Social contacts in Switzerland during the COVID-19 pandemic: Insights from the CoMix study.

To mitigate the spread of SARS-CoV-2, the Swiss government enacted restrictions on social contacts from 2020 to 2022. In addition, individuals changed their social contact behavior to limit the risk of COVID-19. In this study, we aimed to investigate the changes in social contact patterns of the Swiss population. As part of the CoMix study, we conducted a survey consisting of 24 survey waves from January 2021 to May 2022. We collected data on social contacts and constructed contact matrices for the age groups 0-4, 5-14, 15-29, 30-64, and 65 years and older. We estimated the change in contact numbers during the COVID-19 pandemic to a synthetic pre-pandemic contact matrix. We also investigated the association of the largest eigenvalue of the social contact and transmission matrices with the stringency of pandemic measures, the effective reproduction number (Re), and vaccination uptake. During the pandemic period, 7084 responders reported an average number of 4.5 contacts (95% confidence interval, CI: 4.5-4.6) per day overall, which varied by age and survey wave. Children aged 5-14 years had the highest number of contacts with 8.5 (95% CI: 8.1-8.9) contacts on average per day and participants that were 65 years and older reported the fewest (3.4, 95% CI: 3.2-3.5) per day. Compared with the pre-pandemic baseline, we found that the 15-29 and 30-64 year olds had the largest reduction in contacts. We did not find statistically significant associations between the largest eigenvalue of the social contact and transmission matrices and the stringency of measures, Re, or vaccination uptake. The number of social contacts in Switzerland fell during the COVID-19 pandemic and remained below pre-pandemic levels after contact restrictions were lifted. The collected social contact data will be critical in informing modeling studies on the transmission of respiratory infections in Switzerland and to guide pandemic preparedness efforts.

Importation of Alpha and Delta variants during the SARS-CoV-2 epidemic in Switzerland: Phylogenetic analysis and intervention scenarios.

The SARS-CoV-2 pandemic has led to the emergence of various variants of concern (VoCs) that are associated with increased transmissibility, immune evasion, or differences in disease severity. The emergence of VoCs fueled interest in understanding the potential impact of travel restrictions and surveillance strategies to prevent or delay the early spread of VoCs. We performed phylogenetic analyses and mathematical modeling to study the importation and spread of the VoCs Alpha and Delta in Switzerland in 2020 and 2021. Using a phylogenetic approach, we estimated between 383-1,038 imports of Alpha and 455-1,347 imports of Delta into Switzerland. We then used the results from the phylogenetic analysis to parameterize a dynamic transmission model that accurately described the subsequent spread of Alpha and Delta. We modeled different counterfactual intervention scenarios to quantify the potential impact of border closures and surveillance of travelers on the spread of Alpha and Delta. We found that implementing border closures after the announcement of VoCs would have been of limited impact to mitigate the spread of VoCs. In contrast, increased surveillance of travelers could prove to be an effective measure for delaying the spread of VoCs in situations where their severity remains unclear. Our study shows how phylogenetic analysis in combination with dynamic transmission models can be used to estimate the number of imported SARS-CoV-2 variants and the potential impact of different intervention scenarios to inform the public health response during the pandemic.

Socio-demographic characteristics associated with COVID-19 vaccination uptake in Switzerland: longitudinal analysis of the CoMix study.

BACKGROUND: Vaccination is an effective strategy to reduce morbidity and mortality from coronavirus disease 2019 (COVID-19). However, the uptake of COVID-19 vaccination has varied across and within countries. Switzerland has had lower levels of COVID-19 vaccination uptake in the general population than many other high-income countries. Understanding the socio-demographic factors associated with vaccination uptake can help to inform future vaccination strategies to increase uptake. METHODS: We conducted a longitudinal online survey in the Swiss population, consisting of six survey waves from June to September 2021. Participants provided information on socio-demographic characteristics, history of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), social contacts, willingness to be vaccinated, and vaccination status. We used a multivariable Poisson regression model to estimate the adjusted rate ratio (aRR) and 95% confidence intervals (CI) of COVID-19 vaccine uptake. RESULTS: We recorded 6,758 observations from 1,884 adults. For the regression analysis, we included 3,513 observations from 1,883 participants. By September 2021, 600 (75%) of 806 study participants had received at least one vaccine dose. Participants who were older, male, and students, had a higher educational level, household income, and number of social contacts, and lived in a household with a medically vulnerable person were more likely to have received at least one vaccine dose. Female participants, those who lived in rural areas and smaller households, and people who perceived COVID-19 measures as being too strict were less likely to be vaccinated. We found no significant association between previous SARS-CoV-2 infections and vaccination uptake. CONCLUSIONS: Our results suggest that socio-demographic factors as well as individual behaviours and attitudes played an important role in COVID-19 vaccination uptake in Switzerland. Therefore, appropriate communication with the public is needed to ensure that public health interventions are accepted and implemented by the population. Tailored COVID-19 vaccination strategies in Switzerland that aim to improve uptake should target specific subgroups such as women, people from rural areas or people with lower socio-demographic status.

