Alpha Variant Coronavirus Outbreak in a Nursing Home Despite High Vaccination Coverage: Molecular, Epidemiological, and Immunological Studies.

BACKGROUND: Vaccination may control the coronavirus disease 2019 (COVID-19) pandemic, including in nursing homes where many high-risk people live. We conducted extensive outbreak investigations. METHODS: We studied an outbreak at a nursing home in Switzerland, where the uptake of messenger RNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 82% among residents as of 21 January 2021. After diagnosis of COVID-19 in a vaccinated symptomatic healthcare worker (HCW) on 22 February, we performed outbreak investigations in house A (47 residents; 37 HCWs), using SARS-CoV-2-specific polymerase chain reaction testing of nasopharyngeal swab samples. We performed whole-genome sequencing of SARS-CoV-2 and serological analyses. RESULTS: We identified 17 individuals with positive polymerase chain reaction results, 10 residents (5 vaccinated) and 7 HCWs (3 vaccinated). The median age (interquartile range) was 86 (70-90) years among residents and 49 (29-59) years among HCWs. Of the 5 vaccinated residents, 3 had mild disease and 2 had no symptoms, whereas all 5 unvaccinated residents had mild to severe disease, and 2 died. Vaccine effectiveness for the prevention of infection among residents was 73.0% (95% confidence interval, 24.7%-90.1%). The 12 available genomes were all alpha variants. Neutralizing titers were significantly higher in vaccinated individuals on reexposure (>1 week after diagnosis) than in vaccinated, unexposed HCWs (P = .01). Transmission networks indicated 4 likely or possible transmissions from vaccinated to other individuals and 12 transmission events from unvaccinated individuals. CONCLUSIONS: COVID-19 outbreaks can occur in nursing homes, including transmission from vaccinated persons to others. Outbreaks might occur silently, underlining the need for continued testing and basic infection control measures in these high-risk settings.

SARS-CoV-2 transmission with and without mask wearing or air cleaners in schools in Switzerland: A modeling study of epidemiological, environmental, and molecular data.

BACKGROUND: Growing evidence suggests an important contribution of airborne transmission to the overall spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in particular via smaller particles called aerosols. However, the contribution of school children to SARS-CoV-2 transmission remains uncertain. The aim of this study was to assess transmission of airborne respiratory infections and the association with infection control measures in schools using a multiple-measurement approach. METHODS AND FINDINGS: We collected epidemiological (cases of Coronavirus Disease 2019 (COVID-19)), environmental (CO2, aerosol and particle concentrations), and molecular data (bioaerosol and saliva samples) over 7 weeks from January to March 2022 (Omicron wave) in 2 secondary schools (n = 90, average 18 students/classroom) in Switzerland. We analyzed changes in environmental and molecular characteristics between different study conditions (no intervention, mask wearing, air cleaners). Analyses of environmental changes were adjusted for different ventilation, the number of students in class, school and weekday effects. We modeled disease transmission using a semi-mechanistic Bayesian hierarchical model, adjusting for absent students and community transmission. Molecular analysis of saliva (21/262 positive) and airborne samples (10/130) detected SARS-CoV-2 throughout the study (weekly average viral concentration 0.6 copies/L) and occasionally other respiratory viruses. Overall daily average CO2 levels were 1,064 ± 232 ppm (± standard deviation). Daily average aerosol number concentrations without interventions were 177 ± 109 1/cm3 and decreased by 69% (95% CrI 42% to 86%) with mask mandates and 39% (95% CrI 4% to 69%) with air cleaners. Compared to no intervention, the transmission risk was lower with mask mandates (adjusted odds ratio 0.19, 95% CrI 0.09 to 0.38) and comparable with air cleaners (1.00, 95% CrI 0.15 to 6.51). Study limitations include possible confounding by period as the number of susceptible students declined over time. Furthermore, airborne detection of pathogens document exposure but not necessarily transmission. CONCLUSIONS: Molecular detection of airborne and human SARS-CoV-2 indicated sustained transmission in schools. Mask mandates were associated with greater reductions in aerosol concentrations than air cleaners and with lower transmission. Our multiple-measurement approach could be used to continuously monitor transmission risk of respiratory infections and the effectiveness of infection control measures in schools and other congregate settings.

