COVID-19: The proteins that predict the course of the disease - What a Greek expert says

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Analysing the latest findings, National and Kapodistrian University of Athens (EKPA) experts identify three key proteins that appear to function as prognostic indicators for assessing the occurrence and severity of long-term COVID-19 in patients who have contracted the coronavirus.

There is no hematological way to date to diagnose the syndrome of long-term COVID-19 (long COVID).

In a study published on January 18, 2024, in the internationally recognised journal Science, the team compared blood samples from people who tested positive for COVID-19 with those from healthy adults and found marked differences in protein composition in people with long COVID in those who they also recovered in those who were never infected. The researchers developed a computational model that predicts how likely a person is to develop long-term COVID based on an analysis of more than 6,500 proteins found in the blood.

The Pathologist, Professor of Epidemiology and Preventive Medicine at the EKPA School of Medicine, Theodora Psaltopoulou and Biologist, Panagiota Zacharaki, report that, according to the analysis, the proteins involved in immune responses, blood clotting and inflammation could be key biomarkers for the diagnosis and monitoring of long COVID, which affects approximately 65 million people worldwide. This syndrome is associated with more than 200 symptoms, including brain fog, collapse, anginal pain and shortness of breath, which may persist for months or years after infection with SARS-CoV-2.

This study included 39 healthy adults who had never tested positive for COVID-19 and 113 people who had tested positive, of whom 40 had long COVID. Of these, 22 had symptoms 12 months after the first positive test.

The researchers analysed 6,596 proteins in 268 blood samples, which were collected from the participants once during the acute phase and six months later. They found several differences in the blood of people with long-term COVID-19 compared to those without, including different levels of proteins involved in blood clotting and inflammation.

Compared to healthy participants and those who had fully recovered from COVID-19, people with long-term COVID had lower levels of a protein called antithrombin III, which helps prevent blood clots, and higher levels of the proteins thrombospondin-1 and factor von Willebrand, proteins associated with clot formation.

When they looked at blood cells from a subset of participants, the researchers found that the expression of a protein called CD41 on white blood cells was lower in healthy people and higher in people who had 12 months of long COVID. The researchers also found increased activation of the complement system – part of the body's immune response, which normally helps fight infections – in people with long-term COVID, both during the initial infection and six months later.

People with six-month-long COVID had decreased levels of some proteins involved in the complement system and increased levels of others, compared to fully recovered or healthy participants.

As the study states, comorbidity and different genetic profiles affect people, and the heterogeneity of this syndrome probably means more research is needed on this topic. It is not a single mechanism that encompasses all symptoms.

We need more such studies further to fuel research on effective long-term treatments for COVID-19.

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