Along with the elevated risk for coronavirus disease 2019 (COVID-19)-related complications in patients with underlying medical conditions, such as diabetes and cardiovascular disease, individuals with autoimmune diseases may also face some risks related to their condition and the nature of their treatment.
Askanase and colleagues discussed the implications of COVID-19 in patients with autoimmune diseases and those receiving immunosuppressant therapies, in a paper published in Lupus Science & Medicine.1 They evaluated the risks and benefits of continuing maintenance immunosuppression for patients infected with or at risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While treatment decisions should ultimately be determined in a joint decision-making process between patient and provider, the authors of this report suggested that it may be appropriate to hold off on immunosuppression for 2 weeks in patients with confirmed exposure to or with symptoms of COVID-19, with continued treatment for those with no evidence of exposure to the virus.
There is also concern that immunocompromised patients may be more susceptible to pneumonia, as has been noted with other types of coronaviruses.2 However, preliminary findings from other research have indicated that some immunomodulatory therapies, including chloroquine, tocilizumab, and baricitinib, may confer protective effects against the “cytokine storm” that has been observed in patients with severe COVID-19 pneumonia.1
We spoke with Maximilian Konig, MD, clinical fellow in the Division of Rheumatology at Johns Hopkins University School of Medicine, Baltimore, Maryland to get a general overview of COVID-19 in autoimmune diseases, based on recent developments.
What may be some of the unique issues affecting patients with autoimmune diseases in the context of COVID-19?
Since the letter by Askanase and colleagues1 was published more than 2 months ago, we have learned a lot about the disease, its clinical manifestations and immunopathogenesis in adults, and more recently, in children. We have a much better understanding of some of the most severe complications of COVID-19, including a form of hyperinflammation often referred to as “cytokine storm,” and we are starting to see evidence that cytokine-directed therapies may improve outcomes in the sickest patients when adminstered at the right time. Unfortunately, the highest level of evidence for these treatments is still lacking and the effect sizes in patients with COVID-19 who already have end-organ damage may be smaller than we would have hoped.
We are starting to appreciate in more granular detail how COVID-19 affects patients with autoimmune diseases and specifically those with rheumatic disease. A large international collaboration of rheumatologists, researchers, and patients has formed under the umbrella of the COVID-19 Global Rheumatology Alliance3 that aims to tackle these questions in particular. This physician-reported registry now captures data from more than 1400 patients with rheumatic disease, which may help to answer some of the most pressing questions such as what are the outcomes of patients with rheumatic disease who are hospitalized for COVID-19? Are specific patient populations at higher risk or relatively protected? Are some of our therapies, including glucocorticoids, hydroxychloroquine, conventional disease-modifying antirheumatic drugs (DMARDs), biologics, or small molecules, associated with better or worse outcomes?
The answers may have a significant effect on how we manage our patients, what drugs we deem safer, and what drugs we should try to avoid. The half-life and dosing frequency of some of the drugs pose a unique challenge, and many [clinicians] have been concerned about how prescribing a drug like rituximab could affect our patients if they became sick from SARS-CoV-2 and needed to mount neutralizing antibodies to a new virus. There are no certain answers for this at the moment, but shared decision-making with our patients on these risk-benefit considerations has never been more important.
Have the initial concerns regarding patients with autoimmune disease been addressed? What other developments have emerged since reports of the virus first surfaced?
There is some good news. Even though large data sets4 suggest an overall increased risk in patients with autoimmune disease, the initial concern that all of our patients may have severe outcomes may not be true. The overall risk for patients with rheumatic disease seems much lower than that seen for other chronically immunocompromised patients such as the transplant population. The increased risks we are now seeing may be primarily driven by comorbidities, age, and sex rather than the underlying rheumatic disease or immunosuppression, but the jury is still out on that. Given the role that some of our drugs that do not significantly impede viral clearance may play in treating cytokine storm and severe inflammatory complications of SARS-CoV-2 infection, it may turn out that baseline therapies are providing benefit, though this data are still inconclusive.
When Askanase and colleagues wrote their letter, access to essential medications was becoming a major problem for our patients, particularly those with lupus and other rheumatic disease that rely on hydroxychloroquine to prevent disease flares and reduce the risk for hospitalization and death. We have now gone through several news cycles around the proclaimed – and to date not proven – benefits of antimalarials (hydroxychloroquine and chloroquine) in COVID-19. This has resulted in acute shortages for patients with lupus and other rheumatic diseases not just in the United States, but many countries worldwide.
In patients who become infected [with SARS-CoV-2], we will need to [evaluate] how stopping or potentially switching their immunosuppressive therapies will affect disease activity. Many rheumatologists have been more careful about dose-escalating medications during this pandemic, and we will have to see whether there is a price to pay for this in the future.
One of the major problems for our patient population may be changes in care, which has moved to telemedicine for the most part. Socioeconomically, additional financial burden, the ability to pay for medication and appointments may have a significant long-term effect on their health. Reports of patients avoiding emergency departments and hospitals, even when needing acute care, will have consequences. Even though I can manage well-established patients from a distance for some time, it is much more challenging to accurately assess new patients through video chat, especially when nuanced and comprehensive assessment is needed.
How should these issues be addressed in clinical practice?
The pandemic is a steep learning curve for all of us – patients, hospital systems, and individual physicians. We will need to find ways to quickly adapt to new information and integrate it into our treatment plans. The pandemic has already had a dramatic effect on innovation and pushing telemedicine onto the main stage. Yet, finding a safe way to allow for direct in-person new patient visits and urgent returns, especially in patients who have active disease, will be essential to mitigate the long-term risks that the pandemic may pose to these individuals.
We cannot anticipate when shortages of essential drugs like hydroxychloroquine will end or if they will get worse again before they get better, and other drugs deemed useful for the treatment of severe COVID-19 will also suffer shortages that affect care for our patients. We should now anticipate these shortages and advocate preemptively to secure access to life-saving medications for patients in whom they have proven efficacy. This will hopefully be achieved through coordinated efforts by advocacy groups and rheumatology societies.
In your opinion, what are the most pressing needs in this area to be addressed in the near future?
Ensuring access to drugs for our patients will be a critical and ongoing task. We are awaiting data on large populations that will inform and guide our decisions regarding which medications to use or not use, when to hold medications and when to start, and how to support our patients who develop COVID-19.
Research in this area has never been more important and time-sensitive. Fortunately, these efforts are ongoing, and data will hopefully be available to guide our decisions until vaccine and other effective therapies become available to reduce the risk for long-term morbidity and mortality from SARS-CoV-2 in patients with rheumatic disease.
- Askanase AD, Khalili L, Buyon JP. Thoughts on COVID-19 and autoimmune diseases. Letter. Lupus Sci Med. 2020;7(1):e000396. doi:10.1136/lupus-2020-000396
- Pene F, Merlat A, Vabret A, et al. Coronavirus 229E-related pneumonia in immunocompromised patients. Clin Infect Dis. 2003;37(7):929‐932.
- COVID-19 Global Rheumatology Alliance. Healthcare provider entered registries. Accessed May 20, 2020. https://rheum-covid.org/provider-registry-gate/
- Williamson E, Walker AJ, Bhaskaran KJ, et al; The OpenSAFELY Collaborative. OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients [published online May 7, 2020] medRxiv. doi:10.1101/2020.05.06.20092999