Poor Lung Function, Steroid Use Tied to Risk of Severe COVID-19

Poor lung function and disease management, along with previous long-term use of corticosteroids, older age, and the presence of cancer are the most significant predictors of severe COVID-19 among people with myasthenia gravis (MG), according to a recent study.

The findings also indicated that the odds of death due to COVID-19 were about 35 times higher in MG patients treated with rituximab, an antibody-based therapy used to treat certain autoimmune disease and cancers. Rituximab is being investigated as a potential therapy for MG.

The study, “Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival,” was published in the European Journal of Neurology.

MG is an autoimmune disease caused by the abnormal production of self-reactive antibodies targeting acetylcholine receptors (AChR) and other proteins that play a key role in muscle contraction and nerve-muscle communication.

Over time, binding of self-reactive antibodies to these receptors causes muscles in the body to become weaker and unable to contract. In some cases, the muscles used for breathing are affected, resulting in shortness of breath.

Immunosuppressant therapies that reduce the activity of the immune system are sometimes prescribed in these situations for people with MG. However, this class of medications may increase the chances of complications in MG patients who contract COVID-19.

Given that, researchers from the Czech Republic now investigated whether certain factors could predict the severity of COVID-19 in people with MG. Among the studied factors were the medications that patients were taking, their MG status before infection, and the presence of other co-exisiting medical conditions.

Another goal of the study was to assess the impact of severe COVID-19 and its treatment, and to determine the risk of MG exacerbations, or acute episodes of disease worsening,  among patients.

A total of 93 MG patients with confirmed COVID-19 were followed for this study and their pre-infection data were analyzed. The diagnosis of MG was based on the presence of antibodies against AChR or muscle-specific receptor kinase (MUSK), or whether patients had at least a 10% decrease on repetitive nerve stimulation tests, which are used to evaluate how well electrical signals travel along nerves into muscles.

COVID-19 severity was classified on a seven-point scale, with a 1 meaning no symptoms and a 2 indicating isolated symptoms, such as a lack of smell or headaches. A 3 on the scale indicated mild signs of infection, such as fatigue, cold, and cough, while a 4 was indicated for flu-like infections without hospitalization. A 5 was assigned to patients admitted to the hospital with proven COVID-19 pneumonia and requiring oxygen therapy, and a 6 indicated severe COVID-19 pneumonia with mechanical lung ventilation. A 7 on the scale meant death due to COVID-19.

Overall, a score of five or higher on the scale was considered severe COVID-19.

Among the 93 patients with MG and COVID-19, 49% were women and 51% were men. The median age was 65 years. A total of 35 patients (38%) were diagnosed with severe pneumonia and 10 died (11%) due to COVID-19.

Researchers calculated the odds ratio (OR), in which values above one represent a greater probability of developing severe COVID-19.

The results showed that the odds of developing severe COVID-19 were 1.062 times higher in older patients.

In contrast, better lung function — as assessed by higher forced vital capacity or FVC values — before infection was associated with a lower risk of severe COVID-19 (OR of 0.957). Of note, FVC is a lung function parameter that measures the total amount of air a person can exhale after taking the deepest breath possible.

The use of corticosteroids, a type of medication that suppresses immune and inflammatory responses, also increased the odds of severe COVID-19 (OR of 14.098). In MG patients, an increase of 5 mg in corticosteroid dosage resulted in a 56% higher chance of severe COVID-19 pneumonia.

Treatment with other immunosuppressants, such as azathioprine, mycophenolate mofetil, and cyclosporin, had no effect on the course of COVID-19.

However, the results showed that the odds of dying from COVID-19 were 35 times higher in MG patients treated with rituximab, an antibody designed to target and lower the levels of a specific type of immune cell that is thought to drive MG.

To evaluate MG status among patients, the team used three scales that assess symptoms and signs of MG. These were the Myasthenia Gravis Foundation of America (MGFA) classification, the Myasthenia Gravis Composite (MGC), and the quantitative myasthenia gravis score (QMG).

The clinical outcome of MG patients was associated with their MG status before contracting the infection.

“Patients with unsatisfied control of MG before infection were also at a higher risk of severe pneumonia incidence,” the researchers wrote.

Cancer was another risk factor, with patients diagnosed with such diseases found to be seven times more likely to develop severe pneumonia. Surprisingly, the team failed to find any evidence indicating that asthma, chronic obstructive pulmonary disease (COPD), and smoking affected the course of COVID-19.

MG exacerbations were defined as worsening of symptoms leading to a drop in a category of the MGFA classification, or as a deterioration of at least two points on the Activity of Daily Living (ADL) scale.

MG exacerbations during infection were found to be relatively rare (15%) and were not caused by specific treatments for COVID-19.

“Our research is, to the best of our knowledge, the largest cohort of 93 MG patients with COVID-19 and as the most important predictors of severe COVID-19 infection we identified unsatisfied condition of MG with lower FVC and previous long-term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment,” the researchers wrote.

“Based on our results we recommend caution in myastenic patients early after rituximab treatment,” the team wrote. “But because of a small number of our patients on this therapy the effect of rituximab on severity of COVID- 19 infection need to be assessed on greater number of patients.”