Two specific cell types in the nose have been identified as likely
initial infection points for COVID-19 coronavirus. Scientists discovered that
goblet and ciliated cells in the nose have high levels of the entry proteins
that the COVID-19 virus uses to get into our cells. The identification of these
cells by researchers from the Wellcome Sanger Institute, University Medical
Centre Groningen, University Cote d’Azur and CNRS, Nice and their
collaborators, as part of the Human Cell Atlas Lung Biological Network, could
help explain the high transmission rate of COVID-19.
Reported in Nature Medicine, this first publication with the Lung
Biological Network is part of an ongoing international effort to use Human Cell
Atlas data to understand infection and disease. It further shows that cells in
the eye and some other organs also contain the viral-entry proteins. The study
also predicts how a key entry protein is regulated with other immune system
genes and reveals potential targets for the development of treatments to reduce
transmission.
Novel
coronavirus disease — COVID-19 — affects the lungs and airways. Patient’s
symptoms can be flu-like, including fever, coughing and sore throat, while some
people may not experience symptoms but still have transmissible virus. In the
worst cases, the virus causes pneumonia that can ultimately lead to death. The
virus is thought to be spread through respiratory droplets produced when an
infected person coughs or sneezes, and appears to be easily transmitted within
affected areas. So far the virus has spread to more than 184 countries and
claimed more than 180,000 lives.
Scientists
around the world are trying to understand exactly how the virus spreads, to
help prevent transmission and develop a vaccine. While it is known that the virus
that causes COVID-19 disease, known as SARS-CoV-2, uses a similar mechanism to
infect our cells as a related coronavirus that caused the 2003 SARS epidemic,
the exact cell types involved in the nose had not previously been pinpointed.
To discover which
cells could be involved in COVID-19 transmission, researchers analysed multiple
Human Cell Atlas (HCA) consortium datasets of single cell RNA sequencing, from
more than 20 different tissues of non-infected people. These included cells
from the lung, nasal cavity, eye, gut, heart, kidney and liver. The researchers
looked for which individual cells expressed both of two key entry proteins that
are used by the COVID-19 virus to infect our cells.
Dr Waradon
Sungnak, the first author on the paper from Wellcome Sanger Institute, said:
“We found that the receptor protein — ACE2 — and the TMPRSS2 protease that can
activate SARS-CoV-2 entry are expressed in cells in different organs, including
the cells on the inner lining of the nose. We then revealed that mucus-producing
goblet cells and ciliated cells in the nose had the highest levels of both
these COVID-19 virus proteins, of all cells in the airways. This makes these
cells the most likely initial infection route for the virus.”
Dr Martijn
Nawijn, from the University Medical Center Groningen in the Netherlands, said,
on behalf of the HCA Lung Biological Network: “This is the first time these
particular cells in the nose have been associated with COVID-19. While there
are many factors that contribute to virus transmissibility, our findings are
consistent with the rapid infection rates of the virus seen so far. The
location of these cells on the surface of the inside of the nose make them
highly accessible to the virus, and also may assist with transmission to other
people.”
The two key
entry proteins ACE2 and TMPRSS2 were also found in cells in the cornea of the
eye and in the lining of the intestine. This suggests another possible route of
infection via the eye and tear ducts, and also revealed a potential for fecal-oral
transmission.
When cells are
damaged or fighting an infection, various immune genes are activated. The study
showed that ACE2 receptor production in the nose cells is probably switched on
at the same time as these other immune genes.
The work was carried
out as part of the global Human Cell Atlas consortium which aims to create
reference maps of all human cells to understand health and disease. More than
1,600 people across 70 countries are involved in the HCA community, and the
data is openly available to scientists worldwide.
Dr Sarah
Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of
the HCA Organising Committee, said: “As we’re building the Human Cell Atlas it
is already being used to understand COVID-19 and identify which of our cells
are critical for initial infection and transmission. This information can be
used to better understand how coronavirus spreads. Knowing which exact cell
types are important for virus transmission also provides a basis for developing
potential treatments to reduce the spread of the virus.”
The global HCA
Lung Biological Network continues to analyse the data in order to provide
further insights into the cells and targets likely to be involved in COVID-19,
and to relate them to patient characteristics.
Professor Sir
Jeremy Farrar, Director of Wellcome, said: “By pinpointing the exact
characteristics of every single cell type, the Human Cell Atlas is helping
scientists to diagnose, monitor and treat diseases including COVID-19 in a
completely new way. Researchers around the world are working at an
unprecedented pace to deepen our understanding of COVID-19, and this new
research is testament to this. Collaborating across borders and openly sharing
research is crucial to developing effective diagnostics, treatments and
vaccines quickly, ensuring no country is left behind.”
Journal article: https://www.nature.com/articles/s41591-020-0868-6
Source: https://myfusimotors.com/2020/04/26/key-nose-cells-identified-as-likely-covid-19-virus-entry-points/
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