The relationship between peripheral immune response and disease severity in SARS‐CoV‐2‐infected subjects: A cross‐sectional study
Coronavirus disease 2019 (COVID‐19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immun...
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| Veröffentlicht in: | Immunology Jg. 165; H. 4; S. 481 - 496 |
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| Sprache: | Englisch |
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England
Wiley Subscription Services, Inc
01.04.2022
John Wiley and Sons Inc |
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| ISSN: | 0019-2805, 1365-2567, 1365-2567 |
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| Abstract | Coronavirus disease 2019 (COVID‐19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID‐19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty‐seven COVID‐19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID‐19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, interleukin (IL)‐12, IL‐6, IL‐10, and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID‐19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL‐10 as a possible prognostic biomarker for COVID‐19.
Coronavirus disease 2019 (COVID‐19) patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in cMo and a reduction in ncMo, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially pDCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, IL‐12, IL‐6, IL‐10 and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome. |
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| AbstractList | Coronavirus disease 2019 (COVID‐19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID‐19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty‐seven COVID‐19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID‐19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, interleukin (IL)‐12, IL‐6, IL‐10, and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID‐19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL‐10 as a possible prognostic biomarker for COVID‐19. Coronavirus disease 2019 (COVID‐19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID‐19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty‐seven COVID‐19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID‐19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, interleukin (IL)‐12, IL‐6, IL‐10, and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID‐19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL‐10 as a possible prognostic biomarker for COVID‐19. Coronavirus disease 2019 (COVID‐19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID‐19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty‐seven COVID‐19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID‐19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, interleukin (IL)‐12, IL‐6, IL‐10, and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID‐19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL‐10 as a possible prognostic biomarker for COVID‐19. Coronavirus disease 2019 (COVID‐19) patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in cMo and a reduction in ncMo, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially pDCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, IL‐12, IL‐6, IL‐10 and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome. Coronavirus disease 2019 (COVID‐19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID‐19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty‐seven COVID‐19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID‐19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, interleukin (IL)‐12, IL‐6, IL‐10, and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID‐19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL‐10 as a possible prognostic biomarker for COVID‐19. Coronavirus disease 2019 (COVID‐19) patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in cMo and a reduction in ncMo, in addition to a reduction in the expression of HLA‐DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially pDCs, also showed a large reduction in moderate to critical patients. COVID‐19 patients showed an increase in MPO, IL‐12, IL‐6, IL‐10 and IL‐8, accompanied by a reduction in IL‐17A and NOx. IL‐10 levels ≥14 pg/ml were strongly related to the worst outcome. Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID-19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty-seven COVID-19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID-19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA-DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID-19 patients showed an increase in MPO, interleukin (IL)-12, IL-6, IL-10, and IL-8, accompanied by a reduction in IL-17A and NOx. IL-10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID-19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL-10 as a possible prognostic biomarker for COVID-19.Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID-19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty-seven COVID-19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID-19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA-DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID-19 patients showed an increase in MPO, interleukin (IL)-12, IL-6, IL-10, and IL-8, accompanied by a reduction in IL-17A and NOx. IL-10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID-19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL-10 as a possible prognostic biomarker for COVID-19. |
| Author | Luiz, Magali Chaves Santos‐Silva, Maria Cláudia Vanny, Patrícia de Almeida Cardoso, Chandra Chiappin Dalmarco, Eduardo Monguilhott Santos‐Pirath, Íris Mattos Gartner, Rafaela Moraes, Ana Carolina Rabello Costa, Heloisa Zorzi Rosa, Julia Salvan Felisberto, Mariano Masukawa, Ivete Ioshiko Werle, Isabel Mohr, Eduarda Talita Bramorski Walter, Laura Otto Kretzer, Iara Fabricia |
