Azithromycin Emerges as a Potential COVID-19 Treatment for Patients with Lung Conditions Like IPF and COPD

Medical News: A groundbreaking new study conducted by researchers from Guangzhou Red Cross Hospital and The First Affiliated Hospital of Jinan University in China is shedding light on the potential benefits of the antibiotic azithromycin (AZM) in treating COVID-19 patients who also suffer from two chronic and deadly lung diseases - idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD).


Azithromycin Emerges as a Potential COVID-19 Treatment for Patients with Lung Conditions Like IPF and COPD

With over 780 million confirmed COVID-19 cases and nearly 8 million deaths reported globally, the search for effective treatments remains urgent, especially for high-risk populations. Among these are patients suffering from pre-existing respiratory illnesses such as COPD and IPF - conditions that cause persistent inflammation and irreversible scarring of lung tissue. These patients are significantly more vulnerable to complications from SARS-CoV-2 due to higher expression of ACE2 receptors in their lungs, which act as entry points for the virus.
 
This Medical News report explores how researchers used a combined bioinformatics and laboratory approach to understand how azithromycin could potentially help these high-risk patients. Though traditionally an antibiotic, azithromycin is also known to exhibit anti-inflammatory and antiviral effects, making it a promising candidate in the fight against COVID-19, particularly among those with chronic respiratory diseases.
 
Why Focus on Azithromycin for COVID-19 with Lung Comorbidities
The research team began by investigating the common biological features of COVID-19, COPD, and IPF. They retrieved thousands of genes linked to each of these conditions using the GeneCards database and compared them to known targets of azithromycin, which were obtained from the STITCH drug interaction database.
 
What they found was compelling: 311 genes were shared between COVID-19, IPF, and COPD. Narrowing it down further, eight of these genes showed strong interaction with azithromycin. These included key inflammatory and regulatory genes such as IL-6, TP53, TGFB1, and SMAD2 - all known to play major roles in disease progression and immune responses.
 
Through experimental validation using lung cell models (specifically A549 cells), the researchers observed that azithromycin significantly inhibited several of these key genes. Notably, it suppressed the expression of IL-6, TGFB1, TP53, SMAD2, and EP300, which are all involved in inflammation, fibrosis, and immune dysregulation seen in COVID-19 and chronic lung diseases.
 
How Azithromycin Targets the Root of the Problem
IL-6 is one of the main drivers behind the cytokine storm - a deadly immune overreaction that occurs in severe COVID-19 cases. By blocking IL-6 and its receptor, azithromycin may reduce these dangerous inflammatory responses. The same goes for TGFB1, a powerful promoter of lung scarring and fibrosis, which is already overexpressed in both IPF and severe COVID-19 cases.
 
Azithromycin was also found to inhibit TP53 and SMAD2 - transcription factors and signaling molecules invol ved in cell death and fibrosis. Through a process known as molecular docking, the researchers simulated how azithromycin physically binds to these target proteins, finding strong binding affinities that suggest potential therapeutic effects.
 
Interestingly, azithromycin failed to significantly inhibit two other targets, androgen receptor (AR) and IL-17A, possibly due to their low expression in the tested lung cells. Nevertheless, the drug still demonstrated a meaningful overall inhibitory pattern across the most critical disease-related genes.
 
Bioinformatics Meets the Lab Bench for a Better Understanding
To validate their computational findings, the researchers conducted gene expression experiments using PCR tests on lung cell lines treated with various concentrations of azithromycin. The results confirmed that AZM was able to downregulate several key pro-inflammatory and pro-fibrotic genes in a dose-dependent manner.
 
Further pathway enrichment analysis showed that these genes are involved in several critical signaling routes such as IL-6 and TGF-beta pathways, which regulate inflammation, cell proliferation, and tissue remodeling. This reveals the extent to which azithromycin can interfere with disease progression mechanisms at the molecular level.
 
Why This Matters for Real World COVID-19 Treatment
While clinical trials have shown inconsistent results regarding azithromycin’s effect on general COVID-19 patients, this study suggests that AZM could still be useful in specific subgroups - especially those with underlying lung conditions like COPD and IPF. The drug’s ability to reduce inflammation and possibly halt fibrosis offers a tailored therapeutic angle.
 
Patients with IPF and COPD who contract COVID-19 are known to have longer hospital stays and higher mortality rates. Inhibiting genes like IL-6 and TGFB1 may reduce the risk of severe outcomes, prevent lung fibrosis, and improve survival rates. Furthermore, azithromycin’s ability to reduce furin expression - a key enzyme SARS-CoV-2 uses to invade cells - adds another layer of antiviral potential.
 
Caution and the Road Ahead
Despite these promising findings, the study also highlighted limitations. Azithromycin did not affect all inflammatory markers, and prolonged use has known side effects such as cardiac issues and antibiotic resistance. Also, the lab-based A549 lung cell model, while useful, does not fully replicate the complex biology of human lungs.
 
As such, the researchers urge further clinical trials specifically involving COVID-19 patients with COPD and IPF to validate these findings in real-world settings. They also recommend combining AZM with other drugs like IL-17A inhibitors for broader anti-inflammatory coverage.
 
Conclusion
This study provides a compelling scientific foundation for the targeted use of azithromycin in COVID-19 patients who also suffer from chronic respiratory conditions like COPD and IPF. By identifying and validating key gene targets and pathways involved in inflammation and fibrosis, the researchers have offered a new therapeutic perspective on an old drug. Azithromycin’s broad-spectrum effects - spanning antibacterial, antiviral, and immunomodulatory actions - make it a potentially valuable tool in managing complex cases of COVID-19 with respiratory comorbidities. However, more human-based studies are required before this treatment can be widely adopted. Personalized treatment strategies may ultimately help reduce the burden of long-term lung damage and improve survival outcomes in vulnerable populations.
 
The study was conducted by researchers from the Department of Endocrinology and Metabolism at Guangzhou Red Cross Hospital and the Department of Pulmonary and Critical Care Medicine at The First Affiliated Hospital of Jinan University, China.
 
The study findings were published in the peer reviewed journal: Scientific Reports
https://www.nature.com/articles/s41598-025-94801-9
 
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