Late presentations and missed opportunities among newly diagnosed HIV patients presenting to a specialty clinic in Lebanon.

Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count < 350 or AIDS-defining event regardless of CD4 count. Advanced disease is defined as having a CD4 count below 200 cells/µL or the presence of an AIDS-defining illness, regardless of the CD4 count. A missed opportunity was defined as the presence of an indicator condition (IC) that suggests infection with HIV/AIDS during 3 years preceding the actual HIV diagnosis and not followed by a recommendation for HIV testing. The proportions for demographic, epidemiological, and clinical characteristics are calculated by excluding cases with missing information from the denominator. Our cohort included 150 subjects (92.7% males; 63.6% men who have sex with men (MSM); 33.3% heterosexuals; median age 30.5 years at diagnosis). 77 (51.3%) were late presenters and 53 (35.3% of all subjects, 68.8% of late presenters) had advanced HIV on presentation. Up to 76.5% of late presenters had a presentation with an HIV-related condition at a healthcare provider without getting HIV test within the previous 3 years. The most frequent ICs were weight loss, generalized lymphadenopathy, constitutional symptoms, and chronic idiopathic diarrhea. Overall mortality rate was 4% (6/150 individuals). All-cause mortality among those who presented with AIDS was 15.4% (6/39 subjects). In our setting, late presentations and missed opportunities for HIV diagnosis are common. In the Middle East, AIDS mortality remains high with a large gap in HIV testing. To effectively influence policies, comprehensive analyses should focus on estimating the preventable health and financial burdens of late HIV presentations. Another concern pertains to healthcare providers' attitudes and competencies.

An Unwanted but Long-Known Company: Post-Viral Symptoms in the Context of Past Pandemics in Switzerland (and Beyond).

Objectives: Some people do not fully recover from an acute viral infection and experience persistent symptoms or incomplete recovery for months or even years. This is not unique to the SARS-CoV-2 virus and history shows that post-viral conditions like post COVID-19 condition, also referred to as Long Covid, are not new. In particular, during and after pandemics caused by respiratory viruses in which large parts of the population were infected or exposed, professional and public attention was increased, not least because of the large number of people affected. Methods: Given the current relevance of the topic, this article aims to narratively review and summarize the literature on post-viral symptoms during past pandemics and to supplement and illustrate it with Swiss examples from the pandemics of 1890, 1918-1920 and later. Results: Post-viral diseases were an increasingly emphasised health topic during and after past pandemics triggered by respiratory infections over the last 150 years. Conclusion: In the next pandemic, it should not be surprising that post-viral conditions will again play a role, and pandemic plans should reflect this.

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study.

Understanding the development of humoral immune responses of children and adolescents to SARS-CoV-2 is essential for designing effective public health measures. Here we examine the changes of humoral immune response in school-aged children and adolescents during the COVID-19 pandemic (June 2020 to July 2022), with a specific interest in the Omicron variant (beginning of 2022). In our study "Ciao Corona", we assess in each of the five testing rounds between 1874 and 2500 children and adolescents from 55 schools in the canton of Zurich with a particular focus on a longitudinal cohort (n=751). By July 2022, 96.9% (95% credible interval 95.3-98.1%) of children and adolescents have SARS-CoV-2 anti-spike IgG (S-IgG) antibodies. Those with hybrid immunity or vaccination have higher S-IgG titres and stronger neutralising responses against Wildtype, Delta and Omicron BA.1 variants compared to those infected but unvaccinated. S-IgG persist over 18 months in 93% of children and adolescents. During the study period one adolescent was hospitalised for less than 24 hours possibly related to an acute SARS-CoV-2 infection. These findings show that the Omicron wave and the rollout of vaccines boosted S-IgG titres and neutralising capacity. Trial registration number: NCT04448717. https://clinicaltrials.gov/ct2/show/NCT04448717 .

Interplay of Digital Proximity App Use and SARS-CoV-2 Vaccine Uptake in Switzerland: Analysis of Two Population-Based Cohort Studies.

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic. Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes. Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40-1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62-1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38-0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27-0.78 [CSM]) compared to participants who did not get vaccinated. Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions.

Factors Associated With COVID-19 Non-Vaccination in Switzerland: A Nationwide Study.

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness.

Post COVID-19 condition, work ability and occupational changes in a population-based cohort.

Background: Evidence on the impact of post COVID-19 condition (PCC) on work ability is limited but critical due to its high prevalence among working-age individuals. This study aimed to evaluate the association between PCC, work ability, and occupational changes in a population-based cohort. Methods: We used data from working-age adults included in a prospective, longitudinal cohort of a random sample of all individuals infected with SARS-CoV-2 between August 2020 and January 2021 in the Canton of Zurich, Switzerland. We evaluated current work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), and PCC-related occupational changes one year after infection. Findings: Of 672 individuals included in this study, 120 (17.9%) were categorised as having PCC (defined as presence of self-reported COVID-19 related symptoms) at 12 months. There was very strong evidence that current work ability scores were mean 0.62 (95% CI 0.30-0.95) points lower among those with PCC compared to those without in adjusted regression analyses. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (adjusted odds ratio (aOR) 0.30, 95% CI 0.20-0.46) and mental (aOR 0.40, 0.27-0.62) demands in individuals with PCC. Higher age and history of psychiatric diagnosis were associated with more substantial reductions in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce. Interpretation: These findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity. Funding: Federal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland; Horizon Europe.

