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
Affiliations
Esmaeil Mortaz
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hamidreza Jamaati
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Neda Dalil Roofchayee
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hakime Sheikhzade
Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Maryam Mirenayat
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mohsen Sadeghi
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Somayeh Lookzadeh
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Neda K. Dezfuli
Department of Immunology and Laboratory Sciences, School of Allied Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran
Gert Folkerts
Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
Sharon Mumby
National Heart and Lung Institute, Imperial College London and the NIHR Imperial Biomedical Research Centre, London, UK
Johan Garssen
Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Center of Excellence Nutricia Research, Utrecht, Netherlands; Corresponding author.
Ian M. Adcock
National Heart and Lung Institute, Imperial College London and the NIHR Imperial Biomedical Research Centre, London, UK; Corresponding author.
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.
