Reported neurological symptoms after severe acute respiratory syndrome coronavirus type 2 infection: A systematic diagnostic approach.

BACKGROUND AND PURPOSE: Following increasing demands of patients with suspected neurological symptoms after infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the Department of Neurology at the Medical University of Vienna established a new outpatient clinic to systematically assess, diagnose, and document neurological complaints potentially associated with a prior SARS-CoV-2 infection. METHODS: The data presented here include prospectively collected 156 outpatients from May 2021 to April 2022. Patients underwent semistandardized interviewing about symptoms with reported onset after SARS-CoV-2 infection, neurological examination, and comprehensive diagnostic workup. RESULTS: Reported new onset symptoms after infection included fatigue (77.6%), subjective cognitive impairment (72.4%), headache (47.7%), loss of smell and/or taste (43.2%), and sleep disturbances (42.2%). Most patients had a mild coronavirus disease (COVID-19) disease course (84%) and reported comorbidities (71%), of which the most frequent were psychiatric disorders (34%). Frequency of symptoms was not associated with age, sex, or severity of COVID-19 course. A comprehensive diagnostic workup revealed no neurological abnormalities in the clinical examination, or electrophysiological or imaging assessments in the majority of patients (n = 143, 91.7%). Neuropsychological assessment of a subgroup of patients (n = 28, 17.9%) showed that cognitive impairments in executive functions and attention, anxiety, depression, and somatization symptoms were highly common. CONCLUSIONS: In this systematic registry, we identified fatigue, cognitive impairment, and headache as the most frequently reported persisting complaints after SARS-CoV-2 infection. Structural neurological findings were rare. We also suspect a link between the growing burden of the COVID-19 pandemic on personal lives and the increase in reported neurological and psychiatric complaints.

Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

BACKGROUND: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. METHODS: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. RESULTS: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). CONCLUSIONS: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Humoral immune response following SARS-CoV-2 mRNA vaccination and infection in pediatric-onset multiple sclerosis

Objective Currently, there is no data available on SARS-CoV-2 vaccine responses in pediatric-onset multiple sclerosis (POMS) and little is known about the course of SARS-CoV-2 infection in this age group. We therefore investigated humoral immune responses after Covid-19 vaccination and/or infection in POMS. Methods We retrospectively analyzed seroconversion rates and SARS-CoV-2 specific antibody levels in 30 POMS and 1 pediatric CIS patient treated with either no disease-modifying therapy (no DMT), immunomodulatory DMT (IM-DMT), or immunosuppressive DMT (IS-DMT) from two Austrian MS centers. Results Median age at MS onset was 15.39 years (IQR 1.97). Median age at first COVID-19 vaccination was 17.43 years (IQR 2.76). After two vaccine doses, seroconversion (≥0.8 BAU/ml) was reached in 25/28 patients (89.3%). All patients with no DMT or IM-DMT generated robust immune responses to vaccination (seroconversion: no DMT: 6/6, IM-DMT: 7/7 (100%);median titers: no DMT: 2075 BAU (IQR 1268.50), IM-DMT: 2500 BAU (IQR 0)). In the IS-DMT group seroconversion was achieved in 12/14 patients (80%), median titers were 50.8 BAU (IQR 254.63). Titers were significantly higher in no DMT versus IS-DMT (p=0.012) and in IM-DMT versus IS-DMT (p=0.001). Infection with SARS-CoV-2 occurred in 11 of 31 patients and symptoms were mild in all cases. One relapse occurred after infection, but no relapses were documented after vaccination. Conclusions Generally, mRNA vaccinations were well tolerated in POMS patients with and without DMT. Immune response was significantly reduced in patients treated with IS-DMT. No unexpected adverse events or relapses related to vaccinations were observed.

Impact of the COVID-19 pandemic on clinical autonomic practice in Europe A survey of the European Academy of Neurology (EAN) and the European Federation of Autonomic Societies (EFAS).