Estimating Tuberculosis Transmission Risks in a Primary Care Clinic in South Africa: Modeling of Environmental and Clinical Data.

BACKGROUND: Congregate settings, such as healthcare clinics, may play an essential role in Mycobacterium tuberculosis (Mtb) transmission. Using patient and environmental data, we studied transmission at a primary care clinic in South Africa. METHODS: We collected patient movements, cough frequency, and clinical data, and measured indoor carbon dioxide (CO2) levels, relative humidity, and Mtb genomes in the air. We used negative binomial regression model to investigate associations. RESULTS: We analyzed 978 unique patients who contributed 14 795 data points. The median patient age was 33 (interquartile range [IQR], 26-41) years, and 757 (77.4%) were female. Overall, median CO2 levels were 564 (IQR 495-646) parts per million and were highest in the morning. Median number of coughs per day was 466 (IQR, 368-503), and overall median Mtb DNA copies/µL/day was 4.2 (IQR, 1.2-9.5). We found an increased presence of Mtb DNA in the air of 32% (95% credible interval, 7%-63%) per 100 additional young adults (aged 15-29 years) and 1% (0-2%) more Mtb DNA per 10% increase of relative humidity. Estimated cumulative transmission risks for patients attending the clinic monthly for at least 1 hour range between 9% and 29%. CONCLUSIONS: We identified young adults and relative humidity as potentially important factors for transmission risks in healthcare clinics. Our approach should be used to detect transmission and evaluate infection control interventions.

Xeno-free induced pluripotent stem cell-derived neural progenitor cells for in vivo applications.

BACKGROUND: Currently, there is no regenerative therapy for patients with neurological and neurodegenerative disorders. Cell-therapies have emerged as a potential treatment for numerous brain diseases. Despite recent advances in stem cell technology, major concerns have been raised regarding the feasibility and safety of cell therapies for clinical applications. METHODS: We generated good manufacturing practice (GMP)-compatible neural progenitor cells (NPCs) from transgene- and xeno-free induced pluripotent stem cells (iPSCs) that can be smoothly adapted for clinical applications. NPCs were characterized in vitro for their differentiation potential and in vivo after transplantation into wild type as well as genetically immunosuppressed mice. RESULTS: Generated NPCs had a stable gene-expression over at least 15 passages and could be scaled for up to 1018 cells per initially seeded 106 cells. After withdrawal of growth factors in vitro, cells adapted a neural fate and mainly differentiated into active neurons. To ensure a pure NPC population for in vivo applications, we reduced the risk of iPSC contamination by applying micro RNA-switch technology as a safety checkpoint. Using lentiviral transduction with a fluorescent and bioluminescent dual-reporter construct, combined with non-invasive in vivo bioluminescent imaging, we longitudinally tracked the grafted cells in healthy wild-type and genetically immunosuppressed mice as well as in a mouse model of ischemic stroke. Long term in-depth characterization revealed that transplanted NPCs have the capability to survive and spontaneously differentiate into functional and mature neurons throughout a time course of a month, while no residual pluripotent cells were detectable. CONCLUSION: We describe the generation of transgene- and xeno-free NPCs. This simple differentiation protocol combined with the ability of in vivo cell tracking presents a valuable tool to develop safe and effective cell therapies for various brain injuries.

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.

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.

HIV Coinfection Is Associated with Low-Fitness rpoB Variants in Rifampicin-Resistant Mycobacterium tuberculosis.

We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis strains isolated from HIV-coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low-fitness rpoB variants can thrive in the context of reduced host immunity.

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

Background: Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. Methods: This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Results: Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/µL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Conclusions: Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

Outcomes of HIV-positive patients lost to follow-up in African treatment programmes.

