tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2024 Jan 3;11(2)
fad630.
doi: 10.1093/ofid/ofad630. eCollection 2024 Feb. Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial
Jennifer Hendrick[SUP] 1 [/SUP], Jennie Z Ma[SUP] 2 [/SUP], Heather M Haughey[SUP] 3 [/SUP], Rachael Coleman[SUP] 1 [/SUP], Uma Nayak[SUP] 4 [/SUP], Alexandra Kadl[SUP] 3 5 [/SUP], Jeffrey M Sturek[SUP] 3 [/SUP], Patrick Jackson[SUP] 1 [/SUP], Mary K Young[SUP] 1 [/SUP], Judith E Allen[SUP] 6 [/SUP], William A Petri[SUP] 1 7 8 [/SUP]
Affiliations
Background: We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions.
Methods: Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk test (6MWT) at the 1-year visit.
Results: Of those survivors who consented to 1-year visits (n = 16), subjects who had originally received dupilumab were less likely than those who received placebo to have an abnormal DLCO or 6MWT (Fisher exact P = .011; adjusted P = .058). As a secondary endpoint, we saw that 16% of subjects in the dupilumab group died by 1 year compared to 38% in the placebo group, though this was not statistically significant (log-rank P = .12). We did not find significant differences in neurocognitive testing, symptoms, or chest computed tomography between treatment groups but observed a larger reduction in eotaxin levels in those who received dupilumab.
Conclusions: In this observational study, subjects who received dupilumab during acute COVID-19 hospitalization were less likely to have a reduced DLCO or 6MWT, with a nonsignificant trend toward reduced mortality at 1 year compared to placebo.
Keywords: COVID-19; dupilumab, post COVID conditions; pulmonary function; type 2 immunity.
. 2024 Jan 3;11(2)
fad630.doi: 10.1093/ofid/ofad630. eCollection 2024 Feb. Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial
Jennifer Hendrick[SUP] 1 [/SUP], Jennie Z Ma[SUP] 2 [/SUP], Heather M Haughey[SUP] 3 [/SUP], Rachael Coleman[SUP] 1 [/SUP], Uma Nayak[SUP] 4 [/SUP], Alexandra Kadl[SUP] 3 5 [/SUP], Jeffrey M Sturek[SUP] 3 [/SUP], Patrick Jackson[SUP] 1 [/SUP], Mary K Young[SUP] 1 [/SUP], Judith E Allen[SUP] 6 [/SUP], William A Petri[SUP] 1 7 8 [/SUP]
Affiliations
- PMID: 38312212
- PMCID: PMC10834240
- DOI: 10.1093/ofid/ofad630
Background: We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions.
Methods: Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk test (6MWT) at the 1-year visit.
Results: Of those survivors who consented to 1-year visits (n = 16), subjects who had originally received dupilumab were less likely than those who received placebo to have an abnormal DLCO or 6MWT (Fisher exact P = .011; adjusted P = .058). As a secondary endpoint, we saw that 16% of subjects in the dupilumab group died by 1 year compared to 38% in the placebo group, though this was not statistically significant (log-rank P = .12). We did not find significant differences in neurocognitive testing, symptoms, or chest computed tomography between treatment groups but observed a larger reduction in eotaxin levels in those who received dupilumab.
Conclusions: In this observational study, subjects who received dupilumab during acute COVID-19 hospitalization were less likely to have a reduced DLCO or 6MWT, with a nonsignificant trend toward reduced mortality at 1 year compared to placebo.
Keywords: COVID-19; dupilumab, post COVID conditions; pulmonary function; type 2 immunity.