Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

Esmaeil Mortaz; Hamidreza Jamaati; Neda Dalil Roofchayee; Hakime Sheikhzade; Maryam Mirenayat; Mohsen Sadeghi; Somayeh Lookzadeh; Neda K Dezfuli; Gert Folkerts; Sharon Mumby; Johan Garssen; Ian M Adcock

doi:10.1016/j.heliyon.2022.e08957

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

Esmaeil Mortaz, Hamidreza Jamaati, Neda Dalil Roofchayee, Hakime Sheikhzade, Maryam Mirenayat, Mohsen Sadeghi, Somayeh Lookzadeh, Neda K Dezfuli, Gert Folkerts, Sharon Mumby, Johan Garssen, Ian M Adcock

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	e08957
Pages (from-to)	1-8
Journal	Heliyon
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/j.heliyon.2022.e08957
Publication status	Published - Feb 2022

Bibliographical note

Funding Information:
Ian M. Adcock was supported by the Welcome Trust ; ( 093080/Z/10/Z ), the EPSRC ( EP/T003189/1 ), the Community Jameel Imperial College COVID-19 Excellence Fund ( G26290 ) and by the UK MRC (MR/T010371/1). Sharon Mumby was supported by EU project 853850.

Publisher Copyright:
© 2022 The Author(s)

Keywords

COVID-19
Cytokines
Dexamethasone
IL-6
Remdesivir

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1-s2.0-S2405844022002456-mainFinal published version, 964 KBLicence: CC BY

Cite this

Mortaz, E., Jamaati, H., Roofchayee, N. D., Sheikhzade, H., Mirenayat, M., Sadeghi, M., Lookzadeh, S., Dezfuli, N. K., Folkerts, G., Mumby, S., Garssen, J., & Adcock, I. M. (2022). Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery. Heliyon, 8(2), 1-8. Article e08957. https://doi.org/10.1016/j.heliyon.2022.e08957

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title = "Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery",

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",

author = "Esmaeil Mortaz and Hamidreza Jamaati and Roofchayee, {Neda Dalil} and Hakime Sheikhzade and Maryam Mirenayat and Mohsen Sadeghi and Somayeh Lookzadeh and Dezfuli, {Neda K} and Gert Folkerts and Sharon Mumby and Johan Garssen and Adcock, {Ian M}",

note = "Funding Information: Ian M. Adcock was supported by the Welcome Trust ; ( 093080/Z/10/Z ), the EPSRC ( EP/T003189/1 ), the Community Jameel Imperial College COVID-19 Excellence Fund ( G26290 ) and by the UK MRC (MR/T010371/1). Sharon Mumby was supported by EU project 853850. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = feb,

doi = "10.1016/j.heliyon.2022.e08957",

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Mortaz, E, Jamaati, H, Roofchayee, ND, Sheikhzade, H, Mirenayat, M, Sadeghi, M, Lookzadeh, S, Dezfuli, NK, Folkerts, G, Mumby, S, Garssen, J & Adcock, IM 2022, 'Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery', Heliyon, vol. 8, no. 2, e08957, pp. 1-8. https://doi.org/10.1016/j.heliyon.2022.e08957

TY - JOUR

T1 - Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19

T2 - normalisation upon disease recovery

AU - Mortaz, Esmaeil

AU - Jamaati, Hamidreza

AU - Roofchayee, Neda Dalil

AU - Sheikhzade, Hakime

AU - Mirenayat, Maryam

AU - Sadeghi, Mohsen

AU - Lookzadeh, Somayeh

AU - Dezfuli, Neda K

AU - Folkerts, Gert

AU - Mumby, Sharon

AU - Garssen, Johan

AU - Adcock, Ian M

N1 - Funding Information: Ian M. Adcock was supported by the Welcome Trust ; ( 093080/Z/10/Z ), the EPSRC ( EP/T003189/1 ), the Community Jameel Imperial College COVID-19 Excellence Fund ( G26290 ) and by the UK MRC (MR/T010371/1). Sharon Mumby was supported by EU project 853850. Publisher Copyright: © 2022 The Author(s)

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

KW - COVID-19

KW - Cytokines

KW - Dexamethasone

KW - IL-6

KW - Remdesivir

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U2 - 10.1016/j.heliyon.2022.e08957

DO - 10.1016/j.heliyon.2022.e08957

M3 - Article

C2 - 35187271

SN - 2405-8440

VL - 8

SP - 1

EP - 8

JO - Heliyon

JF - Heliyon

IS - 2

M1 - e08957

ER -

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery

Abstract

Bibliographical note

Keywords

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