Hypertension and COVID-19 link

1J. ALSAID. 38TH HTN AND CV HIGHLIGHT SESSION 22ND AUG. 2020. CDC
image
COVID 19 AND HTN. WHAT IS THE LINK?
JAFAR ALSAID, M. B. CHB. MD. FASN. FACP
NEPHROLOGY AND INTERNAL MEDICINE CONSULTANT.

PRESENTATION SCHEME
 Introduction.
 Epidemiology COVID-19.
 Prevalence of HTN among COVID-19
 Severe COVID-19 and HTN.
 RAAS.
 ACE2 in COVID 19 patient.
 Link with RASS inh.
 Conclusion.
2J. ALSAID. 38TH HTN AND CV HIGHLIGHT SESSION 22ND AUG. 2020.

J. ALSAID. 38TH HTN AND CV HIGHLIGHT SESSION 22ND AUG. 2020. 3

INTRODUCTION.
 First case reported Wuhan, Hubei Province China 31, Dec. 2019.
 More than 20 million cases of COVID globally.
 600,000 global mortality.
 Every continent, except Antarctica, had reported cases.
 HTN, DM, Elderly, CHD, Lung disease patients are more susceptible and with
more comorbidities.
 75% of cases died in Italy have Hypertension.

TTPS://COVID19.WHO.INT/?GCLID=EAIAIQOBCHMITV_ZNS6Z6WIV4D6TBH3PBAEKEAAYASAAEGKRHPD_BWE
WHO: Global increase of COVID-19 cases
DEC.2019firstcasereport.
Global
Pandemic
Social
distancing ?

https://coronavirus.jhu.edu/map.html

CONFIRMED NEW CASES BY 11 Aug. 2020

Cumulative cases Aug 11th 2020

HTTPS://CORONAVIRUS.JHU.EDU/MAP.HTML

WHERE IS THE LINK BETWEEN HTN & COVID -19??

Prevalence of HTN in COVID -19 patients?

RISK FACTORS FOR COVID AND ITS SEVERITY
 Age.
 DM.
 CV disease & HTN.
 COPD
 Smoking.
 Obesity
 CKD.
 Malignancies.
Drager L, Pio-Abreu A, Lopes R. Bortolotto L. Is HTN a real risk factor for poor prognosis in COVID-19 Pandemic? Current Hypertension Reports (2020) 22:43.
https://doi.org/10.1007/s11906-020-01057-x
Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109(5):531–538.
Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis.
2020:S1201–9712(20)30136–3.
Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and meta-analysis. Arch Acad
Emerg Med. 2020;8(1):e35.

PREVALENCE OF HTN AMONG COVID-19
 15%-35% of COVID-19 patients have HTN.
 Advance age contribution.
 Obesity and CKD could be other confounders.
Guan WJ, Ni Zy, Hu Y, et al. Clinical characteristic of COVID disease in China, N Eng J Med.2020;382(18): 1708-1720.
Lian J, Jin X, Hao S, et al. Analysis of epidemiological and clinical features in older patients with coronavirus disease 2019 (COVID-19) out of
Wuhan. Clin Infect Dis. 2020.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort
study. Lancet. 2020;395(10229):1054-1062.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and
meta-analysis. Arch Acad Emerg Med. 2020;8(1):e35.

