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Sex differences in immune responses that underlie COVID-19 disease outcomes

机译：免疫反应的性差异，底部疾病 - 19疾病结果

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摘要

Male patients with COVID-19 have higher plasma levels of innate immune cytokines and chemokines such as IL-8, IL-18 and CCL5 and more non-classical monocytes than female patients, whereas female patients mount robust T cell activation maintained even in older age.There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women(1-5). However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.
机译：患有Covid-19的男性患者具有更高的血浆水平，先天免疫细胞因子和趋化因子，如IL-8，IL-18和CCL5和更多的非古典单核细胞比女性患者更高，而女性患者均在老年龄较大的情况下保持稳健的T细胞活化。 。越来越多的证据表明2019年冠状病毒疾病（Covid-19）在男性中产生了更严重的症状和更高的死亡率，而不是女性（1-5）。然而，无论对严重急性呼吸综合征冠状病毒（SARS-COV-2）之间的免疫应答是否不同，以及这种差异是否与Covid-19疾病过程中的性别差异相关，目前未知。在这里，我们检查了在不接受免疫调节药物的中度Covid-19患者的病毒载荷，SARS-COV-2特异性抗体滴度，血浆细胞因子和血细胞表型的性差异。男性患者具有更高的血浆水平的先天免疫细胞因子，例如IL-8和IL-18以及更强大的非典型单核细胞的诱导。相比之下，在SARS-COV-2感染期间，女性患者比男性患者更强大的T细胞活化。值得注意的是，我们发现一种差的T细胞反应与患者年龄负相关，并且与男性患者的疾病结果较差，但不与女性患者有关。相比之下，较高水平的先天免疫细胞因子与女性患者的更严重的疾病进展相关，但不是在男性患者中。这些发现提供了对Covid-19中观察到的性别偏见的可能解释，并为开发基于性的治疗和护理Covid-19患者的性别方法提供了重要的基础。

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  • 来源
    《Nature》 |2020年第7837期|315-320|共6页
  • 作者

    Takahashi Takehiro; Ellingson Mallory K.; Wong Patrick; Israelow Benjamin; Lucas Carolina; Klein Jon; Silva Julio; Mao Tianyang; Oh Ji Eun; Tokuyama Maria; Lu Peiwen; Venkataraman Arvind; Park Annsea; Liu Feimei; Meir Amit; Sun Jonathan; Wang Eric Y.; Casanovas-Massana Arnau; Wyllie Anne L.; Vogels Chantal B. F.; Earnest Rebecca; Lapidus Sarah; Ott Isabel M.; Moore Adam J.; Shaw Albert; Fournier John B.; Odio Camila D.; Shelli Farhadian; Dela Cruz Charles; Grubaugh Nathan D.; Schulz Wade L.; Ring Aaron M.; Ko Albert I; Omer Saad B.; Iwasaki Akiko;

  • 作者单位

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA|Yale Univ Sch Med Dept Med Sect Infect Dis New Haven CT 06510 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA|Yale Sch Engn & Appl Sci Dept Biomed Engn New Haven CT USA;

    Yale Univ Dept Microbial Pathogenesis Boyer Ctr Mol Med New Haven CT USA;

    Yale Univ Dept Comparat Med Sch Med New Haven CT USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA|Yale Univ Dept Ecol & Evolutionary Biol New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Dept Med Sect Infect Dis New Haven CT 06510 USA;

    Yale Univ Sch Med Dept Med Sect Infect Dis New Haven CT 06510 USA;

    Yale Univ Sch Med Dept Med Sect Infect Dis New Haven CT 06510 USA;

    Yale Univ Sch Med Dept Med Sect Infect Dis New Haven CT 06510 USA;

    Yale Univ Sch Med Dept Med Sect Pulm & Crit Care Med New Haven CT 06510 USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Dept Lab Med New Haven CT 06510 USA|Yale New Haven Med Ctr Ctr Outcomes Res & Evaluat 20 York St New Haven CT 06504 USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA|Yale Univ Sch Med Dept Med Sect Infect Dis New Haven CT 06510 USA|Yale Univ Yale Inst Global Hlth New Haven CT USA|Yale Univ Yale Sch Nursing Orange CT USA;

    Yale Univ Dept Immunobiol Sch Med New Haven CT 06520 USA|Howard Hughes Med Inst Chevy Chase MD 20815 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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