tetano
Editor, Senior Moderator
BMC Infect Dis
. 2024 Jul 3;24(1):663.
doi: 10.1186/s12879-024-09321-0. Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions
Gulrayz Ahmed[SUP] 1 [/SUP], Yasir Abdelgadir[SUP] 1 [/SUP], Amro Abdelghani[SUP] 1 [/SUP], Pippa Simpson[SUP] 1 [/SUP], Jody Barbeau[SUP] 1 [/SUP], Donald Basel[SUP] 1 [/SUP], Christy S Barrios[SUP] 1 [/SUP], Brandon A Smith[SUP] 1 [/SUP], Kala F Schilter[SUP] 1 [/SUP], Rupa Udani[SUP] 1 [/SUP], Honey V Reddi[SUP] 1 [/SUP], Rodney E Willoughby[SUP] 2 3 [/SUP]
Affiliations
Background: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC).
Methods: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10.
Results: Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in 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 vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals.
Conclusions: This work elucidates 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.
Keywords: Angiotensin-converting enzyme 2; Transcription; COVID-19; Genetic; Leukocytes; Matrix metalloprotease-9; Mononuclear; Biomarkers; N-terminal peptide of procollagen III; Post-acute COVID-19 syndrome; Tissue inhibitor of metalloprotease-1.
. 2024 Jul 3;24(1):663.
doi: 10.1186/s12879-024-09321-0. Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions
Gulrayz Ahmed[SUP] 1 [/SUP], Yasir Abdelgadir[SUP] 1 [/SUP], Amro Abdelghani[SUP] 1 [/SUP], Pippa Simpson[SUP] 1 [/SUP], Jody Barbeau[SUP] 1 [/SUP], Donald Basel[SUP] 1 [/SUP], Christy S Barrios[SUP] 1 [/SUP], Brandon A Smith[SUP] 1 [/SUP], Kala F Schilter[SUP] 1 [/SUP], Rupa Udani[SUP] 1 [/SUP], Honey V Reddi[SUP] 1 [/SUP], Rodney E Willoughby[SUP] 2 3 [/SUP]
Affiliations
- PMID: 38956476
- PMCID: PMC11221185
- DOI: 10.1186/s12879-024-09321-0
Background: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC).
Methods: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10.
Results: Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in 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 vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals.
Conclusions: This work elucidates 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.
Keywords: Angiotensin-converting enzyme 2; Transcription; COVID-19; Genetic; Leukocytes; Matrix metalloprotease-9; Mononuclear; Biomarkers; N-terminal peptide of procollagen III; Post-acute COVID-19 syndrome; Tissue inhibitor of metalloprotease-1.