DEMOGRAPHIC PARAMETERS AND COMORBIDITIES IN COVID-19 PATIENTS
Reference Sample Mean
Age
Women(
%)
HTN (%) DM (%) CVD
(%)
COPD (%)
Guan et al (3) 1099 47 459 (42) 165 (15) 81 (7) 42 (4) 12 (1)
Lian et al (4) 788 46 381(45) 126 (16) 57 (7) 11 (1) 3 (0.4)
Shi et al (5) 416 64 211 (50) 127 (31) 60 (14) 83 (20) 12 (3)
Guo et al 187 58.5 96 (51) 61(33) 28 (15) 29 (16) 4 (2)
Chen et al (7) 374 62 103 (38) 93(34) 47( 17) 28 (10) 18 (7)
Yang et al (8) 52 59.7 17(33) 9(17) 12 (23) 4 (8)
Zhou et al (9) 191 56 72(38) 58(30) 36(19) 15(8) 6(3)
Huang et al (11) 41 49 11(27) 6(15) 8(20) 6(15) 1(2)
Guan et al (12) 1590
Wang et al (13) 138 56 63(46) 43(31) 14(10) 27(20) 4(3)
Liu et al (15) 137 57 76(56) 13(10) 14(10) 10(7) 2(2)
Wu et al ( 16) 201 51 73(36) 39(19) 22(11) 8(4) 5(3)
Li et al (17) 1527 261(17) 148(10) 250(16)
Rodrigues Morales et al 656 52 289(44) 122(18.6) 94(14.4) 78(11.9)
Tadic, M, Cuspidi C, Grassi G, Mancia G. COVID-19 and arterial HTN: Hypothesis or evidence? J Clin Hypertens, 2020;00:1-7 21J. ALSAID. 38TH HTN AND CV HIGHLIGHT SESSION 22ND AUG. 2020.

15
16
31
33
34
30
15
31
10
19
17
18.6
0
5
10
15
20
25
30
35
40
Comorbidities percentage among COVID patients
%HTN %DM %CVD %COPD
Tadic, M, Cuspidi C, Grassi G, Mancia G. COVID-19 and arterial HTN: Hypothesis or evidence? J Clin Hypertens, 2020;00:1-7

0
5
10
15
20
25
30
35
40
%HTN %DM %CVD %COPD
COMORBIDITIES IN COVID-19 PATIENTS
Mean 22.5%
Mean 3%
Mean 12%
Mean 13%
MEAN AGE

22.50%
13%
12%
3%MEAN COMORBIDITIES AMONG COVID-19 PATIETNS
HTN DM CV COPD

References:
Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720.
Lian J, Jin X, Hao S, et al. Analysis of epidemiological and clinicalfeatures in older patients with coronavirus disease 2019 (COVID-19) out of Wuhan. Clin Infect Dis. 2020.
Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020.
Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020.
Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;26(368):m1091.
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single- centered, retrospective, observational study.
Lancet Respir Med. 2020;8(5):475–481.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet.
2020;395(10229):1054-1062.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: a nationwide analysis. Eur Respir J. 2020;55(55):2000547.
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalizedpatients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069.
Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;133(11):1261–1267.
Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratorydistress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA
Intern Med. 2020.
Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109(5):531–538.
Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID- 19: a systematic review and meta-analysis. Travel Med
Infect Dis. 2020;13:101623.

-1.04 0 1.04
Hypertensio
n
Proportion(95%
CI)
Zhou Y., Yang Q., Chi J. et al. Comorbidities and the risk of sever or fatal outcome associate with
COVID 19: A Meta-analysis. International Journal of Infectious Diseases 99 (2020)
Prevalence of HTN among COVID patients in different populations

HTN IN RELATION TO HOSPITALIZATION AND TREATMENT
Andrew Ip, Parikh K, Parrillo JE, Mathura S, Hansen E, et al. Hypertension and
renineangiotensinealdosterone system inhibitors in patients with covid-19. medRxiv; 2020.
https://doi.org/10.1101/2020.04.24.20077388.
53% of hospitalized patient had HTN.
Mortality of COVID patients on:
• ACE inh. were 27%.
• ARB 33%.
• Other antiHTN were 39%.

ICU ADMISSION AND HYPERTENSION
Among 1382 patients.
Mean age 51.5 years.
57.7 % were males.
Odd ratio of ICU admission was 2.54 (CI 1.83-3.54) for HTN. P < 0.0001
Roncon L, Zuin M, Zuliani G, Rigatelli G. Patients with arterial hypertension and COVID-19 are at higher risk of ICU admission. Br J Anaesth
2020;912(20): 30271e3. https://doi.org/10.1016/j.bja.2020.04.056.

