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Background: Exertional dyspnoea in post-COVID syndrome is a debilitating manifestation, requiring appropriate comprehensive management. However, limited-resources healthcare systems might be unable to expand their healthcare-providing capacity and are expected to be overwhelmed by increasing healthcare demand. Furthermore, since post-COVID exertional dyspnoea is regarded to represent an umbrella term, encompassing several clinical conditions, stratification of patients with post-COVID exertional dyspnoea, depending on risk factors and underlying aetiologies might provide useful for healthcare optimization and potentially help relieve healthcare service from overload. Hence, we aimed to investigate the frequency, functional characterization, and predictors of post-COVID exertional dyspnoea in a large cohort of post-COVID patients in Apulia, Italy, at 3-month post-acute SARS-CoV-2 infection., Methods: A cohort of laboratory-confirmed 318 patients, both domiciliary or hospitalized, was evaluated in a post-COVID Unit outpatient setting. Post-COVID exertional dyspnoea and other post-COVID syndrome manifestations were collected by medical history. Functional characterization of post-COVID exertional dyspnoea was performed through a 6-min walking test (6-mwt). The association of post-COVID exertional dyspnoea with possible risk factors was investigated through univariate and multivariate logistic regression analysis., Results: At medical evaluation, post-COVID exertional dyspnoea was reported by as many as 190/318 patients (59.7%), showing relatively high prevalence also in domiciliary-course patients. However, functional characterization disclosed a 6-mwt-based desaturation walking drop in only 24.1% of instrumental post-COVID exertional dyspnoea patients. Multivariate analysis identified five independent predictors significantly contributing to PCED, namely post-COVID-fatigue, pre-existing respiratory co-morbidities, non-asthmatic allergy history, age, and acute-phase-dyspnoea. Sex-restricted multivariate analysis identified a differential risk pattern for males (pre-existing respiratory co-morbidities, age, acute-phase-dyspnoea) and females (post-COVID-fatigue and acute-phase-dyspnoea)., Conclusion: Our findings revealed that post-COVID exertional dyspnoea is characterized by relevant clinical burden, with potential further strain on healthcare systems, already weakened by pandemic waves. Sex-based subgroup analysis reveals sex-specific dyspnoea-underlying risk profiles and pathogenic mechanisms. Knowledge of sex-specific risk-determining factors might help optimize personalized care management and healthcare resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. One of the authors declared that he is an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Resta, Cuscianna, Pierucci, Custodero, Solfrizzi, Sabbà, Palmisano, Barratta, De Candia, Tummolo, Capozza, Lomuscio, De Michele, Tafuri, Resta and Lenato.)

Objectives: There are no comparative studies between patients belonging to the first and second waves of the SARS-CoV-2 pandemic, the virus triggering coronavirus disease 2019 (COVID-19). In this retrospective observational study, we analyzed the clinical characteristics and the short-term outcomes of two groups of laboratory-confirmed COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS) belonging to two different waves of the pandemic.  Methods: We analyzed 97 consecutive patients from 11 March 2020 to 31 May 2020 and 52 consecutive patients from 28 August 2020 to 15 October 2020.  Results: Patients belonging to the second wave were younger, had a lower number of concomitant chronic conditions (multimorbidity), and had a milder clinical phenotype. Medical treatments and respiratory support use have changed during the COVID-19 pandemic, based on different laboratory results and disease clinical features. Patients in the second wave had better short-term clinical outcomes, with lower death rates and more step-down transfers to a general ward.  Conclusion: The present findings show a clear phenotypic difference in patients hospitalized at different stages of the COVID-19 pandemic in Italy. These results can help to stratify clinical risk and to better tailor medical treatments and respiratory support for patients with ARDS and COVID-19 pneumonia.