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

随着 COVID-19 的严重程度,血清血管紧张素转换酶 (ACE)2 水平下降,细胞因子水平升高:疾病康复后恢复正常

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作者: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

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.

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.

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.

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.

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.

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