Distinct systemic immune networks define severe vs. mild COVID-19 in hematologic and solid cancer patients.
Distinct systemic immune networks define severe vs. mild COVID-19 in hematologic and solid cancer patients.
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DOI：
10.3389/fimmu.2022.1052104
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
由冠状病毒SARS-CoV-2引起的COVID-19大流行已影响到社会各阶层的健康。细胞因子释放综合征，加上先天免疫细胞对直接对抗病毒的低效反应，是严重形式的COVID-19的特征。虽然在普通人群中参与严重COVID-19发展的免疫因素越来越清楚，但对肿瘤患者严重疾病背后的免疫机制的识别仍然不确定。在这里，我们通过分析可溶性血液免疫因子和抗SARS-CoV-2抗体来评估肿瘤患者在SARS-CoV-2诊断阳性早期的全身免疫反应。死于COVID-19的血液恶性肿瘤患者在诊断时表现为严重的白细胞减少，针对SARS-CoV-2蛋白的抗体产生低，先天免疫细胞募集和激活因子的产生升高。这些患者也显示出以IL-2、IL-13、tnf - α、ifn - γ和FGF2为焦点的相关网络。以IL-4、IL-5、IL-12A、IL-15和IL-17A为核心的抗sars - cov -2抗体产生高度网络化和协调的血液学癌症患者，仅出现轻度COVID-19。相反，炎症细胞因子IL-6、CXCL8水平升高、抗病毒抗体协同产生丧失的实体瘤患者发展为严重的COVID-19并死亡。在抗病毒抗体和涉及IL-10和炎症细胞因子的调节轴之间显示正相关网络的患者从疾病中恢复。我们还提供证据表明，CXCL8是肿瘤患者死亡的一个强有力的预测因子，可能是SARS-CoV-2感染诊断阳性后几天内预后不良的一个指标。我们的研究结果定义了与癌症和COVID-19患者的临床结果相关的不同的全身免疫谱。这些系统性免疫网络揭示了与疾病结果相关的潜在免疫机制，并确定了潜在的临床有用的生物标志物。
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain. Here we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients. Individuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection. Our findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.
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影响因子：
12.4
作者：
Ha H;Debnath B;Neamati N
通讯作者：
Neamati N
DOI：
10.4049/jimmunol.1003049
发表时间：
2011-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Goswami R;Kaplan MH
通讯作者：
Kaplan MH
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
5.5
作者：
Jackson DA;Elsawa SF
通讯作者：
Elsawa SF
影响因子：
4
作者：
Fernandes GA;Feriani D;França E Silva ILA;Mendonça E Silva DR;Arantes PE;Canteras JDS;da Silva RR;Curado MP
通讯作者：
Curado MP