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, .

Adverse effects, perceptions and attitudes related to BNT162b2, mRNA-1273 or JNJ-78436735 SARS-CoV-2 vaccines: Population-based cohort.

Long-term control of SARS-CoV-2 requires effective vaccination strategies. This has been challenged by public mistrust and the spread of misinformation regarding vaccine safety. Better understanding and communication of the longer-term and comparative experiences of individuals in the general population following vaccination are required. In this population-based longitudinal study, we included 575 adults, randomly selected from all individuals presenting to a Swiss reference vaccination center, for receipt of BNT162b2, mRNA1273, or JNJ-78436735. We assessed the prevalence, onset, duration, and severity of self-reported adverse effects over 12 weeks following vaccination. We additionally evaluated participants' perceptions of vaccines, trust in public health authorities and pharmaceutical companies, and compliance with public health measures. Most participants reported at least one adverse effect within 12 weeks following vaccination. Adverse effects were mostly mild or moderate, resolved within three days, and rarely resulted in anaphylaxis or hospitalizations. Female sex, younger age, higher education, and receipt of mRNA-1273 were associated with reporting adverse effects. Compared to JNJ-78436735 recipients, a higher proportion of mRNA vaccine recipients agreed that vaccination is important, and trusted public health authorities. Our findings provide real-world estimates of the prevalence of adverse effects following SARS-CoV-2 vaccination and highlight the importance of transparent communication to ensure the success of current or future vaccination campaigns.

Changes in socioeconomic resources and mental health after the second COVID-19 wave (2020-2021): a longitudinal study in Switzerland.

BACKGROUND: During the 2020/2021 winter, the labour market was under the impact of the COVID-19 pandemic. Changes in socioeconomic resources during this period could have influenced individual mental health. This association may have been mitigated or exacerbated by subjective risk perceptions, such as perceived risk of getting infected with SARS-CoV-2 or perception of the national economic situation. Therefore, we aimed to determine if changes in financial resources and employment situation during and after the second COVID-19 wave were prospectively associated with depression, anxiety and stress, and whether perceptions of the national economic situation and of the risk of getting infected modified this association. METHODS: One thousand seven hundred fifty nine participants from a nation-wide population-based eCohort in Switzerland were followed between November 2020 and September 2021. Financial resources and employment status were assessed twice (Nov2020-Mar2021, May-Jul 2021). Mental health was assessed after the second measurement of financial resources and employment status, using the Depression, Anxiety and Stress Scale (DASS-21). We modelled DASS-21 scores with linear regression, adjusting for demographics, health status, social relationships and changes in workload, and tested interactions with subjective risk perceptions. RESULTS: We observed scores above thresholds for normal levels for 16% (95%CI = 15-18) of participants for depression, 8% (95%CI = 7-10) for anxiety, and 10% (95%CI = 9-12) for stress. Compared to continuously comfortable or sufficient financial resources, continuously precarious or insufficient resources were associated with worse scores for all outcomes. Increased financial resources were associated with higher anxiety. In the working-age group, shifting from full to part-time employment was associated with higher stress and anxiety. Perceiving the Swiss economic situation as worrisome was associated with higher anxiety in participants who lost financial resources or had continuously precarious or insufficient resources. CONCLUSION: This study confirms the association of economic stressors and mental health during the COVID-19 pandemic and highlights the exacerbating role of subjective risk perception on this association.

Post COVID-19 condition after Wildtype, Delta, and Omicron SARS-CoV-2 infection and prior vaccination: Pooled analysis of two population-based cohorts.

BACKGROUND: Post COVID-19 condition (PCC) is an important complication of SARS-CoV-2 infection, affecting millions worldwide. This study aimed to evaluate the prevalence and severity of post COVID-19 condition (PCC) with novel SARS-CoV-2 variants and after prior vaccination. METHODS: We used pooled data from 1350 SARS-CoV-2-infected individuals from two representative population-based cohorts in Switzerland, diagnosed between Aug 5, 2020, and Feb 25, 2022. We descriptively analysed the prevalence and severity of PCC, defined as the presence and frequency of PCC-related symptoms six months after infection, among vaccinated and non-vaccinated individuals infected with Wildtype, Delta, and Omicron SARS-CoV-2. We used multivariable logistic regression models to assess the association and estimate the risk reduction of PCC after infection with newer variants and prior vaccination. We further assessed associations with the severity of PCC using multinomial logistic regression. To identify groups of individuals with similar symptom patterns and evaluate differences in the presentation of PCC across variants, we performed exploratory hierarchical cluster analyses. RESULTS: We found strong evidence that vaccinated individuals infected with Omicron had reduced odds of developing PCC compared to non-vaccinated Wildtype-infected individuals (odds ratio 0.42, 95% confidence interval 0.24-0.68). The odds among non-vaccinated individuals were similar after infection with Delta or Omicron compared to Wildtype SARS-CoV-2. We found no differences in PCC prevalence with respect to the number of received vaccine doses or timing of last vaccination. The prevalence of PCC-related symptoms among vaccinated, Omicron-infected individuals was lower across severity levels. In cluster analyses, we identified four clusters of diverse systemic, neurocognitive, cardiorespiratory, and musculoskeletal symptoms, with similar patterns across variants. CONCLUSION: The risk of PCC appears to be lowered with infection by the Omicron variant and after prior vaccination. This evidence is crucial to guide future public health measures and vaccination strategies.

