Department of Anesthesiology and Intensive Care Medicine, University Medical Center Göttingen, Göttingen, Germany.
Université Paris 7 Cité Sorbonne, UMR INSERM 1160, Paris, France.
Front Immunol. 2021 Nov 1;12:753849. doi: 10.3389/fimmu.2021.753849. eCollection 2021.
CD14+ monocytes present antigens to adaptive immune cells monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy.
We report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected , were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of . A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70.
Superinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient's own immunity by IFNγ was a plausible option to boost the patient's immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies.
After a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.
CD14+单核细胞将抗原呈递给适应性免疫细胞——单核细胞人类白细胞抗原受体（mHLA-DR），这被描述为免疫突触。mHLA-DR 水平降低可显示获得性免疫缺陷，这种缺陷在脓毒症中很常见，易继发感染和导致致命结局。单核细胞 HLA-DR 表达可被干扰素-γ（IFNγ）治疗可靠诱导。
我们报告了一例在体外膜肺氧合（ECMO）支持下发生的多重耐药超级感染 COVID-19 急性呼吸窘迫综合征（ARDS）病例。检测到的 ， 对所有四类抗生素（包括碳青霉烯类）耐药，而 则对头孢地尔肟耐药。没有有效的因果治疗抗生素策略。因此，我们测量了患者的免疫状态，以确定潜在的获得性免疫缺陷。通过 FACS 分析鉴定的单核细胞 HLA-DR 表达显示 34%的阳性单核细胞表达水平，提示严重的免疫抑制。我们给予 IFNγ 治疗，结果 mHLA-DR 表达迅速增加（96%），侵袭性血流感染迅速得到解决，患者于第 70 天出院。
超级感染是 COVID-19 肺炎的一种危险并发症，而脓毒症引起的免疫抑制是其危险因素。免疫抑制表现为单核细胞向适应性免疫系统细胞的抗原呈递紊乱。本例之所以引人注目，是因为针对导致 COVID-19 ARDS 患者严重肺炎和血流感染的细菌病原体，不存在经过验证的抗生素方案。通过 IFNγ 恢复患者自身免疫可能是增强患者免疫系统、消除鉴定出的 4MRGNs 并允许肺部恢复的可行选择。这得出结论，免疫状态监测对复杂 COVID-19-ARDS 有用，同时 IFNγ 治疗可能支持抗生素策略。
在通过抑制 mHLA-DR 水平检测到免疫系统受损后，可通过 IFNγ 安全地重新激活免疫系统。