OBJECTIVE: To investigate the impact of the coronavirus-disease-2019 (COVID-19) pandemic on European clinical autonomic practice. METHODS: Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021. RESULTS: Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every-third center reported major adverse events due to postponed examinations or visits. The most frequent newly-diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and recurrent vasovagal syncope, deemed likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new-onset of orthostatic intolerance, but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly-diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently POTS and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50-100% recovery rates at follow-up. CONCLUSIONS: Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, while the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

Humoral Immune Response Following SARS-CoV-2 mRNA Vaccination and Infection in Pediatric-Onset Multiple Sclerosis.

OBJECTIVE: Currently, there are no data available on SARS-CoV-2 vaccine responses in pediatric-onset multiple sclerosis (POMS), and little is known about the course of SARS-CoV-2 infection in this age group. We therefore investigated humoral immune responses after COVID-19 vaccination and/or infection in POMS. METHODS: We retrospectively analyzed seroconversion rates and SARS-CoV-2-specific antibody levels in 30 POMS and one pediatric CIS patient treated with no disease-modifying therapy (no DMT), immunomodulatory DMT (IM-DMT), or immunosuppressive DMT (IS-DMT) from two Austrian MS centers. RESULTS: The median age at MS onset was 15.39 years (interquartile range [IQR]: 1.97). The median age at the first COVID-19 vaccination was 17.43 years (IQR: 2.76). After two vaccine doses, seroconversion (≥0.8 BAU/ml) was reached in 25 of 28 patients (89.3%). All patients with no DMT or IM-DMT generated robust immune responses to vaccination (seroconversion: no DMT: 6/6, IM-DMT: 7/7 [100%]; median titers: no DMT: 2075 BAU [IQR: 1268.50], IM-DMT: 2500 BAU [IQR: 0]). In the IS-DMT group, seroconversion was achieved in 12 of 14 patients (80%), and median titers were 50.8 BAU (IQR 254.63). Titers were significantly higher in no DMT versus IS-DMT (P = 0.012) and in IM-DMT versus IS-DMT (P = 0.001). Infection with SARS-CoV-2 occurred in 11 of 31 patients, and symptoms were mild in all cases. One relapse occurred after infection, but no relapses were documented after vaccination. CONCLUSIONS: Generally, mRNA vaccinations were well tolerated in POMS patients with and without DMT. Immune response was significantly reduced in patients treated with IS-DMT. No unexpected adverse events or relapses related to vaccinations were observed.

Impact of vaccination on COVID-19 outcome in multiple sclerosis.

BACKGROUND: COVID-19 continues to challenge neurologists in counselling persons with multiple sclerosis (pwMS) regarding disease-modifying treatment (DMT) and vaccination. The objective here was to characterize predictors of COVID-19 outcome in pwMS. METHODS: We included pwMS with PCR-confirmed COVID-19 diagnosis from a nationwide population-based registry. COVID-19 outcome was classified as either mild or severe. Impact of DMT, specifically anti-CD20 monoclonal antibodies, and vaccination on COVID-19 outcome was determined by multivariable models adjusted for a-priori-risk (determined by a cumulative risk score comprising age, disability and comorbidities). RESULTS: Of 317 pwMS with COVID-19 (mean age 41.8 years [SD 12.4], 72.9% female, median EDSS 1.5 [range 0-8.5], 77% on DMT [16% on antiCD20]), 92.7% had a mild course and 7.3% a severe course with 2.2% dying from COVID-19. Ninety-seven pwMS (30.6%) were fully vaccinated. After a median 5 months from vaccination to SARS-CoV-2 infection (range 1-9), severe COVID-19 occurred in 2.1% of fully vaccinated pwMS compared to 9.5% in unvaccinated pwMS (p=0.018). A-priori-risk robustly predicted COVID-19 severity (R2 0.605; p<0.001). Adjusting for a-priori-risk, anti-CD20 treatment was associated with increased COVID-19 severity (odds ratio [OR] 3.3; R2 0.113; p=0.003), but exposure to any other DMT was not. Fully vaccinated pwMS showed a significantly decreased risk for severe COVID-19 (OR 0.21, R2 0.144, p<0.001). CONCLUSIONS: In a population-based MS cohort, COVID-19 course is primarily predicted by a-priori-risk (depending on age, disability and comorbidities) explaining about 60% of variance. Anti-CD20 treatment is associated with a moderately increased risk, while reassuringly vaccination provides protection from severe COVID-19.

