Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients

COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the...

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Main Authors: Lilly May, Chang-Feng Chu, Christina E. Zielinski
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/13/4/300
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author Lilly May
Chang-Feng Chu
Christina E. Zielinski
author_facet Lilly May
Chang-Feng Chu
Christina E. Zielinski
author_sort Lilly May
collection DOAJ
description COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the detailed molecular mechanisms underlying an asymptomatic, mild or severe disease course, particularly in patients without relevant comorbidities, remain poorly understood. While previous studies have mainly focused on the cellular and molecular dissection of ongoing COVID-19, we set out to characterize transcriptomic immune cell dysregulation at the single-cell level at different time points in patients without comorbidities after disease resolution to identify signatures of different disease severities in convalescence. With single-cell RNA sequencing, we reveal a role for hypoxia-inducible factor 1-alpha (HIF1A) as a severity-sensitive long-term immunological scar in circulating monocytes of convalescent COVID-19 patients. Additionally, we show that circulating complexes formed by monocytes with either T cells or NK cells represent a characteristic cellular marker in convalescent COVID-19 patients irrespective of their preceding symptom severity. Together, these results provide cellular and molecular correlates of recovery from COVID-19 and could help in immune monitoring and in the design of new treatment strategies.
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spelling doaj.art-3429ca0510144447aebed9f1b6b77d772024-02-23T15:11:39ZengMDPI AGCells2073-44092024-02-0113430010.3390/cells13040300Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 PatientsLilly May0Chang-Feng Chu1Christina E. Zielinski2Leibniz Institute for Natural Products Research and Infection Biology, Department of Infection Immunology, 07745 Jena, GermanyLeibniz Institute for Natural Products Research and Infection Biology, Department of Infection Immunology, 07745 Jena, GermanyLeibniz Institute for Natural Products Research and Infection Biology, Department of Infection Immunology, 07745 Jena, GermanyCOVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the detailed molecular mechanisms underlying an asymptomatic, mild or severe disease course, particularly in patients without relevant comorbidities, remain poorly understood. While previous studies have mainly focused on the cellular and molecular dissection of ongoing COVID-19, we set out to characterize transcriptomic immune cell dysregulation at the single-cell level at different time points in patients without comorbidities after disease resolution to identify signatures of different disease severities in convalescence. With single-cell RNA sequencing, we reveal a role for hypoxia-inducible factor 1-alpha (HIF1A) as a severity-sensitive long-term immunological scar in circulating monocytes of convalescent COVID-19 patients. Additionally, we show that circulating complexes formed by monocytes with either T cells or NK cells represent a characteristic cellular marker in convalescent COVID-19 patients irrespective of their preceding symptom severity. Together, these results provide cellular and molecular correlates of recovery from COVID-19 and could help in immune monitoring and in the design of new treatment strategies.https://www.mdpi.com/2073-4409/13/4/300COVID-19SARS-CoV-2immunomonitoringsingle-cell RNA sequencinghypoxia-inducible factor 1-alphaHIF1A
spellingShingle Lilly May
Chang-Feng Chu
Christina E. Zielinski
Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients
Cells
COVID-19
SARS-CoV-2
immunomonitoring
single-cell RNA sequencing
hypoxia-inducible factor 1-alpha
HIF1A
title Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients
title_full Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients
title_fullStr Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients
title_full_unstemmed Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients
title_short Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients
title_sort single cell rna sequencing reveals hif1a as a severity sensitive immunological scar in circulating monocytes of convalescent comorbidity free covid 19 patients
topic COVID-19
SARS-CoV-2
immunomonitoring
single-cell RNA sequencing
hypoxia-inducible factor 1-alpha
HIF1A
url https://www.mdpi.com/2073-4409/13/4/300
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