OBJECTIVE: The retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow-up (LTFU) can be substantial, with unknown outcomes for patients lost to ART programmes. We examined changes in outcomes of patients LTFU over calendar time, assessed associations with other study and programme characteristics and investigated the relative success of different tracing methods. METHODS: We performed a systematic review and logistic random-effects meta-regression analysis of studies that traced adults or children who started ART and were LTFU in sub-Saharan African treatment programmes. The primary outcome was mortality, and secondary outcomes were undocumented transfer to another programme, treatment interruption and the success of tracing attempts. RESULTS: We included 32 eligible studies from 12 countries in sub-Saharan Africa: 20 365 patients LTFU were traced, and 15 708 patients (77.1%) were found. Compared to telephone calls, tracing that included home visits increased the probability of success: the adjusted odds ratio (aOR) was 9.35 (95% confidence interval [CI] 1.85-47.31). The risk of death declined over calendar time (aOR per 1-year increase 0.86, 95% CI 0.78-0.95), whereas undocumented transfers (aOR 1.13, 95% CI 0.96-1.34) and treatment interruptions (aOR 1.31, 95% CI 1.18-1.45) tended to increase. Mortality was lower in urban than in rural areas (aOR 0.59, 95% CI 0.36-0.98), but there was no difference in mortality between adults and children. The CD4 cell count at the start of ART increased over time. CONCLUSIONS: Mortality among HIV-positive patients who started ART in sub-Saharan Africa, were lost to programmes and were successfully traced has declined substantially during the scale-up of ART, probably driven by less severe immunodeficiency at the start of therapy.

Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country.

Immigrants from regions with a high incidence of tuberculosis (TB) are a risk group for TB in low-incidence countries such as Switzerland. In a previous analysis of a nationwide collection of 520 Mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [MIRU-VNTR] typing and spoligotyping). Here, we used whole-genome sequencing (WGS) to revisit these transmission clusters. Genome-based transmission clusters were defined as isolate pairs separated by ≤12 single nucleotide polymorphisms (SNPs). WGS confirmed 17/35 (49%) MIRU-VNTR typing clusters; the other 18 clusters contained pairs separated by >12 SNPs. Most transmission clusters (3/4) of Swiss-born patients were confirmed by WGS, as opposed to 25% (4/16) of the clusters involving only foreign-born patients. The overall clustering proportion was 17% (90 patients; 95% confidence interval [CI], 14 to 21%) by standard genotyping but only 8% (43 patients; 95% CI, 6 to 11%) by WGS. The clustering proportion was 17% (67/401; 95% CI, 13 to 21%) by standard genotyping and 7% (26/401; 95% CI, 4 to 9%) by WGS among foreign-born patients and 19% (23/119; 95% CI, 13 to 28%) and 14% (17/119; 95% CI, 9 to 22%), respectively, among Swiss-born patients. Using weighted logistic regression, we found weak evidence of an association between birth origin and transmission (adjusted odds ratio of 2.2 and 95% CI of 0.9 to 5.5 comparing Swiss-born patients to others). In conclusion, standard genotyping overestimated recent TB transmission in Switzerland compared to WGS, particularly among immigrants from regions with a high TB incidence, where genetically closely related strains often predominate. We recommend the use of WGS to identify transmission clusters in settings with a low incidence of TB.

Molecular detection of SARS-CoV-2 and other respiratory viruses in saliva and classroom air: a two winters tale.

OBJECTIVES: To compare the prevalence of SARS-CoV-2 and other respiratory viruses in saliva and bioaerosols between two winters and to model the probability of virus detection in classroom air for different viruses. METHODS: We analysed saliva, air, and air cleaner filter samples from studies conducted in two Swiss secondary schools (students aged 14-17 years) over 7 weeks during the winters of 2021/22 and 2022/23. Two bioaerosol sampling devices and high efficiency particulate air (HEPA) filters from air cleaners were used to collect airborne virus particles in four classrooms. Daily bioaerosol samples were pooled for each sampling device before PCR analysis of a panel of 19 respiratory viruses and viral subtypes. The probability of detection of airborne viruses was modelled using an adjusted Bayesian logistic regression model. RESULTS: Three classes (58 students) participated in 2021/22, and two classes (38 students) in 2022/23. During winter 2021/22, SARS-CoV-2 dominated in saliva (19 of 21 positive samples) and bioaerosols (9 of 10). One year later, there were 50 positive saliva samples, mostly influenza B, rhinovirus, and adenovirus, and two positive bioaerosol samples, one rhinovirus and one adenovirus. The weekly probability of airborne detection was 34% (95% credible interval [CrI] 22-47%) for SARS-CoV-2 and 10% (95% CrI 5-16%) for other respiratory viruses. DISCUSSION: There was a distinct shift in the distribution of respiratory viruses from SARS-CoV-2 during the omicron wave to other respiratory viruses one year later. SARS-CoV-2 is more likely to be detected in the air than other endemic respiratory viruses, possibly reflecting differences in viral characteristics and the composition of virus-carrying particles that facilitate airborne long-range transmission.