AN OVERVIEW OF RETROSPECTIVE OBSERVATIONAL STUDIES AND
INVESTIGATING HYPERTENSION EFFECT ON COVID-19 SEVERITY
Zaki N., Alashwal H., Ibrahim S. Association of hypertension, DM, stroke, cancer, kidney disease and high cholesterol with COVID -19 disease
severity and fatality: A systemic review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 1133e1142

AN OVERVIEW OF ARTICLES INVESTIGATING KIDNEY DISEASE IN COVID-19
PATIENTS.
Zaki N., Alashwal H., Ibrahim S. Association of hypertension, DM, stroke, cancer, kidney disease and high cholesterol with COVID -19 disease severity
and fatality: A systemic review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 1133e1142

CVD AMONG FATAL AND SURVIVORS WITH COVID-19
18%
31%
24%
20%
12%
9%
4%
10%
1%
3%
10%
0%
5%
10%
15%
20%
25%
30%
35%
Chen et al Yang et al Zhou et al Du et al. Deng et al Wu et al
Fatal Survived

48%
30%
37% 36%
24% 23%
16%
18%
0%
10%
20%
30%
40%
50%
60%
Chen et al Zhou et al Deng et al Wu et al
Fatal Survived
HTN prevalence among fatal and survived cases of COVID-19

PREVALENCE OF COMORBID DISEASE AMONG MORTALITY CASES WITH COVID-19.
38%
23%
19%
9%
0%
5%
10%
15%
20%
25%
30%
35%
40%
HTN DM CVD COPD

WHAT ABOUT COMMUNITY ACQUIRED
PNEUMONIA?
IS THERE ANY LINK WITH HTN?

HTN AND PNEUMONIA.
 > 65 years of age is risk factor for Community acquired Pneumonia.
 HTN increase with old age.
 In elderly patients with Pneumonia, HTN was one of the most common
comorbid factors.
Gutierrez F, Masia M et al. The influence of Age and gender on the population based incidence of
community-aquired pneumonia caused by different mocropathogenes. J infect 2006;53:166-174
Koivula I, Sten M, Makela PH. Risk factors for pneumonia in the elderly Am J Med 1994;96:313-320.

ASSOCIATION OF ACE INH & ARB WITH COMMUNITY AQUIRED
PNEUMONIA.
 ACE inh and ARB had been shown to reduce the risk of community acquired pneumonia.
 ACE inh. and ARB were associated with lower incidence of community acquired pneumonia as
compared with CCB.
 ACE inh. and ARB are linked to lower CV mortality in patients with Community acquired
pneumonia.
J. ALSAID. 38TH HTN AND CV HIGHLIGHT SESSION 22ND AUG. 2020.
36
Caldeira D, Alarcao. Risk of pneumonia associated with use of ACE inh and ARB, systemic review and metanalysis. . BMJ 2012:345-
e4260.
Shah S, MaArthur E et al. Risk of Hospitalization for community acquired pneumonia with RAAS blockage in elderly patients: a
population-bases study. Plos One 2014;9:e85797

RAAS
Renin Angiotensin Aldosterone System

39
D’Ardes D., Boccatonda A., et al. COVID-19 and RAS: Unravelling an Unclear Relationship. Int. J. Mol. Sci. 2020, 21, 3003;
doi:10.3390/ijms21083003
RAAS CASCADE AND TARGET OUTCOME

ACE2, RAAS & COVID-19 INFECTION
Mackey K. King V. Gurley S. et al. Risks and Impact of ACE Inh or ARB on SARS-COv-2 Infection in
Adults. Annals of Internal Medicine. Vol. 173. No. 3. 4 Aug. 2020
RAAS

https://www.nejm.org/doi/pdf/10.1056/NEJMsr2005760?articleTools=tru
e

COVID-19 effect on
ACE2
Kertutz R. Algharably E., Azizi M, et al

20-50% of COVID had DM.
DM had more sever type of infection.
22-43% of COVID mortalities had DM.
DM and COVID
Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, et al. Practical recommendations for the management of diabetes in patients with
COVID-19. Lancet 2020;8(6):546e50. https://doi.org/10.1016/S2213-8587(20)30152-2.
Gupta R, Ghosh A, Kumar AS, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes & Metabolic
Syndrome: Clin Res Rev 2020;14(3):211e2.

