Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave. New Orleans, 70112, New Orleans, LA, USA.
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
BMC Infect Dis. 2022 Oct 12;22(1):784. doi: 10.1186/s12879-022-07776-7.
The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19.
This is a retrospective cohort analysis based on the National COVID Cohort Collaborative (N3C). We included 574,391 adult patients admitted for COVID-19 at hospitals or emergency rooms between 01/01/2020 and 12/31/2021.
We defined comorbidities at or before the first admission for COVID-19 by Charlson Comorbidity Index (CCI) and CCI components. We used the averaged lab values taken within 15 days before or after the admission date to measure biomarkers including c-reactive protein (CRP), ferritin, procalcitonin, N-terminal pro b-type natriuretic peptide (NT proBNP), d-dimer, absolute lymphocyte counts, absolute neutrophil counts, and platelets. Our primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation (IMV) and hospital length of stay (LOS). We used logistic regression adjusted for age, race, ethnicity, visit type, and medications to assess the association of comorbidities, biomarkers, and mortality disaggregating by sex.
Moderate to severe liver disease, renal disease, metastatic solid tumor, and myocardial infarction were the top four fatal comorbidities among patients who were hospitalized for COVID-19 (adjusted odds ratio [aOR] > 2). These four comorbid conditions remained the most lethal in both sexes, with a higher magnitude of risk in women than in men (p-interaction < 0.05). Abnormal elevations of CRP, ferritin, procalcitonin, NT proBNP, neutrophil, and platelet counts, and lymphocytopenia were significantly associated with the risk of death, with procalcitonin and NT proBNP as the strongest predictors (aOR > 2). The association between the abnormal biomarkers and death was stronger in women than in men (p-interaction < 0.05).
There are sex differences in inpatient mortality associated with comorbidities and biomarkers. The significant impact of these clinical determinants in women with COVID-19 may be underappreciated as previous studies stressed the increased death rate in male patients that is related to comorbidities or inflammation. Our study highlights the importance and the need for sex-disaggregated research to understand the risk factors of poor outcomes and health disparities in COVID-19.
合并症和生物标志物对 COVID-19 严重程度的影响因性别而异，但尚未在基于人群的研究中得到证实。我们研究了合并症、炎症生物标志物与因 COVID-19 住院的男性和女性患者严重结局之间的关联。
这是一项基于国家 COVID 队列协作（N3C）的回顾性队列分析。我们纳入了 2020 年 1 月 1 日至 2021 年 12 月 31 日期间因 COVID-19 在医院或急诊室就诊的 574391 名成年患者。
我们通过 Charlson 合并症指数（CCI）及其组成部分，定义了首次 COVID-19 住院前或住院时的合并症。我们使用在入院日期前 15 天内采集的平均值来测量生物标志物，包括 C 反应蛋白（CRP）、铁蛋白、降钙素原、N 末端 pro B 型利钠肽（NT proBNP）、D-二聚体、绝对淋巴细胞计数、绝对中性粒细胞计数和血小板计数。主要结局是全因死亡率；次要结局是有创机械通气（IMV）和住院时间（LOS）。我们使用 logistic 回归模型调整了年龄、种族、民族、就诊类型和药物等因素，以评估性别分层的合并症、生物标志物与死亡率之间的关系。
在因 COVID-19 住院的患者中，中度至重度肝脏疾病、肾脏疾病、转移性实体瘤和心肌梗死是导致死亡的前四大合并症（调整后比值比[aOR]＞2）。这四种合并症在男女中都是最致命的，女性的风险比男性更高（p 交互作用＜0.05）。CRP、铁蛋白、降钙素原、NT proBNP、中性粒细胞和血小板计数升高以及淋巴细胞减少与死亡风险显著相关，降钙素原和 NT proBNP 的预测作用最强（aOR＞2）。女性中生物标志物异常与死亡之间的相关性强于男性（p 交互作用＜0.05）。
住院患者死亡率与合并症和生物标志物相关，存在性别差异。COVID-19 女性患者中这些临床因素的显著影响可能被低估，因为之前的研究强调了与合并症或炎症相关的男性患者死亡率增加。本研究强调了进行性别分层研究的重要性和必要性，以了解 COVID-19 不良结局和健康差异的相关风险因素。
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