| AuthorAffiliation | 5 Infectious Disease Service Nereu Ramos Hospital. State Health Department Florianópolis Santa Catarina Brazil 1 Postgraduate Program in Pharmacy Federal University of Santa Catarina Florianópolis Santa Catarina Brazil 3 Clinical Analysis Department Health Sciences Center, Postgraduate Program in Pharmacy Federal University of Santa Catarina Florianópolis Santa Catarina Brazil 2 Division of Clinical Analysis Flow Cytometry Service University Hospital of the Federal University of Santa Catarina Florianópolis Santa Catarina Brazil 4 Infectious Disease Service University Hospital of the Federal University of Santa Catarina Florianópolis Santa Catarina Brazil |
| AuthorAffiliation_xml | – name: 3 Clinical Analysis Department Health Sciences Center, Postgraduate Program in Pharmacy Federal University of Santa Catarina Florianópolis Santa Catarina Brazil – name: 2 Division of Clinical Analysis Flow Cytometry Service University Hospital of the Federal University of Santa Catarina Florianópolis Santa Catarina Brazil – name: 4 Infectious Disease Service University Hospital of the Federal University of Santa Catarina Florianópolis Santa Catarina Brazil – name: 5 Infectious Disease Service Nereu Ramos Hospital. State Health Department Florianópolis Santa Catarina Brazil – name: 1 Postgraduate Program in Pharmacy Federal University of Santa Catarina Florianópolis Santa Catarina Brazil |
| Author_xml | – sequence: 1 givenname: Laura Otto orcidid: 0000-0003-3957-619X surname: Walter fullname: Walter, Laura Otto email: laurao.walter@gmail.com organization: Federal University of Santa Catarina – sequence: 2 givenname: Chandra Chiappin surname: Cardoso fullname: Cardoso, Chandra Chiappin organization: University Hospital of the Federal University of Santa Catarina – sequence: 3 givenname: Íris Mattos surname: Santos‐Pirath fullname: Santos‐Pirath, Íris Mattos organization: University Hospital of the Federal University of Santa Catarina – sequence: 4 givenname: Heloisa Zorzi surname: Costa fullname: Costa, Heloisa Zorzi organization: University Hospital of the Federal University of Santa Catarina – sequence: 5 givenname: Rafaela surname: Gartner fullname: Gartner, Rafaela organization: Federal University of Santa Catarina – sequence: 6 givenname: Isabel surname: Werle fullname: Werle, Isabel organization: Federal University of Santa Catarina – sequence: 7 givenname: Eduarda Talita Bramorski surname: Mohr fullname: Mohr, Eduarda Talita Bramorski organization: Federal University of Santa Catarina – sequence: 8 givenname: Julia Salvan orcidid: 0000-0001-9921-9683 surname: Rosa fullname: Rosa, Julia Salvan organization: Federal University of Santa Catarina – sequence: 9 givenname: Mariano orcidid: 0000-0001-9268-4195 surname: Felisberto fullname: Felisberto, Mariano organization: Federal University of Santa Catarina – sequence: 10 givenname: Iara Fabricia orcidid: 0000-0003-1228-7670 surname: Kretzer fullname: Kretzer, Iara Fabricia organization: Federal University of Santa Catarina – sequence: 11 givenname: Ivete Ioshiko surname: Masukawa fullname: Masukawa, Ivete Ioshiko organization: Nereu Ramos Hospital. State Health Department – sequence: 12 givenname: Patrícia de Almeida surname: Vanny fullname: Vanny, Patrícia de Almeida organization: University Hospital of the Federal University of Santa Catarina – sequence: 13 givenname: Magali Chaves surname: Luiz fullname: Luiz, Magali Chaves organization: Nereu Ramos Hospital. State Health Department – sequence: 14 givenname: Ana Carolina Rabello orcidid: 0000-0003-1088-472X surname: Moraes fullname: Moraes, Ana Carolina Rabello organization: University Hospital of the Federal University of Santa Catarina – sequence: 15 givenname: Eduardo Monguilhott orcidid: 0000-0002-5220-5396 surname: Dalmarco fullname: Dalmarco, Eduardo Monguilhott organization: University Hospital of the Federal University of Santa Catarina – sequence: 16 givenname: Maria Cláudia orcidid: 0000-0003-3916-6473 surname: Santos‐Silva fullname: Santos‐Silva, Maria Cláudia email: maria.claudia.silva@ufsc.br organization: Federal University of Santa Catarina |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35146763$$D View this record in MEDLINE/PubMed |
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| IngestDate | Tue Sep 30 16:56:44 EDT 2025 Fri Sep 05 14:26:24 EDT 2025 Fri Oct 03 11:01:43 EDT 2025 Wed Feb 19 02:24:11 EST 2025 Sat Nov 29 07:49:11 EST 2025 Tue Nov 18 22:11:26 EST 2025 Wed Jun 11 08:24:49 EDT 2025 |
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| Issue | 4 |
| Keywords | COVID-19 immune system SARS-CoV-2 inflammation IL-10 |
| Language | English |
| License | 2022 John Wiley & Sons Ltd. This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. |
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| Notes | Funding information This study was supported by JBS S.A. (grant number: 14120/FEESC ‐ Santa Catarina Teaching and Engineering Foundation) and by grants and fellowships from CAPES (Coordination for the Improvement of Higher Education Personnel ‐ Brazil). M. C. Santos‐Silva and E. M. Dalmarco are recipients of a research fellowship from the Brazilian National Council for Scientific and Technological Development (CNPq). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
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| SubjectTerms | Biomarkers Coronaviruses COVID-19 Cross-Sectional Studies Cytokines Cytokines - metabolism Dendritic cells Flow cytometry Histocompatibility antigen HLA Humans IL‐10 Immune response Immune system Immunity Immunosuppression Inflammation Inflammatory response Interleukin 6 Leukocytes (neutrophilic) Monocytes Myelopoiesis Neutrophilia Nitric oxide Original Peroxidase Reduction Respiratory diseases SARS-CoV-2 Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Viral diseases |
| Title | The relationship between peripheral immune response and disease severity in SARS‐CoV‐2‐infected subjects: A cross‐sectional study |
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