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COVID-19 Vaccines in Multiple Sclerosis
Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations.
2. COVID-19 Vaccine in MS Patients on DMTs
The COVID-19 vaccination has been heralded as a key step to overcome this pandemic. As the virus uses its outer spike protein (S protein) to bind to angiotensin-converting enzyme-related carboxypeptidase 2 (ACE2) on the host cell surface , many vaccines use this protein as their target antigen . Despite their distinct mechanisms of action, they all intend to mimic the natural process of infection. In December 2020, the lipid nanoparticle-formulated Pfizer-BioNTech® (New York, USA/ Mainz, Germany) (BNT162b2) COVID-19 vaccine  was the first to receive conditional emergency approval worldwide, followed by the mRNA-1273 vaccine from Moderna® (Cambridge, MA, USA)  in January 2021. Both feature viral genetic material and are based on nucleoside-modified mRNA vectors encoding the spike glycoprotein of SARS-CoV-2. These vaccines have proven an efficacy superior to 90% in preventing severe and mild forms of COVID-19, independently of age, race and certain comorbidities including asthma, COPD, diabetes, hypertension and obesity (BMI ≥ 30 kg/m2) . COVID-19 Vaccine AstraZeneca® (Cambridge, UK) (Vaxzevria) is an adenoviral vector-based vaccine in which the DNA encoding the coronavirus spike protein antigen is cloned into a viral vector that lacks the ability to reproduce and cause disease itself. The vaccine has demonstrated an efficacy ranging from 60–94% at protecting people from the extremely serious risks of COVID-19, including death, hospitalization and severe disease in clinical trials, including in aged people over 65 years old . The most common side effects with AstraZeneca® (Cambridge, UK) vaccine were usually mild or moderate and typically short-limited. Similarly, another adenovirus-based vaccine from Janssen® (Beerse, Belgium) led to 67% reduction in the number of symptomatic COVID-19 cases weeks after immunization, also with mild or moderate side effects which mostly consisted of pain at injection site, headache, tiredness, muscle pain and nausea. New very rare side effects have been recognized such as embolic and thrombotic events with a focus on thrombosis in combination with thrombocytopenia for both the Janssen® (Beerse, Belgium) and Vaxzevria COVID-19 vaccines. With any of these vaccines, the goal is to activate the immune system, namely B and T cells to produce neutralizing antibodies (equivalent to the titer found in convalescent patients) and prevent a future infection. While vaccines from Pfizer-BioNTech® (New York, NY, USA/Mainz, Germany) and Moderna® are administered intramuscularly in two administrations 21 days or 28 days apart, respectively, AstraZeneca® (Cambridge, UK) vaccine requires two intramuscular injections administered 4–12 weeks apart. Other new generation vaccines are under study and include recombinant protein vaccine, bacterial vector-based vaccine, plasmid DNA vaccine and trained immunity-based vaccine.
While vaccine supplies are still limited, priority is being given to healthcare workers and others at higher risk of exposure or complications such as older and immunosuppressed patients. As live and attenuated viruses’ vaccines are contraindicated in MS patients, these new DNA-RNA vaccines are well welcomed in patients on DMTs . Yet, common concerns of the population and medical community are vaccine safety and effectiveness. Recent studies have focused on the willingness of MS patients to get the COVID-19 vaccine. 80.9% of European MS patients were willing to receive the vaccine, however 54.1% would prefer to postpone vaccination until they seek advice of their physician. Interestingly, older patients and those with comorbidities were the ones with the biggest interest in getting the protection of the vaccine . In the US, the acceptability was slightly inferior, but 66% of the participants were still willing to get a COVID-19 vaccine. The information sources most highly trusted were healthcare providers and the National MS Society, confirming the importance of review studies and expert recommendations . Several studies have shown that there is no difference in vaccine responses between MS patients and healthy individuals  but, given the variable immune responses and the absence of clinical trials in this population, the safety and efficacy of approved SARS-CoV-2 vaccines in MS patients is still unknown to us, . A recent study conducted in Israel, a country where vaccination has been a keen priority, evaluated the adverse event profile and immediate risk of acute relapses in 555 MS patients who received the COVID-19 BNT162b2 vaccine . No events of anaphylaxis or life-threatening responses were registered. Between the two doses, three patients (0.5%) were infected by SARS-CoV-2, all being asymptomatic or with mild disease. A pseudo-relapse with flu-like symptomatology was reported in 2% and 4.8% of patients after the first and second vaccination doses, respectively. Acute relapses shortly after vaccination corresponded to the expected relapse rate and so the vaccine was not associated with increased disease activity.
The entry is from 10.3390/vaccines9070773
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