Air Cleaners and Respiratory Infections in Schools: A Modeling Study Based on Epidemiologic, Environmental, and Molecular Data.

Background: Using a multiple-measurement approach, we examined the real-world effectiveness of portable HEPA air filtration devices (air cleaners) in a school setting. Methods: We collected data over 7 weeks during winter 2022/2023 in 2 Swiss secondary school classes: environmental (CO2, particle concentrations), epidemiologic (absences related to respiratory infections), audio (coughing), and molecular (bioaerosol and saliva samples). Using a crossover design, we compared particle concentrations, coughing, and risk of infection with and without air cleaners. Results: All 38 students participated (age, 13-15 years). With air cleaners, mean particle concentration decreased by 77% (95% credible interval, 63%-86%). There were no differences in CO2 levels. Absences related to respiratory infections were 22 without air cleaners vs 13 with them. Bayesian modeling suggested a reduced risk of infection, with a posterior probability of 91% and a relative risk of 0.73 (95% credible interval, 0.44-1.18). Coughing also tended to be less frequent (posterior probability, 93%), indicating that fewer symptomatic students were in class. Molecular analysis detected mainly non-SARS-CoV-2 viruses in saliva (50/448 positive) but not in bioaerosols (2/105) or on the HEPA filters of the air cleaners (4/160). The molecular detection rate in saliva was similar with and without air cleaners. Spatiotemporal analysis of positive saliva samples identified several likely transmissions. Conclusions: Air cleaners improved air quality and showed potential benefits in reducing respiratory infections. Airborne detection of non-SARS-CoV-2 viruses was rare, suggesting that these viruses may be more difficult to detect in the air. Future studies should examine the importance of close contact and long-range transmission and the cost-effectiveness of using air cleaners.

Contact tracing for COVID-19 in a Swiss canton: analysis of key performance indicators.

BACKGROUND: Contact tracing (CT) has played an important role in strategies to control COVID-19. However, there is limited evidence on the performance of digital tools for CT and no consensus on which indicators to use to monitor their performance. We aimed to describe the system and analyse outcomes of CT with a partially automated workflow in the Swiss canton of Solothurn, using key performance indicators (KPIs). METHODS: We describe the process of CT used in the canton of Solothurn between November 2020 and February 2022, including forward and backward CT. We developed 16 KPIs representing CT structure (S1-2), process (P1-11) and outcome (O1-3) based on previous literature to analyse the relative performance of CT. We report the changes in the indicators over waves of SARS-CoV-2 infections caused by several viral variants. RESULTS: The CT team in Solothurn processed 57,363 index cases and 71,809 contacts over a 15-month period. The CT team successfully contacted 99% of positive cases within 24 hours (KPI P7) throughout the pandemic and returned almost all test results on the same or next day (KPI P6), before the delta variant emerged. Three-quarters of contacts were notified within 24 hours of the CT interview with the index (KPI P8) before the emergence of the alpha, delta and omicron variants, when the proportions decreased to 64%, 36% and 54%, respectively. The percentage of new symptomatic cases tested and interviewed within 3 days of symptom onset was high at >70% (KPI P10) and contacts started quarantine within a median of 3 days of index case symptom onset (KPI P3). About a fifth of new index cases had already been in quarantine by the time of their positive test (KPI O1), before the delta variant emerged. The percentage of index cases in isolation by day of testing remained at almost 100% throughout the period of analysis (KPI O2). CONCLUSIONS: The CT in Solothurn used a partially automated workflow and continued to perform well throughout the pandemic, although the relative performance of the CT system declined at higher caseloads. CT remains an important tool for controlling the spread of infectious diseases, but clearer standards should improve the performance, comparability and monitoring of infection in real time as part of pandemic preparedness efforts.

Long-term course of neutralising antibodies against SARS-CoV-2 in vaccinated and unvaccinated staff and residents in a Swiss nursing home: a cohort study 2021-2022.

