Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery
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Working paper
Author(s)
Type
Working Paper
Abstract
Background:SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2), the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity. Objective: In this pilot study we 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). Serum sACE2 levels increased in patients with severe disease recovered over time compared with moderate (p=0.0021) and severe (p=0.0411) COVID-19 subjects at 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.
Funding: IMA is financially supported by the Welcome Trust (093080/Z/10/Z), the EPSRC (EP/T003189/1), and the Community Jameel Imperial College COVID-19 Excellence Fund (G26290) and by the UK MRC (MR/T010371/1). SM is supported by EU project 853850.
Declaration of Interests: The authors declare that there is no conflict of interest to this article.
Ethics Approval Statement: The study was approved by the institutional ethics board of the Masih Daneshvari Hospital (Ethics number SBMU.NRITLD.REC.1399.226).
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). Serum sACE2 levels increased in patients with severe disease recovered over time compared with moderate (p=0.0021) and severe (p=0.0411) COVID-19 subjects at 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.
Funding: IMA is financially supported by the Welcome Trust (093080/Z/10/Z), the EPSRC (EP/T003189/1), and the Community Jameel Imperial College COVID-19 Excellence Fund (G26290) and by the UK MRC (MR/T010371/1). SM is supported by EU project 853850.
Declaration of Interests: The authors declare that there is no conflict of interest to this article.
Ethics Approval Statement: The study was approved by the institutional ethics board of the Masih Daneshvari Hospital (Ethics number SBMU.NRITLD.REC.1399.226).
Date Issued
2021-11-12
Citation
2021
Publisher
Elsevier BV
Copyright Statement
© 2021 The Author(s).
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Medical Research Council (MRC)
Community Jameel Imperial College COVID-19 Excellence Fund
Identifier
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3961252
Grant Number
EP/T003189/1
MR/T010371/1
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Subjects
COVID-19
remdesivir
dexamethasone
cytokines
IL-6
Publication Status
Published