Another COVID-19 Mystery Unraveled: Why Some Are More Susceptible to Severe Infection
Update 21.06.2022
New
study reveals the biological mechanisms underlying the greater vulnerability of
smokers, diabetics, and people with stroke to severe COVID-19 infection
Worldwide, COVID-19 trends so far indicate that the disease is much more severe in certain groups of individuals, such as those who smoke, are older, or have diabetes. But the causes underlying this trend remain unknown. Now, researchers at the National Institute of Health, Korea, find that the cell surface receptor ACE2, which is the novel coronavirus’ gateway into a cell, increases at various sites in our bodies with smoking, diabetes, and stroke.
In a new study, researchers from Korea discovered that individuals with smoking habits, strokes, and diabetes show higher levels of ACE2, the receptor that binds to the spike protein on the novel coronavirus, putting them at a greater risk of infection.
Photo courtesy: Kateryna Kon from
Shutterstock.
Over 2020, as the COVID-19 pandemic progressed, it became clear that the
virus was more likely to cause severe disease in certain “high-risk”
populations, such as older folks, those with diabetes, and people with
cardiovascular and cerebrovascular conditions like high blood pressure or
stroke. A year into the pandemic, several variants of the virus down the line,
this trend continues to hold true.
But, in this time, while we’ve made considerable progress in terms of
understanding the mechanisms by which the virus acts in our bodies, we have not
been able to definitively find out what makes these high-risk populations more
vulnerable than everyone else.
Now, a group of researchers from the National Institute of Health, Korea,
presents an explanation. Their findings are published in Biochemical and Biophysical Research
Communications.
Speaking of their motivations for the study, lead scientist Dr. Young Ho Koh says, “Patients
with chronic disease account for about 98.5% of the COVID-19-related mortality
in Korea. Scientific study of the underlying causes of this trend are needed to
increase understanding and reduce anxiety among the public about groups
vulnerable to COVID-19 infection.” This study
was supported by the fund (2020-NI-024-00) from Research of Korea Centers for
Disease Control and Prevention.
The scientists began with a key finding related to how the novel
coronavirus causes infection in our body. The virus’ name comes from the fact
that its shell is covered with spike proteins, which give it a distinctive
crown (corona)-like shape. It uses these spikes to bind to a receptor on cell
surfaces called “angiotensin-converting enzyme 2” (ACE2) and enters the cells.
So, people who have increased expression of ACE2 on some tissue or another in
the body are more susceptible to greater infection.
The ACE2 receptor is found on various bodily tissues, such as the heart,
lungs, kidney, intestines, blood vessels, and certain neurons. It is an
important enzyme for regulating blood vessel contraction and certain
inflammatory responses (immune responses). ACE2 also serves as the entry point
into cells for some coronaviruses, including SARS-CoV-2 (the virus that causes
COVID-19). And as it turned out, recent clinical studies revealed the presence of the
novel coronavirus in tissues other than the lungs and blood vessels, even in
postmortem brains. Thus, speaking of how they began the study, Dr. Koh
explains, “Since cells that express ACE2
are potentially at risk of novel coronavirus infection, ACE2 expression
profiling under various conditions in the brain can help us understand the
process of COVID-19 infection.”
Dr. Koh's research group conducted a series of experiments. An mRNA sequencing of brain tissues from
rat models with ischemic stroke (where a blood vessel has a blockage) in the
brain showed an increased expression of ACE2. Further, human brain microvessel and astrocyte (a type
of neuron) cells exposed to cigarette smoke extract showed greatly increased
ACE2 expression. In
addition, a comparison of human aortic endothelial cells of patients with types 1 and 2
diabetes and those of healthy people showed higher ACE2 expressions in the
cells of those with diabetes. Finally, analysis
of the brain tissues of mice with type 2 diabetes showed increased ACE2
expression as well.
These findings are preliminary and remain to be verified clinically, but
undoubtedly, they are one of the first significant steps towards understanding
why individuals with smoking habits, diabetes, and stroke are more vulnerable
to the severe symptoms of COVID-19, such as cerebrovascular diseases: they have
an increased expression of the ACE2 receptor in their brain vascular and
neuronal (astrocyte) cells.
The researchers are also hopeful of extending these findings beyond the
vulnerable groups explored in their study. Speaking of the potential scientific
and socio-economic ripple effects of their study, Dr. Koh says, “While this study focused on strokes,
diabetes, and smoking, the approach followed can be applied to other groups at
high risk of severe COVID-19 infection, such as the elderly and patients with chronic diseases like chronic
respiratory disease or cancer. Furthermore, our results have been used as the
basis for some COVID-19 prevention and quarantine guidelines, such as smoking
cessation and observance of social distancing rules.”
These findings are, after all, a firmer affirmation of the fact that some
groups of people are more vulnerable to the disease than others and should be protected.
Reference
Authors Ji-Young
Choi, Hye-Kyung Lee, Jung Hyun Park, Sun-Jung Cho, Munjin Kwon, Chulman Jo,
Young Ho Koh
Title of original paper Altered COVID-19 receptor ACE2 expression in a higher risk group for cerebrovascular disease and ischemic stroke
Journal Biochemical and Biophysical
Research Communications
DOI 10.1016/j.bbrc.2020.05.203
Affiliations Division
of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of
Health
About
National Institute of Health in Korea
The
Korea National Institute of Health (KNIH), one of the major operating
components of the Ministry of Health and Welfare, leads the nation’s medical
research. Over the past seven decades, the KNIH has made unwavering efforts to
enhance the public’s health and innovate biomedical research. The KNIH seeks to
eradicate diseases and make people healthier. The KNIH establishes a scientific
basis and evidence underlying health policy as well as provides national
research infrastructures. We also promote public health research. To this end,
we make efforts to enrich a health research environment by granting funds to
research projects and keeping our resources, data, and facilities more open and
accessible to researchers.
Website:
http://www.nih.go.kr/eng/
About Professor Young Ho Koh