ACE 2 EFFECT ON RAAS
Kertutz R. Algharably E., Azizi M, et
al
ACE2 Upregulation:
• ACE inh./ARB. ??
• NSAID.
• Thiazides.
• Tobacco.
• DM.
• Cytokines.
Mackey K. King V. Gurley S. et al.
Risks and Impact of ACE Inh or ARB on SARS-
COv-2 Infection in Adults.
Annals of Internal Medicine. Vol. 173. No. 3. 4
Aug. 2020

ACE 2 UPREGULATED
 ACE inh./ARB. ??
 NSAID.
 Thiazides.
 Tobacco.
 DM.
 Cytokines.
47
Mackey K. King V. Gurley S. et al. Risks and Impact of ACE Inh or ARB on SARS-COv-2 Infection in Adults. Annals of
Internal Medicine. Vol. 173. No. 3. 4 Aug. 2020

ACE 2
 Membrane bound MonocarboxyPeptidase,
 Present in Lung, heart, kidney and GI.
 Convert Angiotensin II to Angiotensin 1-7.
 SARS COV2 binds to ACE2 receptors at the Alveolar epith. Cells. Reducing the ACE2 levels.
 transform Angiotensin II to Angiotensin 1-7.
 Reducing ACE 2 leads to increase Angiotensin II with its deleterious vasoconstriction, Na+
retention, Inflammation and increase fibrosis.
Tadic, M, Cuspidi C, Grassi G, Mancia G. COVID-19 and arterial HTN: Hypothesis or evidence?
J Clin Hypertens, 2020;00:1-7

ACE2
 Down regulation of ACE2 is associated with sever lung injury in experimental animals.
 Angio II- AT1 receptor axis activation has been associated with the severity of lung injury.
 ACE 2 reduction is associated with Bradykinin receptor B1 causing more sever lung injury.
Imai Y, Kuba K et al. ACE2 protects form sever lung acute lung failure. Mature 2005; 436:112-116.
Imai Y, Kuba K, Pennonger JM. The discovery of ACE2 and its role in Acute lung injury in mice. Exp Physiol 2008;93:543-548.
Sobhi CP et al. Attenuation of Pulmonary ACE 2 activation impairs inactivation of de-Arg(9) bradykinin/BKB1R axis and facilitates LPS induced
neutrophil infiltration. Am J Physiol Lung Cell Mol Physiol 2018:314:L17-L131

ARB
effect
ACE inh
ACE inh & ARB action on RASS with COVID-19
Infection
al

EFFECT OF RAAS
BLOCKADE ON
ACE2
al

What happen to the patient using
ACE inh /ARB?

Association of ACE/ARB with mortality in COVID adjusted and unadjusted
samples
Drager L, Pio-Abreu A, Lopes R. Bortolotto L. Is HTN a real risk factor for poor prognosis in COVID-19 Pandemic? Current Hypertension
Reports (2020) 22:43. https://doi.org/10.1007/s11906-020-01057-x

INFLAMMATORY CASCADE IN COVID AND THE LINK WITH
HTN

INFLAMMATION AND COVID-19 AND HTN
 Deterioration of COVID-19 is associated with proinflammatory
cytokines. IL2, IL6, IL7, TNF, Chemokines.
 Cytokines is linked with inflammatory Cytokines as IL6.
 CD4 and CD 8 are deregulated in HTN.
 Immune mechanism is associated with target organ damage in
HTN.
Huange C, Wang y et al. Clinical features of patients infected with 2019 Novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Carnevale D Wenzel P. Mechanical stretch on endothelial cells interconnects innate and adaptive immune response in HTN. Cardiovasc
Res 2018:114:1432-1434.
Loperena R, Van Beusecum. Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and
activation. Roles of STAT3, interlukin 6 adb Hydrogen peroxide. Cardiovasc Res 2018:114:1547-1563.

