Cells
(Sep 2022)
Immune Determinants of Viral Clearance in Hospitalised COVID-19 Patients: Reduced Circulating Naïve CD4+ T Cell Counts Correspond with Delayed Viral Clearance
Mihaela Zlei,
Igor A. Sidorov,
Simone A. Joosten,
Mirjam H. M. Heemskerk,
Sebenzile K. Myeni,
Cilia R. Pothast,
Caroline S. de Brouwer,
A. Linda Boomaars-van der Zanden,
Krista E. van Meijgaarden,
Shessy T. Morales,
Els Wessels,
Jacqueline J. Janse,
Jelle J. Goeman,
Christa M. Cobbaert,
Aloys C. M. Kroes,
Suzanne C. Cannegieter,
Meta Roestenberg,
Leonardus G. Visser,
Marjolein Kikkert,
Mariet C. W. Feltkamp,
Sesmu M. Arbous,
Frank J. T. Staal,
Tom H. M. Ottenhoff,
Jacques J. M. van Dongen,
Anna H. E. Roukens,
Jutte J. C. de Vries,
in collaboration with BEAT-COVID,
in collaboration with LUMC COVID
Affiliations
Mihaela Zlei
Department of Immunology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Igor A. Sidorov
Clinical Microbiological Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Simone A. Joosten
Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Mirjam H. M. Heemskerk
Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Sebenzile K. Myeni
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Cilia R. Pothast
Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Caroline S. de Brouwer
Clinical Microbiological Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
A. Linda Boomaars-van der Zanden
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Krista E. van Meijgaarden
Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Shessy T. Morales
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Els Wessels
Clinical Microbiological Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Jacqueline J. Janse
Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Jelle J. Goeman
Medical Statistics Section, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Christa M. Cobbaert
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Aloys C. M. Kroes
Clinical Microbiological Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Suzanne C. Cannegieter
Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Meta Roestenberg
Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Leonardus G. Visser
Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Marjolein Kikkert
Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Mariet C. W. Feltkamp
Clinical Microbiological Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Sesmu M. Arbous
Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Frank J. T. Staal
Department of Immunology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Tom H. M. Ottenhoff
Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Jacques J. M. van Dongen
Department of Immunology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Anna H. E. Roukens
Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Jutte J. C. de Vries
Clinical Microbiological Laboratory, Department of Medical Microbiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
in collaboration with BEAT-COVID
in collaboration with LUMC COVID
DOI
https://doi.org/10.3390/cells11172743
Journal volume & issue
Vol. 11,
no. 17
Abstract
Read online
Virus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the components to viral clearance remains unclear. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 102 hospitalised patients with moderate and severe COVID-19 in a longitudinal design. Delayed viral clearance was associated with more severe disease and was associated with higher levels of SARS-CoV-2-specific (neutralising) antibodies over time, increased numbers of neutrophils, monocytes, basophils, and a range of pro-inflammatory cyto-/chemokines illustrating ongoing, partially Th2 dominating, immune activation. In contrast, early viral clearance and less critical illness correlated with the peak of neutralising antibodies, higher levels of CD4 T cells, and in particular naïve CD4+ T cells, suggesting their role in early control of SARS-CoV-2 possibly by proving appropriate B cell help. Higher counts of naïve CD4+ T cells also correlated with lower levels of MIF, IL-9, and TNF-beta, suggesting an indirect role in averting prolonged virus-induced tissue damage. Collectively, our data show that naïve CD4+ T cell play a critical role in rapid viral T cell control, obviating aberrant antibody and cytokine profiles and disease deterioration. These data may help in guiding risk stratification for severe COVID-19.
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