Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients
BackgroundThe host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation ha...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:708bdcdeb96043cba2aa2368d921ecc92021-12-02T10:16:41ZRegulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients1664-322410.3389/fimmu.2021.789735https://doaj.org/article/708bdcdeb96043cba2aa2368d921ecc92021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.789735/fullhttps://doaj.org/toc/1664-3224BackgroundThe host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify.MethodsWe performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses.ResultsThe immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%.ConclusionsThe present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.Sara CaldrerCristina MazziMilena BernardiMarco PratoNiccolò RonzoniPaola RodariAndrea AnghebenChiara PiubelliNatalia TibertiFrontiers Media S.A.articleCOVID-19immunophenotypeT cell subtypesregulatory T cellsdisease severityImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
COVID-19 immunophenotype T cell subtypes regulatory T cells disease severity Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
COVID-19 immunophenotype T cell subtypes regulatory T cells disease severity Immunologic diseases. Allergy RC581-607 Sara Caldrer Cristina Mazzi Milena Bernardi Marco Prato Niccolò Ronzoni Paola Rodari Andrea Angheben Chiara Piubelli Natalia Tiberti Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients |
| description |
BackgroundThe host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify.MethodsWe performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses.ResultsThe immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%.ConclusionsThe present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management. |
| format |
article |
| author |
Sara Caldrer Cristina Mazzi Milena Bernardi Marco Prato Niccolò Ronzoni Paola Rodari Andrea Angheben Chiara Piubelli Natalia Tiberti |
| author_facet |
Sara Caldrer Cristina Mazzi Milena Bernardi Marco Prato Niccolò Ronzoni Paola Rodari Andrea Angheben Chiara Piubelli Natalia Tiberti |
| author_sort |
Sara Caldrer |
| title |
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients |
| title_short |
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients |
| title_full |
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients |
| title_fullStr |
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients |
| title_full_unstemmed |
Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients |
| title_sort |
regulatory t cells as predictors of clinical course in hospitalised covid-19 patients |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/708bdcdeb96043cba2aa2368d921ecc9 |
| work_keys_str_mv |
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| _version_ |
1718397413362761728 |