BACKGROUND: Given their high-risk resident population, nursing homes were critical institutions in the COVID-19 pandemic, calling for continued monitoring and vaccine administration to healthcare workers and residents. Here, we studied long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in vaccinated and unvaccinated healthcare workers and residents of a nursing home in Switzerland between February 2021 and June 2022. METHODS: Our study comprised 45 participants, of which 39 were healthcare workers and six were residents. All participants were offered a maximum of three mRNA vaccine doses (Pfizer/BioNTech, BNT162b2) in December 2020, January 2021, and November/December 2021. Thirty-five participants received three vaccinations, seven either one or two, and three remained unvaccinated. We collected four blood samples: one in March 2021 and three during follow-ups in November 2021, February 2022, and June 2022. We performed a multifactorial serological SARS-CoV-2 assay (ABCORA) for immunoglobulin G, A, and M responses to spike (receptor-binding domain, S1, and S2) and nucleocapsid (N) proteins. Furthermore, we assessed predicted neutralisation activity based on signal over cutoff in ABCORA. We collected epidemiological data from participants via a standardised questionnaire. RESULTS: Thirty-two (71%) of the 45 participants showed hybrid immunity from combined vaccination and previous infection; 10 (22%) had only vaccine-induced immunity; and three (7%) had only post-infection immunity. Participants with hybrid immunity showed the highest predicted neutralisation activity at the end of the study period (median Sum S1 = 273), and unvaccinated participants showed the lowest (median Sum S1 = 41). Amongst participants who reported a SARS-CoV-2 infection, median Sum S1 levels increased with the number of vaccinations (p = 0.077). The healthcare worker group showed a significant time-dependent decrease in median Sum S1 after base immunisation (93% decrease, p = 0.0005) and the booster dose (26% decrease, p = 0.010). Predicted neutralisation activity was lower amongst residents (adjusted ratio of means [AM] = 0.7, 95% confidence interval [CI] = 0.3-1.0) and amongst smokers (AM = 0.5, 95% CI 0.3-0.8). Activity increased with the number of vaccinations (booster: AM = 3.6, 95% CI 1.5-8.8; no booster: AM = 2.3, 95% CI 0.9-2.5). Positive SARS-CoV-2 infection status tended to confer higher predicted neutralisation levels (AM = 1.5, 95% CI 0.9-2.5). CONCLUSIONS: Our study of the long-term serological course of SARS-CoV-2 in a nursing home showed that the first SARS-CoV-2 booster vaccine was essential for maintaining antiviral antibody levels. Hybrid immunity sustained SARS-CoV-2 immunity at the highest level. In critical settings such as nursing homes, monitoring the SARS-CoV-2 immune status may guide booster vaccinations.

Air cleaners and respiratory infections in schools: A modeling study using epidemiological, environmental, and molecular data.

Background: Using a multiple-measurement approach, we examined the real-world effectiveness of portable HEPA-air filtration devices (air cleaners) in a school setting. Methods: We collected environmental (CO2, particle concentrations), epidemiological (absences related to respiratory infections), audio (coughing), and molecular data (bioaerosol and saliva samples) over seven weeks during winter 2022/2023 in two Swiss secondary school classes. Using a cross-over study design, we compared particle concentrations, coughing, and the risk of infection with vs without air cleaners. Results: All 38 students (age 13-15 years) participated. With air cleaners, mean particle concentration decreased by 77% (95% credible interval 63%-86%). There were no differences in CO2 levels. Absences related to respiratory infections were 22 without vs 13 with air cleaners. Bayesian modeling suggested a reduced risk of infection, with a posterior probability of 91% and a relative risk of 0.73 (95% credible interval 0.44-1.18). Coughing also tended to be less frequent (posterior probability 93%). Molecular analysis detected mainly non-SARS-CoV-2 viruses in saliva (50/448 positive), but not in bioaerosols (2/105 positive) or HEPA-filters (4/160). The detection rate was similar with vs without air cleaners. Spatiotemporal analysis of positive saliva samples identified several likely transmissions. Conclusions: Air cleaners improved air quality, showed a potential benefit in reducing respiratory infections, and were associated with less coughing. Airborne detection of non-SARS-CoV-2 viruses was rare, suggesting that these viruses may be more difficult to detect in the air. Future studies should examine the importance of close contact and long-range transmission, and the cost-effectiveness of using air cleaners.

Intracerebral Transplantation and In Vivo Bioluminescence Tracking of Human Neural Progenitor Cells in the Mouse Brain.

