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Determinants of the Onset and Prognosis of the Post-COVID-19 Condition: A 2-Year Prospective Cohort Study

21 Pages Posted: 12 Jul 2023

See all articles by Lourdes Mateu

Lourdes Mateu

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Cristian Tebe

Hospital Universitari Germans Trias i Pujol - Biostatistics Unit

Cora Loste

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

José Ramón Santos

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Gemma Lladós

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Cristina López

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Sergio España-Cueto

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Ruth Toledo

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Marta Font

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Anna Chamorro

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Francisco Muñoz-López

Hospital Universitari Germans Trias i Pujol - IrsiCaixa AIDS Research Institute

Maria Nevot

Hospital Universitari Germans Trias i Pujol - IrsiCaixa AIDS Research Institute

Nuria Vallejo

Hospital Germans Trias i Pujol - Cardiology Department

Albert Teis

Hospital Germans Trias i Pujol - Cardiology Department

Jordi Puig

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Carmina Rodríguez Fumaz

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

José Antonio Muñoz-Moreno

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Anna Prats

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Carla Estany-Quera

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Roser Coll-Fernández

Red Española de la Investigación en COVID Persistente (REiCOP)

Cristina Herrero

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Patricia Casares

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Anna Garcia

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Roger Paredes

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department

Bonaventura Clotet

IrsiCaixa AIDS Research Institute-HIVACAT; Hospital Universitari Germans Trias i Pujol; Universitat de Vic - Universitat Central de Catalunya (UVic-UCC); Autonomous University of Barcelona

Marta Massanella

Hospital Universitari Germans Trias i Pujol - IrsiCaixa AIDS Research Institute

More...

Abstract

Background: At least 5-10% of subjects surviving COVID-19 develop the post-COVID-19 condition (PCC) or “Long COVID”. The clinical presentation of PCC is heterogeneous, its pathogenesis is being deciphered, and objective, validated biomarkers are lacking. It is unknown if PCC is a single entity or a heterogeneous syndrome with overlapping pathophysiological basis. In a large crossectional evaluation, the RECOVER study in the US identified four clusters of subjects with PCC according to their presenting symptoms. The long-term clinical implications of PCC remain unknown.

Methods: We conducted a 2-year prospective cohort study of subjects surviving COVID-19, including individuals fulfilling the WHO PCC definition and subjects with full clinical recovery. We systematically collected post-COVID-19 symptoms using prespecified questionnaires and performed additional diagnostic imaging tests when needed. Factors associated with PCC were identified and modeled using logistic regression. Unsupervised clustering analysis was used to group subjects with PCC according to their presenting symptoms. Factors associated with PCC recovery were modelled using a direct acyclic graph approach.

Findings: The study included 548 individuals, 341 with PCC, followed for a median of 23 months (IQR 16·5 – 23·5), and 207 subjects fully recovered. In the model with the best fit, subjects who were male and had tertiary studies were less likely to develop PCC, whereas a history of headache, or presence of tachycardia, fatigue, neurocognitive and neurosensitive complaints and dyspnea at COVID-19 diagnosis predicted the development of PCC. The cluster analysis revealed the presence of three symptom clusters with an additive number of symptoms. Only 26 subjects (7·6%) recovered from PCC during follow-up; almost all of them (n=24) belonged to the less symptomatic cluster A, dominated mainly by fatigue. Recovery from PCC was more likely in subjects who were male, required ICU admission, or had cardiovascular comorbidities, hyporexia and/or smell/taste alterations during acute COVID-19. Subjects presenting with muscle pain, impaired attention, dyspnea, or tachycardia, conversely, were less likely to recover from PCC.

Interpretation: Preexisting medical and socioeconomic factors, as well as acute COVID-19 symptoms, predict the development of and recovery from the PCC. Recovery is extremely rare during the first 2 years, posing a major challenge to healthcare systems.

