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People with myasthenia gravis were at higher risk for severe cases of COVID-19, including infections leading to hospitalization and death, a Canadian population-based study showed.

Among people in Ontario during the first year and a half of the pandemic, those with myasthenia gravis had a 25% greater risk for a positive COVID test compared with the general population (HR 1.25, 95% CI 1.06-1.48), reported Carolina Barnett, MD, PhD, of the Ellen and Martin Prosserman Centre for Neuromuscular Diseases at Toronto General Hospital, and colleagues.

In addition, they detailed in , people with the autoimmune disorder had a roughly twofold greater risk of emergency department (ED) visits (HR 1.84, 95% CI 1.29-2.62), hospitalizations (HR 2.48, 95% CI 1.61-3.79) and death (HR 2.11, 95% CI 1.17-3.78) versus the general population.

"Our results support the prioritization of people with MG [myasthenia gravis] for vaccination as well as for consideration of early therapeutics for COVID-19, such as antivirals," the group said.

Myasthenia gravis is "caused by antibodies targeting the neuromuscular junction, resulting in fatigue and fluctuating muscle weakness," Barnett and colleagues explained. "The recent COVID-19 pandemic has disproportionally affected people with chronic comorbidities, including MG, who are usually immunosuppressed and, therefore, are at risk of worse infection outcomes."

In order to account for limited data on the use of immunosuppressive therapies in the general population, the researchers also performed comparisons with a rheumatoid arthritis (RA) control group, and found similarly higher risks for infection and ED visits among the individuals with myasthenia gravis, as well as for COVID-related hospitalization and death:

• Hospitalization: HR 1.79 (95% CI 1.30-2.48)
• Death at 30 days: HR 1.83 (95% CI 1.17-2.89)

COVID-associated hospitalizations were reported in 30.5% of myasthenia gravis patients, as compared with 15.1% of people in the general population and 20.7% of RA controls. And deaths due to COVID-19 were reported in 14.6%, 8.5%, and 9.9%, respectively, the study found.

Comorbidities in the myasthenia gravis group were well balanced with the control group with RA, "where immunosuppression is also common, suggesting that there may be factors specific to MG associated with these worse outcomes," the researchers said. "The known association of MG worsening with infections, including the , may explain in part the higher risk of admissions and death among patients with MG."

Given the study timeframe for these outcomes (January 2020 to May 2021), most deaths occurred among unvaccinated individuals, Barnett and colleagues noted.

There was some good news, however, as vaccine uptake was as high in people with myasthenia gravis as the general population following the introduction of mRNA vaccines, with 80% and 82% of the two groups having received two doses from December 2020 through August 2021.

And while the study was not designed to assess vaccine efficacy, the reduction of COVID infection with vaccines was more pronounced among the group with myasthenia gravis (HR 0.43, 95% CI 0.30-0.60) than the control group (HR 0.70, 95% CI 0.57-0.84), suggesting that vaccination "is effective for people with MG, despite immunosuppressive treatments."

"In addition, we found that there was a negligible number of MG-related hospital admissions in the 30 days after vaccination, suggesting that the vaccine is safe from an MG perspective," the researchers wrote. "Although we cannot rule out mild MG flare-ups not requiring hospital admission, the risks of severe COVID-19 infection with hospital admission and death were much higher among people with MG in this study."

Barnett's group looked at 4,411 individuals with myasthenia gravis among the 11,365,233 Ontario residents eligible for the Ontario Health Insurance Plan. The myasthenia gravis group was matched by age, sex, and geographic area in a 1:5 ratio to 22,055 general population controls and 22,055 RA controls.

Study participants had a mean age of 68 years, 52% were women, and about 88% lived in an urban area. Myasthenia gravis patients had higher mean Charlson Comorbidity Index scores and more comorbidities on average than the general population, but these variables were balanced when compared with the RA group.

Overall, a positive COVID test was recorded in 3.7% of people with myasthenia gravis, 3% of the general population, and 3% of people with RA, while ED visits for COVID-19 occurred in 36.6%, 24.4%, and 29.9% of the three groups, respectively.

Of the 3,461 individuals with myasthenia gravis who received a first dose of COVID vaccine, fewer than six were hospitalized due to their disorder within 30 days of vaccination. Furthermore, none of the patients who received a second dose were admitted. In total, fewer than six of the 24 deaths from COVID-19 among the myasthenia gravis patients occurred in vaccinated individuals.

A limitation cited by the authors included the early study time frame capturing initial pandemic waves, which were associated with more severe respiratory infections compared with more recent waves.

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