N 126 patients with COVID.
Retrospective randomized study:
HTN patient with RAAS inh. against non HTN.
Results:
Critical cases 9.3% against 22.9%. P not significant.
Mortality was less 4.7 against 13.3%. P not significant.
Yang G, Tan Z, Zhou L, Yang M, Peng L, et al. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors usage is
associated with improved inflammatory status and clinical outcomes in COVID-19 patients with hypertension. medRxiv; 2020.
OUT COME OF COVID CASES WITH HTN ON RAAS

ANTIHYPERTENSIVE MEDICATION AND COVID INFECTION SEVERITY
Patients using ARB were having less sever disease.
Not significant change for ACE inh, CC and beta blockers.
Liu Y, Huang F, Xu J, Yang P, Qin Y, et al. Anti-hypertensive Angiotensin II receptor blockers associated
to mitigation of disease severity in elderly COVID-19 patients. medRxiv; 2020

CA. CHANNEL BLOCKERS.
Retrospective study.
Ca channel blocker reduced viral replication.
Zhang L, Sun Y, Zeng H, Peng Y, Jiang X, et al. Calcium channel blocker amlodipine besylate is
associated with reduced case fatality rate of COVID-19 patients with hypertension. medRxiv; 2020.

MORE SEVER OUT COME WITH ACE/ARB.
Patient with ACE and ARB had more sever COVID infection.
ACE and ARB increased ACE 2 expression.
Zeng Z, Sha T, Zhang Y, Wu F, Hu H, et al. Hypertension in patients hospitalized with COVID-19 in Wuhan, China: a single-center
retrospective observational study. medRxiv; 2020.
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
Lancet 2020;8. https://doi.org/10.1016/S2213-2600(20)30116-8.
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from wuhan: an analysis based on
decade-long structural studies of SARS coronavirus. J Virol 2020;94(7). https://doi.org/10.1128/JVI.00127-20.

RESEARCH QUESTIONS?
1. Whether ACE inh/ARB would increase the possibility of infected with
COVID-19?
2. If ACE lnh/ARB would cause more sever disease in patients taking them?
3. Adding ACE inh/ARB to a COVID patient would change the disease
course?

USE ACE INH. OR ARB AND ODDS OF GETTING A POSITIVE COVID-19 TEST RESULTS.
Mackey K. King V. Gurley S. et al. Risks and Impact of ACE Inh or ARB on SARS-COv-2 Infection in Adults. Annals of Internal
Medicine. Vol. 173. No. 3. 4 Aug. 2020

 No, for moderate to severe cases.
 Do not know for mild or asymptomatic cases?
DOES THE USE OF ACE INH. OR ARB INCREASE THE POSSIBILITY OF ACQUIRING
COVID- 19 INFECTION?

Study Area Duration
days
N Mean
Age
%
Male
%
HTN
%DM %IHD Adj. OR for sever illness
Bean et al UK 21 205 63 52 51 30 15 0.29 +(0.1-0.75)
Fong et al China 45 476 53 57 24 10 8 NS
Li et al China 60 386 66 52 100 35 17 NS
Liu et AL China 62 46 NS
Mancia et al Italy 6272 68 63 58 30 ACE inh. 0.91 (0.69-1.21),
ARB 0.83 (0.63-1.1)
Mehra et al Asia,
Europe,
N.
America
87 8910 49 26 14 11 ACE inh 0.33 (0.2-0.54)
ARB 1.23 (0.87-1.74)
Meng et al China 43 42 65 57 100 NS
Rentsch et al USA 56 585 66 95 72 44 Hospitalization 1.24 (0.79-1.95)
ICU 1.69(1.01-2.84)
Reynolds et
al
USA 45 2573 64 51 100 40 11 0.55
Giorgi Rossi
et
Italy 33 2653 63 50 18 12 6 Hospital. ACE inh 1.13 (1.1-1.2)
Yang et al China 48 126 66 49 100 30 18 NS
Pong et al China 45 112 62 47 82 21 100 NS
Zeng et al China 60 75 55 55 100 31 NS
Zhang et al China 50 1128 53 53 100 Septic Shock 0.36 (0.16-0.84)
ARDS 0.69(0.47-1.02)
64
USE of ACE inh or ARB and the odds of sever covid-19 illness.

