Previously independent patients with mild-symptomatic COVID-19 are at high risk of developing cognitive impairment but not depression or anxiety.

OBJECTIVES: The aim of the study was to explore the cognitive functions of a large sample of hospitalised subjects with mild symptomatic Coronavirus Disease (COVID-19) who were previously independent at home and without neurological diseases. METHODS: Patients admitted in a COVID-19 Unit for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection between November 2020 and March 2021 were recruited. Inclusion criteria were: being independent at home before the infection, radiologically confirmed COVID-19 pneumonia, positive reverse transcriptase-polymerase chain reaction nasopharyngeal swab and no oxygen supplementation at the time of evaluation. EXCLUSION CRITERIA: cognitive impairment or neurological diseases previous to the infection, delirium episodes, and history of any mechanical ventilation use. They were evaluated with Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Out of 522 subjects admitted in the COVID-19 Unit, 90 were enrolled [mean age = 68.32(11.99); 46M/44F]. An impaired MoCA (cut-off < 23) was found in 60 subjects (66.66 %). Pathological scores were obtained by 36.7 % of the subjects with <65 years and 78.3 % of those older than 65 years. A high prevalence of executive function and memory impairment was detected. CONCLUSIONS: The results underline a high rate of cognitive impairment in previously independent mild COVID-19 patients. This might represent a potential threat for the everyday independence of these patients due to the consequences on everyday life activities and work following discharge from hospital. These subjects should, therefore, be monitored in order to allow a better understanding of the progression and consequences of the so-called "Long COVID".

Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies.

BACKGROUND: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. OBJECTIVE: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). METHODS: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. RESULTS: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74-4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75-4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02). CONCLUSIONS: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.

Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic.

In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p < 0.05). EID was associated with an increased risk of MRI activity during the A-C interval (OR 5.373, 95% CI 1.203-24.001, p = 0.028). Being on SID or EID did not influence CDP (V-Cramer 0.47, p = 0.342). EID seemed to be associated with a higher risk of MRI activity in our cohort. EID needs to be carefully considered for OCR-treated patients.

Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.