Risk factors for severe disease are age, disability, or obesity

Multiple sclerosis (MS) patients receiving disease-modifying therapies (DMT) do not have an increased risk of severe Covid-19 infection, according to a team of French investigators who analyzed data from a retrospective, observational study of 347 MS patients with confirmed SARS-C0V-2; however, older age, increased disability, and obesity were identified as risk factors for Covid-19 severity.

Moreover, MS patients who were not receiving DMT were more likely to have a higher Covid-19 severity score than those on DMT regimens (46.0% vs 15.5% [P < .001]), wrote Céline Louapre, MD, of Sorbonne Université, Clinical Investigation Center Neuroscience Unit in Paris, and colleagues in JAMA Neurology.

That observation will be reassuring to many neurologists given the initial concerns about DMT in MS. As Gavin Gionannoni, MBBCh, PhD, of Blizard Institute, Barts, and The London School of Medicine and Dentistry, and colleagues wrote in Multiple Sclerosis Related Disorders as recently as April 2020, “Clearly, any decision to start a DMT during the Covid-19 pandemic will need to be taken carefully and will depend on the state of the Covid-19 pandemic, not only in the particular country concerned, but in the specific area the patient lives and receives therapy. For example, aggressive public health steps to contain the spread of the virus locally may make it relatively safe for a patient to start an immunosuppressive therapy. Our concern is that the Covid-19 pandemic may trigger a large number of neurologists and patients to reconsider treatment strategy and choice of initial DMT and to opt for less effective immunomodulatory DMTs. This change needs to be considered carefully… Neurologists have spent an extraordinary amount of time and effort to activate the MS community: to advance the principle that ’time is brain’, to treat MS proactively to a target of no evident disease activity (NEDA) and more recently, to flip the pyramid and use higher efficacy treatments first line. These treatment principles are evidence-based and should not be thrown out in the context of a potential, but yet undefined, risk to our patients.”

For their analysis, Louapre and colleagues used the Covisep registry of MS patients to identify 347 patients with confirmed or suspected Covid-19 treated from March 1, 2020 and May 21, 2020. Infection was confirmed with “a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.”

They assessed Covid-19 severity using a 7-point scale — with 1 indicating mild disease and 7 indicating death — with “a cutoff at 3 (hospitalized and not requiring supplemental oxygen).”

Patient-specific data included demographic profile, neurological history, Expanded Disability Severity Scale score (EDSS), comorbidities, and Covid-19 symptoms/characteristics.

Among the findings:

  • Mean age 44.6.
  • 249 of the 347 were women.
  • Mean MS duration was 13.5 years.
  • Median EDSS was 2.
  • 81.8% (n=284) were receiving DMT.

Patients with a Covid-19 severity score of 3 or more were more likely to present with fever (91.8%) and dyspnea (74%). Among patients with less severe Covid-19, “anosmia/ageusia and headache were more common in patients who were not hospitalized (135 of 274 [49.3%] and 164 of 274 [59.8%], respectively) versus patients who were hospitalized (15 of 73 [20.5%] and 16 of 73 [21.9%], respectively; P < .001).”

Although a minority of MS patients (n=73) had a Covid-19 severity score of 3 or more, more than 16% (n=12) of the patients with severe Covid-19 died.

“Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS !6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a Covid-19 severity score of 3 or more (indicating hospitalization or higher severity),” Louapre et al wrote. “The EDSS was associated with the highest variability of Covid-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). ”

The fact that age and obesity were associated with more severe disease confirms observations reported in studies of Covid-19 by other researchers, they wrote. For example, age was “identified in the earliest published study as a risk factor for severity of Covid-19 infection.”

The authors also conducted a multivariate analysis using a Covid-19 severity cutoff of 4 or more and found “an independent outcome of male sex as risk factor for severe Covid-19, beside age, obesity, and EDSS.”

In the cohort as a whole, “the exposure to DMTs and the level of immunosuppression were not factors that independently modified the risk of developing a severe form of Covid-19,” they wrote, but cautioned that “it is possible that a larger cohort could identify a subgroup of patients with 1 or more DMTs that modify the risk of Covid-19. Therefore, the pooling of registries and/or replication of results in other cohorts from several countries will be important to reinforce this result. In our population, 2 patients with relapsing-remitting MS who were receiving ocrelizumab have developed acute respiratory distress syndrome. Although these 2 patients also had obesity, it cannot be excluded that their DMTs may have increased their susceptibility to Covid-19 severity. In the literature, cases of patients with MS and Covid-19 who were receiving ocrelizumab were reported, with 1 being asymptomatic and the other having a favorable outcome.”

Louapre and colleagues acknowledge a potential for referral bias “toward severe Covid-19 or patients receiving DMTs who may have been more concerned about Covid-19 symptoms than patients who are untreated. It is also important to note that some immunosuppressive treatments, notably cladribine and alemtuzumab, are not commonly used in France, so it is not possible to analyze specifically whether these treatments could increase the risk associated with Covid-19.”

Finally, they concluded that the Covid-19 pandemic has changed the practice of medicine regardless of specialty, and this change is likely to persist for months. “Our data do not support an increased risk of severe outcome associated with DMTs, which should reinforce the recommendation of not stopping current DMTs and not delaying treatment initiation in patients who have higher disease inflammatory activity, risk for relapses, or subsequent disability,” they wrote. “Conversely, patients with high EDSS and older age are at highest risk of severe Covid-19. Given the importance of these 2 variables on Covid-19 outcomes, the identification of a potential outcome of certain DMTs on Covid-19 risk would require a large international effort to collect data and a specific focus on patients with less advanced disease that also considers known comorbidities for Covid-19.”

  1. Be aware that this cohort study of MS patients found no association between disease-modifying therapy and Covid-19 risk or severity.
  2. Note that in a cohort of MS patients, obesity, age, and neurological disability were identified as risk factors for severe forms of Covid-19.

Peggy Peck, Editor-in-Chief, BreakingMED™

Louapre received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono outside the submitted work.

Giovannoni reported personal fees from AbbVie, GW Pharma, Fiveprime, Synthon BV, Eisai, Elan, Genentech, GSK, and Pfizer, grants and personal fees from Biogen, Canbex, Merck-Serono, Novartis, Teva, Roche, Bayer-Schering, Ironwood, and Genzyme/Sanofi, and grants from UCB Pharma.

 

Cat ID: 130

Topic ID: 82,130,730,933,190,926,130,36,192,927,151,928,925,934