tetano
Editor, Senior Moderator
Crit Care Explor
. 2026 Jun 23;8(7):e1405.
doi: 10.1097/CCE.0000000000001405. eCollection 2026 Jul 1.
Impact of Fostamatinib on Inflammatory Biomarkers in Hospitalized Patients With COVID-19
Raquel S Da Cruz[SUP] 1 2 [/SUP], Heather L Teague[SUP] 1 2 [/SUP], Marcos J Ramos-Benitez[SUP] 3 [/SUP], Sonya J Malavez-Cajigas[SUP] 3 [/SUP], Trenton Williams[SUP] 1 2 [/SUP], Rui Miao[SUP] 4 5 [/SUP], Xin Tian[SUP] 4 [/SUP], Gefei Lin[SUP] 4 [/SUP], Laurence W Busse[SUP] 6 [/SUP], Akram Khan[SUP] 7 [/SUP], Ari Moskowitz[SUP] 8 [/SUP], David N Hager[SUP] 9 [/SUP], Todd W Rice[SUP] 10 11 [/SUP], Adit A Ginde[SUP] 12 [/SUP], Nicole M Iovine[SUP] 13 [/SUP], Peter Chen[SUP] 14 [/SUP], Basmah Safdar[SUP] 15 [/SUP], Kevin W Gibbs[SUP] 16 [/SUP], Ali Javaheri[SUP] 17 [/SUP], Marjolein de Wit[SUP] 18 [/SUP], Michelle Harkins[SUP] 19 [/SUP], Kris Hudock[SUP] 20 [/SUP], Lisa H Merck[SUP] 13 18 [/SUP], Aaron Barksdale[SUP] 21 [/SUP], Jeffrey M Sturek[SUP] 22 [/SUP], Harry Schrager[SUP] 23 [/SUP], Nathan I Shapiro[SUP] 24 [/SUP], Michael Lanspa[SUP] 25 [/SUP], Estelle Harris[SUP] 26 [/SUP], Subhashini Sellers[SUP] 27 [/SUP], Andrew J Goodwin[SUP] 28 [/SUP], Mark A Tidswell[SUP] 29 [/SUP], Michael R Filbin[SUP] 30 [/SUP], Matthew S Shotwell[SUP] 31 [/SUP], Matthew W Semler[SUP] 32 [/SUP], Wesley H Self[SUP] 11 33 [/SUP], Sean P Collins[SUP] 11 33 34 [/SUP], Jeffrey R Strich[SUP] 1 2 [/SUP]; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue Investigators
Affiliations
Objectives: Understanding the mechanistic impact of fostamatinib, a spleen tyrosine kinase inhibitor, in severe COVID-19 using biomarkers associated with disease severity is crucial for the development of host-directed therapeutics. We analyzed samples from a randomized clinical trial to investigate the impact of fostamatinib on multiple inflammatory biomarkers associated with COVID-19 disease severity.
Design: Secondary analyses of biomarkers from a randomized clinical trial.
Setting: Multicenter randomized clinical trial.
Patients: A total of 400 adults hospitalized with COVID-19 were enrolled in a phase 3 randomized clinical trial. Absolute neutrophil counts (ANCs) were analyzed across 392 patients and biomarkers were measured in 190 patients with available plasma samples.
Interventions: Adults hospitalized with COVID-19 were randomized to receive either fostamatinib (150 mg bid) or placebo. ANCs and 24 biomarkers were assessed at day 0 and over time using a multiplexed Meso Scale Discovery assay (Meso Scale Diagnostics LLC, Rockville, MD).
Measurements and main results: At day 0, participants with World Health Organization ordinal scale 5-7 had elevated ANC counts, compared with ordinal scale 4. In addition, the levels of neutrophil-associated biomarkers, inflammatory cytokines, and mediators of endothelial dysfunction at day 0 were increased in the participants who were ordinal scale 5-7 vs. ordinal scale 4. Randomization to fostamatinib compared with placebo resulted in a decrease in ANC and several neutrophil-associated biomarkers, pro-inflammatory cytokines, and mediators of endothelial dysfunction/tissue damage. This differential finding was also demonstrated in a subgroup of patients (n = 85) with a hypoinflammatory phenotype.
Limitations: Missing plasma samples and neutral phase 3 trial results.
Conclusions: Randomization to fostamatinib resulted in lower neutrophil counts and levels of circulating biomarkers in hospitalized patients with COVID-19; however, the observed impact of fostamatinib was modest compared with prior studies.
Keywords: COVID-19; fostamatinib; inflammatory biomarkers; spleen tyrosine kinase inhibitor.
