Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study
<p><strong>Background:</strong> Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local i...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2022
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| _version_ | 1826313909724774400 |
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| author | Melero, I Villalba-Esparza, M Recalde-Zamacona, B Álvaro, T Argueta, A García-Tobar, L Álvarez-Gigli, L Sainz, C Garcia-Ros, D Toledo, E Abengozar-Muela, M Fernandez-Alonso, M Rodriguez-Moreno, M Reina, G Carmona-Torre, F Quiroga, JA Pozo, JD Cross, A Echeveste, J Lozano, M Ho, L-P Klenerman, P Issa, F Landecho, M Andrea, CD |
| author_facet | Melero, I Villalba-Esparza, M Recalde-Zamacona, B Álvaro, T Argueta, A García-Tobar, L Álvarez-Gigli, L Sainz, C Garcia-Ros, D Toledo, E Abengozar-Muela, M Fernandez-Alonso, M Rodriguez-Moreno, M Reina, G Carmona-Torre, F Quiroga, JA Pozo, JD Cross, A Echeveste, J Lozano, M Ho, L-P Klenerman, P Issa, F Landecho, M Andrea, CD |
| author_sort | Melero, I |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but have also been shown to mediate tissue damage in a number of diseases.</p>
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<p><strong>Research Question:</strong> Could NETs and their tissue-damaging properties inherent to neutrophil-associated functions play a role in the respiratory failure seen in patients with severe COVID-19, and how does this relate to the SARS-CoV-2 viral loads, IL-8 (CXCL8) chemokine expression, and cytotoxic T-lymphocyte infiltrates?</p>
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<p><strong>Study Design and Methods:</strong> Sixteen lung biopsy samples obtained immediately after death were analyzed methodically as exploratory and validation cohorts. NETs were analyzed quantitatively by multiplexed immunofluorescence and were correlated with local levels of IL-8 messenger RNA (mRNA) and the density of CD8+ T-cell infiltration. SARS-CoV-2 presence in tissue was quantified by reverse-transcriptase polymerase chain reaction and immunohistochemistry analysis.</p>
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<p><strong>Results:</strong> NETs were found in the lung interstitium and surrounding the bronchiolar epithelium with interindividual and spatial heterogeneity. NET density did not correlate with SARS-CoV-2 tissue viral load. NETs were associated with local IL-8 mRNA levels. NETs were also detected in pulmonary thrombi and in only one of eight liver tissues. NET focal presence correlated negatively with CD8+ T-cell infiltration in the lungs.</p>
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<p><strong>Interpretation:</strong> Abundant neutrophils undergoing NETosis are found in the lungs of patients with fatal COVID-19, but no correlation was found with viral loads. The strong association between NETs and IL-8 points to this chemokine as a potentially causative factor. The function of cytotoxic T-lymphocytes in the immune responses against SARS-CoV-2 may be interfered with by the presence of NETs.</p> |
| first_indexed | 2024-09-25T04:23:46Z |
| format | Journal article |
| id | oxford-uuid:941bd08f-217e-4ce8-8c72-5aa358d323c6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:23:46Z |
| publishDate | 2022 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:941bd08f-217e-4ce8-8c72-5aa358d323c62024-08-19T15:23:37ZNeutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:941bd08f-217e-4ce8-8c72-5aa358d323c6EnglishSymplectic ElementsElsevier2022Melero, IVillalba-Esparza, MRecalde-Zamacona, BÁlvaro, TArgueta, AGarcía-Tobar, LÁlvarez-Gigli, LSainz, CGarcia-Ros, DToledo, EAbengozar-Muela, MFernandez-Alonso, MRodriguez-Moreno, MReina, GCarmona-Torre, FQuiroga, JAPozo, JDCross, AEcheveste, JLozano, MHo, L-PKlenerman, PIssa, FLandecho, MAndrea, CD<p><strong>Background:</strong> Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but have also been shown to mediate tissue damage in a number of diseases.</p> <br> <p><strong>Research Question:</strong> Could NETs and their tissue-damaging properties inherent to neutrophil-associated functions play a role in the respiratory failure seen in patients with severe COVID-19, and how does this relate to the SARS-CoV-2 viral loads, IL-8 (CXCL8) chemokine expression, and cytotoxic T-lymphocyte infiltrates?</p> <br> <p><strong>Study Design and Methods:</strong> Sixteen lung biopsy samples obtained immediately after death were analyzed methodically as exploratory and validation cohorts. NETs were analyzed quantitatively by multiplexed immunofluorescence and were correlated with local levels of IL-8 messenger RNA (mRNA) and the density of CD8+ T-cell infiltration. SARS-CoV-2 presence in tissue was quantified by reverse-transcriptase polymerase chain reaction and immunohistochemistry analysis.</p> <br> <p><strong>Results:</strong> NETs were found in the lung interstitium and surrounding the bronchiolar epithelium with interindividual and spatial heterogeneity. NET density did not correlate with SARS-CoV-2 tissue viral load. NETs were associated with local IL-8 mRNA levels. NETs were also detected in pulmonary thrombi and in only one of eight liver tissues. NET focal presence correlated negatively with CD8+ T-cell infiltration in the lungs.</p> <br> <p><strong>Interpretation:</strong> Abundant neutrophils undergoing NETosis are found in the lungs of patients with fatal COVID-19, but no correlation was found with viral loads. The strong association between NETs and IL-8 points to this chemokine as a potentially causative factor. The function of cytotoxic T-lymphocytes in the immune responses against SARS-CoV-2 may be interfered with by the presence of NETs.</p> |
| spellingShingle | Melero, I Villalba-Esparza, M Recalde-Zamacona, B Álvaro, T Argueta, A García-Tobar, L Álvarez-Gigli, L Sainz, C Garcia-Ros, D Toledo, E Abengozar-Muela, M Fernandez-Alonso, M Rodriguez-Moreno, M Reina, G Carmona-Torre, F Quiroga, JA Pozo, JD Cross, A Echeveste, J Lozano, M Ho, L-P Klenerman, P Issa, F Landecho, M Andrea, CD Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study |
| title | Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study |
| title_full | Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study |
| title_fullStr | Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study |
| title_full_unstemmed | Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study |
| title_short | Neutrophil extracellular traps, local IL-8 expression, and cytotoxic T-lymphocyte absence in the lungs of fatal COVID-19: a retrospective histopathology cohort study |
| title_sort | neutrophil extracellular traps local il 8 expression and cytotoxic t lymphocyte absence in the lungs of fatal covid 19 a retrospective histopathology cohort study |
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