Natural course of post COVID-19 condition and implications for trial design and outcome selection: A population-based longitudinal cohort study

BackgroundEvidence from population-based studies on the longer-term natural course of post COVID-19 condition is limited, but crucial for informing patients and healthcare providers and for effectively designing clinical trials. ObjectivesTo evaluate longer-term symptoms and health outcomes within a cohort of SARS-CoV-2 infected individuals. DesignPopulation-based, longitudinal cohort. SettingGeneral population, Canton of Zurich, Switzerland. Patients1543 adults with confirmed SARS-CoV-2 infection and 628 adults without infection. MeasurementsChanges in self-reported health status over time, factors associated with persistence of non-recovery, and prevalence and excess risk of symptoms at 6 and 12 months post-infection compared to non-infected individuals. Results25% of SARS-CoV-2 infected individuals did not recover by 6 months. Of those, 67% and 58% also did not recover at 12 and 18 months after infection, respectively. Hospitalization for acute COVID-19, pre-existing fatigue and pain or discomfort, and presence of specific systemic, cardiovascular, or musculoskeletal symptoms at 6 months were associated with persistent non-recovery. Symptom prevalence was higher among infected individuals compared to non-infected individuals at 6 months (adjusted risk difference (aRD)=17%) and 12 months (aRD=20%). aRDs for individual symptoms ranged from 2% to 12%, with the highest excess risks observed for altered taste or smell, post-exertional malaise, fatigue, and reduced concentration and memory. LimitationsWe relied on self-reported assessments and did not assess the effects of vaccination or infection with emerging variants of concern. ConclusionThese findings emphasize the need for effective interventions to reduce the burden of post COVID-19 condition. They further demonstrate the importance of using multiple outcome measures and of considering the expected rates of natural recovery and heterogenous patient trajectories in the design and interpretation of clinical trials.

Ready-To-Go Questionnaire - Development and validation of a novel medical pre-travel risk stratification tool.

BACKGROUND: There are no validated pre-travel self-assessment tools to stratify travellers' health risks and identify their needs for pre-travel medical preparation. This study presents a novel pre-travel risk stratification tool (Ready-To-Go Questionnaire). METHODS: The Ready-To-Go Questionnaire was developed by travel medical experts. It assesses information on travellers' itinerary and current health status, thereby assigning travellers to one out of four risk categories. To explore the Ready-To-Go Questionnaire's validity, we analysed the agreement between the risk categories resulting from the questionnaire and predefined validation criteria. This study was carried out at the Travel Clinic, University of Zurich, Switzerland. RESULTS: One hundred travellers attending a pre-travel consultation were included. 82% corresponded to the substantial-risk category, 17% to the high-risk category, 1% to the moderate-risk category and 0% to the low-risk category. The concordance between the risk categories and the consultants' risk assessment, was 0.39 and 0.29 (unweighted/weighted Cohen's Kappa). No significant concordance was found between the risk categories and additional validation criteria. CONCLUSION: The Ready-To-Go Questionnaire is a medical triage tool developed to identify different levels of travel-related health risks. This tool assists in better understanding travellers' needs, shaping modern travel consultations and offering patient-centred travel medicine services. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN10172086.

Estimating the burden of post-COVID-19 syndrome in a population-based cohort study of SARS-CoV-2 infected individuals: Implications for healthcare service planning

BackgroundLonger-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization. MethodsThis population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes. ResultsSymptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care. ConclusionsIn this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care. RegistrationISRCTN14990068