Prednisone, but not biologic use, tied to increased COVID-19 severity

Use of prednisone prior to SARS-CoV-2 diagnosis may be linked to a higher risk of severe COVID-19 outcomes such as hospitalization, intensive care unit (ICU) admission, and death, according to a retrospective community-based study.

“Outpatient use of prednisone was associated with severe illness after diagnosis with SARS-CoV-2,” presented Dr Fernando Velayos from the Kaiser Permanente San Francisco Medical Center, San Francisco, California, US, at DDW 2021.

“Our results suggest the optimal patient management of immune-modifying therapies during the COVID-19 pandemic should focus on minimizing outpatient steroids where possible,” said Velayos and co-authors.

The researchers used the Kaiser Permanente Northern California database to identify 39,686 adults (52.1 percent female, 42.2 percent age 30–49 years, 49 percent Hispanic) who had a positive SARS-CoV-2 PCR nasal swab between 25 February and 9 September, 2020. Outpatient use of medications with immunosuppressive potential (prednisone, small molecule or biologic therapy, or immunomodulators) for treatment of ulcerative colitis, Crohn’s disease, rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, lupus, or autoimmune hepatitis, or prevention of solid organ transplant rejection in the 105 days before SARS-CoV-2 diagnosis was determined through electronic pharmacy records.

About 73 percent of patients had no comorbidities (Charlson score 0) and 29.0 and 42.6 percent were overweight and obese, respectively.

A total of 958 patients (2.4 percent) used prednisone, 327 (0.8 percent) used immunomodulators, 47 (0.1 percent) small molecule therapy, and 152 (0.4 percent) biologic therapy. The most common immune condition was asthma (12.8 percent).

A total of 3,977 patients had at least one severe outcome (hospitalization, ICU admission, or death) in the 45 days after SARS-CoV-2 diagnosis (46.1 percent female, 68.8 percent age >55 years).

After adjustment for COVID-19 risk factors, use of prednisone prior to SARS-CoV-2 diagnosis was associated with an increased risk of any severe outcome (odds ratio [OR], 1.31, 95 percent confidence interval [CI], 1.08–1.60), specifically hospitalization (OR, 1.32, 95 percent CI, 1.08–1.60), ICU admission (OR, 1.84, 95 percent CI, 1.38–2.46), or death (OR, 1.70, 95 percent CI, 1.17–2.47). [DDW 2021, abstract 252]

Conversely, immunomodulator therapy use was not associated with an increased risk of severe outcomes (composite: OR, 0.88), nor was small molecule or biologic therapy use (composite: OR, 1.26), with no significant increased risk noted with any of the individual outcomes.

Inflammatory bowel disease was not associated with increased risk of any of the outcomes (composite: OR, 1.22). There was a borderline increased risk of hospitalization among patients with asthma (OR, 1.11), organ transplantation was associated with an increased risk of the composite outcome, and specifically hospitalization (ORs, 1.84 and 1.86, respectively), and psoriasis was tied to an increased risk of ICU admission (OR, 1.63). In contrast, spondyloarthropathy was associated with a reduced risk of the composite (OR, 0.37) and individual outcomes.

In a subgroup analysis, prednisone as monotherapy was tied to an increased risk of any severe outcome (OR, 1.25), though no risk was noted with either immunomodulator or small molecule/biologic monotherapy (ORs, 0.76 and 0.82, respectively). The combination of prednisone and small molecule/biologic therapy was tied to a greater risk of severe outcomes (OR, 3.57), though only few patients were on this combination (n=17).

“Suppression of the immune system is a potential major risk factor for severe and fatal infection due to SARS-CoV-2,” explained Velayos.

“[While] immunosuppressive therapy is necessary to control a dysregulated immune system in a variety of immune-mediated diseases and after organ transplantation, patients fear that the therapy … may also impair the immune system and could allow SARS-CoV-2 to spread unchecked,” he continued. Due to this concern, some patients have chosen to change or cease their immunotherapy regimens.

“Our data should reassure patients that most of these therapies that are non-steroids do not appear to increase the odds of severe illness if diagnosed with SARS-CoV-2. Therefore, stopping, reducing, or altering treatments is unlikely to significantly reduce the odds of severe illness,” Velayos concluded.

Most immune-mediated diseases also do not seem to increase the risk of severe outcomes, he added. However, the risks may be elevated in certain subgroups of patients and these groups should be identified and targeted for mitigating strategies.