The COVID-19 pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted significant challenges, especially for patients with underlying respiratory conditions like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). A new study published on March 23, 2025, in Scientific Reports focuses on azithromycin (AZM), a broad-spectrum antibiotic, exploring its potential as an effective therapeutic agent for COVID-19 patients suffering from these chronic conditions.
The urgency for effective treatments stems from the heightened vulnerability of COPD and IPF patients during COVID-19 infections, which have shown to increase mortality rates and prolong hospital stays significantly. The study highlights essential research conducted using genetic data obtained from various databases, analyzing common differentially expressed genes (DEGs) among COVID-19, COPD, and IPF patients. Notably, it identified 311 DEGs common to these diseases.
Further investigation revealed that AZM interacts with eight key genes implicated in the pathophysiology of these diseases. Among these genes are interleukin-6 (IL-6), tumor protein p53 (TP53), and transforming growth factor beta 1 (TGFB1), which are crucial players in cytokine storms often observed in severe COVID-19 cases.
The bioinformatics analysis utilized the STITCH database to retrieve over 40 drug targets associated with AZM, assessing how AZM’s pharmacological properties might inhibit these target genes' actions. Significantly, the findings suggested that AZM has a notable inhibitory effect on several hub genes, except for the androgen receptor (AR) and IL-17 A, underscoring its selective efficacy.
Azithromycin's ability to modulate inflammation has been less consistent in clinical settings, particularly in COVID-19 treatment. Prior systematic evaluations have yielded mixed results concerning its effectiveness, particularly when combined with other agents like hydroxychloroquine. Nevertheless, this new study argues for AZM's use as a potentially beneficial option for chronic patients, considering its unique properties.
The researchers further examined its inhibitory effects via in vitro studies with the A549 cell line, which represents a human lung adenocarcinoma model. They demonstrated the effects of AZM at varying concentrations (10, 20, 40, and 80 µmol/L) on mRNA levels in critical gene expressions such as IL-6 and TGFB1. These insights point towards AZM's capacity to mitigate inflammation and possibly lower viral loads in patients.
The bioinformatics approach of the study presents a robust framework for further exploring azithromycin’s molecular mechanisms and therapeutic implications, especially for patients suffering from COVID-19 amid their respiratory conditions. The implications of AZM’s action on key DEGs reveal a broader narrative on addressing the severity of COVID-19 in vulnerable populations.
The authors concluded that diligent research and clinical trials focusing on AZM's efficacy in patients with COPD and IPF are warranted. While AZM is not without its challenges, the proposed study lays foundational insights into its potential role in treating COVID-19 co-infected patients with chronic respiratory diseases. Further investigations should also examine combination therapies that may enhance AZM's efficacy, considering its limited impact on inflammatory pathways implicated by AR and IL-17 A.
In summary, while azithromycin shows promise as a candidate treatment for SARS-CoV-2 infection in patients with COPD and IPF, the need for additional robust clinical trials remains critical to substantiate these findings and optimize therapeutic strategies for at-risk populations affected by the ongoing pandemic.
