Coronavirus Disease 2019

Update on Coronavirus Disease 2019 Outcomes and Vaccine Efficacy in Patients With Immune-Mediated Inflammatory Disease

Jeffrey A. Sparks; Zachary S. Wallace; Philip C. Robinson


Curr Opin Rheumatol. 2021;33(5):412-418. 

In This Article

Rheumatic Diseases

Rheumatic diseases are broadly characterized by autoimmunity, systemic inflammation and fibrosis -- also identified to be prominent features of COVID-19 even early in the pandemic.[13,14] Throughout the pandemic, there has been intense interest in re-purposing immunomodulatory medications, such as hydroxychloroquine, tocilizumab and baricitinib as therapies for COVID-19.[10,15,16] Some rheumatic disease manifestations, such as interstitial lung disease and acquired comorbid conditions, such as cardiovascular disease may place people with rheumatic diseases susceptible to infection and poor outcomes from COVID-19.[11,17] Thus, studying the intersection of rheumatic diseases and COVID-19 has been of intense interest. However, this also offered challenges as rheumatic diseases are both uncommon and heterogeneous.

One of the first reports of rheumatic disease and COVID-19 was a case series mostly consisting of inflammatory arthritis who seemed to mostly have a mild disease course.[18] Another case series showed that most people with systemic lupus erythematosus (SLE) did not develop COVID-19 and only a very few had poor outcomes.[19] However, two comparative studies suggested that rheumatic disease patients may be at increased risk for mechanical ventilation compared with general population controls.[20,21] Risks for hospitalization and mortality were similar in both of those small studies. In a large nationwide English study OpenSAFELY, people with rheumatoid arthritis (RA), lupus, or psoriasis were identified to have a modest but statistically significantly increased risk for mortality (hazard ratio 1.19).[11] However, the identification of these diseases using administrative codes alone may be prone to misclassification and the three conditions are quite heterogeneous. Thus, the associations of specific rheumatic diseases with COVID-19-related mortality is not clear. A large study analyzed multiple electronic health records compared people with rheumatic disease to age-matched and sex-matched comparators.[12] This study found that people with rheumatic diseases were at increased risk for many poor outcomes including hospitalization, intensive care unit admission, acute kidney injury and venous thromboembolism.[12] Most associations were attenuated or eliminated after adjustment for comorbidities, suggesting that these mediated the relationship between rheumatic diseases and poor COVID-19 outcomes.

These studies were mostly performed early in the pandemic when hospital systems were commonly overwhelmed and the clinical benefits of drugs, such as remdesivir and dexamethasone were not yet established.[22,23] Two studies showed that the excess risk of mechanical ventilation and other poor COVID-19 outcomes improved over calendar time.[24,25] This suggests that people with rheumatic disease may have similar outcomes to the general population later in the pandemic now with effective treatments and health system capacity. A nationwide study in Sweden showed that the excess relative risk of mortality for RA and other inflammatory joint diseases was relatively stable in 2020 compared with earlier years.[26] People with RA or other inflammatory joint diseases had slightly higher rates of severe COVID-19 outcomes, such as hospitalization, ICU admission, and mortality but these were infrequent and generally not statistically different than general population comparators.[26] Another matched comparative study of hospitalized patients suggested that severe COVID-19 outcomes were more common in connective tissue diseases, such as SLE than general population controls; inflammatory arthritis had similar outcomes to their controls.[27] A meta-analysis reported that autoimmune disease patients had two-fold odds of COVID-19 than controls.[28] Overall, the current literature suggests that rheumatic diseases may modestly increase risk of severe COVID-19 compared with the general population.

The COVID-19 Global Rheumatology Alliance (GRA) formed early in the pandemic and allowed physicians to voluntarily enter cases of COVID-19 in rheumatic patients.[4–6] After an initial, early descriptive report of 110 patients, the first large GRA paper with 600 patients investigated risk factors for hospitalization among rheumatic patients.[29,30] This verified general population risk factors for severe COVID-19, such as older age and comorbidities.[29] This also showed that baseline use of glucocorticoids were associated with increased odds of hospitalization.[29] Importantly, biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs), particularly tumor necrosis factor inhibitors (TNFi) were associated with lower odds of hospitalized COVID-19 compared with no DMARDs.[29] Other reports also support this finding seen with TNFi.[31] Similar findings implicating glucocorticoids with worse COVID-19 outcomes were reported in a large single-center study in New York City.[32] This offered early reassurance to patients and clinicians that use of these medications were not clearly associated with poor outcomes.

A more recent, larger GRA study that included 3729 patients showed that higher baseline rheumatic disease activity was associated with higher odds of COVID-19-related mortality.[33,34] This study also showed that rituximab and sulfasalazine were each associated with higher odds of COVID-19-related mortality than methotrexate monotherapy. In another French cohort study, rituximab use in rheumatic diseases was also associated with higher risk of severe COVID-19 outcomes than rheumatic diseases not treated with rituximab.[35] These poor outcomes may be because of prolonged SARS-CoV-2 infection related to B-cell depletion and impaired antibody response. Some reports have suggested that immunocompromised patients, particularly those on rituximab, may be a reservoir for prolonged SARS-CoV-2 infection that may result in accelerated viral evolution that has resulted in variants that could increase virulence and evade vaccination efforts.[36] Thus, rheumatic patients and other immunocompromising states are likely to remain a central player as the pandemic continues to unfold. Finally, the differences in outcome based on race and ethnicity seen in the wider population has also been reflected in the rheumatic disease population, likely mediated by multiple medical and nonmedical factors.[37]