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Why are asthma patients not at increased susceptibility to COVID?


Evelyn Lewin


19/01/2021 2:19:09 PM

Researchers believe the answer may relate to reduced expression of ACE-2 receptors in the lower airway.

Man using asthma puffer.
According to the new research, people with asthma have reduced levels of expression of ACE-2 receptors in their lower airway.

‘People with chronic respiratory disease, especially asthma and chronic obstructive pulmonary disease [COPD], are usually at heightened risk of complications from acute respiratory viral infections.
 
‘This is, however, not clearly the case with COVID‐19.
 
‘Asthma alone is not over‐represented in people with COVID‐19 nor is it associated with greater disease severity. This raises the question as to why people with asthma are not at increased susceptibility to SARS‐CoV‐2.’
 
Such is the discussion in a new paper by Australian researchers, published on 17 January in Respirology.
 
For the study, researchers obtained lower airway epithelial cells from 145 people from two separate cohorts in Newcastle and Perth.
 
The researchers found that patients with asthma had reduced expression of angiotensin converting enzyme (ACE)-2 receptors, while increased ACE-2 expression was found in older people and males.
 
‘Altered ACE-2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over‐represented in those with COVID‐19 complications,’ the authors concluded.
 
Conjoint Professor Peter Wark from the Department of Respiratory and Sleep Medicine and the Centre for Healthy Lungs at the University of Newcastle and John Hunter Hospital is the lead author of this paper.
 
‘Very early on in the pandemic, when the SARS-CoV-2 virus had been identified as using the human ACE-2 receptor in order to gain access to host cells, we were very interested in looking at the level of expression of the ACE-2 receptor in the lower airways of people with chronic lung disease,’ he told newsGP.
 
‘We were concerned that people with chronic airways disease would be at greater risk of complications related to the virus.’
 
But as time wore on, Professor Wark says it became apparent that, while certain groups of people with airway disease – such as those with COPD and pulmonary fibrosis – were likely to experience more severe disease with COVID-19, those with asthma were not.
 
‘Increasingly it became obvious throughout last year that people with asthma were certainly not over-represented in people who had more severe disease, and they were not being over-represented in terms of people being hospitalised with COVID-19,’ he said.
 
‘And that’s quite opposite to what we see with all other viral respiratory infections, particularly the influenza pandemic. While people with asthma and influenza didn’t become particularly unwell, they were more likely to end up in hospital.
 
‘If they ended up in hospital, they weren’t as likely to die as other groups with comorbidities, but certainly they had a more severe presentation and more severe symptoms that landed them in hospital compared to their peers who didn’t have asthma.’
 
Associate Professor Louis Irving, Director of Respiratory and Sleep Medicine at the Royal Melbourne Hospital, told newsGP he agrees there was initial concern that asthmatics would be at higher risk of contracting COVID-19 and that those who did would fare badly.
 
‘That was the concern at the beginning of the epidemic,’ he said.
 
However, Associate Professor Irving says this has not turned out to be the case.
 
‘That sort of fits in with our clinical experience, that at the moment, asthmatics are not over-represented,’ he said.

ACE-2-article.jpg
Conjoint Professor Peter Wark says the research also found a relationship between higher levels of ACE-2 expression in older people and males.

While the researchers explored expression of ACE-2 receptors in lower airway samples, Professor Wark says they also looked for the presence of proteases that can affect the ability of SARS-CoV-2 to be internalised by the host cell.
 
He says the two most common proteases SARS-CoV-2 uses to allow its cleavage and unwrapping within the host cell are furin and TMPRSS2.
 
‘What we found was that people with asthma had a lower level of expression of ACE-2 receptor for the virus in their lower airway cells, compared to healthy controls and compared to people with COPD,’ he said.
 
‘In addition to that, we found there was no difference to TMPRSS2, but furin expression was increased in people with asthma.
 
‘So we feel that it is certainly possible this may be one reason why people with asthma have a relative degree of protection against more serious complications from COVID-19.
 
‘If there are lower levels of expression of ACE-2 in the lower respiratory tract cells, then there may well be lower transit of virus to the lungs and less development of pneumonia.’
 
Professor Wark says this effect could be partially related to the fact that a large number of patients with asthma in the study were on inhaled corticosteroids.
 
‘We can’t rule out that inhaled steroids might have a partially protective effect – that is possible,’ he said.
 
‘But it is also possible that the type of airway inflammation associated with asthma, particularly that mediated by IL-13, might down-regulate ACE-2 expression and alter the functioning of furin as well within the airway epithelial cells, and there are some other studies out there that support this concept.’
 
Associate Professor Irving also queried whether that finding might relate to the use of inhaled steroids.
 
He says that is particularly interesting because in the beginning of the pandemic there was concern that asthmatics may be more at risk due to their steroid use.
 
‘But in fact that didn’t eventuate,’ he said.
 
Professor Wark says the thinking has now changed to the point that the use of inhaled corticosteroids may be protective against COVID-19, and that further studies are underway to explore this.
 
Associate Professor Irving says this research may have implications on public health measures such as vaccination.
 
And even though it is already understood that older people are at higher risk of severe disease with COVID-19, Associate Professor Irving says this research adds further weight to that notion, and also greater understanding about why COVID-19 is more likely to be severe in men.
 
‘That’s important because the risk groups inform who we should be trying to protect with vaccination and other measures,’ he said.
 
However, Associate Professor Irving says it is also important to remember that this is only one part of the puzzle.
 
‘One would assume that there are probably other factors that determine the effect that older people have more severe [COVID-19] disease,’ he said.
 
Despite these findings, Professor Wark does not want people with asthma, nor those treating such patients, to interpret this research incorrectly.
 
‘I don’t want people to go away and think that people with asthma are overly protected [from COVID-19],’ he said.
 
‘There’s no doubt that [patients with asthma] can both acquire COVID-19, and can go on and get very severe disease.’
 
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