Rather than being a risk factor, asthma could protect patients from progressing to severe COVID-19

Researchers in São Paulo state analyzed data for over 1 million patients hospitalized for treatment by the public health service after contracting COVID-19. Lower levels of inflammatory cytokines and fewer ACE2 receptors for the virus to bind to may be the explanation.

By Monica Tarantino  |  Agência FAPESP – Since the onset of the pandemic in 2020, many researchers and health workers have assumed that asthma can contribute to the severity and lethality of COVID-19. The results of the largest study conducted to date with patients treated for severe COVID-19 at hospitals affiliated with the SUS (Sistema Único de Saúde), Brazil’s national health service, suggest the opposite. Asthma may not aggravate the patient’s symptoms and can actually play a protective role against infection by SARS-CoV-2.

An article on the study is published in the journal Frontiers in Medicine. 

“Although they developed more clinical symptoms, patients with asthma were less likely to die from COVID-19 than those without asthma,” said Fernando Augusto Lima Marson, last author of the article. Marson is a professor at São Francisco University (USF) in Bragança Paulista, São Paulo state, Brazil. He has a degree in biology and a PhD in health sciences. He heads USF’s Cellular and Molecular Biology Laboratory. He is also responsible for marking degree monographs at USF, where all graduate students have full scholarships. 

The study conducted by Marson and four other researchers analyzed clinical records and demographic data for 1,129,838 patients hospitalized in Brazil with COVID-19, 3.8% of whom (43,245) had asthma. This low prevalence had been noted in previous research. All datasets were obtained from OpenDataSUS, a free-to-use data portal maintained by the Brazilian Ministry of Health. The study was supported by FAPESP. 

Among the COVID-19 patients who required invasive ventilatory support, 74.7% of those with asthma died, compared with 78% of those without asthma. Among the COVID-19 patients who received non-invasive ventilatory support, 20% of those with asthma died, compared with 23.5% of those without asthma. Among patients who did not require ventilatory support, 11.2% of those with asthma died, compared with 15.8% of those without asthma.

The researchers concluded that the specific characteristics of the immune response to asthma counteract the hyperinflammation typical of severe COVID-19. People with asthma produce less inflammatory cytokines, a group of proteins (such as interferons, for example) that increase the body’s capacity to destroy tumor cells, viruses and bacteria. This stimulates an immune response mediated by CD4⁺ T helper 2 (Th2) lymphocytes to the detriment of subtype Th1.

“The predominance of the Th2 response is beneficial because it regulates and reduces the impact of the late stage of hyperinflammation, a critical point in severe respiratory infections,” Marson said.

According to the researchers, other obstacles asthma may offer SARS-CoV-2 include lower levels of ACE2 (angiotensin-converting enzyme 2) receptors due to chronic inflammation of the alveoli in the lungs of asthmatics. The coronavirus binds to host ACE2 receptors in order to invade the patient’s cells and multiply. ACE2 is a protein present on the surface of several cell types, including respiratory tract epithelium. 

“Lower production of inflammatory cytokines and lower levels of ACE2 receptors for the virus to use result in less likelihood of severe infection,” Marson said. Higher levels of eosinophils (a type of disease-fighting white blood cell) in asthmatic patients also may hinder progression to severe COVID-19. The effects of all these factors, he added, could explain why only 3.8% of the COVID-19 patients in the study had asthma, although the proportion of the total population with asthma is about 10%.

More research needed

For Marson, the size of the sample makes a difference and may have diluted some biases. “For example, a study conducted in the United States at the same time as ours analyzed data for 300-400 patients and concluded that asthma was a risk factor,” he said.

The study he led may contain some errors due to the nature of the data analyzed, he acknowledged. “Our study was based on data collected by a government agency. We may have gotten close to the actual situation in Brazil as far as severe COVID-19 patients and the response to asthma is concerned, owing to the large number of patients used in data analysis, but the database has limitations. For instance, there are no descriptions of laboratory tests that could confirm the asthma diagnosis,” he said.

The USF group plan to conduct further analysis of data collected from a universe of some 4 million people hospitalized after being infected by SARS-CoV-2. “We’re going to work with a more robust database. We’ll focus on outcomes again, but also on the influence of vaccination against the virus,” Marson said.

Publication of the article on the study has had repercussions. A group of data scientists plan to verify the incidence of COVID-19 among asthmatics in nine cities of the region of São Paulo state in which USF is located. An invitation has come to partner with the University of Lisbon in Portugal on a study regarding the incidence of COVID-19 among cystic fibrosis patients. “Cystic fibrosis involves physiological alterations that are similar to those involved in asthma, including a large amount of mucus in the lungs, which could prevent the virus from entering cells there,” Marson said.

The article “Profile of coronavirus disease enlightened asthma as a protective factor against death: An epidemiology study from Brazil during the pandemic” is at: www.frontiersin.org/articles/10.3389/fmed.2022.953084/full. 

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