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Harmonizing Global Cohorts to Understand Long COVID: Insights from Gabriella Scarlatti

By 8 October 2025October 10th, 2025No Comments

Gabriella Scarlatti is the head of the Viral Evolution and Transmission Unit, a research group dedicated to studying viruses, particularly HIV, and the immune responses associated with HIV infection.

What motivated you join EPIVINF?

We joined EPIVINF for several reasons. Firstly, we were already familiar with some of the groups in the consortium. From a scientific perspective, we believed we could contribute our expertise in neuro-HIV, long COVID, and immunology. At the same time, we recognized the value of gaining insights from other areas of expertise within the consortium, such as epigenetics, animal models, and advanced statistical approaches.

What is your work within the project?

I am responsible for coordinating the cohorts as well as the collection and harmonization of their data. We identified cohorts from different countries where we could contribute our expertise; however, we also discovered that the manifestation and development of long COVID varied significantly across countries. For instance, in one country, there was a higher proportion of women than men among participants, which made data harmonization more challenging.

What type of cohorts do you have?

Essentially, we study patients who had COVID-19 with varying disease outcomes. Approximately one in three developed long COVID, a debilitating condition due to its prolonged course and significant impact on those affected. We also aimed to compare long COVID with other conditions that share similar neurological symptoms. For this reason, we examined neuro-HIV, as HIV can also manifest with neurological complications.

What does harmonization of the cohorts mean?

Harmonization means identifying and using comparable parameters across cohorts to enable meaningful comparisons. This involves defining common symptoms, but also considering key variables such as gender, age, and clinical trial participation. For instance, we must ensure that inclusion and exclusion criteria—determining who could or could not participate in a trial—are as similar as possible. A thorough understanding of the data is essential to decide how to compare cohorts and obtain reliable results. While it is possible to compare very different groups, they must share a common foundation. This ensures that the parameters we analyse truly reflect long COVID and are not confounded by unrelated factors, given the substantial variability across cohorts.

What challenges have you encountered when harmonizing the cohorts?

At first, we thought the process would be straightforward, as many assumed that long COVID was the same for everyone. However, we soon realized that this was not the case, different parameters emerged, and the characteristics of people who developed long COVID varied from country to country. For example, in Italy, hospitalized patients were predominantly male, whereas in Spain, most were women who had not been hospitalized. Ultimately, we were able to harmonize the cohorts, but it required great attention to detail and considerable time before we could draw conclusions and begin working effectively on the parameters we aimed to analyse such as the epigenetic, immunological, and virological aspects of the disease.

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