DOES ACE INH OR ARB CAUSE MORE SEVER INFECTION?
Total 13 retrospective observational studies.
 8 in china.
 2 in Italy.
 1 UK.
 2 in USA.
Total patients 23 565.
Conclusion: use of ACE inh or ARB was not associated with increased severity of COVID
illness.

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COVID-19 INFECTION IN A MULTI-SITE UK ACUTE HOSPITAL TRUST. MEDRXIV. 2020. DOI: HTTPS: //DOI.ORG/10.1101/2020.04.07.20056788
FENG Y, LING Y, BAI T, ET AL. COVID-19 WITH DIFFERENT SEVERITY: A MULTI-CENTER STUDY OF CLINICAL FEATURES. AM J RESPIR CRIT
CARE MED. 2020. [PMID: 32275452] DOI:10.1164/RCCM.202002-0445OC
LI J, WANG X, CHEN J, ET AL. ASSOCIATION OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS WITH SEVERITY OR RISK OF DEATH IN
PATIENTS WITH HYPERTENSION
HOSPITALIZED FOR CORONAVIRUS DISEASE 2019 (COVID-19) INFECTION IN WUHAN, CHINA. JAMA CARDIOL. 2020. [PMID: 32324209]
DOI:10 .1001/JAMACARDIO.2020.1624
LIU Y, HUANG F, XU J, ET AL. ANTI-HYPERTENSIVE ANGIOTENSIN II RECEPTOR BLOCKERS ASSOCIATED TO MITIGATION OF DISEASE
SEVERITY IN ELDERLY COVID-19 PATIENTS. MEDRXIV. 2020:2020.03.20.20039586. DOI: 10 .1101/2020.03.20.20039586.
MANCIA G, REA F, LUDERGNANI M, ET AL. RENIN-ANGIOTENSINALDOSTERONE SYSTEM BLOCKERS AND THE RISK OF COVID-19. N ENGL
J MED.
2020. [PMID: 32356627] DOI:10.1056/NEJMOA2006923
MEHRA MR, DESAI SS, KUY S, ET AL. CARDIOVASCULAR DISEASE, DRUG THERAPY, AND MORTALITY IN COVID-19. N ENGL J MED. 2020.
[PMID: 32356626] DOI:10.1056/NEJMOA2007621
MENG J, XIAO G, ZHANG J, ET AL. RENIN-ANGIOTENSIN SYSTEM INHIBITORS IMPROVE THE CLINICAL OUTCOMES OF COVID-19
PATIENTS WITH HYPERTENSION
[LETTER]. EMERG MICROBES INFECT. 2020;9:757-760. [PMID: 32228222] DOI:10.1080/22221751.2020.1746200
RENTSCH CT, KIDWAI-KHAN F, TATE JP, ET AL. COVID-19 TESTING, HOSPITAL ADMISSION, AND INTENSIVE CARE AMONG 2,026,227
UNITED STATES VETERANS AGED 54-75 YEARS. MEDRXIV. 2020:2020.04.09.20059964. DOI: 10.1101/2020.04.09.20059964
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DOES ACE INH OR ARB CAUSE MORE SEVER INFECTION?
 An ongoing Prospective trial from Ireland.
 Enrolling COVID patients receiving ACE or ARM.
 Randomize to continue ACE/ARB or change to other AntiHTN medications.
U.S. National Library of Medicine. Coronavirus (COVID-19) ACEi/ARB Investigation (CORONACION).ClinicalTrials.gov
Identifier:NCT04330300 [updated April 13, 2020]. Accessed at
https://clinicaltrials.gov/ct2/show/NCT04330300?term=NCT04330300&draw=2&rank=1 on 29 April 2020.

