CNS inflammatory demyelinating events after COVID-19 vaccines: A case series and systematic review.

Background: Vaccinations provided the most effective tool to fight the SARS-CoV-2 pandemic. It is now well established that COVID-19 vaccines are safe for the general population; however, some cases of rare adverse events following immunization have been described, including CNS Inflammatory Demyelinating Events (CIDEs). Although observational studies are showing that these events are rare and vaccines' benefits highly outweigh the risks, collecting and characterizing post-COVID-19 vaccine CIDEs might be relevant to single out potential risk factors and suggest possible underlying mechanisms. Methods: Here we describe six CIDEs, including two acute transverse myelitis (ATM), three multiple sclerosis (MS), and one neuromyelitis optica spectrum disorder (NMOSD), occurring between 8 and 35 days from a COVID-19 vaccine. Moreover, we performed a systematic literature search of post-COVID-19 vaccines CIDEs, including ATM, ADEM, MS, and NMOSD/MOGAD, published worldwide between December 2020 and December 2021, during 1 year of the vaccination campaign. Clinical/MRI and CSF/serum characteristics were extracted from reviewed studies and pooled-analyzed. Results: Forty-nine studies were included in the systematic review, reporting a total amount of 85 CIDEs. Considering our additional six cases, 91 CIDEs were summarized, including 24 ATM, 11 ADEM, 47 MS, and nine NMOSD/MOGAD. Overall, CIDEs occurred after both mRNA (n = 46), adenoviral-vectored (n = 37), and inactivated vaccines (n = 8). Adenoviral-vectored vaccines accounted for the majority of ADEM (55%) and NMOSD/MOGAD (56%), while mRNA vaccines were more frequent in MS new diagnoses (87%) and relapses (56%). Age was heterogeneous (19-88) and the female sex was prevalent. Time from vaccine to symptoms onset was notably variable: ADEM and NMOSD/MOGAD had a longer median time of onset (12.5 and 10 days) compared to ATM and MS (6 and 7 days) and further timing differences were observed between events following different vaccine types, with ATM and MS after mRNA-vaccines occurring earlier than those following adenoviral-vectored ones. Conclusion: Both the prevalence of vaccine types for certain CIDEs and the heterogeneity in time of onset suggest that different mechanisms-with distinct dynamic/kinetic-might underly these events. While epidemiological studies have assessed the safety of COVID-19 vaccines, descriptions and pooled analyses of sporadic cases may still be valuable to gain insights into CIDE's pathophysiology.

ADEM after ChAdOx1 nCoV-19 vaccine: A case report.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS), clinically defined by an acute polyfocal neurological syndrome usually with monophasic course. ADEM often occurs after infections, but 5%-10% of cases are preceded by vaccinations. Several cases of ADEM have been described after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas no case has been reported after adenovirus-vectored or mRNA COVID-19 vaccine administration. Here we describe a case of ADEM presenting 2 weeks after receiving the first dose of ChAdOx1 nCoV-19 vaccine. Patient clinical/magnetic resonance imaging (MRI) status spontaneously improved and rapidly resolved with corticosteroids. A 4-month follow-up showed complete recovery and no relapses.

Case Report: Multiple Sclerosis Relapses After Vaccination Against SARS-CoV2: A Series of Clinical Cases.

Objective: To describe a temporal association between COVID-19 vaccine administration and multiple sclerosis (MS) relapses. Methods: This case series study was collected in four MS Centres in Central Italy, using data from 16 MS patients who received COVID-19 vaccination and presented both clinically and radiologically confirmed relapses between March and June 2021. We collected patients' relevant medical history, including demographics, MS clinical course, disease-modifying treatment (DMT) received (if applicable), and data from MRI scans obtained after the COVID-19 vaccination. Results: Three out of 16 patients received a diagnosis of MS with a first episode occurring after COVID-19 vaccination; 13 had already a diagnosis of MS and, among them, 9 were on treatment with DMTs. Ten patients received BNT162b2/Pfizer-BioNTech, 2 patients mRNA-1273/Moderna, and 4 patients ChAdOx1 nCoV-19/AstraZeneca. All MS relapses occurred from 3 days to 3 weeks after receiving the first dose of the COVID-19 vaccination or the booster. All patients had evidence of radiological activity on MRI. Discussion: Clinical and radiological findings in these cohort of MS patients confirmed disease re/activation and suggested a temporal association between disease activity and COVID-19 vaccination. The nature of this temporal association, whether causative or incidental, remains to be established.

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host's genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host's response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.