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

Background Evidence 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. Objectives To evaluate longer-term symptoms and health outcomes within a cohort of SARS-CoV-2 infected individuals. Design Population-based, longitudinal cohort. Setting General population, Canton of Zurich, Switzerland. Patients 1543 adults with confirmed SARS-CoV-2 infection and 628 adults without infection. Measurements Changes 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. Results 25% 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. Limitations We relied on self-reported assessments and did not assess the effects of vaccination or infection with emerging variants of concern. Conclusion These 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

Delivering Safe Surgical Care While Simultaneously Caring for Patients With COVID-19; Assessment of Patient Selection, Volume and Outcomes in a Tertiary Care Hospital

Objectives: Compare patient selection and postoperative outcomes after surgical treatment for gastrointestinal disorders before and during the SARS-CoV-2 pandemic.Methods: We assessed gastrointestinal surgeries conducted at a tertiary center from 2017–2021 for differences in patient populations and procedures before (up to February 2020) and during the pandemic (March 2020 to December 2021). We analyzed mortality, Intensive Care Unit (ICU) length of stay, admission to ICU and postoperative complications for complex procedures using descriptive statistics and regression models.Results: 7309 procedures were analyzed, showing a caseload reduction in March and October 2020, but no statistical evidence for fewer overall procedures overall. Population characteristics differed with lower Body Mass Indices in 2020 and 2021, more patients smoking and with diabetes treated in 2020. There was no increased mortality, ICU length of stay and in 1,144 complex procedures assessed low overall morbidity at 90 days postoperative.Conclusion: Delivering surgical care while treating patients for COVID-19 in the same hospital was safe. Healthcare officials should consider continuing surgical care during future health crises as consequences of limiting surgical treatment for gastrointestinal disorders may be fatal for patients

Individual-Level Evaluation of the Exposure Notification Cascade in the SwissCovid Digital Proximity Tracing App: Observational Study

Background: Digital proximity tracing (DPT) aims to complement manual contact tracing (MCT) in identifying exposed contacts and preventing further transmission of SARS-CoV-2 in the population. Although several DPT apps, including SwissCovid, have shown to have promising effects on mitigating the pandemic, several challenges have impeded them from fully achieving the desired results. A key question now relates to how the effectiveness of DPT can be improved, which requires a better understanding of factors influencing its processes. Objective: In this study, we aim to provide a detailed examination of the exposure notification (EN) cascade and to evaluate potential contextual influences for successful receipt of an EN and subsequent actions taken by cases and contacts in different exposure settings. Methods: We used data from 285 pairs of SARS-CoV-2-infected cases and their contacts within an observational cohort study of cases and contacts identified by MCT and enrolled between August 6, 2020, and January 17, 2021, in the canton of Zurich, Switzerland. We surveyed participants with electronic questionnaires. Data were summarized descriptively and stratified by exposure setting. Results: We found that only 79 (58.5%) of 135 contacts using the SwissCovid app whose corresponding cases reported to have triggered the EN also received one. Of these, 18 (22.8%) received the EN before MCT. Compared to those receiving an EN after MCT (61/79, 77.2%), we observed that a higher proportion of contacts receiving an EN before MCT were exposed in nonhousehold settings (11/18, 61.1%, vs 34/61, 55.7%) and their corresponding cases had more frequently reported mild-to-moderate symptoms (14/18, 77.8%, vs 42/61, 68.9%). Of the 18 contacts receiving an EN before MCT, 14 (77.8%) took recommended measures: 12 (66.7%) were tested for SARS-CoV-2, and 7 (38.9%) called the SwissCovid Infoline. In nonhousehold settings, the proportion of contacts taking preventive actions after receiving an EN was higher compared to same-household settings (82%, vs 67%). In addition, 1 (9%) of 11 ENs received in the nonhousehold setting before MCT led to the identification of a SARS-CoV-2-infected case by prompting the contact to get tested. This corresponds to 1 in 85 exposures of a contact to a case in a nonhousehold setting, in which both were app users and the case triggered the EN. Conclusions: Our descriptive evaluation of the DPT notification cascade provides further evidence that DPT is an important complementary tool in pandemic mitigation, especially in nonhousehold exposure settings. However, the effect of DPT apps can only be exerted if code generation processes are efficient and exposed contacts are willing to undertake preventive actions. This highlights the need to focus efforts on keeping barriers to efficient code generation as low as possible and promoting not only app adoption but also compliance with the recommended measures upon an EN. Trial registration: International Standard Randomised Controlled Trial Number Registry 14990068; https://doi.org/10.1186/ISRCTN14990068. Keywords: COVID-19; SARS-CoV-2; SwissCovid; app; contact tracing; digital proximity tracing; epidemiology; evaluation; exposure; mHealth; mobile app; notification; observational; public health; surveillance; tracking

Mental health of individuals infected with SARS-CoV-2 during mandated isolation and compliance with recommendations-A population-based cohort study