[Myalgic encephalomyelitis/chronic fatigue syndrome: an overview of current evidence]. / Myalgische Enzephalomyelitis/chronisches Fatigue-Syndrom: eine Übersicht zur aktuellen Evidenz.

Over the past 5 years both media and scientific interest has surged regarding the disorder myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS), not least because of the clinically similar manifestation in long COVID or post-COVID. In this review we discuss the process of clinical diagnosis and randomized controlled therapeutic studies on ME/CFS, and the similarities or differences to long COVID and post-COVID. So far, neither clear pathophysiologically causal nor therapeutic evidence-based results on ME/CFS have been identified in the many years of scientific research. Given the evident psychiatric comorbidity rates in patients with a diagnosis of ME/CFS, a psychosomatic etiology of this syndrome should be considered. Furthermore, a precise and reliable diagnostic classification based on stricter criteria would benefit both pathophysiological and therapeutic research.

High Anti-CoV2S Antibody Levels at Hospitalization Are Associated with Improved Survival in Patients with COVID-19 Vaccine Breakthrough Infection.

BACKGROUND: Although vaccination against COVID-19 is highly effective, breakthrough infections occur, often leading to severe courses and death. The extent of protection provided by individual antibody levels in breakthrough infections is still unknown and cut-off levels have yet to be determined. METHODS: In 80 consecutive fully vaccinated patients hospitalized between August and December 2021 with COVID-19 breakthrough infection (Delta variant), anti-CoV2S antibody levels were analyzed for the endpoint of death. RESULTS: Ten out of the 12 patients who died (83.3%) had antibody levels < 600 U/mL; 5 (41.7%) of these had antibody levels < 200 U/mL. Only 2 patients with a level of >600 U/mL died from vaccine breakthrough infection. Correction for the number of comorbidities and age revealed that anti-CoV2S antibody levels at the time of hospitalization were a significant predictor for reduced risk of death (OR = 0.402 for every 1000 U/mL, p = 0.018). CONCLUSIONS: In this retrospective data analysis, we show that almost all patients who died from COVID-19 vaccine breakthrough infection had antibody levels < 600 U/mL, most of them below 200 U/mL. In logistic regression corrected for the number of comorbidities and age, anti-CoV2S antibody levels at the time of hospitalization proved to be a significantly protective predictor against death.

Anti-SARS-CoV-2 vaccination in people with multiple sclerosis: Lessons learnt a year in.

It has been over a year since people with multiple sclerosis (pwMS) have been receiving vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a negligible number of cases in which vaccination led to a relapse or new onset MS, experts around the world agree that the potential consequences of COVID-19 in pwMS by far outweigh the risks of vaccination. This article reviews the currently available types of anti-SARS-CoV-2 vaccines and the immune responses they elicit in pwMS treated with different DMTs. Findings to date highlight the importance of vaccine timing in relation to DMT dosing to maximize protection, and of encouraging pwMS to get booster doses when offered.

Gender-related and geographic trends in interactions between radiotherapy professionals on Twitter.

