The risk of developing severe COVID-19 is particularly high for patients with interstitial lung disease, according to US research that explored the association between different phenotypic subgroups of rheumatoid arthritis (RA) and disease severity.

The retrospective analysis found that patients with RA were 1.75 times more at risk of severe COVID-19 (hospitalisation or death) than the general population, but for those with ILD the risk was 2.5 times higher versus the control group.

The risk for severe COVID-19 was also found to be greater in RA patients who were seropositive (for anti-cyclic citrullinated peptide, rheumatoid factor, or both; HR 1·97) or had erosive disease (1·93) versus the comparator group, according to the paper, published in The Lancet Rheumatology.

“Our findings suggest that one driver of the increased risk of severe COVID-19 in patients with rheumatoid arthritis is the presence of interstitial lung disease or its treatment,” the authors noted.

“We found that all phenotypes with interstitial lung disease had a higher risk of severe COVID-19 outcomes than their matched comparators without rheumatoid arthritis. These differences were less obvious in the non-interstitial lung disease phenotypes”.

The authors suggested that the higher risk of severe COVID in patients with RA-associated ILD could be down to the parenchymal lung disease or exposure to medications such as rituximab or mycophenolate mofetil, which are known to be linked with poor COVID-19 outcomes. However, the trial was not able to assess this as patients in the comparator group had not been taking immunosuppressive medications.

The study included 582 patients with RA and 2,875 matched comparators, all of whom had COVID-19.

In the RA group, the mean age was 62 years, 72% were women, and 79% were White, 11% were Hispanic or Latino, and 7% were Black. Nine percent of the group had ILD, 68% were seropositive, and 27% had bone erosions.

Overall, severe COVID-19 was recorded for 22% of patients with RA, versus 13% in the comparator group.

The data also showed that: the risk of severe COVID-19 among women with RA was two-fold higher than for those without RA (HR 2·03), though this was not seen in men; that hospitalisations were significant higher in patients with RA than those without (2.90 versus 1.56 per 1,000 person days, respectively); and that mortality was also significantly higher for patients with RA compared to the comparator group (0.51 vs 0.23 per 1,000 person-days, respectively).

Key limitations of the study included potential under-representation of ethnic groups, and that the small number of patients with RA and ILD did not allow for additional analyses assessing the impact of differences in use of DMARDs, such as B-cell depleting agents, on outcomes.

However, the findings have “important implications for the management of patients with rheumatoid arthritis during the ongoing COVID-19 pandemic,” the investigators noted.

“Having rheumatoid arthritis should be considered a risk factor for severe COVID-19, but the severity of this risk might vary across phenotypes,” they stressed.