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Series GSE157344 Query DataSets for GSE157344
Status Public on Jan 27, 2021
Title Deciphering the state of immune silence in fatal COVID-19 patients
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocytosis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely impeding the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune signature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found monocyte and neutro-phil immune suppression loss associated with fatal clinical outcome in severe patients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allele, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of my-eloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.
Overall design Cells from blood or bronchoalveloar lavage samples from COVID-19 patients or healthy donors were sequenced using the Chromium 10X scRNA-seq technology (NextGEM Single Cell 3′ GEM, Library& Gel Bead kit v3.1 )
Contributor(s) Bost P, De Sanctis F, Canè S, Ugel S, Donadello K, Castellucci M, Eyal D, Fiore A, Anselmi C, Barouni RM, Trovato R, Caligola S, Lamolinara A, Iezzi M, Facciotti F, Mazzariol AR, Gibellini D, De Nardo P, Tacconelli E, Gottin L, Polati E, Schwikowski B, Amit I, Bronte V
Citation(s) 33674591
Submission date Sep 02, 2020
Last update date Mar 07, 2021
Contact name Ido Amit
Phone 972-8-9343338
Organization name Weizmann Institute of Science
Department Immunology
Street address 234 Herzl st.
City Rehovot
ZIP/Postal code 760001
Country Israel
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (54)
GSM4762139 BAL1
GSM4762140 BAL10
GSM4762141 BAL11
BioProject PRJNA661032
SRA SRP279746

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Supplementary file Size Download File type/resource
GSE157344_RAW.tar 661.6 Mb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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