Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains
Abstract Background Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evide...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13000-024-01445-w |
| _version_ | 1797276075568398336 |
|---|---|
| author | Roy H. Rhodes Gordon L. Love Fernanda Da Silva Lameira Maryam Sadough Shahmirzadi Sharon E. Fox Richard S. Vander Heide |
| author_facet | Roy H. Rhodes Gordon L. Love Fernanda Da Silva Lameira Maryam Sadough Shahmirzadi Sharon E. Fox Richard S. Vander Heide |
| author_sort | Roy H. Rhodes |
| collection | DOAJ |
| description | Abstract Background Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients. Methods Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups. Results The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls. Conclusions Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative. |
| first_indexed | 2024-03-07T15:23:08Z |
| format | Article |
| id | doaj.art-a1935f8cd2b342dba68ccc4fae210f34 |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-03-07T15:23:08Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-a1935f8cd2b342dba68ccc4fae210f342024-03-05T17:30:19ZengBMCDiagnostic Pathology1746-15962024-02-0119112310.1186/s13000-024-01445-wAcute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brainsRoy H. Rhodes0Gordon L. Love1Fernanda Da Silva Lameira2Maryam Sadough Shahmirzadi3Sharon E. Fox4Richard S. Vander Heide5Department of Pathology, Louisiana State University Health Sciences CenterDepartment of Pathology, Louisiana State University Health Sciences CenterDepartment of Pathology, Louisiana State University Health Sciences CenterDepartment of Pathology, Louisiana State University Health Sciences CenterDepartment of Pathology, Louisiana State University Health Sciences CenterDepartment of Pathology, Louisiana State University Health Sciences CenterAbstract Background Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients. Methods Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups. Results The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls. Conclusions Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.https://doi.org/10.1186/s13000-024-01445-wAcute neutrophilic vasculitisAntigen-antibody complexCentral nervous systemComplement componentCOVID-19Karyorrhexis |
| spellingShingle | Roy H. Rhodes Gordon L. Love Fernanda Da Silva Lameira Maryam Sadough Shahmirzadi Sharon E. Fox Richard S. Vander Heide Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains Diagnostic Pathology Acute neutrophilic vasculitis Antigen-antibody complex Central nervous system Complement component COVID-19 Karyorrhexis |
| title | Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains |
| title_full | Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains |
| title_fullStr | Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains |
| title_full_unstemmed | Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains |
| title_short | Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains |
| title_sort | acute neutrophilic vasculitis leukocytoclasia in 36 covid 19 autopsy brains |
| topic | Acute neutrophilic vasculitis Antigen-antibody complex Central nervous system Complement component COVID-19 Karyorrhexis |
| url | https://doi.org/10.1186/s13000-024-01445-w |
| work_keys_str_mv | AT royhrhodes acuteneutrophilicvasculitisleukocytoclasiain36covid19autopsybrains AT gordonllove acuteneutrophilicvasculitisleukocytoclasiain36covid19autopsybrains AT fernandadasilvalameira acuteneutrophilicvasculitisleukocytoclasiain36covid19autopsybrains AT maryamsadoughshahmirzadi acuteneutrophilicvasculitisleukocytoclasiain36covid19autopsybrains AT sharonefox acuteneutrophilicvasculitisleukocytoclasiain36covid19autopsybrains AT richardsvanderheide acuteneutrophilicvasculitisleukocytoclasiain36covid19autopsybrains |