COVID-19 is known to be largely influenced by a person’s immune response. In a recent study, an international team of researchers led by the German Center for Neurodegenerative Diseases (DNZE) set out to uncover the cellular and molecular mechanisms underlying how the body responds to severe COVID.* With better disease knowledge, more effective treatment plans for COVID, and interventions for Long COVID, may be possible.

What the researchers did

COVID research findings can be difficult to generalize among patients, since recovery often varies between individuals (through differences in symptoms onset and length of hospitalization, for instance). The researchers overcame this challenge with an innovative data analysis approach. 

• Since a person’s response to COVID-19 is evidenced in white blood cells, the researchers focused on blood analysis.
• Blood samples from 139 adults, aged 21-86 and mostly male, were taken while the patients were in intensive care.
• Of those 139 patients, 105 were eventually released from intensive care, and 34 had succumbed to their illness.

Explained lead study author Amit Frishberg, Ph.D., a bioinformatics and genomics researcher, “Our computational approach is designed to discover common patterns in the variety of findings from different patients that may not be obvious.”

What they found

Published in the journal Cell Reports Medicine, the study uncovered a common factor among very ill patients: recovery was associated with a gradual decrease in the amount of mature white blood cells (WBCs) called neutrophils. Neutrophils are the most numerous of the WBCs, and are primary defenders against infection. 

The researchers observed that having high levels of mature neutrophils over an extended period was “very likely” to cause death. According to Frishberg, this could be due to the higher likelihood of a hyperimmune response. Blood levels of neutrophils could therefore act as better predictors of disease progression than current indicators being considered, he added.

The team also noticed further changes during recovery that affected immune system signaling paths and regulation. Frishberg said it was “remarkable” that the pattern of all these changes during recovery was the same in everyone regardless of recovery time—”a common thread.”

Special assessment tool

The study’s blood analysis relied on what are called blood transcriptomes, the sum total of all gene activity in all of a person’s blood cells. These give scientists a very detailed picture of individual immune systems. 

• A unique algorithm was developed that arranged all patient transcriptomes into a shared sequence, based on their similarities and the belief that all patients take the same path to recovery.
• Each transcriptome gave a separate, evolving disease picture. Pieced together, they generated a whole disease model showing the course of recovery.

Study author Joachim Schultze, M.D., DZNE’s Director of Systems Medicine, explained that conventional time isn’t a good representation of this process, since everyone’s recovery time is different. Instead, the disease model was generated by computing a “pseudotime” for each patient sample. Low pseudotime designated severe disease or initial recovery; high pseudotime meant advanced recovery. 

What it means

The researchers were able to pick up on immune response patterns not seen in the raw data, showing the value of algorithmic disease modeling. This means patients could ultimately receive better treatment.

“The bottom line is that our study presents a novel approach to assess disease recovery status in ICU patients,” said Schultze. “In practice, this may contribute to more targeted and thus more effective treatment of COVID-19. Considering this, it might be worthwhile to evaluate to what extent such examinations can be implemented in clinical routine.”

*German Center for Neurodegenerative Diseases. (2022, June 14). New insights into the processes of recovery after severe COVID-19. MDLinx. https://www.mdlinx.com/news/new-insights-into-the-processes-of-recovery-after-severe-covid-19/68F0LxVIzOo5dw864T7j1n

“Segmented neutrophils.” by Mgiganteus is licensed under CC BY-SA 3.0