Longitudinal Transcriptome Analyses Show Robust T Cell Immunity During Recovery from COVID-19

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2020 Dec 28

PMID 33361761

Citations 49

Authors

Hong-Yi Zheng

Min Xu

Cui-Xian Yang

Ren-Rong Tian

Mi Zhang

Jian-Jian Li

Xi-Cheng Wang

Zhao-Li Ding

Gui-Mei Li

Xiao-Lu Li

Yu-Qi He

Xing-Qi Dong

Yong-Gang Yao

Yong-Tang Zheng

Affiliations

Soon will be listed here.

Abstract

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for improving treatment. Here, we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples from 18 patients with coronavirus disease 2019 (COVID-19) during their treatment, convalescence, and rehabilitation. After analyzing the regulatory networks of differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) between the different clinical stages, we found that humoral immunity and type I interferon response were significantly downregulated, while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19. The formation of this T cell immune response might be driven by the activation of activating protein-1 (AP-1) related signaling pathway and was weakly affected by other clinical features. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.

Citing Articles

MeTEor: an R Shiny app for exploring longitudinal metabolomics data.

Grabert G, Dehncke D, More T, List M, Kraft A, Cornberg M Bioinform Adv. 2024; 4(1):vbae178.

PMID: 39659589 PMC: 11631383. DOI: 10.1093/bioadv/vbae178.

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression.

Medina M, Fuentes-Villalobos F, Quevedo C, Aguilera F, Riquelme R, Rioseco M Elife. 2024; 13.

PMID: 39470726 PMC: 11521369. DOI: 10.7554/eLife.94242.

Longitudinal transcriptomic analysis reveals persistent enrichment of iron homeostasis and erythrocyte function pathways in severe COVID-19 ARDS.

Eltobgy M, Johns F, Farkas D, Leuenberger L, Cohen S, Ho K Front Immunol. 2024; 15:1397629.

PMID: 39161760 PMC: 11330807. DOI: 10.3389/fimmu.2024.1397629.

Bacterial sepsis causes more dramatic pathogenetic changes in the Th1 pathway than does viral (COVID-19) sepsis: a prospective observational study of whole blood transcriptomes.

Muratsu A, Oda S, Onishi S, Yoshimura J, Matsumoto H, Togami Y Virol J. 2024; 21(1):190.

PMID: 39160575 PMC: 11334310. DOI: 10.1186/s12985-024-02451-6.

The knowns and unknowns of long COVID-19: from mechanisms to therapeutical approaches.

Gheorghita R, Soldanescu I, Lobiuc A, Caliman Sturdza O, Filip R, Constantinescu-Bercu A Front Immunol. 2024; 15:1344086.

PMID: 38500880 PMC: 10944866. DOI: 10.3389/fimmu.2024.1344086.

References

Mauvais-Jarvis F . Aging, Male Sex, Obesity, and Metabolic Inflammation Create the Perfect Storm for COVID-19. Diabetes. 2020; 69(9):1857-1863. PMC: 7458034. DOI: 10.2337/dbi19-0023. View

Wong G, Bi Y, Wang Q, Chen X, Zhang Z, Yao Y . Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important?. Zool Res. 2020; 41(3):213-219. PMC: 7231470. DOI: 10.24272/j.issn.2095-8137.2020.031. View

Liu Y, Ma C, Zhang N . Tissue-Specific Control of Tissue-Resident Memory T Cells. Crit Rev Immunol. 2018; 38(2):79-103. PMC: 6156774. DOI: 10.1615/CritRevImmunol.2018025653. View

Long Q, Liu B, Deng H, Wu G, Deng K, Chen Y . Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020; 26(6):845-848. DOI: 10.1038/s41591-020-0897-1. View

Du Z, Wei L, Murti A, Pfeffer S, Fan M, Yang C . Non-conventional signal transduction by type 1 interferons: the NF-kappaB pathway. J Cell Biochem. 2007; 102(5):1087-94. DOI: 10.1002/jcb.21535. View

Nussing S, Koay H, Sant S, Loudovaris T, Mannering S, Lappas M . Divergent SATB1 expression across human life span and tissue compartments. Immunol Cell Biol. 2019; 97(5):498-511. PMC: 6618325. DOI: 10.1111/imcb.12233. View

Paolini R, Bernardini G, Molfetta R, Santoni A . NK cells and interferons. Cytokine Growth Factor Rev. 2014; 26(2):113-20. DOI: 10.1016/j.cytogfr.2014.11.003. View

Volders P, Anckaert J, Verheggen K, Nuytens J, Martens L, Mestdagh P . LNCipedia 5: towards a reference set of human long non-coding RNAs. Nucleic Acids Res. 2018; 47(D1):D135-D139. PMC: 6323963. DOI: 10.1093/nar/gky1031. View

Chen Y, Wang X . miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2019; 48(D1):D127-D131. PMC: 6943051. DOI: 10.1093/nar/gkz757. View

10.

Zhou Y, Zhang Z, Tian J, Xiong S . Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Ann Palliat Med. 2020; 9(2):428-436. DOI: 10.21037/apm.2020.03.26. View

11.

Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N . Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369(6504):718-724. PMC: 7402632. DOI: 10.1126/science.abc6027. View

12.

Helgeland H, Gabrielsen I, Akselsen H, Sundaram A, Flam S, Lie B . Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells. BMC Genomics. 2020; 21(1):350. PMC: 7216358. DOI: 10.1186/s12864-020-6755-1. View

13.

Chan J, Yuan S, Kok K, To K, Chu H, Yang J . A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020; 395(10223):514-523. PMC: 7159286. DOI: 10.1016/S0140-6736(20)30154-9. View

14.

Yamazaki S, Tanaka Y, Araki H, Kohda A, Sanematsu F, Arasaki T . The AP-1 transcription factor JunB is required for Th17 cell differentiation. Sci Rep. 2017; 7(1):17402. PMC: 5727176. DOI: 10.1038/s41598-017-17597-3. View

15.

Bert N, Tan A, Kunasegaran K, Tham C, Hafezi M, Chia A . SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020; 584(7821):457-462. DOI: 10.1038/s41586-020-2550-z. View

16.

Wiersinga W, Rhodes A, Cheng A, Peacock S, Prescott H . Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324(8):782-793. DOI: 10.1001/jama.2020.12839. View

17.

Kozomara A, Birgaoanu M, Griffiths-Jones S . miRBase: from microRNA sequences to function. Nucleic Acids Res. 2018; 47(D1):D155-D162. PMC: 6323917. DOI: 10.1093/nar/gky1141. View

18.

Thevarajan I, Nguyen T, Koutsakos M, Druce J, Caly L, van de Sandt C . Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020; 26(4):453-455. PMC: 7095036. DOI: 10.1038/s41591-020-0819-2. View

19.

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

20.

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Stralin K, Gorin J, Olsson A . Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020; 183(1):158-168.e14. PMC: 7427556. DOI: 10.1016/j.cell.2020.08.017. View