Association between corticosteroid therapy during acute COVID-19 and Long COVID symptoms: a propensity score overlap-weighted analysis

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BACKGROUND: The association between acute-phase corticosteroid therapy and subsequent Long COVID symptoms remains uncertain. Therefore, we aimed to evaluate the association between systemic corticosteroid therapy during hospitalization and patient-reported Long COVID symptoms during follow-up. METHODS: In this prospective multicenter observational study, we enrolled adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 26 hospitals in Japan between January 2020 and February 2021. To account for evolving corticosteroid prescription practices, we used propensity score overlap weighting with calendar time adjustment relative to the RECOVERY trial announcement and fit overlap-weighted mixed-effects logistic regression models to estimate longitudinal associations across follow-up (3, 6, and 12 months). Additionally, symptom-specific outcomes were evaluated at 3 months. RESULTS: Among the 1044 participants, 373 received systemic corticosteroids and 671 did not. Corticosteroid therapy was associated with higher odds of any Long COVID symptom during follow-up (OR: 1.71; 95% CI: 1.12-2.63). In exploratory subgroup analyses stratified by oxygen requirement, no clear association was observed among patients who required oxygen therapy during hospitalization, whereas the association was more apparent among those who did not require oxygen therapy. At 3 months, corticosteroid therapy was associated with muscle weakness (OR: 2.43; 95% CI: 1.27-4.65). CONCLUSIONS: In this observational overlap-weighted analysis, acute-phase systemic corticosteroid therapy during COVID-19 hospitalization was associated with higher odds of patient-reported Long COVID symptoms during follow-up. However, these findings should not be interpreted as evidence against appropriately indicated corticosteroid therapy in patients with hypoxemic COVID-19 or respiratory failure.

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