Background and purpose: Twitter presence in academia has been linked to greater research impact which influences career progression. The purpose of this study was to analyse Twitter activity of the radiotherapy community around ESTRO congresses with a focus on gender-related and geographic trends. Materials and methods: Tweets, re-tweets and replies, here designated as interactions, around the ESTRO congresses held in 2012-2021 were collected. Twitter activity was analysed temporally and, for the period 2016-2021, the geographical span of the ESTRO Twitter network was studied. Tweets and Twitter users collated during the 10 years analysed were ranked based on number of 'likes', 're-tweets' and followers, considered as indicators of leadership/influence. Gender representation was assessed for the top-end percentiles. Results: Twitter activity around ESTRO congresses was multiplied by 60 in 6 years growing from 150 interactions in 2012 to a peak of 9097 in 2018. In 2020, during the SARS-CoV-2 pandemic, activity dropped by 60 % to reach 2945 interactions and recovered to half the pre-pandemic level in 2021. Europe, North America and Oceania were strongly connected and remained the main contributors. While overall, 58 % of accounts were owned by men, this proportion increased towards top liked/re-tweeted tweets and most-followed profiles to reach up to 84 % in the top-percentiles. Conclusion: During the SARS-CoV-2 pandemic, Twitter activity around ESTRO congresses substantially decreased. Men were over-represented on the platform and in most popular tweets and influential accounts. Given the increasing importance of social media presence in academia the gender-based biases observed may help in understanding the gender gap in career progression.

Evaluating the Efficacy of a Guided and Unguided Internet-Based Self-help Intervention for Chronic Loneliness: Protocol for a 3-Arm Randomized Controlled Trial.

BACKGROUND: Loneliness, or perceived social isolation, is prevalent in both the general population and clinical practice. Although loneliness has repeatedly been associated with mental and physical health, research on interventions that reduce loneliness effectively is still rather scarce. OBJECTIVE: This study aims to evaluate the efficacy of a guided and an unguided version of the same internet-based cognitive behavioral self-help program for loneliness (SOLUS-D) for adults. METHODS: A total of 250 participants will be randomly assigned to 1 of 2 intervention groups (SOLUS-D with guidance or SOLUS-D without guidance) or a wait-list control group (2:2:1 allocation ratio). Adult participants experiencing high levels of loneliness will be recruited from the general population. Individuals currently experiencing at least moderately severe depressive symptoms, an ongoing severe substance use disorder, previous or current bipolar or psychotic disorder, or acute suicidality will be excluded from the trial. Assessments will take place at baseline, 5 weeks (midassessment), and 10 weeks (postassessment). The primary outcome is loneliness assessed using the 9-item University of California, Los Angeles Loneliness Scale at the posttreatment time point. Secondary outcomes include depressive symptoms, symptoms of social anxiety, satisfaction with life, social network size, and variables assessing cognitive bias and social behavior. The maintenance of potentially achieved gains will be assessed and compared at 6 and 12 months after randomization in the 2 active conditions. Potential moderators and mediators will be tested exploratorily. Data will be analyzed on an intention-to-treat basis. RESULTS: Recruitment and data collection started in May 2021 and are expected to be completed by 2022, with the 12-month follow-up to be completed by 2023. As of the time of submission of the manuscript, 134 participants were randomized. CONCLUSIONS: This 3-arm randomized controlled trial will add to the existing research on the efficacy of loneliness interventions. Furthermore, it will shed light on the role of human guidance in internet-based treatments for individuals with increased levels of loneliness and the possible mechanisms of change. If SOLUS-D proves effective, it could provide a low-threshold, cost-efficient method of helping and supporting individuals with increased levels of loneliness. TRIAL REGISTRATION: ClinicalTrials.gov NCT04655196; https://clinicaltrials.gov/ct2/show/NCT04655196. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36358.

Remote visits for people with multiple sclerosis during the COVID-19 pandemic in Austria: The TELE MS randomized controlled trial.

