tetano
Editor, Senior Moderator
Heliyon
. 2022 Feb 16;e08957.
doi: 10.1016/j.heliyon.2022.e08957. Online ahead of print.
Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery
Esmaeil Mortaz[SUP] 1 2 [/SUP], Hamidreza Jamaati[SUP] 3 [/SUP], Neda Dalil Roofchayee[SUP] 1 [/SUP], Hakime Sheikhzade[SUP] 2 [/SUP], Maryam Mirenayat[SUP] 3 [/SUP], Mohsen Sadeghi[SUP] 3 [/SUP], Somayeh Lookzadeh[SUP] 3 [/SUP], Neda K Dezfuli[SUP] 4 [/SUP], Gert Folkerts[SUP] 5 [/SUP], Sharon Mumby[SUP] 6 [/SUP], Johan Garssen[SUP] 5 7 [/SUP], Ian M Adcock[SUP] 6 [/SUP]
Affiliations
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2)2, the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity.
Objective: This pilot study followed the time-course of sACE2 levels in relation to systemic cytokines in severe and moderate COVID-19 patients treated with remdesivir/dexamethasone in combination.
Methods: Peripheral blood was obtained upon admission from 30 patients (12 with moderate disease and 18 with severe disease) and 14 patients with PCR-confirmed mild COVID-19. Severe and moderate patients were treated with remdesivir (200mg/first day and 100mg/day for the remaining days) and dexamethasone (100mg/day). 6 healthy control subjects (HC) were also enrolled. Serum interleukin (IL)-6 and IL-8 and sACE2 levels were measured by ELISA at baseline and during treatment in severe and moderate patients and at baseline in mild and HCs.
Results: Baseline sACE2 levels were lower in severe (p=0.0005) and moderate (p=0.0022) patients than in patients with mild COVID-19 and in HC (p=0.0023 and p=0.0012 respectively). Treatment significantly increased sACE2 levels in patients with moderate disease (p=0.0156) but only 50% of patients with severe disease showed enhanced levels compared to baseline. Systemic IL-6 and IL-8 levels were higher in all patient groups compared with HC and were not significantly affected over time or by remdesivir/dexamethasone treatment for 5 days. Conclusion: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected. Future studies should link these results to clinical outcomes.
Keywords: COVID-19; Cytokines; Dexamethasone; IL-6; Remdesivir.
. 2022 Feb 16;e08957.
doi: 10.1016/j.heliyon.2022.e08957. Online ahead of print.
Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery
Esmaeil Mortaz[SUP] 1 2 [/SUP], Hamidreza Jamaati[SUP] 3 [/SUP], Neda Dalil Roofchayee[SUP] 1 [/SUP], Hakime Sheikhzade[SUP] 2 [/SUP], Maryam Mirenayat[SUP] 3 [/SUP], Mohsen Sadeghi[SUP] 3 [/SUP], Somayeh Lookzadeh[SUP] 3 [/SUP], Neda K Dezfuli[SUP] 4 [/SUP], Gert Folkerts[SUP] 5 [/SUP], Sharon Mumby[SUP] 6 [/SUP], Johan Garssen[SUP] 5 7 [/SUP], Ian M Adcock[SUP] 6 [/SUP]
Affiliations
- PMID: 35187271
- PMCID: PMC8847112
- DOI: 10.1016/j.heliyon.2022.e08957
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2)2, the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity.
Objective: This pilot study followed the time-course of sACE2 levels in relation to systemic cytokines in severe and moderate COVID-19 patients treated with remdesivir/dexamethasone in combination.
Methods: Peripheral blood was obtained upon admission from 30 patients (12 with moderate disease and 18 with severe disease) and 14 patients with PCR-confirmed mild COVID-19. Severe and moderate patients were treated with remdesivir (200mg/first day and 100mg/day for the remaining days) and dexamethasone (100mg/day). 6 healthy control subjects (HC) were also enrolled. Serum interleukin (IL)-6 and IL-8 and sACE2 levels were measured by ELISA at baseline and during treatment in severe and moderate patients and at baseline in mild and HCs.
Results: Baseline sACE2 levels were lower in severe (p=0.0005) and moderate (p=0.0022) patients than in patients with mild COVID-19 and in HC (p=0.0023 and p=0.0012 respectively). Treatment significantly increased sACE2 levels in patients with moderate disease (p=0.0156) but only 50% of patients with severe disease showed enhanced levels compared to baseline. Systemic IL-6 and IL-8 levels were higher in all patient groups compared with HC and were not significantly affected over time or by remdesivir/dexamethasone treatment for 5 days. Conclusion: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected. Future studies should link these results to clinical outcomes.
Keywords: COVID-19; Cytokines; Dexamethasone; IL-6; Remdesivir.