. 2026 Jun 23;8(7):e1405.
doi: 10.1097/CCE.0000000000001405. eCollection 2026 Jul 1.
Impact of Fostamatinib on Inflammatory Biomarkers in Hospitalized Patients With COVID-19
Raquel S Da Cruz[SUP] 1 2 [/SUP], Heather L Teague[SUP] 1 2 [/SUP], Marcos J Ramos-Benitez[SUP] 3 [/SUP], Sonya J Malavez-Cajigas[SUP] 3 [/SUP], Trenton Williams[SUP] 1 2 [/SUP], Rui Miao[SUP] 4 5 [/SUP], Xin Tian[SUP] 4 [/SUP], Gefei Lin[SUP] 4 [/SUP], Laurence W Busse[SUP] 6 [/SUP], Akram Khan[SUP] 7 [/SUP], Ari Moskowitz[SUP] 8 [/SUP], David N Hager[SUP] 9 [/SUP], Todd W Rice[SUP] 10 11 [/SUP], Adit A Ginde[SUP] 12 [/SUP], Nicole M Iovine[SUP] 13 [/SUP], Peter Chen[SUP] 14 [/SUP], Basmah Safdar[SUP] 15 [/SUP], Kevin W Gibbs[SUP] 16 [/SUP], Ali Javaheri[SUP] 17 [/SUP], Marjolein de Wit[SUP] 18 [/SUP], Michelle Harkins[SUP] 19 [/SUP], Kris Hudock[SUP] 20 [/SUP], Lisa H Merck[SUP] 13 18 [/SUP], Aaron Barksdale[SUP] 21 [/SUP], Jeffrey M Sturek[SUP] 22 [/SUP], Harry Schrager[SUP] 23 [/SUP], Nathan I Shapiro[SUP] 24 [/SUP], Michael Lanspa[SUP] 25 [/SUP], Estelle Harris[SUP] 26 [/SUP], Subhashini Sellers[SUP] 27 [/SUP], Andrew J Goodwin[SUP] 28 [/SUP], Mark A Tidswell[SUP] 29 [/SUP], Michael R Filbin[SUP] 30 [/SUP], Matthew S Shotwell[SUP] 31 [/SUP], Matthew W Semler[SUP] 32 [/SUP], Wesley H Self[SUP] 11 33 [/SUP], Sean P Collins[SUP] 11 33 34 [/SUP], Jeffrey R Strich[SUP] 1 2 [/SUP]; Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) Host Tissue Investigators
Affiliations
- PMID: 42329789
- DOI: 10.1097/CCE.0000000000001405
Objectives: Understanding the mechanistic impact of fostamatinib, a spleen tyrosine kinase inhibitor, in severe COVID-19 using biomarkers associated with disease severity is crucial for the development of host-directed therapeutics. We analyzed samples from a randomized clinical trial to investigate the impact of fostamatinib on multiple inflammatory biomarkers associated with COVID-19 disease severity.
Design: Secondary analyses of biomarkers from a randomized clinical trial.
Setting: Multicenter randomized clinical trial.
Patients: A total of 400 adults hospitalized with COVID-19 were enrolled in a phase 3 randomized clinical trial. Absolute neutrophil counts (ANCs) were analyzed across 392 patients and biomarkers were measured in 190 patients with available plasma samples.
Interventions: Adults hospitalized with COVID-19 were randomized to receive either fostamatinib (150 mg bid) or placebo. ANCs and 24 biomarkers were assessed at day 0 and over time using a multiplexed Meso Scale Discovery assay (Meso Scale Diagnostics LLC, Rockville, MD).
Measurements and main results: At day 0, participants with World Health Organization ordinal scale 5-7 had elevated ANC counts, compared with ordinal scale 4. In addition, the levels of neutrophil-associated biomarkers, inflammatory cytokines, and mediators of endothelial dysfunction at day 0 were increased in the participants who were ordinal scale 5-7 vs. ordinal scale 4. Randomization to fostamatinib compared with placebo resulted in a decrease in ANC and several neutrophil-associated biomarkers, pro-inflammatory cytokines, and mediators of endothelial dysfunction/tissue damage. This differential finding was also demonstrated in a subgroup of patients (n = 85) with a hypoinflammatory phenotype.
Limitations: Missing plasma samples and neutral phase 3 trial results.
Conclusions: Randomization to fostamatinib resulted in lower neutrophil counts and levels of circulating biomarkers in hospitalized patients with COVID-19; however, the observed impact of fostamatinib was modest compared with prior studies.
Keywords: COVID-19; fostamatinib; inflammatory biomarkers; spleen tyrosine kinase inhibitor.