Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Acute Arterial Ischemic Stroke Following COVID-19 Vaccination: A Systematic Review and Meta-analysis.

BACKGROUND: Acute arterial-ischemic-stroke (AIS) has been reported as a rare adverse-event following COVID-19-vaccination with mRNA or viral-vector vaccines. However, data are sparse regarding the risk of post-vaccination AIS and its potential association with thrombotic-thrombocytopenia-syndrome (TTS). METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs), pharmacovigilance registries, registry-based studies, observational cohorts and case-series was performed with the aim to calculate: (1) the pooled proportion of patients presenting with AIS following COVID-19-vaccination; (2) the prevalence of AIS after mRNA and vector-based vaccination; (3) the proportion of TTS among post-vaccination AIS-cases. Patient characteristics were assessed as secondary outcomes. RESULTS: Two RCTs, three cohort and eleven registry-based studies comprising 17,481 AIS-cases among 782,989,363 COVID-19-vaccinations were included in the meta-analysis. The pooled proportion of AIS following exposure to any COVID-19-vaccine type was 4.7 cases per 100,000 vaccinations (95%CI:2.2-8.1; I2=99.9%). The pooled proportion of AIS following mRNA-vaccination (9.2 cases per 100,000 vaccinations; 95%CI: 2.5-19.3; I2=99.9%) did not differ compared to adenovirus-based-vaccination (2.9 cases per 100,000 vaccinations; 95%CI: 0.3-7.8; I2=99.9%). No differences regarding demographics were disclosed between patients with AIS following mRNA- or vector-based vaccination. The pooled proportion of TTS among post-vaccination AIS-cases was 3.1% (95%CI: 0.7-7.2%; I2=78.8%). CONCLUSIONS: The pooled proportion of AIS following COVID-19 vaccination is comparable to the prevalence of AIS in the general population and much lower than the AIS prevalence among SARS-CoV-2-infected patients. TTS is very uncommonly reported in patients with AIS following COVID-19 vaccination.