Despite widespread concern regarding cytokine storms leading to severe morbidity in COVID-19, rapid cytokine assays are not routinely available for monitoring critically ill patients. We report the clinical application of a digital protein microarray platform for rapid multiplex quantification of cytokines from critically ill COVID-19 patients admitted to the intensive care unit (ICU) at the University of Michigan Hospital. The platform comprises two low-cost modules: (i) a semi-automated fluidic dispensing/mixing module that can be operated inside a biosafety cabinet to minimize the exposure of the technician to the virus infection and (ii) a 12–12–15 inch compact fluorescence optical scanner for the potential near-bedside readout. The platform enabled daily cytokine analysis in clinical practice with high sensitivity (<0.4 pg mL⁻¹), inter-assay repeatability (∼10% CV), and rapid operation providing feedback on the progress of therapy within 4 hours. This test allowed us to perform serial monitoring of two critically ill patients with respiratory failure and to support immunomodulatory therapy using the selective cytopheretic device (SCD). We also observed clear interleukin-6 (IL-6) elevations after receiving tocilizumab (IL-6 inhibitor) while significant cytokine profile variability exists across all critically ill COVID-19 patients and to discover a weak correlation between IL-6 to clinical biomarkers, such as ferritin and C-reactive protein (CRP). Our data revealed large subject-to-subject variability in patients' response to COVID-19, reaffirming the need for a personalized strategy guided by rapid cytokine assays.

中文翻译：

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用于监测 COVID-19 细胞因子风暴的数字蛋白质微阵列

尽管人们普遍担心细胞因子风暴会导致 COVID-19 严重发病，但快速细胞因子测定通常无法用于监测危重患者。我们报告了数字蛋白微阵列平台的临床应用，用于对密歇根大学医院重症监护室 (ICU) 入住的重症 COVID-19 患者的细胞因子进行快速多重定量。该平台包括两个低成本模块：(i) 半自动流体分配/混合模块，可在生物安全柜内操作，以最大程度地减少技术人员接触病毒感染的机会；(ii) 12-12-15英寸紧凑型荧光光学扫描仪，用于潜在的床边读数。该平台能够在临床实践中进行日常细胞因子分析，具有高灵敏度（<0.4 pg mL ^-1）、测定间重复性（∼10% CV）和快速操作，可在 4 小时内提供治疗进展反馈。该测试使我们能够对两名患有呼吸衰竭的危重患者进行连续监测，并支持使用选择性细胞分离装置 (SCD) 进行免疫调节治疗。我们还观察到接受托珠单抗（IL-6 抑制剂）后白细胞介素 6 (IL-6) 明显升高，而所有危重 COVID-19 患者中存在显着的细胞因子谱变异，并发现 IL-6 与临床生物标志物之间存在弱相关性，例如铁蛋白和C反应蛋白（CRP）。我们的数据显示，患者对 COVID-19 的反应存在很大的个体差异，再次证实需要以快速细胞因子测定为指导的个性化策略。