COVID-19 and the Rheumatologist: What Have We Learned?

by Cassandra Calabrese, DO

While we continue to encounter more unknowns than knowns with COVID-19, it is incredible to reflect on how much we have learned since the start of the pandemic. Just over one year ago we were bracing our patients for hydroxychloroquine shortages, when it was thought this would be the panacea for COVID-19. Over the past year we as rheumatology providers witnessed many of our medications (from colchicine to tocilizumab) being studied and used to treat COVID-19. And while there have been many more negative than positive studies, there have been success stories (e.g., dexamethasone). Despite this work, many unanswered questions remain, in particular about patients with immune-mediated inflammatory diseases (IMID), including their risk for infection and poor outcomes, management and, perhaps most importantly, vaccine responses in our IMID patient population.

It is impossible to keep up with the outpouring of COVID-related data. As of April 1, 2021, more than 130,000 COVID-19 related publications have been posted. This number continues to grow (Figure 1) and we wonder if/when it will level out. Here I hope to highlight where we have been and where we are going in terms of managing patients with IMIDs amid the COVID-19 pandemic.

Figure 1. Cumulative COVID-19 articles stratified by database

COVID-19 vaccination in IMID patients

I have been privileged to be a member of the American College of Rheumatology (ACR) COVID-19 Vaccine Clinical Guidance Task Force, along with 12 other specialists from rheumatology, infectious disease and public health. Led by Jeffrey Curtis, MD, MS, MPH, at the University of Alabama at Birmingham, this group had the tall task of drafting guidance for rheumatology providers on vaccinating IMID patients against COVID-19 in the absence of data. The guidance summary was released on February 11, 2021 and discussed at a town hall hosted by the ACR on February 16. The peer-reviewed manuscript was published in Arthritis & Rheumatology on March 17, 2021.1 Overall, we intended this document to provide guidance and to serve as a basis for shared and informed discussion between rheumatologists and their patients. We intend it to be a living document and will update it as new data emerges.

To that end, we undertook a multidisciplinary study to evaluate vaccine response in specific IMID populations. Of pressing clinical concern is our lack of data on vaccine response in numerous special populations who were underrepresented or censored from the pivotal trials of each currently available COVID-19 vaccine. In collaboration with the Lederman/Freeman lab at Case Western Reserve University, this pilot study examines humoral and cellular immune responses to COVID-19 vaccination in anti-neutrophil cytoplasmic autoantibody-associated vasculitis and rheumatoid arthritis patients receiving rituximab, as well as common variable immunodeficiency patients receiving immunoglobulin replacement, in order to increase our understanding of the adaptive immune host response to vaccination, and to provide data and insights for patients and providers regarding vaccination. Thus far, there have been several reports of reduced immunogenicity after a single dose of a COVID-19 mRNA vaccine in solid organ transplant patients.2,3 Small studies examining vaccine responses in IMID patients provide reassurance of safety and efficacy; however, these were small studies.4,5

Post-acute sequelae of COVID-19

Finally, the entity now referred to as Post-Acute Sequelae of COVID-19 (PASC) is one that rheumatologists will encounter with increasing frequency.6 In PASC, patients suffer from persistent symptoms after recovering from the acute phase of infection. Most commonly, symptoms of PASC include fatigue, brain fog, shortness of breath, musculoskeletal pain and autonomic dysfunction. These lingering symptoms can be debilitating and may prevent previously healthy persons from returning to work. Even more puzzling is that patients with PASC often had a fairly mild infection course with COVID-19.

Cleveland Clinic has launched the ReCOVer Clinic, an effort led by Kristin Englund, MD, for evaluation of patients with PASC, which involves collaboration across specialists from 18 different clinical areas. This is likely to have a great impact on the field of rheumatology, and we already have been seeing a growing number of patients. This collaboration not only serves to help patients, but also helps providers gain insight into the many unanswered questions about PASC, including immunopathogenesis, risk factors and optimal management. The clinic is currently seeing patients by referral from Cleveland Clinic providers, but plans to expand in the future.

References

1. Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology Guidance for COVID-19 Vaccination in Patients with Rheumatic and Musculoskeletal Diseases – Version 1. Arthritis Rheumatol. 2021 Mar 17. doi: 10.1002/art.41734. Online ahead of print.
2. Boyarsky BJ, Werbel WA, Avery RK et al. Immunogenicity of a Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. 2021 Mar 15;e214385.
3. Benotmane I, Gauiter-Vargas G, Cognard N, et al. Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients. Kidney Int. 2021 Mar 25;S0085-2538(21)00348-3.
4. Geisen UM, Berner DK, Tran F, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021 Mar24;annrheumdis-2021-220272.
5. Boyarsky BJ, Ruddy JA, Connolly CC, et al. Antibody response to a single dose of SARS-CoV-2 mRNA vaccine in patients with rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2021 Mar 21;annrheumdis-2021-220289.
6. del Rio C, Collins LF, Malani P. Long-term health consequences of COVID-19. JAMA. 2020 Oct 5; 324(17):1723-1724.