Long-term outcome of patients with vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis

Introduction In early 2021, unanticipated thromboses, including cerebral venous sinus thrombosis (CVST) with thrombocytopenia, emerged as an adverse reaction (ADR) in patients who had been vaccinated with the AstraZeneca ChAdOx1 nCoV-19 vaccine. This ADR was termed vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). Although sporadic in nature, VITT can result in severe disease in the individual vaccinee. We followed up on the outcomes and status of neurological recovery of 49 cases of VITT with CVST that were reported to PEI. Method Assessment of the Extended Glasgow Outcome Scale (GOS-E) was performed within 3-6 months after the initial hospital admissions. Individual Glasgow Coma Scale (GCS) scores were reported by phone or electronically via a questionnaire or medical report by the treating physician of the hospital to which the patient was initially admitted. If a GCS score was not reported, an expert determined a score based on the patient's medical report. For most patients, follow-up was pursued about 3-6 months after hospital admission. The reported outcomes describe the patients' neurological status at 5-38 weeks (mean 20 weeks) after hospital admission. Outcomes were identified in 44 of the original 49 cases. Results Patient outcomes ranged from good recovery (13 patients, 29.6 %) to moderate disability (11 patients, 25.0 %) and severe disability or vegetative state (6 patients, 13.6 %). Fatal outcomes were reported in 14 patients (31.8 %). As anticipated, initial low GCS scores were associated with poor outcomes. By contrast, GCS scores > 10 were typically associated with improved neurological outcomes. Moreover, platelet count nadirs were correlated with patient outcomes. Low platelet counts were observed in fatal cases (GOS-E 1) with a mean count of 17,000 platelets/muL). Likewise, patients with better neurological outcomes (GOS-E scores of 5-6 and 7-8) presented with mean counts of 61,000 thrombocytes/muL. However, the course of the disease was not always predictable and showed significant individual variability. Conclusion We provide data on the outcome of VITT cases with CVST upon vaccination with the AstraZeneca adenoviral vector ChAdOx1 nCoV-19 COVID- 19 vaccine and found that the recovery of patients from CVST was very heterogeneous. While some patients exhibited good recoveries, others developed severe disabilities and major long-term complications. Collectively, our findings highlight the importance of paying attention to early signs of increased intracranial pressure and the onset of thrombocytopenia in patients with a recent history of vaccination with the AstraZeneca adenoviral vector ChAdOx1 nCoV-19 COVID-19 vaccine.

Letter to the editor: COVID in patients with brain injury with a disorder of consciousness: a pathogenetic theory.

We recently published in this journal (Caronni and colleagues, Brain Injury, 2021-04-16) the first description of the spread of the SARS-CoV-2 infection in a cohort of brain injured patients with a disorder of consciousness (DOC). Surprisingly enough we showed that, in these patients, the COVID was moderate and did not result in fatalities. The pathogenesis of the COVID is characterized by the profound dysregulation of the immune system. To explain our findings, we speculated that the immunosuppression due to the brain injury could be protective against the development of the COVID in patients with DOC. More recently, a second group of authors (Marino and colleagues, PLoSOne, 2021-06-30) described the course of the COVID in an independent cohort of patients with DOC. Since our results were quite unexpected, we have been very comforted by the data reported by Marino and colleagues. Moreover, these data also offer a unique opportunity to further evaluate our theory regarding the COVID pathogenesis in patients with DOC. In the current Letter to the Editor it is shown that the independent data presented by Marino and colleagues do support our theory. Waiting for larger cohorts to further test it (and in case falsify it), our interpretation seems to remain valid.

Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study.

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.