Impact of cross-border-associated cases on the SARS-CoV-2 epidemic in Switzerland during summer 2020 and 2021.

During the summers of 2020 and 2021, the number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Switzerland remained at relatively low levels, but grew steadily over time. It remains unclear to what extent epidemic growth during these periods was a result of the relaxation of local control measures or increased traveling and subsequent importation of cases. A better understanding of the role of cross-border-associated cases (imports) on the local epidemic dynamics will help to inform future surveillance strategies. We analyzed routine surveillance data of confirmed cases of SARS-CoV-2 in Switzerland from 1 June to 30 September 2020 and 2021. We used a stochastic branching process model that accounts for superspreading of SARS-CoV-2 to simulate epidemic trajectories in absence and in presence of imports during summer 2020 and 2021. The Swiss Federal Office of Public Health reported 22,919 and 145,840 confirmed cases of SARS-CoV-2 from 1 June to 30 September 2020 and 2021, respectively. Among cases with known place of exposure, 27% (3,276 of 12,088) and 25% (1,110 of 4,368) reported an exposure abroad in 2020 and 2021, respectively. Without considering the impact of imported cases, the steady growth of confirmed cases during summer periods would be consistent with a value of Re that is significantly above the critical threshold of 1. In contrast, we estimated Re at 0.84 (95% credible interval, CrI: 0.78-0.90) in 2020 and 0.82 (95% CrI: 0.74-0.90) in 2021 when imported cases were taken into account, indicating that the local Re was below the critical threshold of 1 during summer. In Switzerland, cross-border-associated SARS-CoV-2 cases had a considerable impact on the local transmission dynamics and can explain the steady growth of the epidemic during the summers of 2020 and 2021.

Availability and experiences of differentiated antiretroviral therapy delivery at HIV care facilities in rural Zimbabwe: a mixed-method study.

INTRODUCTION: Zimbabwe adopted differentiated HIV care policies in 2015 to promote client-centred care and relieve strain on health facilities. We examined the availability, experiences and perceptions of differentiated antiretroviral therapy (ART) delivery in rural Zimbabwe following the policy adoption. METHODS: We undertook a cross-sectional mixed methods study in all the 26 facilities providing HIV care in a rural district in Zimbabwe. We collected quantitative data about ART delivery and visit durations from 31 healthcare providers and a purposive stratified sample of 378 clients obtaining ART either through routine care or differentiated ART delivery models. We performed 26 semi-structured interviews among healthcare providers and seven focus group discussions (FGDs) among clients to elicit their perceptions and experiences of ART delivery. Data were collected in 2019, with one follow-up FGD in 2021. We analysed the transcripts thematically, with inductive coding, to identify emerging themes. RESULTS: Twenty facilities (77%) offered at least one differentiated ART delivery models, including community ART refill groups (CARGs; 13 facilities, 50%), fast-track refill (8, 31%), family refill (6, 23%) or club refill (1, 4%). Thirteen facilities (50%) offered only one model. The median visit duration was 28 minutes (interquartile range [IQR]: 16-62). Participants in fast-track had the shortest visit durations (18 minutes, IQR: 11-24). Confidentiality and disclosure of HIV status, travelling long distances, travel costs and waiting times were the main issues influencing clients' views on differentiated ART delivery. Fast-track refill was perceived as the preferred model of clients for its limited involuntary disclosure and efficiency. In contrast, group- and community-based refill models reduced travel costs but were felt to be associated with involuntary disclosure of HIV status, which could discourage clients. Healthcare providers also experienced an additional workload when offering facility-based group models, such as CARGs. CONCLUSIONS: Differentiated ART delivery models were widely available in this rural setting, but most facilities did not offer a choice of models to address clients' diverse preferences. A minority offered fast-track refills, although this model was often mentioned as desirable. Confidentiality, travel expenses and client waiting times are key elements to consider when planning and rolling out differentiated HIV care.

Acquired HIV drug resistance mutations on first-line antiretroviral therapy in Southern Africa: Systematic review and Bayesian evidence synthesis.