Introduction: Continuous monitoring is the hallmark of managing chronic disease. Multiple sclerosis (MS), in particular, requires patients to visit their treating neurologists typically twice a year, at least. In that respect, the COVID-19 pandemic made us rethink our communication strategies. This study determined satisfaction with remote visits for people with MS (pwMS) by comparing non-inferiority to conventional visits. Methods: TELE MS was a randomized controlled trial that was open to any person with MS. We randomized a volunteer sample of 45 patients. We compared satisfaction with remote visits (via phone or via videochat) with conventional outpatient visits. The primary endpoint was patient satisfaction determined by the Telemedicine Perception Questionnaire (TMPQ, min: 17 and max: 85 points) with the hypothesis of non-inferiority of televisits to conventional visits. Physician satisfaction measured on the PPSM score (Patient and Physician Satisfaction with Monitoring, min: 5 and max: 25 points) was the secondary endpoint. Results: The trial met both endpoints. Mean (SD) TMPQ scores in the individual groups were 58 (6.7) points for conventional visits, 65 (7.5) points for phone visits, and 62 (5.5) points for video visits. Physician satisfaction over the whole cohort was similarly high. Median (range) PPSM scores were 23 (16-25) for the whole cohort, 19 (16-25) for conventional visits, 25 (17-25) for phone visits, and 25 (16-25) for video visits. Conclusions: Televisits in multiple sclerosis yield a high level of satisfaction for both patients and treating physicians. This concept for remote patient monitoring adopted during the current pandemic may be communicable to other chronic diseases as well. ClinicalTrials.gov identifier: NCT04838990.

Humoral immune response to SARS-CoV-2 third vaccination in patients with multiple sclerosis and healthy controls: A prospective multicenter study.

BACKGROUND: Third vaccination against SARS-CoV-2 is recommended for patients with multiple sclerosis (pwMS), usually six months after the last vaccination. METHODS: In this prospective multicenter study on 292 pwMS and 46 healthy controls (HC), who had all received two vaccinations prior to study enrollment, SARS-CoV-2 IgG response was measured in the month before and 2-4 months after third vaccination. PwMS were categorized as follows: untreated (N-DMT, n = 32), receiving disease-modifying therapy (DMT) with expected humoral response (er-DMT: interferon-beta preparations, glatiramer acetate, dimethyl fumarate, teriflunomide, natalizumab, cladribine, alemtuzumab; n = 120) or no expected humoral response (nr-DMT: S1PMs, CD20mAb; n = 140). RESULTS: PwMS on nr-DMT had significantly lower median antibody levels before (12.1 U/ml [0.4-2500]) and after third vaccination (305 U/ml [0.4-2500]) in comparison to other groups (p<0.001). We did not find differences in antibody levels after homologous (n = 281; 2500 [0.4-2500]) and heterologous (n = 57; 2500 [0.4-2500]) vaccination regime regardless of the DMT group. The DMT group (ß= -0.60; 95% CI -1195.73, -799.10; p<0.001) was associated with antibody levels after third vaccination, while time to revaccination (6 months [1-13]) was not. After third vaccination, seropositivity was reached in 75.8% and 82.2% of pwMS on anti-CD20 mAbs and S1PMs, respectively. Complete B-cell depletion significantly decreased the probability of seroconversion even after the third vaccination (OR 0.14; p = 0.021), whereas time interval to last DMT intake and time to revaccination did not. Twenty-two patients reported a SARS-CoV-2 infection (3 N-DMT, 9 er-DMT, 10 nr-DMT), one being asymptomatic and the rest having a mild course. CONCLUSION: Humoral response to SARS-CoV-2 third vaccination in pwMS is excellent. While reduced by S1PMs and CD20mAb, protective response is still expected in the majority of patients.

Long-term outcome after COVID-19 infection in multiple sclerosis: a nation-wide multicenter matched-control study.

