PIIS2213260020301168

www.thelancet.com/respiratory Published online March 11, 2020 https://doi.org/10.1016/S2213-2600(20)30116-8 1

Are patients with

hypertension and

diabetes mellitus at

increased risk for
COVID-19 infection?

The most distinctive comorbidities

of 32 non-survivors from a group

of 52 intensive care unit

patients

with novel coronavirus disease

2019 (COVID-19) in the study by

Xiaobo Yang and colleagues

were

cerebrovascular diseases (22%)

and diabetes (22%). Another

study

included 1099 patients

with confirmed COVID-19, of

whom 173 had severe disease with

comorbidities of hypertension

(23¿%), diabetes mellitus (16º%),

coronary heart diseases (5·8%), and

cerebrovascular disease (2»%). In a

third study,3

of 140 patients who were

admitted to hospital with COVID-19,

30% had hypertension and 12% had

diabetes. Notably, the most frequent

comorbidities reported in these three

studies of patients with COVID-19

are often treated with angiotensin-

converting enzyme (ACE) inhibitors;

however, treatment was not assessed
in either study.

Human pathogenic coronaviruses

(severe acute respiratory syndrome

coronavirus [SARS-CoV

CoV-2) bind to their target cells

through angiotensin-converting

enzyme 2 (ACE2), which is expressed
by epithelial cells of the lung, intestine,

kidney, and blood vessels.4

The

expression of ACE2 is substantially

increased in patients with type 1 or

type 2 diabetes, who are treated with

ACE inhibitors and angiotensin II
type-I receptor blockers (ARBs).

Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2.

ACE2 can

also be increased by thiazolidinediones

and ibuprofen. These data suggest

that ACE2 expression is increased

in diabetes and treatment with

ACE inhibitors and ARBs increases

ACE2 expression. Consequently, the

increased expression of ACE2 would

facilitate infection with COVID-19. We

therefore hypothesise that diabetes

and hypertension treatment with

ACE2-stimulating drugs increases the

risk of developing severe and fatal
COVID-19.

If this hypothesis were to be

conrmed, it could lead to a conict

regarding treatment because ACE2

reduces inammation and has been

suggested as a potential new therapy

for inammatory lung diseases, cancer,

diabetes, and hypertension. A further

aspect that should be investigated

is the genetic predisposition for

an increased risk of SARS-CoV-2

infection, which might be due to

ACE2 polymorphisms that have been

linked to diabetes mellitus, cerebral

stroke, and hypertension, specically

in Asian populations. Summarising

this information, the sensitivity of

an individual might result from a

combination of both therapy and
ACE2 polymorphism.

We suggest that patients with

cardiac diseases, hypertension, or

diabetes, who are treated with ACE2-

increasing drugs, are at higher risk

for severe COVID-19 infection and,

therefore, should be monitored for

ACE2-modulating medications, such

as ACE inhibitors or ARBs. Based on a

PubMed search on Feb 28, 2020, we

did not nd any evidence to suggest

that antihypertensive calcium channel

blockers increased ACE2 expression
or activity, therefore these could be a suitable alternative treatment in these patients.We declare no competing interests.Lei Fang, George Karakiulakis,

*Michael Roth

michael.roth@usb.ch

Pulmonary Cell Research and Pneumology,
Department of Biomedicine and Internal Medicine,
University Hospital Basel, CH-4031 Basel,

Switzerland (LF, MR); and Department of
Pharmacology, School of Medicine, Aristotle
University of Thessaloniki, Thessaloniki, Greece (GK)

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; published
online Feb 24. https://doi.org/10.1016/S2213-
2600(20)30079-5.

Guan W
, Ni Z, Hu Y, et al. Clinical characteristics
of coronavirus disease 2019 in China.

N Engl J Med
2020; published online Feb 28.
DOI:10.1056/NEJMoa2002032.

3 Zhang JJ, Dong X

, Cao YY, et al. Clinical
characteristics of 140 patients infected by
SARS-CoV-2 in Wuhan, China. Allergy 2020;

published online Feb 19. DOI:10.1111/
all.14238.

Wan
Y, Shang J, Graham R, Baric RS, Li F.
Receptor recognition by novel coronavirus from

Wuhan: An analysis based on decade-long
structural studies of SARS. J Virology 2020;

published online Jan 29. DOI:10.1128/
JVI.00127-20.

Li X

C, Zhang J, Zhuo JL. The vasoprotective
axes of the renin-angiotensin system:

physiological relevance and therapeutic
implications in cardiovascular, hypertensive
and kidney diseases. Pharmacol Res 2017;
125:

21³8.Lancet Respir Med 2020

Published

Online

March 11, 2020

https://doi.org/10.1016/PII

Juan Gaertner/Science Photo Library


PIIS2213260020301168

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Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?