WHAT WOULD BE THE EFFECT OF STARTING ACE INH OR ARB FOR
PATIENTS WITH COVID-19?
 No current date.
 Four trails on the way:
1. Efficacy of Captopril in Covid-19 Patients With Severe Acute Respiratory Syndrome (SARS) CoV-2 Pneumonia
(CAPTOCOVID). ClinicalTrials.gov Identifier: NCT04355429 [updated April 28, 2020]. Accessed at https://clinical
trials.gov/ct2/show/NCT04355429?term=NCT04355429&draw =2&rank=1 on 29 April 2020.
2. Angiotensin Converting Enzyme Inhibitors in Treatment of Covid 19. ClinicalTrials.gov Identifier: NCT04345406
[updated April 14, 2020]. Accessed at https: //clinicaltrials.gov/ct2/show/NCT04345406?term=NCT04345406
&draw=2&rank=1 on 29 April 2020.
3. Losartan for Patients With COVID-19 Not Requiring Hospitalization. ClinicalTrials.gov Identifier: NCT04311177 2020
[updated March 23, 2020]. Accessed at https: //clinicaltrials.gov/ct2/show/results/NCT04311177 on 25 March 2020.
4. Losartan for Patients With COVID-19 Requiring Hospitalization. ClinicalTrials.gov Identifier: NCT04312009 2020
[updated March 23, 2020]. Accessed at ht 44

ACE INH./ARB
 Insufficient evidence to conclude on the deleterious or beneficious effect of ACE
inh.
 Over expression of ACE receptors could be deleterious.
 Less controlled BP, heart failure, CKD. Withholding ACE inh. could be more
harmful.
 Alteration of immunity could be beneficious.
 Studies from China, Italy and USA did not confirm any association.
Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin- Angiotensin-Aldosterone System Blockers and the Risk of Covid-19. N Engl J Med.
2020;382(25):2431–2440.
Reynolds HR, Adhikari S, Pulgarin C, et al. Renin-Angiotensin- Aldosterone System Inhibitors and Risk of Covid-19. N Engl J Med.
2020;382(25):2441–2448.
Li J, Wang X, Chen J, Zhang H, Deng A. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of patients with
hypertension hospitalized for coronavirus disease 2019 (COVID-19)infection in Wuhan, China. JAMA Cardiol. 2020.
Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension.
Emerg Microbes Infect. 2020;9(1):757-760.

ONGOING TRIALS ON THE SAFETY AND EFFECT OF ACE/ARB IN COVID-19
PATIENT
Drager L, Pio-Abreu A, Lopes R. Bortolotto L. Is HTN a real risk factor for poor prognosis in COVID-19 Pandemic?
Current Hypertension Reports (2020) 22:43. https://doi.org/10.1007/s11906-020-01057-x

EDITORIAL: HYPERTENSION IN THE
TIME OF THE COVID-19 PANDEMIC:
NEW ISSUES AND ENDURING
CONTROVERSIES
SUZANNE OPARIL, MD
Nephrology Self-Assessment Program - Vol 19, No 1, May

POSSIBLE THERAPY
 ACE 2 analogs.
 Angio 1-7 analog.
 G protein couple receptor for Angio 1-7.
 Mas receptor Agonist.
Drager L, Pio-Abreu A, Lopes R. Bortolotto L. Is HTN a real risk factor for poor prognosis in COVID-19
Pandemic? Current Hypertension Reports (2020) 22:43. https://doi.org/10.1007/s11906-020-01057-x

CONCLUSIONS
 Hypertension is a common comorbidity factor in COVID infection.
 It had been highly prevalent among severe cases as well as fatal COVID inf.
 The link is the ACE2 receptors.
 Alteration of ACE2 representation could affect COVID disease.
 RAAS inh. is not linked with the infection susceptibility in moderate and sever
cases.
 It does not affect the disease outcome.

IS THERE ANY GOOD ASPECT BEHIND
COVID–19 INFECTION ??

Hypertension and COVID-19 link

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