Estimating Long COVID-19 prevalence across definitions and forms of sample selection, 2025, Lovaglio et al

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Estimating Long COVID-19 prevalence across definitions and forms of sample selection

Pietro Giorgio Lovaglio, Fabio Borgonovo, Alessandro Manzo Margiotta, Mohamed Mowafy, Marta Colaneri, Alessandra Bandera, Andrea Gori, Amedeo Ferdinando Capetti

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Abstract
Long COVID (LC) is a multisystem condition with prolonged symptoms persisting beyond acute SARS-CoV-2 infection. However, prevalence estimates vary widely due to differences in case definitions and sampling methodologies. This study aims to determine the prevalence of LC across different definitions and correct for selection bias using advanced statistical modeling.

We conducted a retrospective, observational study at Luigi Sacco Hospital (Milan, Italy), analyzing 3,344 COVID-19 patients from two pandemic waves (2020-2021). Participants included 1,537 outpatients from the ARCOVID clinic and 1,807 hospitalized patients. LC was defined based on WHO and NICE criteria, as well as two alternative definitions: symptoms persisting at 3 and 6 months post-infection. We used a bivariate censored Probit model to account for selection bias and estimate adjusted LC prevalence.

LC prevalence varied across definitions: 67.4% (WHO), 76.3% (NICE), 80.2% (3 months), and 79.6% (6 months). Adjusted prevalence estimates remained consistent across definitions. The most common symptoms were fatigue (58.6%), dyspnea (41.1%), and joint/muscle pain (39.2%).

Risk factors included female sex (OR 2.165-2.379), metabolic disease (OR 1.587-1.629), and older age (40-50 years, OR 1.847). Protective factors included antiplatelets (OR 0.640-0.689), statins (OR 0.616), and hypoglycemics (OR 0.593-0.706). Vaccination, hydroxychloroquine, and antibiotics were associated with an increased risk of LC. Selection bias significantly influenced prevalence estimates, underscoring the need for robust statistical adjustments.

Our findings highlight the high prevalence of LC, particularly among specific subgroups, with strong selection effects influencing outpatient participation. Differences in prevalence estimates emphasize the impact of case definitions and study designs on LC research. The identification of risk and protective factors supports targeted interventions and patient management strategies.

This study provides one of the most comprehensive analyses of LC prevalence while accounting for selection bias. Our findings call for standardized LC definitions, improved epidemiological methodologies, and targeted prevention strategies. Future research should explore prospective cohorts to refine LC prevalence estimates and investigate long-term health outcomes.

Link (Frontiers in Epidemiology) [Provisionally accepted, currently only abstract]
 
Risk factors included female sex (OR 2.165-2.379), metabolic disease (OR 1.587-1.629), and older age (40-50 years, OR 1.847). Protective factors included antiplatelets (OR 0.640-0.689), statins (OR 0.616), and hypoglycemics (OR 0.593-0.706).

Vaccination, hydroxychloroquine, and antibiotics were associated with an increased risk of LC.
Why didn't they include the odds ratios for the last three medication risk factors?
 
Vaccination was also significantly and positively associated with LC. This conflicts with Antonelli et al. (33), where LC symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals. However, our vaccination variable simply indicates whether a patient ever received at least one dose, without distinguishing the number of doses or timing relative to infection, and most of our cohort (first and second waves) acquired COVID-19 before Italy's vaccine rollout began in December 2020. As a result, vaccination followed rather than preceded infection.

Then, also if our findings are in line with those of the Scottish study (9), we cannot confirm their results because only a small fraction of our sample was vaccinated before the infection, and broader evidence links incomplete or absent vaccination to increased LC risk (34, 35).
So it sounds more like long COVID caused vaccination rather than vaccination caused long COVID.
 
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