and necrotic alveolar epithelial debris to form a transparent membrane, leading to lung consolidation ( 3 – 6 , 38 , 39 ).…”

Section: Introductionmentioning

confidence: 99%

“…The frequently reported pulmonary arterial, venous, and capillary thrombotic events at autopsy suggest that the transformation of stable vascular endothelial cells to the prothrombotic state is not negligible ( 8 , 25 , 27 – 29 , 35 , 38 – 47 ). We therefore hypothesize that the effects of thrombosis may persist long after the patient has met the criteria for discharge ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Persistent Lung Injury and Prothrombotic State in Long COVID

et al. 2022

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Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is to investigate the basis of pulmonary susceptibility during sequelae and the possibility that prothrombotic states may influence long-term pulmonary symptoms of COVID-19. The patient’s lungs remain vulnerable during the recovery stage due to persistent shedding of the virus, the inflammatory environment, the prothrombotic state, and injury and subsequent repair of the blood-air barrier. The transformation of inflammation to proliferation and fibrosis, hypoxia-involved vascular remodeling, vascular endothelial cell damage, phosphatidylserine-involved hypercoagulability, and continuous changes in serological markers all contribute to post-discharge lung injury. Considering the important role of microthrombus and arteriovenous thrombus in the process of pulmonary functional lesions to organic lesions, we further study the possibility that prothrombotic states, including pulmonary vascular endothelial cell activation and hypercoagulability, may affect long-term pulmonary symptoms in long COVID. Early use of combined anticoagulant and antiplatelet therapy is a promising approach to reduce the incidence of pulmonary sequelae. Essentially, early treatment can block the occurrence of thrombotic events. Because impeded pulmonary circulation causes large pressure imbalances over the alveolar membrane leading to the infiltration of plasma into the alveolar cavity, inhibition of thrombotic events can prevent pulmonary hypertension, formation of lung hyaline membranes, and lung consolidation.

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“…Pineton de Chambrun et al were the first to report a fatal relapse of SCLS during a SARS-CoV-2 infection in a patient with a history of MGUS [ 87 ], and Lacout et al reported the first SCLS episode elicited by COVID-19 in a patient with no medical history [ 88 ]. Since then, a few other case reports have been published, mainly regarding patients with a known history of Clarkson’s disease [ 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. However, in the report by Case et al, the patient’s medical history was important only for the presence of systemic hypertension [ 92 ].…”

Section: Capillary Leak Syndrome In the Cardiometabolic Covid-19 Patientmentioning

confidence: 99%

COVID-19, Endothelium and the Cardiometabolic Patient: A Possible Role for Capillary Leak Syndrome

et al. 2022

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Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients.

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Fatal Exacerbations of Systemic Capillary Leak Syndrome Complicating Coronavirus Disease

Cited by 29 publications

References 27 publications

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation

Persistent Lung Injury and Prothrombotic State in Long COVID

COVID-19, Endothelium and the Cardiometabolic Patient: A Possible Role for Capillary Leak Syndrome

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