RESUMEN
Background and aims: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome of unclear aetiology occurring after vaccinations against COVID-19. The aim of this study was to investigate the DNA vaccine-encoded Sars-cov-2 soluble spike protein (SP) as a potential trigger of platelet activation in VITT. Methods: We studied three VITT patients and seven healthy controls (HCs) within 3 weeks from the first dose of ChAdOx1 nCoV-19. Serum levels of SP, soluble angiotensin-converting enzyme 2 (sACE2), and platelet response to VITT serum stimulation were studied. A thrombus retrieved from middle cerebral artery during mechanical thrombectomy of one VITT patient, was analysed by immunohistochemistry for SP and ACE2. Neutrophil extracellular traps (NETs) markers and coagulation parameters were also measured. Results: We detected SP and sACE2 in all VITT patients, and in two and three out of 7 HCs, respectively. VITT sera markedly activated platelets and this activation was inhibited by both anti-SP and anti-FcγRIIA blocking antibodies. The retrieved thrombus showed positive immunohistochemical labelling of platelets using an anti-SP antibody with reduced ACE2 expression, compared to a thrombus from a pre-pandemic stroke patient. Markers of endothelial dysfunction, NETs and hypercoagulability state were present in VITT sera. Conclusions: The present data provide first evidence that DNA vaccineencoded Sars-cov-2 SP is detectable in VITT sera (up to several weeks post-vaccination) and in a platelet-rich thrombus, and suggest that SP may contribute to the initial platelet stimulation in VITT patients. Anti-PF4/ polyanion antibodies development could represent an epiphenomenon, which amplifies platelet aggregation, NETosis, and coagulation cascade.
RESUMEN
Background: Several evidence have identified the role of Interleukin- 6 (IL-6) in the cytokine storm induced by CoViD-19 pneumonia. Interestingly, the correlation between the serum levels of IL-6 and the plasma aldosterone has already been demonstrated in patients affected by primary aldosteronism (PA). Therefore, we suppose that aldosteronism may increase IL-6 levels in CoViD-19. Presentation of the case:We report a case of a 47-year-old female CoViD-19 patient who had developed severe pneumonia complicated by Guillain-Barre syndrome (GBS). The blood test revealed high levels of IL-6 (serum IL-6: 402 pg/mL) and of its soluble receptor (soluble IL-6 receptor >1900pg/mL) and she required mechanical ventilation for severe hypoxemia. Furthermore, evidence of right adrenal adenoma, resistant hypertension, severe hypokalemia and high serum levels of aldosterone with high aldosterone/renin ratio were also consistent with diagnosis of PA. Thus, tocilizumab and spironolactone were administered with rapid improvement in clinical condition. Finally, she was diagnosed with acute motor sensitive neuropathy and began the rehabilitation phase. Conclusions: Increased aldosterone levels in PA may be associated with more severe forms of CoViD-19 by stimulating IL-6 production. This association could have a synergic effect in development of complications such as GBS. Increased aldosterone activity/levels could be involved in CoViD-19 patients with secondary aldosteronism. Further studies are needed to.
RESUMEN
Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.