Abstract
Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.
摘要
目的
评估血管紧张素受体阻滞剂 (ARB) 的使用对新型冠状病毒肺炎 (COVID-19) 高血压患者疾病转归的影响。
创新点
揭示了ARB使用对COVID-19高血压患者病毒载量和抗体水平动态变化过程的影响, 进一步利用转录组学揭示了ARB使用后基因表达谱的变化对疾病转归的影响。
方法
收集浙江大学医学院附属第一医院COVID-19高血压患者病历资料, 分析并评估ARB使用对COVID-19高血压患者病毒载量、抗体水平和转录特征的影响。
结论
ARB使用与COVID-19高血压患者病情加重不存在相关性: ARB使用显著降低COVID-19高血压患者病毒持续时间与病毒载量; ARB使用对抗体水平以及可溶性血管紧张素转换酶2 (ACE2) 水平无显著影响; 转录组分析显示, 两组差异基因主要富集于氧转运、碳酸氢盐转运和血凝等。
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References
Bean DM, Kraljevic Z, Searle T, et al., 2020. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust. Eur J Heart Fail, 22(6):967–974. https://doi.org/10.1002/ejhf.1924
Cox RJ, Brokstad KA, 2020. Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol, 20(10):581–582. https://doi.org/10.1038/s41577-020-00436-4
Fang L, Karakiulakis G, Roth M, 2020. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. Lancet Respir Med, 8(4):e21. https://doi.org/10.1016/s2213-2600(20)30116-8
Fosbol EL, Butt JH, Østergaard L, et al., 2020. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA, 324(2):168–177. https://doi.org/10.1001/jama.2020.11301
Gao C, Cai Y, Zhang K, et al., 2020. Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. Eur Heart J, 41(22):2058–2066. https://doi.org/10.1093/eurheartj/ehaa433
Grasselli G, Greco M, Zanella A, et al., 2020. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. JAMA Intern Med, 180(10):1345–1355. https://doi.org/10.1001/jamainternmed.2020.3539
Imai Y, Kuba K, Rao S, et al., 2005. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 436(7047):112–116. https://doi.org/10.1038/nature03712
Kreutz R, Algharably EAEH, Azizi M, et al., 2020. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence. Cardiovasc Res, 116(10):1688–1699. https://doi.org/10.1093/cvr/cvaa097
Kuba K, Imai Y, Rao S, et al., 2005. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med, 11(8):875–879. https://doi.org/10.1038/nm1267
Lam KW, Chow KW, Vo J, et al., 2020. Continued in-hospital angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use in hypertensive COVID-19 patients is associated with positive clinical outcome. J Infect Dis, 222(8):1256–1264. https://doi.org/10.1093/infdis/jiaa447
Lan J, Ge JW, Yu JF, et al., 2020. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 581(7807):215–220. https://doi.org/10.1038/s41586-020-2180-5
Levi M, Thachil J, Iba T, et al., 2020. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol, 7(6):e438–e440. https://doi.org/10.1016/s2352-3026(20)30145-9
Liao DY, Zhou F, Luo LL, et al., 2020. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol, 7(9):e671–e678. https://doi.org/10.1016/s2352-3026(20)30217-9
Liu X, Speranza E, Munoz-Fontela C, et al., 2017. Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus. Genome Biol, 18:4. https://doi.org/10.1186/s13059-016-1137-3
Mackey K, King VJ, Gurley S, et al., 2020. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review. Ann Intern Med, 173(3):195–203. https://doi.org/10.7326/m20-1515
Mancia G, Rea F, Ludergnani M, et al., 2020. Renin-angiotensin-aldosterone system blockers and the risk of COVID-19. New Engl J Med, 382(25):2431–2440. https://doi.org/10.1056/NEJMoa2006923
Mehta N, Kalra A, Nowacki AS, et al., 2020. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol, 5(9):1020–1026. https://doi.org/10.1001/jamacardio.2020.1855
Meng J, Xiao GH, Zhang JJ, et al., 2020. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect, 9(1):757–760. https://doi.org/10.1080/22221751.2020.1746200
National Health Commission of the People’s Republic of China, 2020. Guideline for diagnosis and treatment of SARS-CoV-2 (the 7th edition). http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989. shtml (in Chinese).
