Neuroimmunological diseases and their treatment compromise the immune system, thereby increasing the risk of infections and serious illness. Consequently, vaccinations to protect against infections are an important part of the clinical management of these diseases. However, the wide variety of immunotherapies that are currently used to treat neuroimmunological disease - particularly multiple sclerosis and neuromyelitis optica spectrum disorders - can also impair immunological responses to vaccinations. In this Review, we discuss what is known about the effects of various immunotherapies on immunological responses to vaccines and what these effects mean for the safe and effective use of vaccines in patients with a neuroimmunological disease. The success of vaccination in patients receiving immunotherapy largely depends on the specific mode of action of the immunotherapy. To minimize the risk of infection when using immunotherapy, assessment of immune status and exclusion of underlying chronic infections before initiation of therapy are essential. Selection of the required vaccinations and leaving appropriate time intervals between vaccination and administration of immunotherapy can help to safeguard patients. We also discuss the rapidly evolving knowledge of how immunotherapies affect responses to SARS-CoV-2 vaccines and how these effects should influence the management of patients on these therapies during the COVID-19 pandemic. 

/pdf/vaccination-and-immunotherapies-in-neuroimmunological-268iy3gl.pdf

Vaccination and immunotherapies in neuroimmunological diseases

Abstract Objectives To investigate the incidence of COVID-19 hospitalisation in unvaccinated and vaccinated patients with rheumatoid arthritis (RA) compared with matched controls, and in patients with RA according to DMARD treatment. Methods Danish nationwide matched cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalisation (Danish National Patient Register) and first-time positive SARS-CoV2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PY) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. Results In total, 28 447 unvaccinated patients and 568 940 comparators had Irs for COVID-19 hospitalisation of 10.4 (8.0–13.4) and 4.7 (4.3–5.1) per 1000 PY, respectively (aHR 1.88, 1.44–2.46). When fully vaccinated, corresponding Irs were 0.9 (0.5–1.6) and 0.5 (0.4–0.6) per 1000 PY (aHR 1.94, 1.03–3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09–1.57) for testing positive for SARS-CoV2 and 1.09 (0.92–1.14) among vaccinated. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalisation compared with conventional DMARD treated patients. Conclusion The incidence of COVID-19 hospitalisation was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.

/pdf/covid-19-infection-and-hospitalisation-risk-according-to-6y4f8e7n.pdf

COVID-19 infection and hospitalisation risk according to vaccination status and DMARD treatment in patients with rheumatoid arthritis

Seroconversion rate of vaccines varies and requires further elucidation in patients with multiple sclerosis (MS) under treatment with disease-modifying therapies (DMTs). We aimed to investigate this in a systematic review and meta-analysis.MEDLINE(PubMed) and Cochrane databases were searched based on a pre-specified protocol (PROSPERO: CRD42020202018). Studies reporting on patients with MS, diagnosed with McDonald criteria getting vaccinated with any type of vaccine were included in the analysis. The primary endpoint was the incidence of patients being seropositive and experience adverse events after vaccination. Outcomes were expressed as proportions with respective 95% confidence interval (CI). Two reviewers independently screened and reviewed existing literature and assessed study quality with the Methodological index for non-randomized studies.Of 295 articles, 45 studies were analyzed. Seroconversion after COVID-19 vaccines was 76% (95% CI, 70-80; I2 = 95%; 20 studies including 5601 patients. Protection was lower in patients treated with anti-CD20 antibodies and sphingosine-1-phosphate receptor (S1PR) modulators compared to untreated patients or treatment with other DMTs. Relapse occurred in 2% (95% CI, 1-3; I2 = 86%; 16 studies including 7235 patients). Seroconversion after seasonal influenza vaccines was 82% (95% CI, 65-91; I2 = 90%; 6 studies including 490 patients). Relapse rate was similar to this after COVID-19 vaccination.The majority of MS patients vaccinated for COVID-19 or seasonal influenza mount an adequate immune response without safety concerns. Data on other vaccines are limited. 

Immunogenicity and safety of vaccines in multiple sclerosis: A systematic review and meta-analysis

COVID-19 pandemic has affected the management of multiple sclerosis (MS).To explore the impact of COVID-19 on healthcare delivery to people with MS and the subsequent recovery of the system.In this population-based study in the Campania Region (Italy), we included people with MS across pre-COVID-19, lockdown, pre-vaccination, and vaccination periods. Differences in continuous outcomes between periods were explored using linear mixed models (annualized hospitalization rate (AHR) and adherence measured as medication possession ratio (MPR)). Differences in disease-modifying treatment (DMT) prescription rates (first DMT prescription, any DMT switch, switch from platform to highly effective DMT, and combination of first DMT prescription and any DMT switch) were assessed using an interrupted time series design.Compared with pre-COVID-19, AHR decreased during the lockdown (Coeff = 0.64;95%CI = -0.69, -0.59; p < 0.01), and remained lower during pre-vaccination and vaccination periods. Adherence decreased during pre-vaccination (Coeff = -0.04;95%CI = -0.05, -0.03; p < 0.01) and vaccination periods (Coeff = -0.07;95%CI = -0.08, -0.07; p < 0.01). After the lockdown, there was an increase in any DMT switch (IRR 2.05 95%CI 1.38,3.05; p < 0.01), in switch from platform to highly effective DMTs (IRR 4.45;95%CI 2.48,8.26; p < 0.01) and in first DMT prescriptions (IRR 2.48;95%CI 1.64,3.74; p < 0.01).DMT prescriptions quickly returned to pre-pandemic levels, reflecting good health system recovery. However, adherence has remained lower than the past, as from suboptimal care. Assessing long-term COVID-19 impact on MS healthcare is warranted. 

Impact of COVID-19 and system recovery in delivering healthcare to people with multiple sclerosis: a population-based Study.

The purpose of this literature review was to summarise relevant findings regarding the clinical management of multiple sclerosis (MS) in the COVID-19 pandemic, with the focus on patient risks, and the implications of disease-modifying treatment, both on COVID-19 severity and on the response to the SARS-CoV-2 vaccinations. Although MS per se does not seem to put patients at risk for more severe COVID-19, alongside the risk factors known to apply to the general population, progressive disease course, higher disability status, and B-cell depleting therapies may all negatively affect infection severity. The question of COVID-19 sequelae in patients with MS (pwMS) remains unresolved, challenging researchers to further explore this area. The safety profile of COVID-19 vaccinations in pwMS is similar to that of the general population. The efficacy of the vaccination might be affected by B-cell depletion, as well as by S1PR-modulating medications that attenuate humoral responses to the COVID-19 vaccination. Future research should focus on gathering evidence regarding the clinical course of MS following COVID-19 infection and vaccination in larger studies, as well as on establishing the safest and most efficient schedule of COVID-19 vaccination in pwMS on cell-depleting therapies. 

/pdf/navigating-the-landscape-of-covid-19-for-multiple-sclerosis-3mk7gr8r.pdf

Navigating the landscape of COVID-19 for Multiple Sclerosis patients and clinicians

Rituximab Infusion Timing, Cumulative Dose, and Hospitalization for COVID-19 in Persons With Multiple Sclerosis in Sweden

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Rituximab Infusion Timing, Cumulative Dose, and Hospitalization for COVID-19 in Persons With Multiple Sclerosis in Sweden