Mount Sinai researchers have published one in all the primary studies to associate changes in blood gene expression during COVID-19 with the post-acute sequelae of SARS-CoV-2 infection, also often known as “long COVID,” in patients greater than a 12 months after they were hospitalized with severe COVID-19.
The findings, published in Nature Medicine on December 8, highlight the necessity for greater attention on the infection stage to higher understand how the processes that begin then eventually result in long COVID, which could help improve each prevention strategies and treatment options for COVID-19 survivors experiencing persistent symptoms after infection.
The research team identified, amongst other findings, two molecularly distinct subsets of long COVID symptoms with opposing gene expression patterns during acute COVID-19 in plasma cells, the immune system’s antibody-producing cells. In patients who went on to develop lung problems, antibody production genes were less abundant. Nevertheless, for patients with other symptoms reminiscent of the lack of smell or taste and sleep disruptions, the identical antibody production genes were more abundant as a substitute. These opposing patterns observed in the identical cells, in addition to additional unique patterns observed in other cell types, point to the existence of multiple independent processes resulting in different long COVID symptoms; these processes are already present through the acute infection.
Our findings show that molecular processes resulting in long COVID are already detectable during COVID-19 infection. Moreover, we see the beginning of multiple molecularly distinct paths resulting in long COVID, providing a singular viewpoint into differences between long-term symptoms.”
Noam D. Beckmann, PhD, Senior Writer, Assistant Professor of Medicine (Data Driven and Digital Medicine) and Associate Director of Data Science Strategy at The Charles Bronfman Institute for Personalized Medicine on the Icahn School of Medicine at Mount Sinai
Using the Mount Sinai COVID-19 Biobank, the researchers examined gene expression data in blood samples from greater than 500 patients hospitalized with COVID-19 between April and June 2020. Greater than 160 of those patients provided self-reported assessments of symptoms still present six months or more after hospitalization. The team tested each gene expressed within the blood for association with each long COVID symptom, accounting for ICU admission, COVID-19 severity during hospitalization, sex, age, and other variables. The team then tested for associations specific to every of 13 various kinds of immune cells, including plasma cells. Finally, these associations were categorized by whether or not they matched up with changes in patients’ levels of antibodies specific to the virus.
“For long COVID symptoms, like smell or taste problems, connecting antibody gene expression in plasma cells with the actual levels of antibodies against the SARS-CoV-2 spike protein demonstrates a direct link to the body’s response to the virus,” said lead writer Ryan C. Thompson, PhD, Data Science Analyst at The Charles Bronfman Institute for Personalized Medicine. “However, the gene expression pattern for lung problems doesn’t match up with SARS-CoV-2-specific antibody levels, highlighting different immune processes resulting in long COVID which can be triggered by COVID-19.”
The team said long COVID still stays poorly defined and future studies should take the initial stage of infection under consideration to more comprehensively characterize the molecular processes of long COVID and discover biomarkers that might help predict, treat, and stop prolonged symptoms.
“Our findings show there’s the potential to make use of data from the infection stage to predict what might occur to the patient months later,” said co-corresponding writer Alexander W. Charney, MD, PhD, Associate Professor of Genetics and Genomic Sciences, and Co-Director of The Charles Bronfman Institute for Personalized Medicine. “We should always not ignore the infection phase in research on long COVID-;that is clearly a critical window of time where the body’s response to SARS-CoV-2 could be setting the stage for what’s to return.”
The University Hospital of Zurich, University of Zurich, University of Washington, and health intelligence company Sema4 contributed to this research.
Source:
Mount Sinai Health System