Pulmonary embolism in pediatric and adolescent patients with COVID‐19 infection during the SARS‐CoV‐2 delta wave

Cohen, Clay T; Riedl, Ruth A; Gowda, Srinath T.; Sartain, Sarah E.; Bashir, Dalia

doi:10.1002/pbc.29721

Cited by 11 publications

(12 citation statements)

References 14 publications

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“…4 G to I) induced by the κ and δ variants, which was greatest in the κ variant. Together, these data indicate that the κ and δ variants induce stronger platelet activation, which is consistent with clinical reports of severe thrombosis in patients infected with these variants [ 11 , 63 , 64 ].…”

Section: Resultssupporting

confidence: 90%

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

Ma¹,

Liang²,

Zhu³

et al. 2023

Research

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The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD–platelet interaction was partially dependent on the β3 integrin as binding was significantly reduced in β3 −/− mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbβ3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbβ3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

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Section: Resultssupporting

confidence: 90%

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

Ma¹,

Liang²,

Zhu³

et al. 2023

Research

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“…We read the publication on “Pulmonary embolism in pediatric and adolescent patients with COVID‐19 infection during the SARS‐CoV‐2 delta wave”. 1 Cohen et al. concluded that this report stresses the importance of maintaining a high index of suspicion for pulmonary embolism (PE) in pediatric COVID‐19 infection and vaccinating obese adolescent patients.…”

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confidence: 88%

“…concluded that this report stresses the importance of maintaining a high index of suspicion for pulmonary embolism (PE) in pediatric COVID‐19 infection and vaccinating obese adolescent patients. 1 The thrombohemostatic disorder is a possible clinical problem in patients with COVID‐19 and COVID‐19 vaccine recipients. Indeed, after COVID‐19 vaccination or COVID‐19 infection, there is increased blood viscosity that might present a risk for thrombohemostatic disorder.…”

mentioning

confidence: 99%

Comment on: Pulmonary embolism in pediatric and adolescent patients with COVID‐19 infection during the SARS‐CoV‐2 delta wave

Mungmunpuntipantip¹,

Wiwanitkit

2022

Pediatric Blood & Cancer

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“…substantially increased rates of venous thromboembolism secondary to covid-19 disease. [32][33][34] In particular, earlier strains of the SARS-CoV-2 virus were associated with an increased rate of pulmonary embolism (>30%) in patients admitted to hospital. [35][36][37] Nonetheless, we found an increase in the incidence of definite or possible vaccine induced immune thrombocytopenia and thrombosis.…”

Section: Open Access Open Accessmentioning

confidence: 99%

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study)

Jacobson

Schapkaitz

Takalani

et al. 2023

bmjmed

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ObjectiveTo assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population.DesignOpen label, single arm, phase 3B study.SettingSisonke study, South Africa, 17 February to 15 June 2021.ParticipantsThe Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine.Main outcome measuresObserved rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software).ResultsMost of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population.ConclusionsVaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates.Trial registrationClinicalTrials.govNCT04838795.

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Pulmonary embolism in pediatric and adolescent patients with COVID‐19 infection during the SARS‐CoV‐2 delta wave

Cited by 11 publications

References 14 publications

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

Comment on: Pulmonary embolism in pediatric and adolescent patients with COVID‐19 infection during the SARS‐CoV‐2 delta wave

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study)

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