Predictors of Poor Outcomes in Patients With Myasthenia Gravis and COVID-19

Researchers identify certain predictive factors that impact the prognosis of patients with myasthenia gravis and COVID-19 infection.

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Among patients with myasthenia gravis (MG), COVID-19 infection did not significantly alter the course of MG disease in most patients, according to a new study conducted at Tongji Hospital in Wuhan, China. The study, which investigated factors predicting poor outcomes in patients with myasthenia gravis (MG) following COVID-19 infection, was published in the Journal of Inflammation Research.¹

In this retrospective observational analysis, researchers evaluated the medical records of 845 patients with MG who were diagnosed with COVID-19 between January 2020 and March 2023, evaluating the impact of disease severity, comorbidities, and immunosuppressive treatments on the prognosis of these patients. The study found that 18.1% of patients had worsening MG symptoms after COVID-19, with 9.5% (80) of patients needing hospitalization and 3.6% (30) of patients developing a myasthenic crisis (MC). While most patients did not see a change in their MG due to COVID-19, those with generalized MG at onset and conditions like chronic kidney disease (CKD) or certain cancers were more likely to have poor outcomes, including disease exacerbation, hospitalization, and MC.

"Patients achieving minimal manifestation or better status before COVID-19 had a significantly reduced risk for poor outcomes," according to the researchers. The study found that 35.1% of the patients in the cohort had generalized MG. This group was more likely to experience an exacerbation of symptoms (OR, 1.683; 95% CI, 1.037-2.733; P = .035) or require hospitalization (OR, 2.005; 95% CI, 1.124–3.575; P = .018).

CKD, present in 1.8% of the patients, was identified as a key predictor of poor outcomes. It significantly increased the risk of disease exacerbation (OR, 4.576; 95% CI, 1.320- 15.868; P = .017), hospitalization (OR, 5.768; 95% CI,1.635-20.344; P = .006), and MC (OR, 5.964;95% CI,1.314-27.070; P = .021). Similarly, having a malignancy other than thymoma also raised the risk of exacerbation (OR, 3.006; 95% CI, 1.199–7.541; P = .019), hospitalization (OR, 3.412; 95% CI, 1.202-9.686; P = .021), and MC (OR, 4.944; 95% CI, 1.227-19.921; P = .025).

The study suggests age at MG onset also affected outcomes. The median age of MG onset in the cohort was 40 years, with COVID-19 diagnosed at a median age of 46 years. The results of the study showed that for each additional year of age at MG onset, the risk of exacerbation increased by 1.3% (OR, 1.013; 95% CI,1.002-1.026; P = .026), while the risk of hospitalization increased by 2.5% (OR, 1.025; 95% CI, 1.009-1.041; P = .002). However, age at onset was not significantly associated with an increased risk of MC (OR, 1.019; 95% CI, 0.995–1.043; P = .122).

Furthermore, the study discovered that patients who tested positive for anti-acetylcholine receptor (AChR) antibodies had a higher likelihood of experiencing poor outcomes.

In the cohort, 77.5% of patients tested positive for anti-AChR antibodies and were found to have an increased risk of disease exacerbations (OR, 2.470; 95% CI, 1.219-5.007; P = .012) and hospitalization (OR, 2.346; 95% CI,1.008-5.464; P = .048). The authors note, "This can be interpreted as the possibility that antibodies against the SARS-CoV-2 protein may cross-react with AChR subunits due to epitope homology." Additionally, 2.3% of patients were positive for anti-muscle-specific kinase antibodies, and these patients had an even higher risk of exacerbation (OR, 5.077; 95% CI, 1.405-18.347; P = .013).

The authors note it has been speculated that patients with MG are more susceptible to COVID-19 due to the weakened immune system and immunosuppressive treatments.² However, researchers found that immunosuppressive therapy appears to play a protective role in managing MG patients during COVID-19, but its long-term was found to carry risks. Of the cohort, 65% were on prednisone, and 52.4% received immunosuppressants such as tacrolimus, azathioprine, mycophenolate mofetil, or methotrexate. The study found that patients receiving immunosuppressive treatment had a reduced risk of exacerbation (OR, 0.443; 95% CI, 0.278–0.705; P = .001) and hospitalization (OR, 0.387; 95% CI, 0.209–0.715; P = .002) compared with those not receiving treatment​.

However, prolonged use of immunosuppressants was associated with an increased risk of exacerbation (OR, 1.236; 95% CI, 1.102–1.388; P < .001) and hospitalization (OR, 1.287; 95% CI, 1.123–1.474; P < .001). "It is important to note that while prednisone may be safe and effective in the beginning, it should be tapered off in combination with immunosuppressants during long-term follow-up to avoid adverse reactions," the authors added.

Researchers also explored the immune response in 376 patients with MG who contracted COVID-19. Of the 376 patients with available blood test results, those who contracted COVID-19 had higher leukocyte counts (7.4 vs 6.5 ×109/L, P = .001) and elevated inflammatory markers like interleukin-6 (3.6 vs 2.0 pg/mL, P = .003) and hypersensitive C-reactive protein (3.0 vs 0.8 mg/L, P < .001)​ compared with uninfected MG patients.

The study found these patients also had a lower percentages of regulatory T cells (Treg), which was significantly associated with SARS-CoV-2 infection (OR, 0.279; 95% CI, 0.117–0.664; P = .0044)​. Monitoring immune markers, such as interleukin-6 and Treg cell levels, may help identify MG patients at higher risk of poor outcomes.

“Our study suggests COVID-19 did not dramatically influence the course of MG disease in the majority of patients with MG, especially in those with few comorbidities, ocular MG at onset, and satisfactory control of MG before infection,” the authors concluded, adding that, “In addition, disease severity at onset was identified as an important predictive factor for poor outcomes in our cohort.”

References

1. Bi Z, Gao H, Lin J, et al. Predictive factors for poor outcomes associated with COVID-19 in a retrospective cohort of myasthenia gravis patients. J Inflamm Res. 2024;17:5807-5820. doi:10.2147/JIR.S475729
2. Businaro P, Vaghi G, Marchioni E, et al. COVID-19 in patients with myasthenia gravis: Epidemiology and disease course. Muscle Nerve. 2021;64(2):206-211. doi:10.1002/mus.27324