Background. Angiotensing converting enzyme type 2 (ACE2), a key enzyme of the renin-angiotensin-aldosterone system (RAAS), is the receptor of SARS-CoV-2 for cell entry into lungs. Because ACE2 may be modulated by RAAS inhibitors, such as angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEi and ARBs may be at higher risk for COVID-19 infection and severity. Aim. To analyze the associations between COVID-19 and hypertension, and treatments with ACEi and ARBs. Methods. In this retrospective observational study, consecutive patients hospitalized for suspected COVID-19 pneumonia will be divided into 2 groups, whether or not COVID-19 is confirmed. The two groups will be compared for baseline characteristics, mainly prior treatment with ACEi and ARBs, and clinical outcome at 1-month follow-up. The main hypothesis is that ACEi and ARBs, which interact differently with ACE2, may have different relationships with COVID-19 infection or severity.
The coronavirus disease 2019 (Covid-19) pandemic is currently the main challenge facing
healthcare providers. Data are lacking to guide clinical decision.
The renin-angiotensin-aldosterone system (RAAS) is a key process in cardiology. Its
inhibition using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type
1-receptor blockers (ARBs) is a cornerstone of the long-term management of arterial
hypertension, heart failure and acute coronary syndrome. Severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) uses the angiotensin-converting enzyme 2 (ACE2) as a cellular
entry receptor. ACE2 is part of the RAAS and is likely to be modulated by the use of ACEi and
ARBs. Therefore, there is concern that patients who are treated with ACEi and ARBs may be at
higher risk for Covid-19 infection.
However, little is known regarding how ACEi and ARBs could affect Covid-19 infection and
severity. First, ACE2 may have a protective effect against lung injury because it degrades
angiotensin II to angiotensin-(1-7). Second, the effect of RAAS inhibition on ACE2 expression
has been poorly studied in humans. Third, ACE inhibitors and ARB have different effect on the
RAAS and therefore their interaction with Covid-19 may differ.
The COVHYP study is designed to address part of these issues. This is an analytical
retrospective observational study that will collect and analyze data regarding patients
hospitalized with suspected Covid-19. We planned to screen for inclusion all consecutive
patients referred form 10/03/2020 to 15/04/2020 to the emergency department of the Versailles
Hospital, a tertiary center located in greater Paris area - one of the region most affected
by Covid-19 in France through this period. The inclusion criteria are as follows: 1) Clinical
presentation suggestive of COVID-19 pneumonia, at least fever or influenza-like syndrome AND
cough or dyspnea; and 2) Test of the presence of SARS-CoV-2 RNA by RT-PCR in nasopharyngeal
or sputum samples. Two groups of patients will be defined, those with confirmed Covid-19
pneumonia, and those without Covid-19. Hospital data will gathered, and patients or relatives
will be contacted by phone for a one-month follow-up. We will compare baseline
characteristics of patients, especially the previous treatment by ACEi or ARBs, in the two
groups of patients, and evaluate whether these characteristics can be associated with
diagnosis of SARS-CoV-2 infection and severity.
We hope that this study will provide a better understanding of the effect of RAAS inhibitors
on Covid-19 pneumonia and its severity.
Inclusion Criteria:
- Age equal or more than 18;
- Symptoms suggestive of Covid-19 pneumonia. At least : fever > 38°C or influenza-like
illness (asthenia, myalgia, chills, muscular aches, …) AND cough or dyspnea;
- Hospitalization required on clinical criteria including: oxygen saturation <96%
without oxygen support, respiratory frequency > 25 per minute, hemodynamic
instability, medical history or comorbidities known at high risk for Covid-19 (chronic
heart disease, congestive heart failure, chronic bronchopulmonary disease, diabetes
mellitus, age>70, history of cancer, immunosuppression, …);
- Covid-19 confirmation test performed (RT-PCR).
Exclusion Criteria:
- Age < 18
- Refusal to participate in the study
- detainee or prisoner
- Protected adult uncapable to consent
Jean-Louis GEORGES, MD, MPH
33+139638870
jgeorges@ch-versailles.fr
Jean-Baptiste AZOWA
33+139638355
jbazowa@ch-versailles.fr