BACKGROUND: Long-term outcome after COVID-19 in patients with multiple sclerosis (pwMS) is scarcely studied and controlled data are lacking. OBJECTIVE: To compare long-term outcome after COVID-19 in pwMS to a matched control group of pwMS without COVID-19. METHODS: We included pwMS with PCR-confirmed diagnosis of COVID-19 and ≥6 months of follow-up available and, as a control group, pwMS matched 1:1 for age, sex, disability level and disease-modifying treatment type. RESULTS: Of 211 pwMS with COVID-19 (mean age 42.6 years [SD 12.2], 69% female, median EDSS 1.5 [range: 0-7.5], 16% antiCD20), 90.5% initially had a mild COVID-19 course. At follow-up, 70% had recovered completely 3 months (M3) after COVID-19, 83% after 6 months (M6) and 94% after 12 months (M12). Mild initial COVID-19 course was the only significant predictor of complete recovery (odds ratio [OR]: 10.5; p<0.001). Most frequent residual symptoms were fatigue (M3: 18.5%, M6: 13.7%, M12: 7.3%), hyposmia (M3: 13.7%, M6: 5.2%, M12: 1.7%) and dyspnea (M3: 7.1%, M6: 6.6%, M12: 2.8%). Compared to matched controls, fatigue, hyposmia and dyspnea were significantly more frequent at M3 and still slightly at M6, while there was no difference at M12. PwMS with COVID-19 had neither a significantly increased risk for relapses (OR 1.1; p=0.70) nor disability worsening (OR 0.96; p=0.60). DISCUSSION: Long-term outcome of COVID-19 is favourable in a large majority of pwMS with only a small proportion of patients suffering from persistent symptoms usually resolving after 3-6 months. COVID-19 is not associated with increased risk of relapse or disability.

Age, Motivation, and Emotion Regulation Skills Predict Treatment Outcome in an Internet-Based Self-Help Intervention for COVID-19 Related Psychological Distress

Introduction First evidence suggests that internet-based self-help interventions effectively reduce COVID-19 related psychological distress. However, it is yet unclear which participant characteristics are associated with better treatment outcomes. Therefore, we conducted secondary analyses on data from a randomized controlled trial investigating the efficacy of a 3-week internet-based self-help intervention for COVID-19 related psychological distress. In this exploratory analysis, we examined several predictors ranging from sociodemographic variables to psychological distress, resource-related, and treatment-related variables. This includes, for example, age, motivation, and emotion regulation skills. Treatment outcomes were defined as post-treatment depressive symptoms and post-treatment resilience. Methods In a total of 107 participants with at least mild depressive symptoms, possible predictor variables and treatment outcomes were assessed using self-report measures. For example, emotion regulation skills were assessed by the Self-report measure for the assessment of emotion regulation skills. In a first step, we performed a separate linear regression analysis for each potential predictor. In a second step, predictors meeting a significant threshold of p < 0.05 were entered in linear multiple regression models. Baseline scores of the respective outcome measure were controlled for. Results The mean age of the participants was 40.36 years (SD = 14.59, range = 18–81 years) with the majority being female (n = 87, 81.3%). Younger age predicted lower post-treatment depressive symptoms. Additionally, higher motivation to use the intervention and better pre-treatment emotion regulation skills predicted higher post-treatment resilience. Conclusion The current study provides preliminary evidence regarding the relationship between participant characteristics and treatment outcome in internet-based self-help interventions for COVID-19 related distress. Our results suggest that under the circumstances surrounding COVID-19 such interventions might be particularly beneficial for young adults regarding depressive symptoms. Moreover, focusing on participants' existing strengths might be a promising approach to promote resilience through internet-based self-help interventions. However, since this was an exploratory analysis in an uncontrolled setting, further studies are needed to draw firm conclusions about the relationship of participant characteristics and treatment outcome in internet-based self-help interventions for COVID-19 related psychological distress.

Multiple sclerosis in the era of COVID-19: disease course, DMTs and SARS-CoV2 vaccinations.