BACKGROUND: Isolation is an indispensable measure to contain the SARS-CoV-2 virus, but it may have a negative impact on mental health and overall wellbeing. Evidence on the isolation experience, facilitating and complicating factors is needed to mitigate negative effects. METHODS AND FINDINGS: This observational, population-based cohort study enrolled 1547 adults from the general population with SARS-CoV-2 infection reported to authorities between 27 February 2020 and 19 January 2021 in Zurich, Switzerland. We assessed the proportion of individuals reporting symptoms of depression and anxiety before, during and after isolation (by DASS-21), and queried worries, positive experiences, and difficulties. We analyzed the association of these outcomes with socio-demographics using ordinal regression. Additionally, we report free-text statements by participants to capture most important aspects of isolation. The proportion of participants affected by depression or anxiety increased during isolation from 10·0% to 17·1% and 9·1% to 17·6%, respectively. Ordinal regression showed that taking care of children increased the difficulty of isolation (OR 2·10, CI 1·43-3·08) and risk of non-compliance (OR 1·63, CI 1·05-2·53), especially in younger participants. A facilitating factor that individuals commonly expressed was receiving more support during isolation. CONCLUSION: Isolation due to SARS-CoV-2 presents a mental burden, especially for younger individuals and those taking care of children. Public health authorities need to train personnel and draw from community-based resources to provide targeted support, information, and guidance to individuals during isolation. Such efforts could alleviate the negative impact isolation has on the mental and physical health of individuals and ensure compliance of the population with recommendations

Implementation and validation of a novel instrument for the grading of unexpected events in paediatric surgery: Clavien–Madadi classification

Background: Inconsistent definitions of complications and unexpected events have limited accurate analysis of surgical outcomes. Perioperative outcome classifications currently used for adult patients have limitations when used for children./ Methods: A multidisciplinary group of experts modified the Clavien–Dindo classification to increase its utility and accuracy in paediatric surgery cohorts. Organizational and management errors were considered in the novel Clavien–Madadi classification, which focuses on procedural invasiveness rather than anaesthetic management. Unexpected events were prospectively documented in a paediatric surgery cohort. Results of the Clavien–Dindo and Clavien–Madadi classifications were compared and correlated with procedure complexity./ Results: Unexpected events were prospectively documented in a cohort of 17 502 children undergoing surgery between 2017 and 2021. The results of both classifications were highly correlated (ρ = 0.95), although the novel Clavien–Madadi classification identified 449 additional events (organizational and management errors) over the Clavien–Dindo classification, increasing the total number of events by 38 per cent (1605 versus 1158 events). The results of the novel system correlated significantly with the complexity of procedures in children (ρ = 0.756). Furthermore, grading of events > grade III according to the Clavien–Madadi classification showed a higher correlation with procedure complexity (ρ = 0.658) than the Clavien–Dindo classification (ρ = 0.198)./ Conclusion: The Clavien–Madadi classification is a tool for the detection of surgical and non-medical errors in paediatric surgery populations. Further validation in paediatric surgery populations is required before widespread use

Delivering Safe Surgical Care While Simultaneously Caring for Patients With COVID-19; Assessment of Patient Selection, Volume and Outcomes in a Tertiary Care Hospital

Objectives: Compare patient selection and postoperative outcomes after surgical treatment for gastrointestinal disorders before and during the SARS-CoV-2 pandemic. Methods: We assessed gastrointestinal surgeries conducted at a tertiary center from 2017-2021 for differences in patient populations and procedures before (up to February 2020) and during the pandemic (March 2020 to December 2021). We analyzed mortality, Intensive Care Unit (ICU) length of stay, admission to ICU and postoperative complications for complex procedures using descriptive statistics and regression models. Results: 7309 procedures were analyzed, showing a caseload reduction in March and October 2020, but no statistical evidence for fewer overall procedures overall. Population characteristics differed with lower Body Mass Indices in 2020 and 2021, more patients smoking and with diabetes treated in 2020. There was no increased mortality, ICU length of stay and in 1,144 complex procedures assessed low overall morbidity at 90 days postoperative. Conclusion: Delivering surgical care while treating patients for COVID-19 in the same hospital was safe. Healthcare officials should consider continuing surgical care during future health crises as consequences of limiting surgical treatment for gastrointestinal disorders may be fatal for patients

Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection

Using the Results of Benchmarking in Surgical Care to Improve Quality – the Role of Feedback and Communication Strategies: A Rapid Scoping Review Protocol

Using feedback and communications strategies in surgery and interventional medicine to implement results of benchmarking

Adherence and Association of Digital Proximity Tracing App Notifications With Earlier Time to Quarantine: Results From the Zurich SARS-CoV-2 Cohort Study

Objectives: We aimed to evaluate the effectiveness of the SwissCovid digital proximity tracing (DPT) app in notifying exposed individuals and prompting them to quarantine earlier compared to individuals notified only by manual contact tracing (MCT).Methods: A population-based sample of cases and close contacts from the Zurich SARS-CoV-2 Cohort was surveyed regarding SwissCovid app use and SARS-CoV-2 exposure. We descriptively analyzed app adherence and effectiveness, and evaluated its effects on the time between exposure and quarantine among contacts using stratified multivariable time-to-event analyses.Results: We included 393 SARS-CoV-2 infected cases and 261 close contacts. 62% of cases reported using SwissCovid and among those, 88% received and uploaded a notification code. 71% of close contacts were app users, of which 38% received a warning. Non-household contacts notified by SwissCovid started quarantine 1 day earlier and were more likely to quarantine earlier than those not warned by the app (HR 1.53, 95% CI 1.15–2.03).Conclusion: These findings provide evidence that DPT may reach exposed contacts faster than MCT, with earlier quarantine and potential interruption of SARS-CoV-2 transmission chains

Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study.

ObjectiveTo evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection.DesignPopulation based, longitudinal cohort.SettingGeneral population of canton of Zurich, Switzerland.Participants1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection.Main outcome measuresTrajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection.Results22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)).ConclusionsUp to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials.RegistrationsISRCTN18181860,