Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study.
Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study.
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DOI：
10.1016/s2665-9913(20)30343-x
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Brown SM
中科院分区：
文献类型：
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作者：
Webb BJ;Peltan ID;Jensen P;Hoda D;Hunter B;Silver A;Starr N;Buckel W;Grisel N;Hummel E;Snow G;Morris D;Stenehjem E;Srivastava R;Brown SM
一部分COVID-19患者会出现与其他炎症性疾病相似的炎症性综合征。然而，尚未建立专门定义COVID-19相关炎症过度综合征（cHIS）的临床标准。我们的目的是在COVID-19住院患者队列中开发和验证cHIS的诊断标准。我们检索了1990年1月1日至2020年8月20日期间发表的关于继发性噬血细胞性淋巴组织细胞增多症、巨噬细胞活化综合征、脓毒症巨噬细胞活化样综合征、细胞因子释放综合征和COVID-19的特征和诊断标准的临床研究文章。我们将已发表的COVID-19临床数据与其他炎症过度或细胞因子风暴综合征的临床特征进行了比较。基于保守的临床特征框架，我们开发了cHIS的六项标准相加量表：发热、巨噬细胞活化（高铁蛋白血症）、血液学功能障碍（中性粒细胞与淋巴细胞比率）、肝损伤（乳酸脱氢酶或丙氨酸氨基转移酶）、凝血病（D-二聚体）和细胞因子血症（C-反应蛋白、白细胞介素-6或甘油三酯）。然后，我们在山间前瞻性观察性COVID-19（IPOC）登记研究中，验证了cHIS量表与住院期间死亡率和机械通气需求的相关性，这些患者因PCR确认的COVID-19入院。我们使用多状态模型来估计cHIS的时间影响。我们在分析中纳入了2020年3月13日至5月5日期间因COVID-19入院的299名患者。每日最大cHIS评分的未校正区分度为0·81（95%CI 0.74 - 0.88），住院死亡率为0.92（0·88-0·96）机械通气;这些结果在多变量分析中仍然是显著的（死亡率的比值比为1.6 [95%CI 1.2 - 2.1]，p = 0.0020，机械通气的比值比为4.3 [3.0 - 6.0]，p <0.0001）。299例患者中有161例（54%）在住院期间符合两个或更多cHIS标准;这些患者的死亡风险高于评分小于2的患者（138例中有24例[15%] vs 161例中有1例[1%]）和机械通气患者（73例[45%] vs 3例[2%]）。在多状态模型中，使用每日cHIS评分作为时间依赖性变量，从低至中等需氧量恶化的cHIS风险比为1.4（95% CI 1.2 - 1.6），从中等氧气至高流量氧气为2.2（1.1 - 4.4），机械通气为4.0（1.9 - 8.2）。我们提出并验证了COVID-19中炎症过度的标准。这种高度炎症状态（cHIS）通常与机械通气进展和死亡相关。需要外部验证。cHIS量表可能有助于确定试验和免疫调节治疗的目标人群。山间研究和医学基金会。
A subset of patients with COVID-19 develops a hyperinflammatory syndrome that has similarities with other hyperinflammatory disorders. However, clinical criteria specifically to define COVID-19-associated hyperinflammatory syndrome (cHIS) have not been established. We aimed to develop and validate diagnostic criteria for cHIS in a cohort of inpatients with COVID-19. We searched for clinical research articles published between Jan 1, 1990, and Aug 20, 2020, on features and diagnostic criteria for secondary haemophagocytic lymphohistiocytosis, macrophage activation syndrome, macrophage activation-like syndrome of sepsis, cytokine release syndrome, and COVID-19. We compared published clinical data for COVID-19 with clinical features of other hyperinflammatory or cytokine storm syndromes. Based on a framework of conserved clinical characteristics, we developed a six-criterion additive scale for cHIS: fever, macrophage activation (hyperferritinaemia), haematological dysfunction (neutrophil to lymphocyte ratio), hepatic injury (lactate dehydrogenase or asparate aminotransferase), coagulopathy (D-dimer), and cytokinaemia (C-reactive protein, interleukin-6, or triglycerides). We then validated the association of the cHIS scale with in-hospital mortality and need for mechanical ventilation in consecutive patients in the Intermountain Prospective Observational COVID-19 (IPOC) registry who were admitted to hospital with PCR-confirmed COVID-19. We used a multistate model to estimate the temporal implications of cHIS. We included 299 patients admitted to hospital with COVID-19 between March 13 and May 5, 2020, in analyses. Unadjusted discrimination of the maximum daily cHIS score was 0·81 (95% CI 0·74–0·88) for in-hospital mortality and 0·92 (0·88–0·96) for mechanical ventilation; these results remained significant in multivariable analysis (odds ratio 1·6 [95% CI 1·2–2·1], p=0·0020, for mortality and 4·3 [3·0–6·0], p<0·0001, for mechanical ventilation). 161 (54%) of 299 patients met two or more cHIS criteria during their hospital admission; these patients had higher risk of mortality than patients with a score of less than 2 (24 [15%] of 138 vs one [1%] of 161) and for mechanical ventilation (73 [45%] vs three [2%]). In the multistate model, using daily cHIS score as a time-dependent variable, the cHIS hazard ratio for worsening from low to moderate oxygen requirement was 1·4 (95% CI 1·2–1·6), from moderate oxygen to high-flow oxygen 2·2 (1·1–4·4), and to mechanical ventilation 4·0 (1·9–8·2). We proposed and validated criteria for hyperinflammation in COVID-19. This hyperinflammatory state, cHIS, is commonly associated with progression to mechanical ventilation and death. External validation is needed. The cHIS scale might be helpful in defining target populations for trials and immunomodulatory therapies. Intermountain Research and Medical Foundation.