key: cord-1055095-x1uutcmq
authors: Luisa, Vinciguerra; Valentina, Puglisi; Alessia, Giossi; Valeria, De Giuli; Francesca, Caprioli; Chiara, Costanzi; Elisa, Pari; Maria, Tripodi Silvia; Clauida, Trapasso Maria; Bruno, Censori
title: Ischemic stroke shortly after vaccination against SARS-CoV-2: A case-control study
date: 2022-02-27
journal: J Neurol Sci
DOI: 10.1016/j.jns.2022.120209
sha: 354e6de2f0e24a74eae1afc1101f702ee909c533
doc_id: 1055095
cord_uid: x1uutcmq

BACKGROUND AND PURPOSE: Vaccination against SARS-CoV-2 has been associated with rare occurrences of severe venous thromboses. Very little data exist about arterial ischemic strokes. We have assessed the features of ischemic strokes occurring shortly after vaccination against SARS-CoV-2 in the Cremona area, Italy. METHODS: From February 1, to July 31, 2021, all patients with ischemic stroke within four weeks of vaccination against COVID-19 admitted to our stroke unit were consecutively collected, and their main features were compared with those of all other patients with ischemic strokes admitted during the same period. RESULTS: Sixteen strokes after vaccination were collected. They represented 10.5% of all ischemic strokes. Median interval from vaccination was 12 days (range 1–24). Fifteen (93.8%) had received the BNT162b2 (Pfizer–BioNTech) vaccine and 1 (6.2%) the ChAdOx1 nCoV-19 (AstraZeneca). Two patients (12.5%) had a mild thrombocytopenia on admission (128,000 and 142,000/ml), without any evidence of bleeding or venous thrombosis. Thrombolysis and/or thrombectomy were carried out in 4 cases (25.0%). When compared with 137 strokes without recent vaccination, none of the demographic, clinical, and laboratory features of post-vaccination strokes were significantly different. CONCLUSIONS: Ischemic strokes occurring shortly after COVID-19 vaccination at our center were similar to those of non-vaccinated patients. Therefore, the relatively high percentage of such patients probably relates to the very high fraction of elderly people vaccinated against SARS-CoV-2 in the Cremona area, rather than to a consequence of vaccination.

Ischemic strokes occurring shortly after COVID-19 vaccination at our center were similar to those of non-vaccinated patients. Therefore, the relatively high percentage of such patients probably relates to the very high fraction of elderly people vaccinated against SARS-CoV-2 in the Cremona area, rather than to a consequence of vaccination. 

Vaccination against the SARS-CoV-2 virus has brought about the problem of adverse events due to the vaccines. The most widely publicized adverse event has been the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) [1, 2] , due to the development of antibodies against platelet factor 4 [3] . The syndrome has been associated with adenovirus-based vaccines [1, 4] .

While VITT is rare, with the progress of mass vaccination, a patient with acute ischemic stroke shortly after vaccination has become a much more common occurrence. Although this could be just a coincidence, a causal relationship between vaccination and arterial stroke cannot be discarded.

This has several consequences, such as reporting in the national drug adverse event registry, appropriate diagnostic investigations, choice of antithrombotic medication, and counselling about administration of the second dose of the vaccine. In order to clarify the pattern of ischemic stroke associated with recent vaccination against SARS-CoV-2 (ISARVAS), we collected a consecutive series of ischemic strokes within 4 weeks after vaccination, and compared them with all other ischemic strokes admitted to our hospital during the same period.

J o u r n a l P r e -p r o o f 

The consequences of vaccination against the SARS-CoV-2 virus are still incompletely understood, because of the relatively short observation period. We found that about 10% of all ischemic strokes occurring during 6 consecutive months in the Cremona area fell within 4 weeks after vaccination against the SARS-CoV-2 virus. We have concentrated on the first month after vaccination because a potential relationship between stroke and vaccination may be more apparent in this early period.

Furthermore, this interval has also been used to characterize VITT [6] . Such strokes may raise the question of a vaccine-related complication, with all its epidemiological, diagnostic, therapeutic, and medico-legal implications. Severe venous thrombotic complications have occurred with adenovirusbased vaccines [1, 4] . A few cases of ischemic stroke after vaccination have also been described [7, 8] , but such reports are sparse, and mostly focused on the relationship with thrombocytopenia and the ChAdOx vaccine [7, 8] , while a systematic description of these strokes is still lacking. More than 70% of the residents of the Cremona area older than 60 have received at least one dose of the authorized vaccines during the period of our study, and none of the features of the ISARVAS group was significantly different from those of all the other ischemic strokes admitted during the same period. Furthermore, no ISARVAS patient had severe thrombocytopenia or venous thrombosis.

Finally, only one stroke occurred after the ChAdOx vaccine, which has been directly implicated in VITT [8] . These observations suggest that the strokes were probably not triggered by vaccination, but occurred because of the same set of risk factors that lead to ischemic stroke in the general population of our area. The recent vaccination did not decrease use of acute recanalization therapies, and was not associated with a higher initial severity of stroke or an increased death rate in the short term. The main limitation of our study is the relatively small size of the ISARVAS group, which does not allow for very robust comparisons with the overall stroke population, and cannot be assumed to represent all the possible stroke types that may follow COVID-19 vaccination.

J o u r n a l P r e -p r o o f Journal Pre-proof Therefore, our results require confirmation in larger studies. However, although single instances of ischemic stroke directly related to SARS-CoV-2 vaccination may certainly happen [7] , our data seem reassuring, and may be used for subjects who fear the complications of vaccination, and to plan diagnostic and therapeutic strategies by treating physicians.

Funding : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Eichinger Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

Holme Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination

Lester Pathologic antibodies to platelet factor 4 after ChAdOx1 nCov-19 vaccination

Marsh III Classification of subtype of acute ischemic stroke

COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT)

Werring Ischaemic stroke as a presenting feature of ChAdOx1 nCoV-19 vaccineinduced immune thrombotic thrombocytopenia

The German Society of Neurology SARS-CoV-2 Vaccination Study Group. COVID-19 vaccine-associated cerebral venous thrombosis in Germany