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.

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.

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.

Background: This systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients. Methods: We conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach. Results: We identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9–20.8) and PCS (MD 3.4; 95% CI 0.01–6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38–1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI − 1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63–1.27), SF-36 PFS (MD 8.1; 95% CI − 15.3 to 31.4) or PCS (MD − 2.4; 95% CI − 6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low. Conclusion: The evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization. Study Registration: PROSPERO (CRD42019122555).

Background: Digital proximity tracing apps have been released to mitigate the transmission of SARS-CoV-2, the virus known to cause COVID-19. However, it remains unclear how the acceptance and uptake of these apps can be improved. Objective: This study aimed to investigate the coverage of the SwissCovid app and the reasons for its nonuse in Switzerland during a period of increasing incidence of COVID-19 cases. Methods: We collected data between September 28 and October 8, 2020, via a nationwide online panel survey (COVID-19 Social Monitor, N=1511). We examined sociodemographic and behavioral factors associated with app use by using multivariable logistic regression, whereas reasons for app nonuse were analyzed descriptively. Results: Overall, 46.5% (703/1511) of the survey participants reported they used the SwissCovid app, which was an increase from 43.9% (662/1508) reported in the previous study wave conducted in July 2020. A higher monthly household income (ie, income >CHF 10,000 or >US $11,000 vs income ≤CHF 6000 or <US $6600 [reference]: odds ratio [OR] 1.92, 95% CI 1.40-2.64), more frequent internet use (ie, daily [reference] vs less than weekly: OR 0.37, 95% CI 0.16-0.85), better adherence to recommendations for wearing masks (ie, always or most of the time [reference] vs rarely or never: OR 0.28, 95% CI 0.15-0.52), and nonsmoker status (OR 1.32, 95% CI 1.01-1.71) were associated with an increased likelihood for app uptake. Citizenship status (ie, non-Swiss citizenship vs. Swiss [reference]: OR 0.61, 95% CI 0.43-0.87), and language region (French vs Swiss German [reference]: OR 0.61, 95% CI 0.46-0.80) were associated with a lower likelihood for app uptake. Further analysis in a randomly selected subsample (n=712) with more detailed information showed that higher levels of trust in government and health authorities were also associated with a higher likelihood for app uptake (ie, high vs low [reference] trust: OR 3.13, 95% CI 1.58-6.22). The most frequent reasons for app nonuse were lack of perceived benefit of using the app (297/808, 36.8%), followed by the lack of a compatible phone (184/808, 22.8%), and privacy concerns (181/808, 22.4%). Conclusions: Eliminating technical hurdles and communicating the benefits of digital proximity tracing apps are crucial to promote further uptake and adherence of such apps and, ultimately, enhance their effectiveness to aid pandemic mitigation strategies.

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. 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. 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. 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. Federal Office of Public Health, 10.13039/501100006447 Department of Health of the Canton of Zurich , University of Zurich Foundation, Switzerland; 10.13039/100018693 Horizon Europe .