Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients
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Abstract
Background
The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs.
Methods
In this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies.
Findings
Among the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0·343, 95% CI 0·128-0·916, p=0·025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia.
Interpretation
Elderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs.
Funding
National Natural Science Foundation of China, Chinese Academy of Medical Sciences
Research in context
Evidence before this study
We searched PubMed for articles published up to March 15, 2020 using keywords “2019-nCoV”, “SARS-CoV-2”, “novel coronavirus”, and COVID-19 AND “ARB”, and “angiotensin II receptor blocker” for papers published in both English and Chinese. We found three papers: one from our group, published in Science China Life Science that demonstrated an elevated Angiotensin II level in blood samples from COVID-19 patients; another a perspective article in Chinese recommending ACEI and ARBs as potential remedies for SARS-CoV-2 infections; the third a retrospective study in Chinese identifying no significant difference between ACEI/ARB associated with outcomes in 112 COVID-19 patients with CVD comorbidity. The International society of Hypertension stated on March 16 th , 2020: “there are no clinical data in human to show that ACE-inhibitors or ARBs either improve or worsen susceptibility to COVID-19 infection nor do they affect the outcomes of those infected”.
Added value of this study
We retrospectively reviewed different types of anti-hypertensive drugs taken by COVID-19 patients with hypertension comorbidity prior to entering the hospital. We discovered that ARB hypertensive drugs were associated with a decreased risk of severe disease in elderly (age>65) COVID-19 patients (OR=0·343, 95% CI 0·128-0·916, p=0·025), the first evidence of ARBs association to COVID-19 infections in human. We conducted a meta-analysis in the literature and found that ARB has positive effects associated with morbidity and mortality of pneumonia.
Implications of all the available evidence
ARB drugs are widely used in the population with hypertension. Treatments with ACEI and ARBs should be continuous according to medical guidelines. RCT trials of ARB associated with morbidity and mortality of SARS-CoV-2 infection are recommended in the future.
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SciScore for 10.1101/2020.03.20.20039586: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was performed in accordance with guidelines approved by the Ethics Committees from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (002-2020).
Consent: Verbal informed consent was obtained from patients or patients’ family members if available and the requirement for informed consent was waived by the Ethics Commission.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Meta-analysis: We searched the NCBI and Medline databases for potentially eligible records. Medlinesuggested: (MEDLINE, RRID:SCR_00…SciScore for 10.1101/2020.03.20.20039586: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was performed in accordance with guidelines approved by the Ethics Committees from the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (002-2020).
Consent: Verbal informed consent was obtained from patients or patients’ family members if available and the requirement for informed consent was waived by the Ethics Commission.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Meta-analysis: We searched the NCBI and Medline databases for potentially eligible records. Medlinesuggested: (MEDLINE, RRID:SCR_002185)Statistical analyses were performed with SPSS 16·0 for Windows (SPSS, Inc.). SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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