Long-Haul COVID: Why Some Never Fully Recover and What Science Reveals
According to a study of the COVICAT cohort, almost one in four people infected with SARS-CoV-2 suffered from long-COVID.
Long-COVID continues to impact many, with symptoms lasting years in some cases. This study identifies key risk factors, such as severe infection and pre-existing conditions, while highlighting protective factors like vaccination. With three distinct subtypes identified, researchers stress the importance of further studies to understand the full scope of this condition.
Long-COVID: A Lingering Threat
Between 2021 and 2023, 23% of people infected with SARS-CoV-2 developed long-COVID, and more than half of them continued to experience symptoms for at least two years. This finding comes from a study by ISGlobal, in collaboration with the Germans Trias i Pujol Research Institute (IGTP) as part of the European END-VOC project. The research, published in BMC Medicine, highlights that the risk of developing long-COVID depends on multiple factors.
Long-COVID occurs when symptoms persist for at least three months after an initial SARS-CoV-2 infection. These symptoms can affect different parts of the body, including the respiratory, neurological, and digestive systems, and often involve fatigue and exhaustion. Many previous long-COVID studies have been conducted in clinical settings, which may not fully reflect 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.
Who Is Most at Risk?
“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.
Three Types 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.
The Urgent Need for More Research
“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.
Reference: “Risk, determinants, and persistence of long-COVID in a population-based cohort study in Catalonia” by Manolis Kogevinas, Marianna Karachaliou, Ana Espinosa, Susana Iraola-Guzmán, Gemma Castaño-Vinyals, Laura Delgado-Ortiz, Xavier Farré, Natàlia Blay, Neil Pearce, Magda Bosch de Basea, Eva Alonso Nogués, Carlota Dobaño, Gemma Moncunill, Rafael de Cid and Judith Garcia-Aymerich, 14 March 2025, BMC Medicine.
DOI: 10.1186/s12916-025-03974-7
Funding: Horizon Europe END-VOC, Ministerio de Ciencia, Agencia Estatal de Investigación, Instituto de Salud Carlos III, Centro de Excelencia Severo Ochoa 2019-2023, Fundació la Marató de TV3, Generalitat de Catalunya, CERCA Program, Fundació Privada Daniel Bravo Andreu, VEIS project, European Regional Development Fund, RYC 2020-029886-I/AEI/10.13039/501100011033, European Social Fund
About COVICAT
The COVICAT cohort is a GCAT nested cohort designed to characterize the health impact of the COVID-19 pandemic on the population in Catalonia, Spain. Baseline data comes from the GCAT|Genomes for Life population-based cohort at the Germans Trias i Pujol Research Institute (IGTP).