Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
J Innate Immun. 2022;14(3):218-228. doi: 10.1159/000519090. Epub 2021 Dec 1.
Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19.
In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints.
The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment.
Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS.
巨噬细胞活化综合征（MALS）和复杂免疫失调（CID）常为 COVID-19 中急性呼吸窘迫（ARDS）的基础。我们旨在研究个体化免疫疗法对危重症 COVID-19 临床改善的影响。
在这项开放标签的前瞻性试验中，筛选了 102 例由 SARS-CoV-2 引起的 ARDS 患者，以确定是否存在 MALS（铁蛋白>4420ng/ml）和 CID（铁蛋白≤4420ng/ml 且 CD14-单核细胞 HLA-DR 表达低）。对 MALS 或 CID 患者中伴有氨基转移酶升高者给予静脉内阿那白滞素；对 CID 且氨基转移酶正常者给予托珠单抗。主要终点为第 8 天序贯器官衰竭评估（SOFA）评分下降≥25%和/或呼吸比增加≥50%；28 天死亡率、第 28 天 SOFA 评分变化、血清生物标志物和单核细胞产生的细胞因子为次要终点。
阿那白滞素治疗组的主要研究终点为 58.3%，托珠单抗治疗组为 33.3%（p：0.01）。两组患者均接受地塞米松作为标准治疗。次要终点、死亡率和 SOFA 评分变化均无差异。阿那白滞素治疗组铁蛋白下降，托珠单抗治疗组白细胞介素-6、可溶性尿激酶型纤溶酶原激活物受体和 HLA-DR 表达增加。第 28 天存活的患者按 WHO 临床进展量表分布至较低严重程度水平。托珠单抗治疗组继发感染发生率较高。
免疫评估可使 COVID-19 危重症患者和 MALS 特征患者对阿那白滞素产生有利反应。
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