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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.
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To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses. One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.
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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
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BackgroundDigital proximity tracing (DPT) apps may warn exposed individuals faster than manual contact tracing (MCT), leading to earlier interruption of transmission chains through quarantine. However, it is yet unclear whether these apps lead to a reduction in transmissions under real-world conditions. This study aimed at evaluating whether the SwissCovid DPT app is effective in warning close contacts of SARS-CoV-2 infected cases and prompting them to quarantine earlier. MethodsA population-based sample of adult index cases and close contacts identified through MCT and enrolled in the Zurich SARS-CoV-2 Cohort study were surveyed regarding use of the SwissCovid app and SARS-CoV-2 exposure setting. We analyzed ooutcomes related to app effectiveness and adherence (i.e., receipt and uploading of notification codes by index cases; receipt of app warnings and steps taken by close contacts). Furthermore, we performed adjusted time-to-event analyses stratified by exposure setting to estimate the effect of the app on time between relevant exposure and entering quarantine among close contacts. FindingsWe included 393 index cases and 261 close contacts in the analysis. Among index cases using SwissCovid, 88% reported receiving and uploading a notification code in the app to trigger a warning among proximity contacts. Among close contacts using the app, 38% reported receiving an app warning due to the risk exposure. We found that non-household contacts who were notified by the app started quarantine at a median of 2 days after exposure, while those not notified started quarantine at a median of 3 days. In stratified multivariable analyses, app notified contacts had a greater probability of going into quarantine earlier than those without app notification (HR 1{middle dot}53, 95% CI 1{middle dot}15-2{middle dot}03). InterpretationOur study showed that non-household contacts notified by the app started quarantine one day earlier than those not notified by the app. These findings constitute the first evidence that DPT may reach exposed contacts faster than MCT, leading to earlier quarantine and potential interruption of SARS-CoV-2 transmission chains. FundingCantonal Health Directorate Zurich, University of Zurich Foundation and the Swiss Federal Office of Public Health.