SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

Zhang, Si; Liu, Yangyang; Wang, Xiaofang; Li, Yang; Li, Haishan; Wang, Yuyan; Liu, Mengduan; Zhao, Xiaoyan; Xie, Youhua; Yang, Yan; Zhang, Shenghui; Fan, Zhichao; Dong, Jianzeng; Yuan, Zhenghong; Ding, Zhongren; Zhang, Yi; Hu, Liang

doi:10.1186/s13045-020-00954-7

Cited by 599 publications

(957 citation statements)

References 87 publications

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“…Elevated soluble P-selectin levels and platelet flow cytometric studies suggest increased activation of endothelium and/or circulating platelets in COVID-19 patients [102]. Evidence of a direct stimulatory role of SARS-CoV-2 Spike protein upon platelets has also recently been presented [64]. Severe COVID-19 illness is associated with increased platelet activation as well as platelet-monocyte aggregation [104].…”

Section: Resultsmentioning

confidence: 99%

“…The enhancement of platelet aggregation in the patients was similarly observed to be greater in response to lower concentrations than higher concentrations of several platelet agonists [63]. Zhang et al [64] have very recently taken such analysis still further, reporting their detection of ACE2 expression by platelets, the direct stimulatory effects of SARS-CoV-2 or its Spike protein on platelets, and the ability of recombinant human ACE2 protein or anti-Spike monoclonal antibody to inhibit Spike protein-induced platelet activation. Hottz et al [104]have further recently demonstrated increased platelet-monocyte interaction and associated tissue factor expression by monocytes in severe COVID-19 patients.…”

Section: Plateletsmentioning

confidence: 99%

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The Impact of COVID-19 Disease on Platelets and Coagulation

2020

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Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Plateletsmentioning

confidence: 99%

The Impact of COVID-19 Disease on Platelets and Coagulation

2020

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“…Viruses can also activate platelets through indirect interactions with FcγRIIA, a mechanism that may take place uniquely if antibodies directed against SARS‐CoV‐2, or cross‐reacting antibodies against more common coronaviruses that generate minor cold symptoms in humans (229E, NL63, OC43, and HKU1), are present 22 . A mechanism in which SARS‐CoV‐2 directly activates megakaryocytes and platelets appears possible as two independent studies have reported the presence of SARS‐CoV‐2 mRNA in platelets of some COVID‐19 patients 9,12 . However, how SARS‐CoV‐2 interacts with megakaryocytes and platelets has not fully been elucidated and remains controversial.…”

Section: Platelet Activation and Hyperactivty In Covid‐19mentioning

confidence: 99%

Is there a role for the ACE2 receptor in SARS‐CoV‐2 interactions with platelets?

Campbell

Boilard

Rondina

2021

Journal of Thrombosis and Haemostasis

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There is an urgent need to understand the underlying mechanisms contributing to thrombotic and inflammatory complications during COVID‐19. Data from independent groups have identified that platelets are hyperreactive during COVID‐19. Platelet hyperreactivity is accompanied by changes in platelet gene expression, and enhanced interactions between platelets and leukocytes. In some patients, SARS‐CoV‐2 mRNA has been detected in platelets. Together, this suggests that SARS‐CoV‐2 may interact with platelets. However, controversy remains on which receptors mediate SARS‐CoV‐2 platelet interactions. Most, but not all, transcriptomic and proteomic analyses fail to observe the putative SARS‐CoV‐2 receptor, angiotensin converting enzyme‐2, or the cellular serine protease necessary for viral entry, TMPRSS2, on platelets and megakaryocytes. Interestingly, platelets express other known SARS‐CoV‐2 receptors, which induce similar patterns of activation to those observed when platelets are incubated with SARS‐CoV‐2. This article explores these findings and discusses ongoing areas of controversy and uncertainty with regard to SARS‐CoV‐2 platelet interactions.

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“…A postmortem evaluation of peripheral lungs from COVID-19 patients revealed diffuse alveolar damage, severe endothelial injury, and widespread thrombosis with microangiopathy [ 6 ], while an increasing number of reports discussing the role of platelet activation and aggregation in patients with severe COVID-19 is being published [ 7 , 8 ]. Molecular techniques, including transcriptomics, have been able to demonstrate platelet hyperactivity [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients

Vassiliou

Keskinidou

Jahaj

et al. 2021

Cells

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Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. Thirty-eight critically ill COVID-19 patients were included in this observational study, 10 of whom died in the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. The ICU cohort was subsequently divided into survivors and non-survivors; Kaplan–Meier analysis was used to explore associations between biomarkers and survival, while receiver operating characteristic (ROC) curves were generated to determine their potential prognostic value. sE-selectin, sP-selectin, Ang-2, and sICAM-1 were significantly elevated in ICU non-survivors compared to survivors, and also associated with a higher mortality probability in the Kaplan–Meier analysis. The prognostic values of sE-selectin, Ang-2, and sICAM-1 from the generated ROC curves were greater than 0.85. Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors. Elevated levels of these markers upon ICU admission could possibly predict mortality in COVID-19.

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SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

Cited by 599 publications

References 87 publications

The Impact of COVID-19 Disease on Platelets and Coagulation

The Impact of COVID-19 Disease on Platelets and Coagulation

Is there a role for the ACE2 receptor in SARS‐CoV‐2 interactions with platelets?

ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients

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