PURPOSE OF REVIEW: As of January 21st 2022, over 340 million are confirmed cases of coronavirus disease 2019 (COVID-19), including nearly 5.6 million deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is neurotropic and affects the neural parenchyma through direct viral invasion from the nasal mucosa and postinfectious cytokine storm. Further challenges of SARS-CoV-2 infection are nowadays linked to variants of concern. Multiple sclerosis is an inflammatory and progressive degenerative disorder of the central nervous system commonly affecting young adults and potentially generating irreversible disability. Since the beginning of the SARS-CoV-2 pandemic, people with multiple sclerosis (pwMS) have been considered 'extra' vulnerable because of the immune-mediated nature of the disease, the disability status, and the immunomodulatory therapies potentially increasing the risk for viral infection. Today multiple sclerosis neurologists are faced with several challenges in the management of pwMS to both prevent SARS-CoV-2 infection and protection from disease worsening. We aimed to highlight today's most relevant facts about the complex management of pwMS in the COVID-19 era. RECENT FINDINGS: The incidence of COVID-19 among pwMS does not differ from the general population. The prognosis of COVID-19 among pwMS is driven by older age, male sex, nonambulatory status, comorbidity as in the general population, as well as by corticosteroid treatment and B-cell depleting agents which decrease seropositivity from SARS-CoV-2 infection and immune responses to SARS-CoV-2 vaccination. SUMMARY: Disease modifying treatments (DMTs) should be regularly continued in relation to SARS-CoV-2 vaccination, but an ad hoc timing is required with B-cell depleting agents. SARS-CoV-2 vaccination is recommended in pwMS with willingness improving through health education programs. Multiple sclerosis does not seem to worsen after SARS-Cov2 vaccination but COVID-19 may enhance disease activity.

Has the pandemic changed treatment strategy in multiple sclerosis?

BACKGROUND: Social distancing measures during the Covid-19 pandemic reduced access to health care and concerns were raised over the safety of immunosuppressive disease modifying treatments (DMT) for multiple sclerosis (MS). OBJECTIVE: To investigate changes in DMT prescription before and during the pandemic in a large and well-characterized real-world cohort of MS patients. METHODS: From the Vienna MS database (VMSD) we extracted MS patients who were initiated on a new DMT (both treatment-naïve and switching) between January 1st 2017 and December 31st 2021. Two time periods were defined: 1) the preCovid-19 era (January 1st 2017 to March 15th 2020, i.e. the day of the first lockdown in Austria) and the Covid-19 era (March 16th 2020 to December 31st 2021). Average annualized DMT prescription rates were descriptively compared between the two periods. RESULTS: The average annualized number of prescriptions in the preCovid-19 era was 90.3/year and dropped to 74.8/year (-17.2%) in the Covid-19 era, driven by a marked reduction to 41.7/year (-54%) in the first nine months of the Covid-19 era, partly offset by a rise to 101 in 2021. Use of alemtuzumab (-64%), antiCD20 (-49%), cladribine (-46%), and S1PM (-38%) was reduced, while natalizumab increased by 24%. Lower efficacy treatments remained stable. CONCLUSIONS: The pandemic coincides with a drop in DMT prescription, most markedly for immunosuppressive high-efficacy treatments, strongly suggesting the pandemic as the causal factor. If and how much this affects long-term outcome is yet to be determined.

Comparing humoral immune response to SARS-CoV2 vaccines in people with multiple sclerosis and healthy controls: An Austrian prospective multicenter cohort study.

BACKGROUND AND PURPOSE: SARS-CoV2 vaccination is recommended for patients with multiple sclerosis (pwMS), but response may be limited by disease-modifying-treatments (DMTs). The aim of this study was to compare the rates of humoral immune response and safety of SARS-CoV-2 vaccines in pwMS and healthy controls (HCs). METHODS: In this multicenter prospective study on 456 pwMS and 116 HCs, SARS-CoV-2-IgG response was measured 3 months after the first vaccine dose. The primary endpoint was defined as proportion of patients developing antibodies (seroconversion). Secondary endpoints included antibody level, safety and efficacy. RESULTS: Compared to 97.4% in HCs, seroconversion occurred in 96.7% (88/91) untreated pwMS, 97.1% of patients (135/139) on immunomodulatory DMTs and 61.1% (138/226; p < 0.001) on immunosuppressive DMTs. Seroconversion was lowest in patients on antiCD20 monoclonal antibodies (CD20 mAbs; 52.6%) followed by sphingosine-1-phosphate-receptor-modulators (S1PMs; 63.6%). In the S1PM subgroup, seroconversion increased with lymphocyte count (odds ratio [OR] 1.31 per 0.1 G/L; p = 0.035). In pwMS on CD20 mAbs, B-cell depletion decreased seroconversion (OR 0.52; p = 0.038), whereas time since last DMT did not. Safety of SARS-CoV-2 vaccines in pwMS was excellent. CONCLUSIONS: Humoral response to SARS-CoV2 vaccines in pwMS is generally excellent. While reduced by immunosuppressive DMTs, most importantly by B-cell-depleting CD20 mAbs and S1PMs, seroconversion is still expected in the majority of patients. SARS-CoV2 vaccination should be offered to every MS patient.

