How bacterial and viral infections (COVID-19) trigger different immune responses in sepsis

Medical News: Understanding Sepsis - Bacterial vs. Viral Infections
Sepsis, a life-threatening condition that arises when the body's response to an infection injures its tissues and organs, has long been a subject of intense research. But the differences between how the body reacts to bacterial sepsis versus viral sepsis, especially in the case of COVID-19, are still being uncovered. A recent study conducted by researchers from the Osaka University Graduate School of Medicine in Japan has shed new light on these differences by analyzing the molecular responses in patients suffering from these conditions. This Medical News report delves into their findings, providing a clearer picture of the distinct pathways activated in bacterial versus viral sepsis.


How bacterial and viral infections (COVID-19) trigger different immune
responses in sepsis

The study focused on comparing the host responses in patients with bacterial sepsis and those with viral (COVID-19) sepsis by examining messenger RNA (mRNA) and microRNA (miRNA) profiles. These tiny molecules play crucial roles in gene expression and regulation, influencing how the body responds to infections. By understanding these molecular differences, researchers hope to improve diagnostic and therapeutic approaches for sepsis, potentially saving lives.
 
The Scope of the Study
The researchers collected blood samples from 22 patients with bacterial sepsis, 35 patients with viral sepsis due to COVID-19, and 15 healthy individuals. The patients were admitted to the Department of Trauma and Emergency Medicine at Osaka University Graduate School of Medicine. For bacterial sepsis, patients were diagnosed according to the sepsis-3 criterion, which involves an increase in the Sequential Organ Failure Assessment (SOFA) score by two points or more in the presence of a suspected infection. For viral sepsis, diagnosis was confirmed using SARS-CoV-2 RT-PCR testing, along with the presence of pneumonia confirmed through chest CT scans.
 
Whole blood RNA sequencing was employed to analyze mRNA and miRNA profiles. The study included a comprehensive analysis of 14,500 mRNAs, 1,121 miRNAs, and over 2,500 miRNA-targeted mRNAs in bacterial sepsis patients. This article provides an in-depth look at the study's key findings and what they mean for understanding and treating sepsis.
 
Key Findings: A Tale of Two Sepsis Types
One of the most striking findings from the study was the difference in gene expression between bacterial and viral sepsis patients. In bacterial sepsis patients, there were significantly more upregulated and downregulated genes compared to those in viral sepsis patients. Specifically, bacterial sepsis patients had 256 genes upregulated and 2,887 downregulated, while viral sepsis patients had 672 upregulated and 1,147 downregulated. This significant difference highlights the more dramatic pathogenetic changes in bacterial sepsis, particularly in the Th1 pathway, which is crucial for cell-mediated immunity.
 
The study also found that b acterial sepsis patients exhibited activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway. This pathway is known for its role in regulating immune responses and is often associated with immunosuppression. The activation of this pathway in bacterial sepsis suggests that the body might be trying to regulate an overactive immune response, which could lead to severe inflammation and organ damage.
 
In contrast, the Th1 signaling pathway, which is vital for a strong immune response against pathogens, was significantly suppressed in bacterial sepsis patients. This suppression could contribute to the immune dysfunction observed in these patients, making it harder for their bodies to fight off the infection effectively.
 
Viral Sepsis and COVID-19: A Different Immune Landscape
While bacterial sepsis showed a marked suppression of the Th1 pathway, viral sepsis, particularly due to COVID-19, painted a different picture. The study found that COVID-19 sepsis patients had a less dramatic change in gene expression compared to bacterial sepsis patients. However, they still showed significant alterations in pathways related to immune response, particularly the p38 MAPK signaling pathway.
 
The p38 MAPK pathway is involved in cellular responses to stress and inflammation. Its activation in viral sepsis suggests that the body is responding to the viral infection with a different set of immune tools compared to bacterial infections. This pathway's activation might be linked to the cytokine storm observed in severe COVID-19 cases, where the body's immune response becomes excessively aggressive, leading to tissue damage.
 
Implications for Treatment and Diagnosis
The differences in gene expression and pathway activation between bacterial and viral sepsis have significant implications for how these conditions are diagnosed and treated. For instance, the activation of the PD-1 and PD-L1 pathway in bacterial sepsis could potentially be targeted with therapies designed to modulate immune responses, similar to how cancer immunotherapies work. By dampening the overactive immune response, it might be possible to reduce the risk of severe inflammation and organ failure in bacterial sepsis patients.
 
On the other hand, understanding the specific pathways activated in viral sepsis, such as the p38 MAPK pathway, could lead to more targeted treatments for COVID-19 patients. By focusing on these pathways, new therapies could be developed to mitigate the excessive immune response that leads to severe complications in viral sepsis.
 
The Broader Impact of This Research
This study's findings provide a deeper understanding of the molecular mechanisms underlying sepsis, particularly the differences between bacterial and viral infections. As researchers continue to unravel these complex processes, the hope is that this knowledge will lead to more effective treatments and better outcomes for sepsis patients.
 
Moreover, these findings underscore the importance of personalized medicine. By tailoring treatments based on the specific pathways activated in each type of sepsis, healthcare providers can offer more targeted and effective care. This approach could revolutionize how sepsis is treated, moving away from a one-size-fits-all approach to a more nuanced, patient-specific strategy.
 
Conclusion: A Step Forward in Sepsis Research
In conclusion, the study findings provide critical insights into the differences between bacterial and viral sepsis at the molecular level. The activation of the PD-1 and PD-L1 pathway in bacterial sepsis and the suppression of the Th1 pathway highlight the complex immune dysregulation in these patients. Meanwhile, the activation of the p38 MAPK pathway in viral sepsis, particularly in COVID-19 patients, points to a different immune challenge.
 
These findings could pave the way for new diagnostic tools and therapies tailored to the specific type of sepsis a patient is experiencing. As research continues, the ultimate goal is to improve survival rates and quality of life for sepsis patients through more personalized and effective treatments.
 
The study findings were published in the peer-reviewed journal: Virology Journal.
https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02451-6
 
For the latest on Sepsis, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/macrophages-play-a-role-in-causing-endothelial-cell-dysfunction-in-sepsis
 
https://www.thailandmedical.news/news/new-hope-for-sepsis-induced-lung-injury