Funding: This work was funded by the crowdfunding initiatives “yomecorono.com“, BonPreu/Esclat and Correos, and with the collaboration of “Programa de Becas Gilead a la Investigación Biomédica, GLD21_00070”. MM was granted with RYC2020-028934-I/AEI/10.13039/501100011033 from Spanish Ministry of Science and Innovation and State Research Agency and the European Social Fund “investing in your future”. FM was supported by Sorigué Foundation.

Declaration of Interest: RP has participated in advisory boards for Pfizer, Gilead, MSD, GSK, Atea, Lilly, Roche, Astra-Zeneca, ViiV Healthcare and Theratechnologies, has participated in lectures and seminars funded by Gilead, Pfizer, GSK and AstraZeneca, and has received research funds awarded to his institution from Gilead, Pfizer, and MSD. MM participated in lectures and seminars funded by Gilead. The other authors declare no competing interests.

Ethical Approval: The independent ethics committee of the Germans Trias i Pujol Hospital approved the study protocol (PI- 20-217). All procedures were conducted according to good clinical practices and the General Data Protection Regulation 2016/679 on data protection and privacy for all individuals within the European Union. All study participants provided signed informed consent to participate in the study.

Keywords: COVID-19, post-COVID-19 condition, long COVID-19

Suggested Citation

Mateu, Lourdes and Tebe, Cristian and Loste, Cora and Santos, José Ramón and Lladós, Gemma and López, Cristina and España-Cueto, Sergio and Toledo, Ruth and Font, Marta and Chamorro, Anna and Muñoz-López, Francisco and Nevot, Maria and Vallejo, Nuria and Teis, Albert and Puig, Jordi and Fumaz, Carmina Rodríguez and Muñoz-Moreno, José Antonio and Prats, Anna and Estany-Quera, Carla and Coll-Fernández, Roser and Herrero, Cristina and Casares, Patricia and Garcia, Anna and Paredes, Roger and Clotet, Bonaventura and Massanella, Marta, Determinants of the Onset and Prognosis of the Post-COVID-19 Condition: A 2-Year Prospective Cohort Study. Available at SSRN: https://ssrn.com/abstract=4505315 or http://dx.doi.org/10.2139/ssrn.4505315

Lourdes Mateu (Contact Author)

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Cristian Tebe

Hospital Universitari Germans Trias i Pujol - Biostatistics Unit ( email )

Cora Loste

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

José Ramón Santos

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Barcelona
Spain

Gemma Lladós

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Cristina López

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Sergio España-Cueto

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Ruth Toledo

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Marta Font

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Anna Chamorro

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Francisco Muñoz-López

Hospital Universitari Germans Trias i Pujol - IrsiCaixa AIDS Research Institute ( email )

Maria Nevot

Hospital Universitari Germans Trias i Pujol - IrsiCaixa AIDS Research Institute ( email )

Nuria Vallejo

Hospital Germans Trias i Pujol - Cardiology Department ( email )

Albert Teis

Hospital Germans Trias i Pujol - Cardiology Department ( email )

Jordi Puig

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Carmina Rodríguez Fumaz

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

José Antonio Muñoz-Moreno

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Anna Prats

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Carla Estany-Quera

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Roser Coll-Fernández

Red Española de la Investigación en COVID Persistente (REiCOP) ( email )

Cristina Herrero

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Patricia Casares

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Anna Garcia

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Roger Paredes

Hospital Universitari Germans Trias i Pujol - Infectious Diseases Department ( email )

Bonaventura Clotet

IrsiCaixa AIDS Research Institute-HIVACAT

Badalona
Spain

Hospital Universitari Germans Trias i Pujol

Carretera de Canyet
Badalona, Barcelona 08916
Spain

Universitat de Vic - Universitat Central de Catalunya (UVic-UCC)

Vic
Spain

Autonomous University of Barcelona

Plaça Cívica
Cerdañola del Valles
Barcelona, Barcelona 08193
Spain

Marta Massanella

Hospital Universitari Germans Trias i Pujol - IrsiCaixa AIDS Research Institute

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