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

OBJECTIVE: To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection. DESIGN: Population based, longitudinal cohort. SETTING: General population of canton of Zurich, Switzerland. PARTICIPANTS: 1106 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 MEASURES: Trajectories 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. RESULTS: 22.9% (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%)). CONCLUSIONS: Up 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. REGISTRATIONS: ISRCTN18181860, .

Dynamics of racial disparities in all-cause mortality during the COVID-19 pandemic.

As research documenting disparate impacts of COVID-19 by race and ethnicity grows, little attention has been given to dynamics in mortality disparities during the pandemic and whether changes in disparities persist. We estimate age-standardized monthly all-cause mortality in the United States from January 2018 through February 2022 for seven racial/ethnic populations. Using joinpoint regression, we quantify trends in race-specific rate ratios relative to non-Hispanic White mortality to examine the magnitude of pandemic-related shifts in mortality disparities. Prepandemic disparities were stable from January 2018 through February 2020. With the start of the pandemic, relative mortality disadvantages increased for American Indian or Alaska Native (AIAN), Native Hawaiian or other Pacific Islander (NHOPI), and Black individuals, and relative mortality advantages decreased for Asian and Hispanic groups. Rate ratios generally increased during COVID-19 surges, with different patterns in the summer 2021 and winter 2021/2022 surges, when disparities approached prepandemic levels for Asian and Black individuals. However, two populations below age 65 fared worse than White individuals during these surges. For AIAN people, the observed rate ratio reached 2.25 (95% CI = 2.14, 2.37) in October 2021 vs. a prepandemic mean of 1.74 (95% CI = 1.62, 1.86), and for NHOPI people, the observed rate ratio reached 2.12 (95% CI = 1.92, 2.33) in August 2021 vs. a prepandemic mean of 1.31 (95% CI = 1.13, 1.49). Our results highlight the dynamic nature of racial/ethnic disparities in mortality and raise alarm about the exacerbation of mortality inequities for Indigenous groups due to the pandemic.

COVID-19 mortality and excess mortality among working-age residents in California, USA, by occupational sector: a longitudinal cohort analysis of mortality surveillance data.

BACKGROUND: During the first year of the COVID-19 pandemic, workers in essential sectors had higher rates of SARS-CoV-2 infection and COVID-19 mortality than those in non-essential sectors. It is unknown whether disparities in pandemic-related mortality across occupational sectors have continued to occur during the periods of SARS-CoV-2 variants and vaccine availability. METHODS: In this longitudinal cohort study, we obtained data from the California Department of Public Health on all deaths occurring in the state of California, USA, from Jan 1, 2016, to Dec 31, 2021. We restricted our analysis to residents of California who were aged 18-65 years at time of death and died of natural causes. We classified the occupational sector into nine essential sectors; non-essential; or unemployed or without an occupation provided on the death certificate. We calculated the number of COVID-19 deaths in total and per capita that occurred in each occupational sector. Separately, using autoregressive integrated moving average models, we estimated total, per-capita, and relative excess natural-cause mortality by week between March 1, 2020, and Nov 30, 2021, stratifying by occupational sector. We additionally stratified analyses of occupational risk into counties with high versus low vaccine uptake, categorising high-uptake regions as counties where at least 50% of the population were fully vaccinated according to US guidelines by Aug 1, 2021. FINDINGS: From March 1, 2020, to Nov 30, 2021, 24 799 COVID-19 deaths were reported in residents of California aged 18-65 years and an estimated 28 751 (95% prediction interval 27 853-29 653) excess deaths. People working in essential sectors were associated with higher COVID-19 deaths and excess deaths than were those working in non-essential sectors, with the highest per-capita COVID-19 mortality in the agriculture (131·8 per 100 000 people), transportation or logistics (107·1 per 100 000), manufacturing (103·3 per 100 000), facilities (101·1 per 100 000), and emergency (87·8 per 100 000) sectors. Disparities were wider during periods of increased infections, including during the Nov 29, 2020, to Feb 27, 2021, surge in infections, which was driven by the delta variant (B.1.617.2) and occurred during vaccine uptake. During the June 27 to Nov 27, 2021 surge, emergency workers had higher COVID-19 mortality (113·7 per 100 000) than workers from any other sector. Workers in essential sectors had the highest COVID-19 mortality in counties with low vaccination uptake, a difference that was more pronounced during the period of the delta infection surge during Nov 29, 2020, to Feb 27, 2021. INTERPRETATION: Workers in essential sectors have continued to bear the brunt of high COVID-19 and excess mortality throughout the pandemic, particularly in the agriculture, emergency, manufacturing, facilities, and transportation or logistics sectors. This high death toll has continued during periods of vaccine availability and the delta surge. In an ongoing pandemic without widespread vaccine coverage and with anticipated threats of new variants, the USA must actively adopt policies to more adequately protect workers in essential sectors. FUNDING: US National Institute on Aging, Swiss National Science Foundation, and US National Institute on Drug Abuse.

