Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: A case series.
Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: A case series.
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DOI：
10.1016/j.medj.2021.09.003
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发表时间：
2021-10-08
期刊：
影响因子：
--
通讯作者：
Netea MG
中科院分区：
文献类型：
--
作者：
van Laarhoven A;Kurver L;Overheul GJ;Kooistra EJ;Abdo WF;van Crevel R;Duivenvoorden R;Kox M;Ten Oever J;Schouten J;van de Veerdonk FL;van der Hoeven H;Rahamat-Langendoen J;van Rij RP;Pickkers P;Netea MG
在免疫功能低下的2019冠状病毒病（COVID-19）患者中，已描述了持续的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）脱落，导致疾病持续和预后不良。目前还没有改善这组患者病毒清除率和结局的特异性治疗。5名重症COVID-19患者，细胞免疫反应严重缺陷，SARS-CoV-2病毒RNA载量高，呼吸无改善，接受干扰素γ治疗，100 μg皮下注射，每周三次。每48 h收集支气管分泌物用于常规诊断SARS-CoV-2 RT-PCR和病毒培养。γ干扰素给药后，SARS-CoV-2载量迅速下降，病毒培养物由阳性转为阴性。4例患者恢复，未观察到炎症过度体征。干扰素γ可被视为免疫功能低下的COVID-19患者亚组的辅助免疫疗法。A.v.L.和R.v.C.由美国国立卫生研究院（R 01 AI 145781）支持。GJO和R.P.V.R.由荷兰研究理事会（NWO）的维西拨款（016.VICI.170.090）支持。W.F. A由荷兰卫生研究与发展组织的临床奖学金（9071561）资助。M.G. N由ERC高级资助（833247）和荷兰科学研究组织的斯宾诺莎资助。在免疫系统受损的患者中，严重急性呼吸道综合征冠状病毒2（SARS-CoV-2），即引起2019冠状病毒病（COVID-19）的病毒，可以持续很长时间。这导致病程长和预后差。到目前为止，还没有治疗方法可以帮助清除病毒。干扰素γ是一种激活免疫系统细胞的蛋白质。我们对5名免疫系统受损的COVID-19患者应用了干扰素γ。这些患者病情危重，自身并没有清除病毒。干扰素γ治疗后，5名患者清除了SARS-CoV-2，4名患者临床痊愈。这份报告表明，干扰素γ应被视为免疫功能低下的COVID-19患者的研究候选人，这些患者无法自行清除病毒。货车Laarhoven等人报告了5名细胞免疫受损和持续高SARS-CoV-2载量的COVID-19患者，接受了最后的干扰素γ免疫治疗，随后5名患者的病毒清除和4名患者的临床康复。未观察到过度炎症体征。
Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding has been described in immunocompromised coronavirus disease 2019 (COVID-19) patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable. Five critically ill COVID-19 patients with severe defects in cellular immune responses, high SARS-CoV-2 viral RNA loads, and no respiratory improvement were treated with interferon gamma, 100 μg subcutaneously, thrice weekly. Bronchial secretion was collected every 48 h for routine diagnostic SARS-CoV-2 RT-PCR and viral culture. Interferon gamma administration was followed by a rapid decline in SARS-CoV-2 load and a positive-to-negative viral culture conversion. Four patients recovered, and no signs of hyperinflammation were observed. Interferon gamma may be considered as adjuvant immunotherapy in a subset of immunocompromised COVID-19 patients. A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781). G.J.O. and R.P.v.R. are supported by a VICI grant (016.VICI.170.090) from the Dutch Research Council (NWO). W.F.A. is supported by a clinical fellowship grant (9071561) of Netherlands Organization for Health Research and Development. M.G.N. is supported by an ERC advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. In patients with impaired immune systems, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), can persist for a long time. This contributes to a long disease course and poor outcome. Thus far, no therapy is available to help clear the virus. Interferon gamma is a protein that activates cells of the immune system. We applied interferon gamma to five COVID-19 patients with impaired immune systems. These patients were critically ill and did not clear the virus themselves. Interferon gamma therapy was followed by clearance of SARS-CoV-2 in five and clinical recovery in four patients. This report shows that interferon gamma should be considered as a study candidate for immunocompromised COVID-19 patients who are not able to clear the virus themselves. van Laarhoven et al. report five COVID-19 patients with impaired cellular immunity and persistently high SARS-CoV-2 loads, treated with last-resort interferon gamma immunotherapy, which was followed by viral clearance in five and clinical recovery in four patients. No signs of hyperinflammation were observed.
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DOI：
10.3390/v13020282
发表时间：
2021-02-11
期刊：
Viruses
影响因子：
--
作者：
Varghese FS;van Woudenbergh E;Overheul GJ;Eleveld MJ;Kurver L;van Heerbeek N;van Laarhoven A;Miesen P;den Hartog G;de Jonge MI;van Rij RP
通讯作者：
van Rij RP
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1016/j.xcrm.2020.100146
发表时间：
2020-12-22
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Rother N;Yanginlar C;Lindeboom RGH;Bekkering S;van Leent MMT;Buijsers B;Jonkman I;de Graaf M;Baltissen M;Lamers LA;Riksen NP;Fayad ZA;Mulder WJM;Hilbrands LB;Joosten LAB;Netea MG;Vermeulen M;van der Vlag J;Duivenvoorden R
通讯作者：
Duivenvoorden R
影响因子：
8.8
作者：
Armstrong-James, D.;Teo, I. A.;Shaunak, S.
通讯作者：
Shaunak, S.
影响因子：
6.4
作者：
Janssen, Nico A. F.;Grondman, Inge;van de Veerdonk, Frank L.
通讯作者：
van de Veerdonk, Frank L.