Case report: cerebral sinus vein thrombosis in two patients with AstraZeneca SARS-CoV-2 vaccination

Fousse, Mathias; Schub, David; Merzou, Fatma; Faßbender, Klaus; Sester, Martina; Kettner, Mattias; Lochner, Piergiorgio; Schmidt, Tina; Júnior, João Reinoldo Goi

doi:10.1007/s00415-021-10731-2

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…This description was a probable VITT case, given the lack of anti-PF4 positivity. Another paper from Germany has reported two women presenting with cerebral sinus vein thrombosis after the ChAdOx1 vaccine, each carrying an MTHFR variant (heterozygous A1298C and homozygous MTHFR C677T variant) ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis

Mendes-de-Almeida

Kehdy

Martins-Gonçalves

et al. 2023

Front. Cardiovasc. Med.

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The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

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Section: Discussionmentioning

confidence: 99%

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis

Mendes-de-Almeida

Kehdy

Martins-Gonçalves

et al. 2023

Front. Cardiovasc. Med.

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“…So far, only three publications regarding thromboembolic adverse effects after the COVID-19 vaccination have published incidents [26][27][28]. Three patients received mRNAbased vaccine and one patient received vector-based vaccine.…”

Section: Discussionmentioning

confidence: 99%

Association between COVID-19 Infection or Vaccination Outcomes and Methylenetetrahydrofolate Reductase Gene Polymorphism: A Systematic Review of the Literature

Jukic,

Heffernan,

Schelling

et al. 2023

JPM

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Background: Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient’s baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8–20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination. Methods: The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed. Results: From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection (n = 2200), while the remaining four studies failed to demonstrate any significant association (n = 38). Conclusions: This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.

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“…Early case reports of novel coronavirus pneumonia showed that up to 50% of patients had underlying diseases, and 40% of them had cardiovascular or cerebrovascular diseases (Xiong et al, 2020). There have been clinical studies reporting newly diagnosed cases of cerebral sinus vein thrombosis in patients with MTHFR mutations following injection of the vector-based ChAdOx1 COVID-19 vaccine (Fousse et al, 2022). Folic acid can minimize plasma homocysteine concentrations, thereby reducing risk factors for vascular disease.…”

Section: Discussionmentioning

confidence: 99%

Folic acid restricts SARS-CoV-2 invasion by methylating ACE2

Zhang

Pang

et al. 2022

Front. Microbiol.

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The current COVID-19 pandemic is motivating us to elucidate the molecular mechanism of SARS-CoV-2 invasion and find methods for decreasing its transmissibility. We found that SARS-CoV-2 could increase the protein level of ACE2 in mice. Folic acid and 5-10-methylenetetrahydrofolate reductase (MTHFR) could promote the methylation of the ACE2 promoter and inhibit ACE2 expression. Folic acid treatment decreased the binding ability of Spike protein, pseudovirus and inactivated authentic SARS-CoV-2 to host cells. Thus, folic acid treatment could decrease SARS-CoV-2 invasion and SARS-CoV-2-neutralizing antibody production in mice. These data suggest that increased intake of folic acid may inhibit ACE2 expression and reduce the transmissibility of SARS-CoV-2. Folic acid could play an important role in SARS-CoV-2 infection prevention and control.

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Case report: cerebral sinus vein thrombosis in two patients with AstraZeneca SARS-CoV-2 vaccination

Cited by 6 publications

References 13 publications

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis

Association between COVID-19 Infection or Vaccination Outcomes and Methylenetetrahydrofolate Reductase Gene Polymorphism: A Systematic Review of the Literature

Folic acid restricts SARS-CoV-2 invasion by methylating ACE2

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