Leopoldo Nicolas Segal, MD

Some critically ill patients infected with SARS-CoV-2, the virus that causes COVID-19, require mechanical ventilation. We need to better understand which of these patients will benefit from different treatments. To find treatable traits among these most severely ill patients, we need to make comparisons among patients with similar severity. We have built a repository of paired lower airway and blood samples from critically ill COVID-19 patients. We will evaluate the changes at different time points in these samples looking at factors such as viral load, secondary infections and clinical outcome in these patients. Identifying factors associated with poor clinical outcome among critically ill COVID-19 patients will be key for the development of clinically useful biomarkers and/or novel therapeutic targets.

Update:
We are using lower airway samples from critically ill COVID-19 patients to uncover the novel microbiome (the collection of bacteria, viruses and fungi that live on and inside the human body) and immune response signatures that can explain poor prognosis. We are continuing to analyze changes occurring with various treatments. It is critical to identify novel traits amenable for personalized approach among patients suffering from the most severe forms of this disease.

Final Project Update:
The COVID-19 pandemic has posed significant challenges, particularly for patients who require mechanical ventilation to breathe. We need to better understand which of these patients will benefit from different treatments. To find treatable traits among these most severely ill patients, we made comparisons among patients with similar severity. With support from the American Lung Association’s COVID-19 Respiratory Virus Research Award, we used existing samples of lower airway and blood from critically ill COVID-19 patients at NYU to explore the potential mechanism underlying the poor viral control seen in some patients. We are seeking to identify signals linked to weak immune responses. These responses impact the body’s ability to control viral load and prevent secondary infections in the lungs.  

We found that poor control of the virus is linked to weakened immune responses in the lower airways, which don’t match the responses found in the rest of the body. This highlights the importance of understanding immune activity in the lower airways. Additionally, by analyzing microbiome data collected over time, we are identifying microbial patterns that can predict high mortality and are linked to the development of ventilator-associated pneumonia. 

As our research progresses, we hope to uncover important molecular signals that could serve as biomarkers for assessing patient risk or as new targets for treatment.