Pinto BGG, Oliveira AER, Singh Y, et al., 2020. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. J Infect Dis, 222(4):556–563. https://doi.org/10.1093/infdis/jiaa332
Romagnoli S, Peris A, de Gaudio AR, et al., 2020. SARS-CoV-2 and COVID-19: from the bench to the bedside. Physiol Rev, 100(4):1455–1466. https://doi.org/10.1152/physrev.00020.2020
Shang J, Ye G, Shi K, et al., 2020. Structural basis of receptor recognition by SARS-CoV-2. Nature, 581(7807):221–224. https://doi.org/10.1038/s41586-020-2179-y
Vistisen ST, Bodilsen J, Scheeren TWL, et al., 2020. Risk and prognosis of COVID-19 in patients treated with renin-angiotensin-aldosterone inhibitors. Eur J Anaesthesiol, 37(9):739–742. https://doi.org/10.1097/eja.0000000000001277
World Health Organization, 2020. Coronavirus disease (COVID-19): weekly epidemiological update and weekly operational update. Technical Report. World Health Organization, Geneva. https://www.who.int/publications/m/item/weekly-epidemiological-update—-16-march-2021
Wrapp D, Wang NS, Corbett KS, et al., 2020. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483):1260–1263. https://doi.org/10.1126/science.abb2507
Yang G, Tan ZH, Zhou L, et al., 2020. Effects of angiotensin II receptor blockers and ACE (angiotensin-converting enzyme) inhibitors on virus infection, inflammatory status, and clinical outcomes in patients with COVID-19 and hypertension: a single-center retrospective study. Hypertension, 76(1):51–58. https://doi.org/10.1161/hypertensionaha.120.15143
Zhang JS, Wang ML, Ding W, et al., 2020. The interaction of RAAS inhibitors with COVID-19: current progress, perspective and future. Life Sci, 257:118142. https://doi.org/10.1016/j.lfs.2020.118142
Zhang P, Zhu LH, Cai JJ, et al., 2020. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res, 126(12):1671–1681. https://doi.org/10.1161/circresaha.120.317134
Zheng SF, Fan J, Yu F, et al., 2020. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang Province, China, January–March 2020: retrospective cohort study. BMJ, 369:m1443. https://doi.org/10.1136/bmj.m1443
Zheng YY, Ma YT, Zhang JY, et al., 2020. COVID-19 and the cardiovascular system. Nat Rev Cardiol, 17(5):259–260. https://doi.org/10.1038/s41569-020-0360-5
Acknowledgments
This work is supported by the Department of Education of Zhejiang Province (No. Y202043382) and the National Natural Science Foundation of China (Nos. 82072377 and 81971919). We appreciate the selfless dedication of all medical staff of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China in the fight against the epidemic, and the willingness of the patients to participate in the study.
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Baihuan FENG performed the clinical laboratory testing and data analysis, and wrote and edited the manuscript. Dan ZHANG performed the clinical laboratory testing and edited the manuscript. Qi WANG, Fei YU, Qianda ZOU, Guoliang XIE, Ruonan WANG, Xianzhi YANG, Weizhen CHEN, and Bin LOU performed the data collection. Shufa ZHENG contributed to the study design, data analysis, and writing and editing of the manuscript. Yu CHEN contributed to the study design. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Baihuan FENG, Dan ZHANG, Qi WANG, Fei YU, Qianda ZOU, Guoliang XIE, Ruonan WANG, Xianzhi YANG, Weizhen CHEN, Bin LOU, Shufa ZHENG, and Yu CHEN declare that they have no conflict of interest.
This study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (2020IIT A0107). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.
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Feng, B., Zhang, D., Wang, Q. et al. Effects of angiotensin II receptor blocker usage on viral load, antibody dynamics, and transcriptional characteristics among COVID-19 patients with hypertension. J. Zhejiang Univ. Sci. B 22, 330–340 (2021). https://doi.org/10.1631/jzus.B2000730
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DOI: https://doi.org/10.1631/jzus.B2000730
Key words
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
- Coronavirus disease 2019 (COVID-19)
- Renin-angiotensin system (RAS)
- Angiotensin-converting enzyme 2 (ACE2)
- Hypertension