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Covid-19 infects cell factors ‘more abundant in the elderly, men, and smokers’

By Nina Massey, PA Science Correspondent

Coronavirus infects cells via factors that are more abundant in the elderly, men, and smokers, new research suggests.

A large-scale new study reveals which cell types in the human body can be infected by Sars-CoV-2 due to their viral entry factors – what the virus attaches to in order to gain entry to the cell.

The research also suggests that an increased amount of these factors in some people partially explains the differences of Covid-19 severity reported in relation to age, gender and smoking status.

Dr Malte Lucken, computational biologist at Helmholtz Zentrum Munchen in Germany, and a co-first author of the study, said: “Fighting the pandemic, we cannot rely on conclusions that are limited to only a few observations.

“Instead, we must rely on robust analysis of big data.

“For example, to assess whether the ACE2 receptor required for virus entry is more abundant in cells of the elderly population, we need a strong representation of many diverse individuals in our dataset.

“Using data from the Human Cell Atlas, we could model how genetic viral entry factors in cells are expressed across the population.”

Covid-19 does not affect everyone in the same way, and while it manifests in the lung, it can infect other organs too, researchers say.

Clinical observations throughout the pandemic also suggest some population groups – such as elderly people, men and smokers – tend to be more severely affected by the disease.

So far, the molecular reasons for this have not been described.

Previous research indicated that in order to infect human cells, SARS-CoV-2 needs the cell to contain specific genetic viral entry factors – an ACE2 receptor and a TMPRSS2 or CTSL protease.

However, in the new study published in Nature Medicine, researchers from the Human Cell Atlas Lung Biological Network joined forces to contribute and analyse gene expression data from individual cells.

Analysis of 100 datasets revealed that specific cell types in the tissue of the lung and airways, and also in the liver, the colon, and the eye had high expression of the ACE2 receptor and TMPRSS2 protease genes.

This means they could potentially be able to be infected with coronavirus.

Researchers found that these particular cell types from elderly people had higher expression of these entry factors, and that cells from men had slightly greater expression than from women.

Additionally these cells from smokers, in particular airway cells, express more coronavirus entry factors than from non-smokers.

The researchers say the findings match the reported differences in disease severity for Covid-19 patients with age, sex and smoking and offer a molecular explanation for this difference.

Dr Kerstin Meyer, an author on the paper from the Wellcome Sanger Institute, said: “A key aspect of this large-scale study was the age range of samples we were able to analyse.

“This study included data from human developmental stages, samples from children and young adults, as well as samples from elderly people.

“This gave us unique power to assess changes occurring over the human lifetime. The sheer scale of the data allowed us to see molecular differences with age, sex and smoking status.”

The research investigated which cells are most likely to be infected by SARS-CoV-2.

The connection between high expression levels of viral entry factors and increased ease of infection or disease severity has been shown in mice and in the laboratory, but researchers say further validation is needed to prove this connection in humans.

Other possible factors such as immune system strength were not included in this study.

The study was conducted by researchers from Helmholtz Zentrum Munchen, the Broad Institute of MIT and Harvard, the Wellcome Sanger Institute and University Medical Centre Groningen and their collaborators in the Human Cell Atlas Lung Biological Network.

Researchers say the molecular profile of the cells partially explains how disease severity might differ between population groups, and provides a target for further research.

They add that moving forward, the findings may also help better understand the spread of the coronavirus across the body.

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