Center for Reproductive Sciences and Department of ObGyn, University of California San Francisco, San Francisco, CA 94143, USA.
Aseesa Inc., Hillsborough, CA 94010, USA.
Cells. 2023 Nov 8;12(22):2591. doi: 10.3390/cells12222591.
COVID-19-associated intensive care unit (ICU) admissions were recognized as critical health issues that contributed to morbidity and mortality in SARS-CoV-2-infected patients. Severe symptoms in COVID-19 patients are often accompanied by cytokine release syndrome. Here, we analyzed publicly available data from the Yale IMPACT cohort to address immunological misfiring and sex differences in early COVID-19 patients. In 2020, SARS-CoV-2 was considered far more pathogenic and lethal than other circulating respiratory viruses, and the inclusion of SARS-CoV-2 negative patients in IMPACT cohorts confounds many findings. We ascertained the impact of several important biological variables such as days from symptom onset (DFSO); pre-existing risk factors, including obesity; and early COVID-19 treatments on significantly changed immunological measures in ICU-admitted COVID-19 patients that survived versus those that did not. Deceased patients had 19 unique measures that were not shared with ICU patients including increased granzyme-B-producing GzBCD8 T cells and interferon-γ. Male COVID-19 patients in ICU experienced many more changes in immunological and clinical measures than female ICU patients (25% vs. ~16%, respectively). A total of 13/124 measures including CCL5, CCL17, IL-18, IFNα2, Fractalkine, classical monocytes, T cells, and CD4Temra exhibited significant sex differences in female vs. male COVID-19 patients. A total of nine measures including IL-21, CCL5, and CD4Temra differed significantly between female and male healthy controls. Immunosuppressed patients experienced the most decreases in CD4Temra and CD8Tem cell numbers. None of the early COVID-19 treatments were effective in reducing levels of IL-6, a major component of the cytokine storm. Obesity (BMI >30) was the most impactful risk factor for COVID-19-related deaths and worst clinical outcomes. Our analysis highlights the contribution of biological sex, risk factors, and early treatments with respect to COVID-19-related ICU admission and progression to morbidity and mortality.
COVID-19 相关的重症监护病房（ICU）入院被认为是导致 SARS-CoV-2 感染患者发病率和死亡率的关键健康问题。COVID-19 患者的严重症状通常伴随着细胞因子释放综合征。在这里，我们分析了耶鲁大学 IMPACT 队列中公开可用的数据，以解决 COVID-19 早期患者的免疫失调和性别差异问题。2020 年，SARS-CoV-2 被认为比其他循环呼吸道病毒更具致病性和致死性，而将 SARS-CoV-2 阴性患者纳入 IMPACT 队列会混淆许多发现。我们确定了几个重要生物学变量的影响，如从症状出现到住院的天数（DFSO）；包括肥胖在内的预先存在的风险因素；以及 ICU 收治的 COVID-19 患者的早期治疗对存活与未存活患者的显著改变的免疫措施。死亡患者有 19 个独特的措施与 ICU 患者不同，包括增加颗粒酶 B 产生的 GzBCD8 T 细胞和干扰素-γ。入住 ICU 的 COVID-19 男性患者经历了比女性 ICU 患者更多的免疫和临床措施变化（分别为 25%和 16%左右）。在女性 COVID-19 患者中，有 13/124 种措施（包括 CCL5、CCL17、IL-18、IFNα2、Fractalkine、经典单核细胞、T 细胞和 CD4Temra）表现出显著的性别差异，而在男性 COVID-19 患者中，有 13/124 种措施（包括 CCL5、CCL17、IL-18、IFNα2、Fractalkine、经典单核细胞、T 细胞和 CD4Temra）表现出显著的性别差异。有 9 种措施（包括 IL-21、CCL5 和 CD4Temra）在女性和男性健康对照组之间存在显著差异。免疫抑制患者经历了 CD4Temra 和 CD8Tem 细胞数量的最大减少。早期 COVID-19 治疗均不能降低细胞因子风暴的主要成分白细胞介素-6 的水平。肥胖（BMI>30）是 COVID-19 相关死亡和最差临床结局的最具影响力的危险因素。我们的分析强调了生物学性别、危险因素和早期治疗对 COVID-19 相关 ICU 入院以及向发病率和死亡率进展的影响。