B Cell Depletion and SARS-CoV-2 Vaccine Responses in Neuroimmunologic Patients.

OBJECTIVE: The study was undertaken to assess the impact of B cell depletion on humoral and cellular immune responses to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccination in patients with various neuroimmunologic disorders on anti-CD20 therapy. This included an analysis of the T cell vaccine response to the SARS-CoV-2 Delta variant. METHODS: We investigated prospectively humoral and cellular responses to SARS-CoV-2 mRNA vaccination in 82 patients with neuroimmunologic disorders on anti-CD20 therapy and 82 age- and sex-matched healthy controls. For quantification of antibodies, the Elecsys anti-SARS-CoV-2 viral spike (S) immunoassay against the receptor-binding domain (RBD) was used. IFN-gamma enzyme-linked immunosorbent spot assays were performed to assess T cell responses against the SARS-CoV-2 Wuhan strain and the Delta variant. RESULTS: SARS-CoV-2-specific antibodies were found less frequently in patients (70% [57/82]) compared with controls (82/82 [100%], p < 0.001). In patients without detectable B cells (<1 B cell/mcl), seroconversion rates and antibody levels were lower compared to nondepleted (≥1 B cell/mcl) patients (p < 0.001). B cell levels ≥1 cell/mcl were sufficient to induce seroconversion in our cohort of anti-CD20 treated patients. In contrast to the antibody response, the T-cell response against the Wuhan strain and the Delta variant was more pronounced in frequency (p < 0.05) and magnitude (p < 0.01) in B-cell depleted compared to nondepleted patients. INTERPRETATION: Antibody responses to SARS-CoV-2 mRNA vaccinnation can be attained in patients on anti-CD20 therapy by the onset of B cell repopulation. In the absence of B cells, a strong T cell response is generated which may help to protect against severe coronavirus disease 2019 (COVID-19) in this high-risk population. ANN NEUROL 2022;91:342-352.

Immunology of COVID-19 and disease-modifying therapies: The good, the bad and the unknown.

OBJECTIVE: The outbreak of the SARS-CoV-2 pandemic, caused by a previously unknown infectious agent, posed unprecedented challenges to healthcare systems and unmasked their vulnerability and limitations worldwide. Patients with long-term immunomodulatory/suppressive therapies, as well as their physicians, were and are concerned about balancing the risk of infection and effects of disease-modifying therapy. Over the last few months, knowledge regarding SARS-CoV-2 has been growing tremendously, and the first experiences of infections in patients with multiple sclerosis (MS) have been reported. METHODS: This review summarizes the currently still limited knowledge about SARS-CoV-2 immunology and the commonly agreed modes of action of approved drugs in immune-mediated diseases of the central nervous system (MS and neuromyelitis optica spectrum disorder). Specifically, we discuss whether immunosuppressive/immunomodulatory drugs may increase the risk of SARS-CoV-2 infection and, conversely, may decrease the severity of a COVID-19 disease course. RESULTS: At present, it can be recommended in general that none of those therapies with a definite indication needs to be stopped per se. A possibly increased risk of infection for most medications is accompanied by the possibility to reduce the severity of COVID-19. CONCLUSIONS: Despite the knowledge gain over the last few months, current evidence remains limited, and, thus, further clinical vigilance and systematic documentation is essential.