OBJECTIVE: To estimate the prevalence of NRTI and NNRTI drug resistance mutations in patients failing NNRTI-based ART in Southern Africa. STUDY DESIGN: We conducted a systematic review to identify studies reporting drug resistance mutations among adult people living with HIV (PLWH) who experienced virological failure on first-line NNRTI-based ART in Southern Africa. We used a Bayesian hierarchical meta-regression model to synthesize the evidence on the frequency of eight NRTI- and seven NNRTI-DRMs across different ART regimens, accounting for ART duration and study characteristics. RESULTS: We included 19 study populations, including 2,690 PLWH. Patients failing first-line ART including emtricitabine or lamivudine showed high levels of the M184V/I mutation after 2 years: 75.7% (95% Credibility Interval [CrI] 61.9%-88.9%) if combined with tenofovir, and 72.1% (95% CrI 56.8%-85.9%) with zidovudine. With tenofovir disoproxil fumarate, the prevalence of the K65R mutation was 52.0% (95% CrI 32.5%-76.8%) at 2 years. On efavirenz, K103 was the most prevalent NNRTI resistance mutation (57.2%, 95% CrI 40.9%-80.1%), followed by V106 (46.8%, 95% CrI 31.3%-70.4%). CONCLUSIONS: NRTI/NNRTI drug resistance mutations are common in patients failing first-line ART in Southern Africa. These patients might switch to dolutegravir-based regimen with compromised NRTIs, which could impair the long-term efficacy of ART.

Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland.

Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland. We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy. Improvements were reported in 59 (66%) study participants. The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young. What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders. What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting. • The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions.

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3-5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant's success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.

Mortality from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing: a multicentre cohort study.

BACKGROUND: Drug resistance threatens global tuberculosis control. We aimed to examine mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and whole-genome sequencing (WGS). METHODS: In this multicentre cohort study, we collected pulmonary Mycobacterium tuberculosis isolates and clinical data from individuals with tuberculosis from antiretroviral therapy programmes and tuberculosis clinics in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, Peru, South Africa, and Thailand, stratified by HIV status and drug resistance. Sites tested drug susceptibility using routinely available methods. WGS was done on Illumina HiSeq 2500 in the USA and Switzerland, and TBprofiler was used to analyse the genomes. We included individuals aged 16 years or older with pulmonary tuberculosis (bacteriologically confirmed or clinically diagnosed). We analysed mortality in multivariable logistic regression models adjusted for sex, age, HIV status, history of tuberculosis, and sputum positivity. FINDINGS: Between Sept 1, 2014, and July 4, 2016, of 634 patients included in our previous analysis, we included 582 patients with tuberculosis (median age 33 years [IQR 27-43], 225 [39%] women, and 247 [42%] HIV-positive). Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-extensively drug-resistant (pre-XDR) or XDR. The analysis of mortality was based on 530 patients; 63 (12%) died and 77 (15%) patients received inappropriate treatment. Mortality ranged from 6% (18 of 310) in patients with pan-susceptible tuberculosis to 39% (nine of 23) in patients with pre-XDR or XDR tuberculosis. The adjusted odds ratio for mortality was 4·92 (95% CI 2·47-9·78) among undertreated patients, compared with appropriately treated patients. INTERPRETATION: In seven countries with a high burden of tuberculosis, we observed discrepancies between drug resistance patterns obtained locally and WGS. The underdiagnosis of drug resistance resulted in inappropriate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information required to improve the outcomes of drug-resistant tuberculosis in high-burden settings. Our results support WHO's call for point-of-care tests based on WGS. FUNDING: National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, and Swiss National Center for Mycobacteria.

Emergence and spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic resulting in unprecedented efforts to reduce transmission and develop therapies and vaccines (WHO Emergency Committee, 2020; Zhu et al., 2020). Rapidly generated viral genome sequences have allowed the spread of the virus to be tracked via phylogenetic analysis (Worobey et al., 2020; Hadfield et al., 2018; Pybus et al., 2020). While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced, allowing continent-specific variants to emerge. However, within Europe travel resumed in the summer of 2020, and the impact of this travel on the epidemic is not well understood. Here we report on a novel SARS-CoV-2 variant, 20E (EU1), that emerged in Spain in early summer, and subsequently spread to multiple locations in Europe. We find no evidence of increased transmissibility of this variant, but instead demonstrate how rising incidence in Spain, resumption of travel across Europe, and lack of effective screening and containment may explain the variant's success. Despite travel restrictions and quarantine requirements, we estimate 20E (EU1) was introduced hundreds of times to countries across Europe by summertime travellers, likely undermining local efforts to keep SARS-CoV-2 cases low. Our results demonstrate how a variant can rapidly become dominant even in absence of a substantial transmission advantage in favorable epidemiological settings. Genomic surveillance is critical to understanding how travel can impact SARS-CoV-2 transmission, and thus for informing future containment strategies as travel resumes.

Natural Polymorphisms in Mycobacterium tuberculosis Conferring Resistance to Delamanid in Drug-Naive Patients.

Mutations in the genes of the F420 signaling pathway of Mycobacterium tuberculosis complex, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, can lead to delamanid resistance. We searched for such mutations among 129 M. tuberculosis strains from Asia, South America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For 10 strains with mutations, we determined the MIC of delamanid. We found one strain from a delamanid-naive patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical delamanid MIC.