The COVID-19 pandemic that gripped the world in 2020 has been repeatedly compared to another deadly pandemic of global proportions that occurred almost exactly a century ago — the Spanish flu. 

In the absence of widespread hygiene awareness or any meaningful epidemiological oversight (the World Health Organization only came into being in 1948), the Spanish flu ravished its way across the globe, killing millions in its wake. It is from this period in history that the images of people wearing facial masks first made their appearance. 

Two important points separate the COVID-19 pandemic of 2020 from the Spanish flu of 1918. First, the world was much more interconnected in 2020; the advent of commercial flying has made it easier for an individual to travel from 1 part of the world to another — and for the virus they are carrying to travel with them. Second, there has been a global movement of research around the effects of the virus on a number of disease categories; scientists across the world are building a library of medical literature exploring the lesser-known effects of COVID-19 on individuals with specific diseases.  

During the thick of the COVID-19 pandemic, public health campaigns highlighted time and again the increased risk of contracting this virus for individuals with substantial comorbidities. Epidemiological data suggests that young, healthy individuals were least likely to suffer from severe disease, while older individuals with comorbidities, especially those that compromise the immune system, were at a greater risk of morbidity/mortality. As with all infections, the state of an individual’s immune system has great bearing on clinical outcomes. 

Myasthenia Gravis and COVID-19 

In the Journal of Neurology, Stascheit and colleagues conducted a study to explore the risk and course of COVID-19 in immunosuppressive patients with myasthenia gravis

“COVID-19 . . .  raised concerns about the risk of severe infections in patients with myasthenia gravis due to several factors, such as preexistent bulbar and respiratory muscle fatigability, exacerbation of symptoms due to infections, and an immunocompromised state due to the immunosuppressive therapies that can be found in up to 80% of patients with myasthenia gravis,” they wrote. 

Read more about myasthenia gravis etiology

Further complicating treatment of immunocompromised patients who contracted COVID-19 is uncertainty about how the virus affects the immune system. Because the virus was novel in every sense of the word, clinicians had to work with limited information while doing their best to treat COVID-19 patients symptomatically. The surprisingly high prevalence of “long COVID”, defined as symptoms persisting after the initial infection has been treated, is testament to the confusion/limited data surrounding the virus. 

In the case of patients with myasthenia gravis who contracted COVID-19, management was guided by expert consensus. During this period, a number of clinicians published case reports detailing how they treated the virus in their patients with myasthenia gravis. In addition, clinical studies were conducted on the impact of COVID-19 on patients with myasthenia gravis. For example, the international CARE-MG registry and the Czech-MG study, 2 of the largest of their kind, reported a mortality of 24% and 11% respectively. 

Nevertheless, Stascheit and colleagues pointed out that it is extremely difficult to avoid reporting bias in the case of rare diseases. This is because physicians are more likely to encounter severe courses in clinical settings (while patients with mild disease stay home). This means that only the most severe cases of infection tend to be reported. In addition, it is difficult to know how much influence the chronic vs the acute illness (ie, myasthenia gravis vs COVID-19 infection) has on overall mortality figures. 

Stascheit et al sought to analyze available clinical data of patients with myasthenia gravis who also contracted COVID-19; their database of choice was the German Myasthenia Gravis Registry, established in 2019. They carefully studied any available information regarding COVID-19 infection, such as length of hospital stays, admission into the intensive care unit, the need for invasive/noninvasive ventilation, acute exacerbations, and eventual outcomes. 

They identified 95 patients who had myasthenia gravis and contracted COVID-19. Of the 95 patients, 76 were receiving immunosuppressive therapy at the time of infection; this was revealed to be a significant risk factor for both hospitalization (34%) and mortality (12%). Nevertheless, they found that the risk of COVID-19 infection had no correlation with immunosuppressive therapy. 

As the worst of the COVID-19 pandemic subsides, a consensus has formed around the idea that patients with myasthenia gravis who were on rituximab were more prone to poorer COVID-19 outcomes. Rituximab is often prescribed long-term in patients with myasthenia gravis. It is also used to treat rheumatoid arthritis and multiple sclerosis. 

Read more about myasthenia gravis treatment 

In addition, the findings of this study validates the cautious approach of the medical community towards COVID-19 infection control. When the pandemic was at its most active phase, physicians sounded the alarm of the need to practice maximum caution in patients with myasthenia gravis, particularly those on immunosuppressive therapy. The association between immunosuppression and COVID-19 morbidity/mortality indicates that such caution was fully warranted. 

In the months and years to come, we are likely to hear from more experts regarding how COVID-19 impacted various disease courses. In this golden age of information-gathering and retrospective analysis, we may yet gather new insights into the best methods for pandemic control and risk reduction for immunocompromised individuals. 


Stascheit F, Grittner U, Hoffmann S, et al. Risk and course of COVID-19 in immunosuppressed patients with myasthenia gravis. J Neurol. Published online September 27, 2022. doi:10.1007/s00415-022-11389-0

Simonetti O, Martini M, Armocida E. COVID-19 and Spanish flu-18: review of medical and social parallelisms between two global pandemics. J Prev Med Hyg. Published online September 15, 2021. doi:10.15167/2421-4248/jpmh2021.62.3.2124