Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19.
Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19.
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DOI：
10.1038/s41392-021-00709-x
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发表时间：
2021-07-30
影响因子：
39.3
通讯作者：
Cheng F
中科院分区：
文献类型：
--
作者：
Hou Y;Zhou Y;Gack MU;Lathia JD;Kallianpur A;Mehra R;Chan TA;Jung JU;Jehi L;Eng C;Cheng F
SARS-CoV-2 感染的易感性和严重程度的性别差异一直存在争议，并且针对性别特异性的 COVID-19 的潜在机制仍未得到充分研究。在这里，我们检查了不同疾病严重程度的 COVID-19 患者的鼻腔、支气管肺泡灌洗液 (BALF) 和外周血单核细胞 (PBMC) 中 SARS-CoV-2 感染、住院、入住重症监护病房 (ICU)、血清炎症生物标志物分析和单细胞 RNA 测序 (scRNA-seq) 分析的性别差异。我们的倾向评分匹配观察结果显示，男性个体 SARS-CoV-2 阳性的可能性增加 29%，住院的风险比 (HR) 1.32（95% 置信区间 [CI] 1.18–1.48），入住 ICU 的 HR 1.51（95% CI 1.24–1.84）。入院时男性患者的血清中性粒细胞-淋巴细胞比率升高，炎症标志物（C 反应蛋白和降钙素原）表达升高。我们发现 SARS-CoV-2 进入因子，包括 ACE2、TMPRSS2、FURIN 和 NRP1，在患有中度和重度 COVID-19 的男性个体的鼻鳞状细胞中表达升高。我们在 BALF 和痰样本中观察到 SARS-CoV-2 感染的巨噬细胞中男性偏向的转录激活，这为性别偏向对病毒感染的易感性提供了潜在的分子机制。细胞-细胞相互作用网络分析揭示了潜在的上皮-免疫细胞相互作用和免疫脆弱性，这些是导致男性在COVID-19中疾病严重程度和死亡率升高的原因。从机制上讲，Toll 样受体 7 (TLR7) 和布鲁顿酪氨酸激酶 (BTK) 的单核细胞表达升高与男性 COVID-19 的严重后果相关。总之，这些发现为破译性别差异背后的免疫反应以及设计针对 COVID-19 的针对性别的干预措施和患者护理提供了基础。
Sex differences in the susceptibility of SARS-CoV-2 infection and severity have been controversial, and the underlying mechanisms of COVID-19 in a sex-specific manner remain understudied. Here we inspected sex differences in SARS-CoV-2 infection, hospitalization, admission to the intensive care unit (ICU), sera inflammatory biomarker profiling, and single-cell RNA-sequencing (scRNA-seq) profiles across nasal, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with varying degrees of disease severities. Our propensity score-matching observations revealed that male individuals have a 29% elevated likelihood of SARS-CoV-2 positivity, with a hazard ratio (HR) 1.32 (95% confidence interval [CI] 1.18–1.48) for hospitalization and HR 1.51 (95% CI 1.24–1.84) for admission to ICU. Sera from male patients at hospital admission had elevated neutrophil–lymphocyte ratio and elevated expression of inflammatory markers (C-reactive protein and procalcitonin). We found that SARS-CoV-2 entry factors, including ACE2, TMPRSS2, FURIN, and NRP1, have elevated expression in nasal squamous cells from male individuals with moderate and severe COVID-19. We observed male-biased transcriptional activation in SARS-CoV-2-infected macrophages from BALF and sputum samples, which offers potential molecular mechanism for sex-biased susceptibility to viral infection. Cell–cell interaction network analysis reveals potential epithelium–immune cell interactions and immune vulnerability underlying male-elevated disease severity and mortality in COVID-19. Mechanistically, monocyte-elevated expression of Toll-like receptor 7 (TLR7) and Bruton tyrosine kinase (BTK) is associated with severe outcomes in males with COVID-19. In summary, these findings provide basis to decipher immune responses underlying sex differences and designing sex-specific targeted interventions and patient care for COVID-19.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
DOI：
10.15585/mmwr.mm6942e1
发表时间：
2020-10-23
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Gold JAW;Rossen LM;Ahmad FB;Sutton P;Li Z;Salvatore PP;Coyle JP;DeCuir J;Baack BN;Durant TM;Dominguez KL;Henley SJ;Annor FB;Fuld J;Dee DL;Bhattarai A;Jackson BR
通讯作者：
Jackson BR
影响因子：
16.6
作者：
Cheng F;Desai RJ;Handy DE;Wang R;Schneeweiss S;Barabási AL;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
46.9
作者：
Chua, Robert Lorenz;Lukassen, Soeren;Eils, Roland
通讯作者：
Eils, Roland
影响因子：
14.9
作者：
Dinkel H;Chica C;Via A;Gould CM;Jensen LJ;Gibson TJ;Diella F
通讯作者：
Diella F