Chronic lung diseases patients are “primed” for severe Coronavirus infections

Richa Prakash, MSc, Central University of Punjab

The whole globe is aware of SARS-CoV-2 as it has infected tens of millions of people worldwide in the first nine months of 2020 making it a deadly pandemic. Along with other comorbidities, people with a history of chronic lung diseases (CLDs) like chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILDs) especially idiopathic pulmonary fibrosis (IPF) are at higher risk of getting severe COVID infection.

According to a recent study, people with chronic lung diseases are “primed” for severe COVID-19 infection with more severe symptoms, comparatively poorer outcomes, and a higher chance of death. An international scientific team led this study which was co-led by the Translational Genomics Research Institute (TGen) affiliated with the City of Hope. The study suggests that the cells damaged by chronic lung diseases are primed for the infection similar to pouring water atop a wellhead before pumping. It has been published in Nature Communications in July 2021.

 Chronic lung diseases genetically modify the molecular makeups of various lung cells including epithelial cells that line the airways and lungs. These genetic changes help the entry of the SARS-CoV-2 virus, the causative agent of COVID-19, into the host’s body, replicate inside the body, and trigger excessive immune responses known as Cytokine Storm filling the lungs with fluids. Patients with these conditions often survive with the help of respirators and lengthy hospital stays. Jonathan Kropski, a senior co-author of this research said that it was known from the starting of the pandemic that people with CLDs were at higher risk to get severely infected by SARS-CoV-2 but our objective was to investigate the changes at the cellular and molecular levels that were responsible for this.

Methodology of the study:

The research team used four published single-cell RNA-sequencing (scRNA-seq) lung datasets to perform an integrated analysis to study the molecular basis of the severity caused by SARS-CoV-2 in CLD patients. They analyzed 611,398 single-cell transcriptomes from 78 samples of healthy persons, 31 samples of COPD patients, 82 samples of IPF patients, and 19 samples of non-IPF ILD patients.

Major findings of the study:

Entry receptors for SARS-CoV-2 include host ACE-2 and other putative factors including BSG, NRP1, and HSPA5, and priming proteases include TMPRSS2, CTSL, or FURIN for cellular entry. Among these, ACE-2 and TMPRSS2 are predominantly expressed in epithelial cells and others expressed in nearly all cell types. Major findings of the study were:

1. There was no significant difference in the number of ACE-2 cells in any cell type in CLD compared to the control.
2. In CLD cells, the viral entry score was found out to be increased including the use of multiple entry factors.
3. Epithelial cells in CLD, especially AT2 cells (the primary target of SARS-CoV-2 in distal lungs), showed dysregulation of genes responsible for viral infection and immune responses in hosts.
4. A high level of ACE2 protein was found out in small airway sections of IPF patients.
5. There was differential expression of genes related to SARS-CoV-2 infection observed in CLD ACE2+ cells compared to ACE2- AT2 cells.
6. There was a unique ACE2 correlated gene found in CLD patients including antiviral and immune regulatory genes to cope with COVID infection.
7. There were baseline differences in the immune population of cells in CLD samples as compared to the control samples.

According to Dr. Linh Bui, author of this study,” The genetic changes in immune cells, especially in specialized white blood cells known as T cells, may diminish the patient’s immune response to viral infection and lead to a higher risk of severe disease and poor outcomes in patients with chronic lung disease.”

Conclusion

The study suggests that although the differences in ACE2 expression and other putative entry factors may be less in CLD, the presence of susceptible cells in the distal lung may lead to increased disease pathogenesis and severity. Because the changes in the cellular makeup of diseased lung epithelial cells may increase ACE2+ cells in distal lungs. The immune microenvironment CLD lungs are dysregulated at both cellular as well as molecular levels resulting in severe infections and comparatively poor outcomes.

Also read: Polygalacturonase: Does it affect plant shape?

References:

1. Bui, L. T., Winters, N. I., Chung, M. I., Joseph, C., Gutierrez, A. J., Habermann, A. C., … & Network, H. C. A. L. B. (2021). Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity. bioRxiv. https://doi.org/10.1038/s41467-021-24467-0

Author’s info:

Richa Prakash is a passionate life science researcher with a post-graduation in Life Sciences with a specialization in Microbial Sciences from the Central University of Punjab and graduation in Biotechnology from Amity University Rajasthan. Currently working as a scientific content writer and aiming for a Ph.D. Her research fields of interest are microbiology, molecular biology, and genetic engineering.

Publications: Singh, H., Das, S., Gupta, P. P., Batra, S., Prakash, R., Srivastava, V. K., … & Kaushik, S. (2020). Binding of metronidazole to Enterococcus faecalis homoserine kinase: Binding studies, docking studies, and molecular dynamics simulation studies. Pharmacognosy Magazine, 16(5), 553. https://www.phcog.com/text.asp?2020/16/5/553/301892

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