Abstract
BackgroundSevere 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. ObjectiveThis 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. MethodsPeripheral 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. ResultsBaseline 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. ConclusionSerum 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.
Highlights
Severe acute respiratory syndrome virus 2 (SARS-CoV-2) causes a respiratory disease that led to the fatal Coronavirus disease 2019 (COVID-19) pandemic [1]
Serum erythrocyte sedimentation rate (ESR) (p 1⁄4 0.0013), CRP (p 1⁄4 0.0067), LDH (p 1⁄4 0.0004) and CPK (p 1⁄4 0.0077) levels were higher in severe COVID-19 patients at baseline than in mild patients whilst baseline levels of all but CPK (p 1⁄4 0.1193) were higher in moderate patients compared with mild patients (Table 2)
We demonstrated that soluble ACE2 (sACE2) levels are lower in severe and moderate COVID-19 patients compared to mild subjects at admission
Summary
Severe acute respiratory syndrome virus 2 (SARS-CoV-2) causes a respiratory disease that led to the fatal Coronavirus disease 2019 (COVID-19) pandemic [1]. RAS operates via two axes: the classic angiotensin converting enzyme (ACE)/Angiotensin (Ang) II/Ang II type 1 (AT1) receptor axis and the non-classical ACE2/Ang 1–7/Mas receptor (MasR) axis. These two pathways have opposing functions: whilst the former is associated with impairment of respiratory conditions the latter plays a protective role in ARDS [7]. 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. Conclusion: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected.
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