School of Basic Medical Science, Wenzhou Medical University, Wenzhou, China.
Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.
PLoS Pathog. 2021 Mar 26;17(3):e1009420. doi: 10.1371/journal.ppat.1009420. eCollection 2021 Mar.
To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.
为了同时确定年轻和老年男女对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的临床和免疫学反应，根据年龄和性别分类，使用多元线性回归分析对 681 名 2019 年冠状病毒病（COVID-19）患者和 369 名正常对照（NC）进行了分析。与年龄匹配的 NC 相比，年轻和老年男性和女性非合并 COVID-19 患者的淋巴细胞计数和丙氨酸转氨酶（ALT）浓度较低，只有年轻的男性和女性患者的中性粒细胞计数较低。与年轻患者相比，老年男性和女性的血浆 ALT 和 AST 浓度均显著升高。与年轻和老年女性相比，年龄匹配的男性血浆 ALT 和 AST 浓度较高，但只有年轻男性的 C 反应蛋白（CRP）浓度较高。与女性相比，老年男性，但不是年轻男性，患有危重病的发生率较高。与年轻患者相比，老年女性的白细胞和中性粒细胞计数高于正常上限和 B 细胞计数低于正常下限（NLL）的情况更多，而老年男性的淋巴细胞和自然杀伤（NK）细胞计数低于 NLL 的情况更多。未观察到性别或年龄与 B 细胞和 NK 细胞计数之间的相关性。然而，在 COVID-19 患者中，男性和女性的 CD8+T 细胞计数均随年龄的增长而减少。年龄与 CD8+T 细胞计数呈负相关，与中性粒细胞计数、CRP、ALT 和 AST 浓度呈正相关，与性别（女性）呈负相关，与中性粒细胞计数、CRP、ALT 和 AST 浓度呈负相关。本研究表明，SARS-CoV-2 感染主要引起 1）有益的性别（女性）相关差异，表现为降低 COVID-19 疾病严重程度，与炎症反应和肝损伤呈负相关，以及 2）有害的年龄相关差异，表现为与 CD8+T 细胞计数呈负相关，与炎症反应和肝损伤呈正相关。因此，性别和年龄是预防和治疗 COVID-19 时应考虑的生物学变量。
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