Profiling Host Responses in COVID-19 Infections: Accelerating Biomarker Research with Ella

LEADING THE WAY TO TARGETED THERAPIES

While a substantial amount of knowledge has been gained about severe acute respiratory coronavirus 2 (SARS-CoV-2) since its emergence, little information is available about the correlation between viral ribonucleic acid (RNA) load in plasma and biological responses to COVID-19 infection.

Dr. Jesús F Bermejo-Martín, Principal Investigator, Group for Biomedical Research in Respiratory Infection and Sepsis (BioSepsis) at the Institute of Biomedical Research of Salamanca (IBSAL) / Hospital Universitario Río Hortega de Valladolid in Spain, is pioneering research into how to effectively profile the host response to COVID-19 infection using next-generation automated ELISA technology. Gaining a deeper understanding of the relation between viral load and disease severity is a core focus for Dr. Bermejo-Martín and his research team.

UNDERSTANDING VIRAL DYNAMICS

Wide variations in the severity of COVID-19 infections have intensified the effort to better understand viral load dynamics as it relates to infectious disease. Effective and reliable analytical techniques are needed to produce fast, efficient, and reproducible results.

As part of his research profiling biomarkers in COVID-19 infections with different degrees of severity, Dr. Bermejo-Martín and his team were able to catalog many of the physiopathological alterations common in individuals with severe COVID-19. In his recently published study¹, Dr. Bermejo-Martín draws links between severity of the illness and the presence of large amounts of the virus’ RNA in blood samples.

“What we found is that there are a number of individuals who are not able to control the infection, resulting in uncontrolled viral replication,” Dr. Bermejo-Martín said. “The problem is that if you are elderly and have multiple chronic diseases, it will affect your endothelium as well as your immune system, which will be unable to develop new responses against a virus like COVID-19.”

ACCELERATING BIOMARKER DISCOVERY AND QUANTIFICATION WITH ELISA AUTOMATION

As quickly obtaining results becomes increasingly more critical in the treatment of accelerated diseases, researchers are seeking more efficient, less labor-intensive alternatives to traditional ELISA approaches. In this case, Dr. Bermejo-Martín and his team found the optimum solution with Simple Plex™ assays running on the fully automated Ella™ platform.

“A major advantage of Ella is that it’s very easy to use with virtually no maintenance, and it’s really fast,” Dr. Bermejo-Martín said. “Simply dilute your sample and you’re ready to go—without the need for manual preparations that can take time and add user variability.”

Dr. Bermejo-Martín found the Simple Plex assays not only matched the accuracy of Luminex assays and traditional ELISAs, but also gave his team better sensitivity, a broader dynamic range, and higher reproducibility while requiring lower sample volumes. The multiplexing capabilities of Ella and the accelerated time to results allowed his team to quickly validate biomarkers and correlate them to specific outcomes.

PROFILING BIOMARKERS WITH SPEED AND EFFICIENCY

In a recent study² published in the New England Journal of Medicine, researchers confirmed that SARS-CoV-2 can infect endothelial cells, demonstrating that endothelial and coagulation activation are additional hallmarks of severe COVID-19. Using the automated Ella platform, Dr. Bermejo-Martín and his team designed a panel of biomarkers covering various alterations inherent in COVID-19 infected individuals, including T-cell survival and function, immunosuppression, helper T-cell responses and endothelial dysfunction.

“The Simple Plex assays running on Ella gave us a fast and efficient way to simultaneously profile endothelial dysfunction and coagulation activation—two hallmarks of severe COVID-19 disease,” Dr. Bermejo-Martín said. “The results confirmed that those individuals needing hospitalization, and moreover, those needing ICU admission, have endothelial dysfunction.”

DEEPER ANALYSIS OF CYTOKINE LEVELS IN HOST RESPONSE TO COVID-19

As part of his comprehensive research effort, Dr. Bermejo-Martín and his team also studied the different levels of cytokines in COVID-19 infections.

“We found a marked elevation of proinflammatory cytokines such as IL-6 and IL-15, which we also identified in the past as a signature of severe pandemic influenza,” Dr. Bermejo-Martín said. “We also found that in severe infections there will typically be the coexistence of an antiinflammatory response mediated by interleukin 10 (IL-10), which is the most potent immunosuppressor in the body. In addition, the most severe infections—those requiring admission to the ICU—were shown to have the highest levels of programmed death-ligand 1 (PD-L1). So, we have two different immunosuppressor factors playing a role here —IL-10 and PD-L1.”

HIGH QUALITY IMMUNOASSAY DATA WITH SUPERIOR REPRODUCIBILITY

Transferability of results proved to be another important advantage of the automated Ella platform for Dr. Bermejo-Martín and his team. Assays conducted on Ella in one laboratory are directly comparable to those performed on the automated Ella in other labs, regardless of who is conducting the test.

“With Ella, our researchers were able to monitor concentrations of key biomarkers in human plasma in near real-time, enabling them to turn out high-quality, quantitative data quickly,” he said.

The Ella format mirrors a conventional sandwich ELISA, yet everything—including the calibration curve—is pre-loaded on to a cartridge. Researchers simply add sample and buffers to the cartridge, introduce this into the instrument, and walk away, thereby avoiding the pitfalls of pipetting errors, material carryover, or user-variation—all of which can impact on results when an ELISA is carried out manually.

“With Simple Plex assays running on Ella the assay setup time is very short,” Dr. Bermejo-Martín said. “Once the run has started, you can come back to thoroughly analyzed results in one hour.”

Watch Dr. Bermejo-Martín’s Webinar - Profiling the Host Response to COVID-19 Infection Using the Next-Generation Automated ELISA, Ella

View additional immunoassay tools to investigate host response to COVID-19 infection.