Thromboinflammation in COVID-19 acute lung injury

Mitchell, W. Beau

doi:10.1016/j.prrv.2020.06.004

Cited by 67 publications

(69 citation statements)

References 42 publications

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“…A number of reports described the issue of pulmonary thrombosis in COVID-19 patients [ 7 , 8 ] and histologic analysis of pulmonary vessels in patients with COVID-19 showed widespread thrombosis with microangiopathy. Several pathological pathways are thought to be involved in microthrombi formation including endothelial damage, thrombin activation, platelet activation, neutrophil extracellular traps (NETs) formation, and contact pathway activation [ 9 ]. It is important to note the autopsy series of the some COVID-19 patients revealed diffusely edematous lung parenchyma and the presence of small and firm thrombi in sections of the peripheral lung, while pulmonary arteries at the hilum were free of thromboembolism and there were no signs of gross inflammation [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

High incidence of venous thrombosis in patients with moderate-to-severe COVID-19

et al. 2021

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Increasing evidence suggests that COVID-19 may be associated with venous thromboembolism, and much data exists regarding high incidence of venous thrombosis in critical COVID-19 patients. However, evidence on this complication in less severe patients is not widely available. The aim of this study was to investigate the incidence of deep-vein thrombosis (DVT) in patients with moderate-to-severe COVID-19, to assess the prevalence of DVT with duplex ultrasound, and to compare patients with DVT and those without it using lung computerized tomography (CT), clinical information and lab data. The subjects of this study were 75 consecutive patients (aged 27-92 y, median-63 y; 36 males and 39 females) with moderateto-severe COVID-19. DVT was found in 15 patients (20%). The vast majority of those with DVT (13 patients, 86.7%) had thrombi in calf veins and 2 (13.3%) had ileofemoral thrombosis. High incidence of DVT (20%) is observed even in patients with moderate-to-severe COVID-19. These patients require early anticoagulation therapy as part of their treatment. Such therapy may be continued after hospital discharge and these patients may also require follow-up vein ultrasonography after recovery to rule out DVT.

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Section: Discussionmentioning

confidence: 99%

High incidence of venous thrombosis in patients with moderate-to-severe COVID-19

et al. 2021

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“…This is especially important because more intense anticoagulation is associated with an increased risk of bleeding. In addition, the exuberant inflammatory response is known to play a role in the pathophysiology of acute respiratory distress syndrome (ARDS) [29] and especially that of COVID-19 [30,31]. Animal studies have shown that the inhibition of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase could modify several underlying mechanisms implicated in the development of ARDS [32].…”

Section: Statin Hypothesis Inclusion Criteria Exclusion Criteriamentioning

confidence: 99%

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

Bikdeli¹,

Talasaz

Rashidi³

et al. 2020

Thrombosis Research

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Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count < 20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes > 3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.

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“…In addition, hydroxyurea lowers VCAM‐1 and other soluble adhesion molecules 21 . Increased inflammatory cytokines, 22 a key role for monocytes and macrophages 23 and endothelialitis 24 have been implicated in COVID‐19 lung injury 25 . Hydroxyurea's therapeutic benefit could be related to the lower absolute monocyte counts, reduction of inflammatory cytokines, and decreased endothelial adhesive markers, but this needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Acute chest syndrome in the setting of SARS‐COV‐2 infections—A case series at an urban medical center in the Bronx

Morrone

Strumph

Liszewski

et al. 2020

Pediatric Blood & Cancer

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New York City has emerged as one of the epicenters of the SARS-COV-2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS-COV-2-positive patients admitted with ACS. SARS-COV-2positive SCD patients, who did not develop ACS, were the comparison group. Hydroxyurea use (P-value = .02) and lower absolute monocyte counts (P-value = .04) were noted in patients who did not develop ACS. These preliminary findings need to be further evaluated in larger cohorts.

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Thromboinflammation in COVID-19 acute lung injury

Cited by 67 publications

References 42 publications

High incidence of venous thrombosis in patients with moderate-to-severe COVID-19

High incidence of venous thrombosis in patients with moderate-to-severe COVID-19

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

Acute chest syndrome in the setting of SARS‐COV‐2 infections—A case series at an urban medical center in the Bronx

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