Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early marker for severe COVID-19

被引:133
作者
Carissimo, Guillaume [1 ,2 ]
Xu, Weili [2 ]
Kwok, Immanuel [2 ]
Abdad, Mohammad Yazid [3 ]
Chan, Yi-Hao [1 ,2 ]
Fong, Siew-Wai [1 ,2 ,4 ]
Puan, Kia Joo [2 ]
Lee, Cheryl Yi-Pin [1 ,2 ]
Yeo, Nicholas Kim-Wah [1 ,2 ]
Amrun, Siti Naqiah [1 ,2 ]
Chee, Rhonda Sin-Ling [1 ,2 ]
How, Wilson [2 ]
Chan, Stephrene [5 ,6 ,7 ,8 ]
Fan, Bingwen Eugene [5 ,6 ,7 ,8 ]
Andiappan, Anand Kumar [2 ]
Lee, Bernett [2 ]
Roetzschke, Olaf [2 ]
Young, Barnaby Edward [3 ,9 ,10 ]
Leo, Yee-Sin [3 ,9 ,10 ,11 ,12 ,13 ]
Lye, David Chien [3 ,9 ,10 ,11 ,12 ]
Renia, Laurent [1 ,2 ]
Ng, Lai Guan [2 ]
Larbi, Anis [2 ]
Ng, Lisa F. P. [1 ,2 ,14 ,15 ]
机构
[1] Agcy Sci Technol & Res, Infect Dis Horizontal Technol Ctr, Immunos 138648, Biopolis, Singapore
[2] Agcy Sci Technol & Res, Singapore Immunol Network, Immunos 138648, Biopolis, Singapore
[3] Natl Ctr Infect Dis, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore
[4] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore
[5] Tan Tock Seng Hosp, Dept Haematol, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
[6] Khoo Teck Puat Hosp, Dept Lab Med, Singapore, Singapore
[7] Lee Kong Chian Sch Med, Singapore, Singapore
[8] Yong Loo Lin Sch Med, Singapore, Singapore
[9] Tan Tock Seng Hosp, Dept Infect Dis, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore
[10] Nanyang Technol Univ, Lee Kong Chian Sch Med, 11 Mandalay Rd, Singapore 308232, Singapore
[11] Natl Univ Singapore, Yong Loo Lin Sch Med, 10 Med Dr, Singapore 117597, Singapore
[12] Natl Univ Hlth Syst, 10 Med Dr, Singapore 117597, Singapore
[13] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, 12 Sci Dr 2, Singapore 117549, Singapore
[14] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, 8 Med Dr, Singapore 117596, Singapore
[15] Univ Liverpool, Inst Infect Vet & Ecol Sci, 8 West Derby St, Liverpool L7 3EA, Merseyside, England
基金
英国医学研究理事会; 新加坡国家研究基金会;
关键词
GAMMA-DELTA; EFFECTOR FUNCTIONS; SUBSETS; PROLIFERATION; CORONAVIRUS;
D O I
10.1038/s41467-020-19080-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 gamma delta T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management. COVID-19 severity is associated with cytokine levels and lymphopenia, but the role of immune cell subsets is not well understood. Here the authors immunophenotype whole blood samples from 54 COVID-19 patients and find that the immature neutrophil-to-VD2 T-cell ratio is associated with severe COVID-19.
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页数:12
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