Rheumatic Disease Drugs Help COVID Virus Stick Around Longer, Study Suggests

Drugs commonly used to treat systemic autoimmune rheumatic diseases (SARDs) may keep the SARS-CoV-2 circulating after COVID-19 infection in patients with these conditions, with researchers documenting substantially increased viral antigen persistence compared with other post-COVID patients.

Tests for 40% of SARDs patients remained positive for at least one SARS-CoV-2 antigen 3 months after infection in one prospectively assembled cohort, compared with 17.5% of COVID-19 patients without SARDs from a separate prospective study, according to Naomi Patel, MD, MPH, of the Mass General Brigham health system in Boston, and colleagues.

At 6 months post-infection, corresponding rates were 30.7% versus 24.7%, the group reported in Arthritis & Rheumatology.

Most striking were the differing rates of nucleocapsid protein positivity. This antigen is not included in vaccines and therefore derives solely from the SARS-CoV-2 virus. It continued to be detected in almost 20% of the SARDs cohort after 6 months, compared with just 2.5% of the non-SARDs cohort, for an odds ratio of 6.62 (95% CI 1.09-40.30) after adjusting for demographic and clinical parameters. Similar differences were also seen for persistence of S1 and Spike proteins, Patel and colleagues found, but the odds ratios did not reach significance after adjustment.

Importantly, the authors noted, the increased viral antigen persistence in SARDs patients “could not be explained by demographics, variant, vaccination status, or receipt of acute COVID-19 treatment.” Moreover, no association could be demonstrated between antigen persistence and post-acute sequelae of COVID-19 (also called long COVID).

All patients in the SARDs cohort were on some type of immunosuppressive treatment, so it was unclear to whether these medications helped the virus to linger. But Patel and colleagues suggested that they may, as a way to explain the persistence of nucleocapsid antigens specifically. They observed that, between months 3 and 6 post-infection, rates of nucleocapsid positivity remained nearly the same in the SARDs cohort, whereas in the non-SARDs group, they declined (albeit the absolute numbers were in the single digits).

“We hypothesize that these findings largely relate to immunosuppressive medication use at or prior to COVID-19 infection, given that prior studies generally found that COVID-19 outcomes do not differ by individual SARD,” the investigators wrote, while acknowledging that other factors such as comorbidities also might contribute.

Patel and colleagues didn’t propose that SARDs patients stop their regular medications following COVID-19 infection, or indeed any other clinical takeaways. They did call for additional research to examine in more detail the longer-term effects of immunosuppressive therapies in COVID-19, as well as to explore “whether there may be any impact of dysregulated immunity in individuals with SARDs independent of immunosuppressive medications.”

Study Details

The investigators performed new analyses of data from two cohorts: RheumCARD (n=210), a set of SARDs patients seen at Mass General Brigham who developed COVID-19, and RECOVER-Adult (n=348), a national cohort that has enrolled more than 10,000 COVID-19 patients. Participants included in the current study were those who had follow-up visits with blood sampling at 3 and 6 months. Both cohorts used the same viral antigen assays.

Mean age in RheumCARD was 56 compared with 45 in RECOVER-Adult, and more of the former cohort were women. RheumCARD patients were also more predominantly white and were more likely to have cardiovascular disease or malignancies. Most people in both cohorts had received COVID-19 vaccines at least once. About two-thirds in both had COVID-19 involving the Omicron variant.

In RheumCARD, 61% had some form of inflammatory arthritis, 23% a connective tissue disease, and 8% vasculitis, with the rest having something else or multiple conditions. Nearly 90% were on some kind of disease-modifying agent, and more than half were taking a targeted drug. About 70% were in remission or had low disease activity at enrollment.

Limitations to the study included small numbers of patients with viral persistence, especially in RECOVER-Adult (e.g., only two members positive for nucleocapsid antigen at month 6), precluding meaningful subgroup analyses. RheumCARD did not track individual members’ results over successive visits, precluding longitudinal analyses. Because vaccination affects S1 and Spike protein titers, the results for those antigens were hard to interpret.