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Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19

Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue d...

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Autores principales: Zhang, Luhao, Li, Rong, Song, Gang, Scholes, Gregory D., She, Zhen-Su
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692966/
https://www.ncbi.nlm.nih.gov/pubmed/34950497
http://dx.doi.org/10.1098/rsos.211606
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author Zhang, Luhao
Li, Rong
Song, Gang
Scholes, Gregory D.
She, Zhen-Su
author_facet Zhang, Luhao
Li, Rong
Song, Gang
Scholes, Gregory D.
She, Zhen-Su
author_sort Zhang, Luhao
collection PubMed
description Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses gives that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells can lead to more significant inflammation, proposing an explanation for the monotonic increase of COVID-19 mortality with age and higher mortality for males. We propose that T cells play a crucial role in the immunity against COVID-19, which provides a new direction–improvement of T cell number for advancing current prevention and treatment.
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spelling pubmed-86929662021-12-22 Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19 Zhang, Luhao Li, Rong Song, Gang Scholes, Gregory D. She, Zhen-Su R Soc Open Sci Mathematics Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses gives that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells can lead to more significant inflammation, proposing an explanation for the monotonic increase of COVID-19 mortality with age and higher mortality for males. We propose that T cells play a crucial role in the immunity against COVID-19, which provides a new direction–improvement of T cell number for advancing current prevention and treatment. The Royal Society 2021-12-22 /pmc/articles/PMC8692966/ /pubmed/34950497 http://dx.doi.org/10.1098/rsos.211606 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Mathematics
Zhang, Luhao
Li, Rong
Song, Gang
Scholes, Gregory D.
She, Zhen-Su
Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19
title Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19
title_full Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19
title_fullStr Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19
title_full_unstemmed Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19
title_short Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19
title_sort impairment of t cells' antiviral and anti-inflammation immunities may be critical to death from covid-19
topic Mathematics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692966/
https://www.ncbi.nlm.nih.gov/pubmed/34950497
http://dx.doi.org/10.1098/rsos.211606
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