23% of people infected with SARS-CoV-2 between 2021 and 2023 developed long-COVID, and in more than half of them the symptoms persisted for two years. These are the main conclusions of a study conducted by ISGlobal, a centre supported by the ”la Caixa” Foundation, and in collaboration with the Germans Trias i Pujol Research Institute (IGTP), as part of the European END-VOC project. The risk of developing long-COVID depends on several factors, according to the results published in BMC Medicine.

After overcoming an initial SARS-CoV-2 infection, some people develop long-COVID. It manifests itself with symptoms that persist for at least three months, including respiratory, neurological, digestive or general symptoms, such as fatigue and exhaustion. Most studies of long-COVID have been conducted in a clinical context, which may not fully capture its impact on the general population.

“A population-based cohort study allowed us to better estimate the magnitude of long-COVID and identify risk and protective factors,” explains Manolis Kogevinas, ISGlobal researcher and lead author of the study. The study followed 2,764 adults from the COVICAT cohort, a population-based study designed to characterize the health impact of the pandemic on the population of Catalonia. Participants completed three questionnaires — in 2020, 2021 and 2023 — and provided blood samples and medical records.

Risk and prevention factors

“Being a woman, having experienced a severe COVID-19 infection and having a pre-existing chronic disease such as asthma are clear risk factors,” says Marianna Karachaliou, co-author of the study and researcher at ISGlobal. “In addition, we observed that people with obesity and high levels of IgG antibodies prior to vaccination were more likely to develop long-COVID,” she adds. The latter factor may reflect hyperactivation of the immune system after the initial infection, which in some cases may contribute to the persistence of long-term symptoms.

The analysis also identified protective factors that could reduce the risk of developing the condition. These include vaccination before infection and a healthy lifestyle, which includes regular physical activity and adequate sleep. In addition, the risk was lower in people who were infected after the Omicron variant became dominant. This could be explained by the tendency for infections to be milder or by greater general immunity to COVID-19.

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Three subtypes of long-COVID

Based on the symptoms reported by the participants and their medical records, the researchers identified three clinical subtypes of long-COVID. They were classified according to whether the symptoms were neurological and musculoskeletal, respiratory, or severe and involved multiple organs. In addition, the researchers found that 56% of people with long-COVID were still experiencing symptoms two years later.

“Our results show that a significant percentage of the population has long-COVID, which in some cases affects their quality of life,” says Judith Garcia-Aymerich, ISGlobal researcher and last author of the study. “Establishing collaborations with other countries will be key to understanding whether these findings can be extrapolated to other populations,” she concludes.

“On the fifth anniversary of COVID-19, significant progress has been made in understanding the disease. However, as this study shows, the pandemic’s impact on mental health, work, and quality of life remains profound. While this research is a step forward, much remains to be done to fully understand this invisible illness,” says Rafael de Cid, scientific director of GCAT at IGTP. “The COVICAT cohort has been instrumental in advancing research, and we need to acknowledge the invaluable contribution of volunteers and the Blood and Tissue Bank team, particularly during the challenging times of 2020”, he adds.