Switch From DEXA6 to High-Dose CS, Anakinra Ineffective in COVID-19 Pneumonia

Patients with COVID19 pneumonia receiving high-dose CS or anakinra had higher in-hospital mortality than those who continued with low-dose CS.

In patients with COVID-19 pneumonia whose respiratory function worsened or was persistently poor when treated with dexamethasone 6 mg daily (DEXA6), escalating immunosuppression with high-dose corticosteroids (CS) or anakinra is not associated with decreased mortality, according to study findings reported in the International Journal of Infectious Diseases.

The retrospective cohort study compared the effectiveness and safety of intensifying immunosuppression or continuing the DEXA6 protocol in patients who were hospitalized with COVID-19 pneumonia and were not responding to DEXA6.

Participants were adults admitted to the hospital from March 1, 2020, to December 31, 2020, with a positive polymerase chain reaction finding for SARS-CoV-2 within 3 weeks before admission or during the hospitalization. Data on exposures, outcomes, and covariates of interest were obtained from the Kaiser Permanente Southern California Research Data Warehouse and the Kaiser Permanente Northern California Virtual Data Warehouse.

Low-dose CS use was defined as a total daily dose of 6 to 10 mg of dexamethasone or equivalent doses of other corticosteroids, and high-dose corticosteroid use was defined as a total daily dose of greater than 10 mg of dexamethasone or the equivalent doses of other corticosteroids.

In-hospital death was the primary outcome. Hospital length of stay, total duration of mechanical ventilation, and infectious complications were secondary outcomes.

The analysis included 6671 participants (mean [SD] age, 61.4 [15.3] years; 61.4% male). About 94% (n=6265) of participants whose respiratory status deteriorated or continued to be poor while being treated with low-dose CS remained on low-dose CS, 232 (3.5%) patients escalated to use of high-dose CS, and 174 (2.6%) initiated anakinra use within 48 hours of deterioration.

Patients who received high-dose CS (41.9%; 95% CI, 35.5%-48.3%) or anakinra (32.8%; 95% CI, 25.8%-39.7%) had a higher crude in-hospital mortality rate vs those in the low-dose group (26.2%; 95% CI, 25.1%-27.3%). These differences also were significant in the propensity score (PS)-adjusted models for use of high-dose CS (odds ratio [OR], 1.53; 95% CI, 1.14-2.07) and anakinra (OR, 1.76; 95% CI, 1.13-2.72).

The anakinra and high-dose CS groups had a significantly longer average length of hospital stay vs the low-dose CS group in PS-adjusted models (4.8 and 2.3 days, respectively). No significant difference in ventilator days occurred for the high-dose or anakinra group compared with the low-dose group.

In crude and PS-adjusted models, anakinra use (PS-adjusted OR, 2.00; 95% CI, 1.28-3.11) or high-dose CS use (PS-adjusted OR, 1.43; 95% CI, 1.00-2.04) was associated with greater odds of hospital-acquired infections compared with remaining on low-dose CS during deterioration.

Sensitivity analyses adjusted for the highest C-reactive protein values within 24 hours of deterioration in 4896 (73.4%) participants demonstrated similar findings. Anakinra use (adjusted OR, 1.94; 95% CI, 1.22-3.07) and high-dose CS use (adjusted OR, 1.71; 95% CI, 1.20-2.44) were associated with higher odds of in-hospital mortality vs continuing with low-dose CS during deterioration.

The main study limitation, according to the researchers, is that the findings of increased odds of in-hospital infections and mortality, especially in patients treated with anakinra, may be explained by unmeasured confounders. Other limitations include the relatively small number of patients who escalated to high-dose CS or anakinra after respiratory status deterioration or persistence. In addition, it is uncertain whether the study findings are applicable to patients with the omicron other variants of COVID-19 or to vaccinated populations in which fewer patients have severe respiratory impairment.

Study authors concluded that “Our findings do not support escalating patients with COVID-19 pneumonia who deteriorate on low-dose corticosteroids to high-dose corticosteroids or anakinra.” Moreover, “These findings add to the growing literature supporting DEXA6 as the dose of choice for COVID-19 pneumonia patients requiring supplemental oxygen,” the investigators stated.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Langer-Gould A, Xu S, Myers LC, et al. Anakinra or high-dose corticosteroids in COVID-19 pneumonia patients who deteriorate on low-dose dexamethasone: an observational study of comparative effectiveness. Int J Infect Dis. Published online November 18, 2022. doi: 10.1016/j.ijid.2022.11.017