ACE2 expression in PBMC and plasma markers of vasculopathy and fibrosis during early COVID – implications for post-COVID conditions Article Swipe
Gulrayz Ahmed
,
Yasir Abdelgadir
,
Amro Abdelghani
,
Pippa Simpson
,
Jody Barbeau
,
Donald Basel
,
Christy S. Barrios
,
Brandon A Smith
,
Kala F. Schilter
,
Rupa Udani
,
Honey V. Reddi
,
Rodney E. Willoughby
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3374090/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3374090/v1
Background : Severe COVID is uncommon, restricted to 19% of the population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether variable expression of angiotensin converting enzyme 2 (ACE2) in blood might identify this difference in risk. Methods : The study was IRB-approved, comparing patients hospitalized with severe COVID to healthy controls. A single blood sample was obtained within a day of admission. ACE2 RNA expression in blood cells was measured by RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-2 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10. Results : 48 subjects and 72 controls were recruited. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID but common in healthy controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculitis (MMP-9) were also elevated. ACE2 RNA expression during severe COVID often responded within hours to convalescent plasma. By analogy to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID (the renin-angiotensin system (RAS), inflammation, fibrosis and vasculopathy) initiate or promote post-COVID conditions (PCC) in susceptible individuals. These may respond to convalescent plasma or its derivatives, fresh-frozen plasma or IVIG. Conclusions : This work is hypothesis-generating, elucidating biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.
Related Topics
Concepts
Peripheral blood mononuclear cell
Angiotensin-converting enzyme 2
Fibrosis
Medicine
Immunology
Inflammation
Population
Biomarker
Coronavirus disease 2019 (COVID-19)
Internal medicine
Biology
Disease
Environmental health
Infectious disease (medical specialty)
Biochemistry
In vitro
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3374090/v1
- https://www.researchsquare.com/article/rs-3374090/latest.pdf
- OA Status
- green
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4387376737
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4387376737Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.21203/rs.3.rs-3374090/v1Digital Object Identifier
- Title
-
ACE2 expression in PBMC and plasma markers of vasculopathy and fibrosis during early COVID – implications for post-COVID conditionsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-10-05Full publication date if available
- Authors
-
Gulrayz Ahmed, Yasir Abdelgadir, Amro Abdelghani, Pippa Simpson, Jody Barbeau, Donald Basel, Christy S. Barrios, Brandon A Smith, Kala F. Schilter, Rupa Udani, Honey V. Reddi, Rodney E. WilloughbyList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-3374090/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-3374090/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-3374090/latest.pdfDirect OA link when available
- Concepts
-
Peripheral blood mononuclear cell, Angiotensin-converting enzyme 2, Fibrosis, Medicine, Immunology, Inflammation, Population, Biomarker, Coronavirus disease 2019 (COVID-19), Internal medicine, Biology, Disease, Environmental health, Infectious disease (medical specialty), Biochemistry, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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45Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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