Biomarkers present at initial COVID-19 infection hint at long COVID

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Researchers at Mount Sinai School of Medicine in New York have found that gene expression patterns in plasma cells during the acute initial COVID-19 infection indicate whether or not the patient will go on to develop post-acute sequelae of SARS-CoV-2 infection, also known as long COVID.

In the research, published in the journal Nature Medicine, the Mount Sinai team determined -- among other findings -- that there are two molecularly distinct subsets of long COVID.

In one subset, the patient would go on to develop lung problems; in the other, the patient would lose the senses of taste and/or smell and develop sleep disruptions. In the subset with lung problems, the patients had antibody production genes that were less abundant. The patients in the subset with sleep disruptions and the loss of smell and/or taste produced more of the same antibody production genes.

The researchers believe that these findings underscore the need for greater attention at the infection stage of COVID to better understand the processes that eventually lead to long COVID. They argue that this understanding could help improve both prevention strategies and treatment options for COVID-19 survivors experiencing persistent symptoms after infection.

 “Our findings show that molecular processes leading to long COVID are already detectable during COVID-19 infection,” senior author Noam Beckmann, assistant professor of medicine and associate director of data science strategy at the Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai, said in a prepared statement. “Furthermore, we see the start of multiple molecularly distinct paths leading to long COVID, providing a unique viewpoint into differences between long-term symptoms.”

In this study, 567 individuals (495 hospitalized with COVID-19 and 72 healthy and hospitalized controls) were enrolled in the Mount Sinai COVID-19 Biobank Study between April and June 2020. More than 160 of these patients provided self-reported assessments of symptoms still present six months or more after hospitalization.

The team tested each gene expressed in the blood for association with each long COVID symptom, accounting for intensive care unit (ICU) admission, COVID-19 severity during hospitalization, sex, age, and other variables. The team then tested for associations specific to each of 13 different types of immune cells, including plasma cells. Finally, these associations were categorized by whether they matched up with changes in the 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,” lead author Ryan C. Thompson, a data science analyst at the Charles Bronfman Institute for Personalized Medicine at Mount Sinai, said in a statement. “On the other hand, the gene expression pattern for lung problems does not match up with SARS-CoV-2-specific antibody levels, highlighting the different immune processes leading to long COVID that are triggered by COVID-19.”

The research team believes that this research shows that the initial stage of infection should be taken into account more comprehensively, including characterizing the molecular processes of long COVID and identifying biomarkers to better predict, treat, and prevent prolonged symptoms.

“Our findings show there is the potential to use data from the infection stage to predict what might happen to the patient months later,” said co-corresponding author Dr. Alexander Charney, codirector of the Charles Bronfman Institute for Personalized Medicine. “We should not ignore the infection phase in research on long COVID -- this is clearly a critical window of time where the body’s response to SARS-CoV-2 might be setting the stage for what is to come.”

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