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region.

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Performance of the Swiss Digital Contact-Tracing App Over Various SARS-CoV-2 Pandemic Waves: Repeated Cross-sectional Analyses.

BACKGROUND: Digital proximity-tracing apps have been deployed in multiple countries to assist with SARS-CoV-2 pandemic mitigation efforts. However, it is unclear how their performance and effectiveness were affected by changing pandemic contexts and new viral variants of concern. OBJECTIVE: The aim of this study is to bridge these knowledge gaps through a countrywide digital proximity-tracing app effectiveness assessment, as guided by the World Health Organization/European Center for Prevention and Disease Control (WHO/ECDC) indicator framework to evaluate the public health effectiveness of digital proximity-tracing solutions. METHODS: We performed a descriptive analysis of the digital proximity-tracing app SwissCovid in Switzerland for 3 different periods where different SARS-CoV-2 variants of concern (ie, Alpha, Delta, and Omicron, respectively) were most prevalent. In our study, we refer to the indicator framework for the evaluation of public health effectiveness of digital proximity-tracing apps of the WHO/ECDC. We applied this framework to compare the performance and effectiveness indicators of the SwissCovid app. RESULTS: Average daily registered SARS-CoV-2 case rates during our assessment period from January 25, 2021, to March 19, 2022, were 20 (Alpha), 54 (Delta), and 350 (Omicron) per 100,000 inhabitants. The percentages of overall entered authentication codes from positive tests into the SwissCovid app were 9.9% (20,273/204,741), 3.9% (14,372/365,846), and 4.6% (72,324/1,581,506) during the Alpha, Delta, and Omicron variant phases, respectively. Following receipt of an exposure notification from the SwissCovid app, 58% (37/64, Alpha), 44% (7/16, Delta), and 73% (27/37, Omicron) of app users sought testing or performed self-tests. Test positivity among these exposure-notified individuals was 19% (7/37) in the Alpha variant phase, 29% (2/7) in the Delta variant phase, and 41% (11/27) in the Omicron variant phase compared to 6.1% (228,103/3,755,205), 12% (413,685/3,443,364), and 41.7% (1,784,951/4,285,549) in the general population, respectively. In addition, 31% (20/64, Alpha), 19% (3/16, Delta), and 30% (11/37, Omicron) of exposure-notified app users reported receiving mandatory quarantine orders by manual contact tracing or through a recommendation by a health care professional. CONCLUSIONS: In constantly evolving pandemic contexts, the effectiveness of digital proximity-tracing apps in contributing to mitigating pandemic spread should be reviewed regularly and adapted based on changing requirements. The WHO/ECDC framework allowed us to assess relevant domains of digital proximity tracing in a holistic and systematic approach. Although the Swisscovid app mostly worked, as reasonably expected, our analysis revealed room for optimizations and further performance improvements. Future implementation of digital proximity-tracing apps should place more emphasis on social, psychological, and organizational aspects to reduce bottlenecks and facilitate their use in pandemic contexts.

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.

A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021.

Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID. Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery. Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study. Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms. Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane. Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

Long COVID Through a Public Health Lens: An Umbrella Review.

Objectives: To synthesize existing evidence on prevalence as well as clinical and socio-economic aspects of Long COVID. Methods: An umbrella review of reviews and a targeted evidence synthesis of their primary studies, including searches in four electronic databases, reference lists of included reviews, as well as related article lists of relevant publications. Results: Synthesis included 23 reviews and 102 primary studies. Prevalence estimates ranged from 7.5% to 41% in non-hospitalized adults, 2.3%-53% in mixed adult samples, 37.6% in hospitalized adults, and 2%-3.5% in primarily non-hospitalized children. Preliminary evidence suggests that female sex, age, comorbidities, the severity of acute disease, and obesity are associated with Long COVID. Almost 50% of primary studies reported some degree of Long COVID-related social and family-life impairment, long absence periods off work, adjusted workloads, and loss of employment. Conclusion: Long COVID will likely have a substantial public health impact. Current evidence is still heterogeneous and incomplete. To fully understand Long COVID, well-designed prospective studies with representative samples will be essential.

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.

Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.