Nat Commun . Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation

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Nat Commun


. 2022 Jan 12;13(1):269.
doi: 10.1038/s41467-021-27723-5.
Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation


Haibo Wu ^{# 1} , Peiqi He ^{# 2 3 4} , Yong Ren ^{# 5} , Shiqi Xiao ⁵ , Wei Wang ¹ , Zhenbang Liu ² , Heng Li ¹ , Zhe Wang ¹ , Dingyu Zhang ⁶ , Jun Cai ⁷ , Xiangdong Zhou ⁸ , Dongpo Jiang ⁸ , Xiaochun Fei ⁷ , Lei Zhao ⁷ , Heng Zhang ⁷ , Zhenhua Liu ⁷ , Rong Chen ⁶ , Weiqing Li ⁹ , Chaofu Wang ⁷ , Shuyang Zhang ¹⁰ , Jiwei Qin ⁴ , Björn Nashan ⁴ , Cheng Sun ^{11 12 13}



Affiliations

• PMID: 35022412
• DOI: 10.1038/s41467-021-27723-5

Abstract

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1⁺ cells being proximal rather than distal to TIM-3⁺ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.