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.

Excess natural-cause deaths in California by cause and setting: March 2020 through February 2021.

Excess mortality has exceeded reported deaths from Covid-19 during the pandemic. This gap may be attributable to deaths that occurred among individuals with undiagnosed Covid-19 infections or indirect consequences of the pandemic response such as interruptions in medical care; distinguishing these possibilities has implications for public health responses. In the present study, we examined patterns of excess mortality over time and by setting (in-hospital or out-of-hospital) and cause of death using death certificate data from California. The estimated number of excess natural-cause deaths from 2020 March 1 to 2021 February 28 (69,182) exceeded the number of Covid-19 diagnosed deaths (53,667) by 29%. Nearly half, 47.4% (32,775), of excess natural-cause deaths occurred out of the hospital, where only 28.6% (9,366) of excess mortality was attributed to Covid-19. Over time, increases or decreases in excess natural non-Covid-19 mortality closely mirrored increases or decreases in Covid-19 mortality. The time series were positively correlated in out-of-hospital settings, particularly at time lags when excess natural-cause deaths preceded reported Covid-19 deaths; for example, when comparing Covid-19 deaths to excess natural-cause deaths in the week prior, the correlation was 0.73. The strong temporal association of reported Covid-19 deaths with excess out-of-hospital deaths from other reported natural-cause causes suggests Covid-19 deaths were undercounted during the first year of the pandemic.

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.

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.

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.

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.

A Data-Driven Simulation of the Exposure Notification Cascade for Digital Contact Tracing of SARS-CoV-2 in Zurich, Switzerland.

Importance: Digital contact tracing (DCT) apps have been released in several countries to help interrupt SARS-CoV-2 transmission chains. However, the effect of DCT on pandemic mitigation remains to be demonstrated. Objective: To estimate key populations and performance indicators along the exposure notification cascade of the SwissCovid DCT app in a clearly defined regional and temporal context. Design, Setting, and Participants: This comparative effectiveness study was based on a simulation informed by measured data from issued quarantine recommendations and positive SARS-CoV-2 test results after DCT exposure notifications in the canton of Zurich. A stochastic model was developed to re-create the DCT notification cascade for Zurich. Population sizes at each cascade step were estimated using triangulation based on publicly available administrative and observational research data for the study duration from September 1 to October 31, 2020. The resultant estimates were checked for internal consistency and consistency with upstream or downstream estimates in the cascade. Stochastic sampling from data-informed parameter distributions was performed to explore the robustness of results. Subsequently, key performance indicators were evaluated to assess the potential contribution of DCT compared with manual contact tracing. Main Outcomes and Measures: Receiving a voluntary quarantine recommendation and/or a positive SARS-CoV-2 test result after exposure notification. Results: In September 2020, 537 app users received a positive SARS-CoV-2 test result in Zurich, 324 of whom received and entered an upload authorization code. This code triggered an app notification for an estimated 1374 (95% simulation interval [SI], 932-2586) proximity contacts and led to 722 information hotline calls, with an estimated 170 callers (95% SI, 154-186) receiving a quarantine recommendation. An estimated 939 (95% SI, 720-1127) notified app users underwent testing for SARS-CoV-2, of whom 30 (95% SI, 23-36) had positive results after an app notification. Key indicator evaluations revealed that the DCT app triggered quarantine recommendations for the equivalent of 5% of all exposed contacts placed in quarantine by manual contact tracing. For every 10.9 (95% SI, 7.6-15.6) upload authorization codes entered in the app, 1 contact had positive test results for SARS-CoV-2 after app notification. Longitudinal indicator analyses demonstrated bottlenecks in the notification cascade, because capacity limits were reached owing to an increased incidence of SARS-CoV-2 infection in October 2020. Conclusions and Relevance: In this simulation study of the notification cascade of the SwissCovid DCT app, receipt of exposure notifications was associated with quarantine recommendations and identification of SARS-CoV-2-positive cases. These findings in notified proximity contacts reflect important intermediary steps toward transmission prevention.

Burden of post-COVID-19 syndrome and implications for healthcare service planning: A population-based cohort study.

BACKGROUND: Longer-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. METHODS: This 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. RESULTS: Symptoms 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. CONCLUSIONS: In 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.