The Omicron Variant Is Associated with a Reduced Risk of the Post COVID-19 Condition and Its Main Phenotypes Compared to the Wild-Type Virus: Results from the EuCARE-POSTCOVID-19 Study
Francesca Bai,
Andrea Santoro,
Pontus Hedberg,
Alessandro Tavelli,
Sara De Benedittis,
Júlia Fonseca de Morais Caporali,
Carolina Coimbra Marinho,
Arnaldo Santos Leite,
Maria Mercedes Santoro,
Francesca Ceccherini Silberstein,
Marco Iannetta,
Dovilé Juozapaité,
Edita Strumiliene,
André Almeida,
Cristina Toscano,
Jesús Arturo Ruiz-Quiñones,
Chiara Mommo,
Iuri Fanti,
Francesca Incardona,
Alessandro Cozzi-Lepri,
Giulia Marchetti
Affiliations
Francesca Bai
Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Science, University of Milan, 20142 Milan, Italy
Andrea Santoro
Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Science, University of Milan, 20142 Milan, Italy
Pontus Hedberg
Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, 17177 Stockholm, Sweden
Alessandro Tavelli
Icona Foundation, 20145 Milan, Italy
Sara De Benedittis
Icona Foundation, 20145 Milan, Italy
Júlia Fonseca de Morais Caporali
School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
Carolina Coimbra Marinho
School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
Arnaldo Santos Leite
School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
Maria Mercedes Santoro
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Francesca Ceccherini Silberstein
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Marco Iannetta
Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Dovilé Juozapaité
Vilnius Santaros Klinikos Biobank, Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania
Edita Strumiliene
Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Medical Faculty, Vilnius University, 03101 Vilnius, Lithuania
André Almeida
Centro Universitário de Lisboa Central, Centro Clínico Académico de Lisboa, 1169-050 Lisboa, Portugal
Cristina Toscano
Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisboa, Portugal
Jesús Arturo Ruiz-Quiñones
Hospital Juan Graham Casasus, Villahermosa 86126, Tabasco, Mexico
Chiara Mommo
EuResist Network GEIE, 00152 Rome, Italy
Iuri Fanti
EuResist Network GEIE, 00152 Rome, Italy
Francesca Incardona
EuResist Network GEIE, 00152 Rome, Italy
Alessandro Cozzi-Lepri
Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London WC1E 6BT, UK
Giulia Marchetti
Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Science, University of Milan, 20142 Milan, Italy
Post COVID-19 condition (PCC) is defined as ongoing symptoms at ≥1 month after acute COVID-19. We investigated the risk of PCC in an international cohort according to viral variants. We included 7699 hospitalized patients in six centers (January 2020–June 2023); a subset of participants with ≥1 visit over the year after clinical recovery were analyzed. Variants were observed or estimated using Global Data Science Initiative (GISAID) data. Because patients returning for a post COVID-19 visit may have a higher PCC risk, and because the variant could be associated with the probability of returning, we used weighted logistic regressions. We estimated the proportion of the effect of wild-type (WT) virus vs. Omicron on PCC, which was mediated by Intensive Care Unit (ICU) admission, through a mediation analysis. In total, 1317 patients returned for a post COVID visit at a median of 2.6 (IQR 1.84–3.97) months after clinical recovery. WT was present in 69.6% of participants, followed by the Alpha (14.4%), Delta (8.9%), Gamma (3.9%) and Omicron strains (3.3%). Among patients with PCC, the most common manifestations were fatigue (51.7%), brain fog (32.7%) and respiratory symptoms (37.2%). Omicron vs. WT was associated with a reduced risk of PCC and PCC clusters; conversely, we observed a higher risk with the Delta and Alpha variants vs. WT. In total, 42% of the WT effect vs. Omicron on PCC risk appeared to be mediated by ICU admission. A reduced PCC risk was observed after Omicron infection, suggesting a possible reduction in the PCC burden over time. A non-negligible proportion of the variant effect on PCC risk seems mediated by increased disease severity during the acute disease.