Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.

Jeong Seok Lee, Seongwan Park, Hye Won Jeong, Jin Young Ahn, Seong Jin Choi, Hoyoung Lee, Baekgyu Choi, Su Kyung Nam, Moa Sa, Ji-Soo Kwon, Su Jin Jeong, Heung Kyu Lee, Sung Ho Park, Su-Hyung Park, Jun Yong Choi, Sung-Han Kim, Inkyung Jung, Eui-Cheol Shin
Author Information
  1. Jeong Seok Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  2. Seongwan Park: Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. ORCID
  3. Hye Won Jeong: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. ORCID
  4. Jin Young Ahn: Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. ORCID
  5. Seong Jin Choi: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  6. Hoyoung Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  7. Baekgyu Choi: Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. ORCID
  8. Su Kyung Nam: Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. ORCID
  9. Moa Sa: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  10. Ji-Soo Kwon: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  11. Su Jin Jeong: Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. ORCID
  12. Heung Kyu Lee: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  13. Sung Ho Park: School of Life Sciences, Ulsan National Institute of Science & Technology (UNIST), Ulsan 44919, Republic of Korea. ORCID
  14. Su-Hyung Park: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ORCID
  15. Jun Yong Choi: Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. ecshin@kaist.ac.kr ijung@kaist.ac.kr shkimmd@amc.seoul.kr seran@yuhs.ac. ORCID
  16. Sung-Han Kim: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. ecshin@kaist.ac.kr ijung@kaist.ac.kr shkimmd@amc.seoul.kr seran@yuhs.ac. ORCID
  17. Inkyung Jung: Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea. ecshin@kaist.ac.kr ijung@kaist.ac.kr shkimmd@amc.seoul.kr seran@yuhs.ac. ORCID
  18. Eui-Cheol Shin: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. ecshin@kaist.ac.kr ijung@kaist.ac.kr shkimmd@amc.seoul.kr seran@yuhs.ac. ORCID

Abstract

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.

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MeSH Term

Adult
Aged
Aged, 80 and over
Betacoronavirus
CD8-Positive T-Lymphocytes
COVID-19
Cells, Cultured
Coronavirus Infections
Female
Healthy Volunteers
Humans
Immunophenotyping
Inflammation
Influenza A virus
Influenza, Human
Interferon Type I
Interleukin-1beta
Male
Middle Aged
Pandemics
Pneumonia, Viral
RNA-Seq
SARS-CoV-2
Severity of Illness Index
Single-Cell Analysis
Transcriptome
Tumor Necrosis Factor-alpha

Chemicals

IL1B protein, human
Interferon Type I
Interleukin-1beta
TNF protein, human
Tumor Necrosis Factor-alpha

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