By Ashley Gallagher

Investigators say that the post-acute sequalae markers are Epstein-Barr virus (EBV) DNA levels in the blood, pre-existing types 2 diabetes, the presence of certain antibodies, and SARS-CoV-2 RNA levels in the blood.

Several factors in autoantibodies can be measured at the initial point of COVID-19 diagnosis that anticipate if an individual is likely to develop long COVID-19, the results of a new study show.

The PASC factors are Epstein-Barr virus (EBV) DNA levels in the blood, pre-existing types 2 diabetes, the presence of certain antibodies, and SARS-CoV-2 RNA levels in the blood.

A significant number of individuals who contract SARS-CoV-2 suffer chronic effects known as post-acute sequalae of COVID-19 (PASC), also known as long COVID. Symptoms include brain fog, fatigue, loss of smell and taste, and shortness of breath.

“Identifying these PASC factors is a major step forward for not only understanding long COVID and potentially treating it but also which patients are at highest risk for the development of chronic conditions,” Jim Heath, PhD, president of the Institute for Systems Biology (ISB), said in a statement. “These findings are also helping us frame our thinking around other chronic conditions, such as post-acute Lyme syndrome, for example.”

Additionally, investigators found that mild cases of COVID-19, not just severe cases, are also associated with long COVID. They also suggest that administering antivirals very early in the disease course could potentially prevent some PASC.

“Our study pairs clinical data and patient-reported outcomes with deep multi-omic analyses to unravel important biological associations that occur in patients with PASC. Certain findings, such as the low cortisol state in patients with long COVID, have potential to translate rapidly to the clinic. Our results form an important foundation for the development of therapeutics to treat long COVID,” Jason Goldman, MD, co-corresponding author of the paper and an infectious disease expert, said in the statement.

Investigators collected blood and swab samples from 309 individuals with COVID-19 at different points to perform comprehensive phenotyping, which was integrated with clinical data and patient-reported symptoms to carry out the investigation.

A key finding of the study is that early blood viral measurements are associated with long covid symptoms that individuals will develop months later, another author of the paper, Yapeng Su, PhD, said in the statement.

Additionally, the EBV, a virus that infects 90% of the human population and is normally inactive in the body after infection, is reactivated early on after a SARS-CoV-2 infection, which is significantly associated with future long COVID symptoms.

Investigators also found that PASC is anticipated by autoantibodies, which associate with autoimmune diseases, such as lupus, at diagnosis, and that as autoantibodies increase, protective SARS-CoV-2 antibodies decrease.

This suggests a relationship among autoantibodies, individuals at elevated risk of re-infection, and long COVID.

“Many patients with high autoantibodies simultaneously have low, protective, antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Daniel Chen, a lab assistant in Health lab at ISB, a co-first author of the paper, said in the statement.

The findings of the research were published in the journal, Cell.

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