Rheumatic Disease and COVID-19: Who Is at Risk?

Patients with rheumatic and inflammatory diseases who develop COVID-19 share risk factors for severe disease with the larger population, including older age, male sex, obesity, and hypertension, but also are at increased risk if they are on corticosteroids, French investigators reported.

In a multivariable analysis, severe COVID-19 was associated with older age (OR 1.08, 95% CI 1.05-1.10), high body mass index (OR 1.07, 95% CI 1.02-1.12), and hypertension (OR 1.86, 95% CI 1.01-3.42), while female sex was protective (OR 0.45, 95% CI 0.25-0.80), according to Eric Hachulla, MD, PhD, of the Université de Lille, and colleagues.

But the use of corticosteroids at any dose among patients with inflammatory rheumatic or musculoskeletal diseases was associated with significantly higher risks for developing severe COVID-19 (OR 1.97, 95% CI 1.09-3.54), the investigators reported online in Annals of the Rheumatic Diseases.

“There is a concern that patients undergoing immunosuppressive therapy for inflammatory rheumatic and musculoskeletal diseases could be more vulnerable to SARS-CoV-2 infection and hospitalization than the general population, particularly in those patients with comorbidities such as diabetes, chronic obstructive pulmonary disease, and renal failure,” they wrote.

A few recent studies have examined the possibility that patients with inflammatory diseases are at risk for severe disease or mortality from COVID-19, suggesting that outcomes may be worse among those on corticosteroids but not for those being treated with biologics such as tumor necrosis factor (TNF) inhibitors. However, these studies were limited by small patient populations.

Therefore, to more fully explore the factors that contribute to severe outcomes with COVID-19 in patients with these underlying diseases, Hachulla and colleagues conducted a retrospective analysis of 694 patients enrolled in a national consortium of confirmed or highly suspected cases of COVID-19.

The most common underlying disease was inflammatory arthritis, but small numbers of many other diseases also were included, such as vasculitis, systemic lupus erythematosus, and autoinflammatory disease.

Two-thirds of patients were women, and mean age was 56. One or more comorbidities were present in 71%, which most commonly were hypertension, obesity, and respiratory or cardiovascular diseases.

Among patients with a polymerase chain reaction (PCR)- or serology-confirmed diagnosis of COVID-19, disease was mild (ambulatory) in 47%, moderate (hospitalized but not in the intensive care unit) in 34%, and severe (intensive care unit or deceased) in 19%.

Among the entire cohort — both confirmed and suspected cases of COVID-19 — the frequency of severe disease was 12.5%. Increasing age was an important driver of disease severity, the investigators noted. For patients ages 18 to 54, only 11 developed severe disease, but the number rose to 20 in those ages 65 to 74 (OR 6.46, 95% CI 2.97-14.06) and to 45 in those older than 75 (OR 19.82, 95% CI 9.69-40.52).

Comorbidities associated with severe COVID-19 included:

• Morbid obesity (BMI ≥40), OR 4.10 (95% CI 1.28-13.11)
• Diabetes, OR 2.14 (95% CI 1.12-4.12)
• Hypertension, OR 2.30 (95% CI 1.34-3.96)
• Interstitial lung disease, OR 2.87 (95% CI 1.06-7.80)
• Chronic renal failure, OR 3.22 (95% CI 1.51-6.90)

Compared with patients whose underlying diagnosis was inflammatory arthritis, higher risk for severe disease was seen in patients with vasculitis (OR 2.25, 95% CI 1.13-4.41) and autoinflammatory disease (OR 7.88, 95% CI 1.39-37.05).

For specific medications, the increased risk seen with corticosteroid treatment also was observed for mycophenolate mofetil (Cellcept; OR 7.67, 95% CI 1.73-28.04) and rituximab (Rituxan; OR 4.34, 95% CI 1.77-10.63). Risks for severe disease were not associated with treatment with TNF inhibitors, interleukin-6 blockers, methotrexate, or hydroxychloroquine.

Increased likelihood of hospitalization was observed in a multivariate analysis for diabetes, high body mass index, and use of corticosteroids or colchicine, while female sex and use of TNF inhibitors were associated with a lower risk for hospitalization.

There were 58 deaths in the cohort, for an overall mortality rate of 8.3%. This did not differ significantly from the death rate for controls without underlying rheumatic/inflammatory diseases in the Lille University Hospital COVID-19 Research Network (OR 1.45, 95% CI 0.87-2.42). Deaths were more frequent, however, in patients who were older and who had comorbidities including interstitial lung disease, coronary heart disease, and diabetes.

The finding that corticosteroid use was associated with the development of severe COVID-19 was similar to what has been seen in other studies of rheumatic/musculoskeletal diseases and inflammatory bowel disease. Nonetheless, methylprednisolone and dexamethasone have been helpful in patients who develop the very severe COVID cytokine storm, suggesting “that the beneficial or aggravating effect of corticosteroids is a matter of timing,” the investigators wrote.

“In addition to monitoring the evolution of COVID-19 severity and outcomes, we confirmed the impact of comorbidities within the population with inflammatory rheumatic and musculoskeletal diseases and generated preliminary data on the effects of antirheumatic therapies on disease prognosis following SARS-CoV-2 infection,” they concluded.

A limitation of the study was the possibility of selection bias, they acknowledged.