Cell therapy has long been an emerging treatment paradigm in experimental neurobiology. However, cell transplantation studies often rely on end-point measurements and can therefore only evaluate longitudinal changes of cell migration and survival to a limited extent. This paper provides a reliable, minimally invasive protocol to transplant and longitudinally track neural progenitor cells (NPCs) in the adult mouse brain. Before transplantation, cells are transduced with a lentiviral vector comprising a bioluminescent (firefly-luciferase) and fluorescent (green fluorescent protein [GFP]) reporter. The NPCs are transplanted into the right cortical hemisphere using stereotaxic injections in the sensorimotor cortex. Following transplantation, grafted cells were detected through the intact skull for up to five weeks (at days 0, 3, 14, 21, 35) with a resolution limit of 6,000 cells using in vivo bioluminescence imaging. Subsequently, the transplanted cells are identified in histological brain sections and further characterized with immunofluorescence. Thus, this protocol provides a valuable tool to transplant, track, quantify, and characterize cells in the mouse brain.

Impact of the COVID-19 pandemic on TB services at ART programmes in low- and middle-income countries: a multi-cohort survey.

INTRODUCTION: COVID-19 stretched healthcare systems to their limits, particularly in settings with a pre-existing high burden of infectious diseases, including HIV and tuberculosis (TB). We studied the impact of COVID-19 on TB services at antiretroviral therapy (ART) clinics in low- and middle-income countries. METHODS: We surveyed ART clinics providing TB services in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in Africa and the Asia-Pacific until July 2021 (TB diagnoses until the end of 2021). We collected site-level data using standardized questionnaires. RESULTS: Of 46 participating ART clinics, 32 (70%) were in Africa and 14 (30%) in the Asia-Pacific; 52% provided tertiary care. Most clinics (85%) reported disrupted routine HIV care services during the pandemic, both in Africa (84%) and the Asia-Pacific (86%). The most frequently reported impacts were on staff (52%) and resource shortages (37%; protective clothing, face masks and disinfectants). Restrictions in TB health services were observed in 12 clinics (26%), mainly reduced access to TB diagnosis and postponed follow-up visits (6/12, 50% each), and restrictions in TB laboratory services (22%). Restrictions of TB services were addressed by dispensing TB drugs for longer periods than usual (7/12, 58%), providing telehealth services (3/12, 25%) and with changes in directly observed therapy (DOT) (e.g. virtual DOT, 3/12). The number of TB diagnoses at participating clinics decreased by 21% in 2020 compared to 2019; the decline was more pronounced in tertiary than primary/secondary clinics (24% vs. 12%) and in sites from the Asia-Pacific compared to Africa (46% vs. 14%). In 2021, TB diagnoses continued to decline in Africa (-8%) but not in the Asia-Pacific (+62%) compared to 2020. During the pandemic, new infection control measures were introduced or intensified at the clinics, including wearing face masks, hand sanitation and patient triage. CONCLUSIONS: The COVID-19 pandemic led to staff shortages, reduced access to TB care and delays in follow-up visits for people with TB across IeDEA sites in Africa and the Asia-Pacific. Increased efforts are needed to restore and secure ongoing access to essential TB services in these contexts.

Integrating services for HIV and multidrug-resistant tuberculosis: A global cross-sectional survey among ART clinics in low- and middle-income countries.

Tuberculosis (TB) is the leading cause of death among PLHIV and multidrug-resistant-TB (MDR-TB) is associated with high mortality. We examined the management for adult PLHIV coinfected with MDR-TB at ART clinics in lower income countries. Between 2019 and 2020, we conducted a cross-sectional survey at 29 ART clinics in high TB burden countries within the global IeDEA network. We used structured questionnaires to collect clinic-level data on the TB and HIV services and the availability of diagnostic tools and treatment for MDR-TB. Of 29 ART clinics, 25 (86%) were in urban areas and 19 (66%) were tertiary care clinics. Integrated HIV-TB services were reported at 25 (86%) ART clinics for pan-susceptible TB, and 14 (48%) clinics reported full MDR-TB services on-site, i.e. drug susceptibility testing [DST] and MDR-TB treatment. Some form of DST was available on-site at 22 (76%) clinics, while the remainder referred testing off-site. On-site DST for second-line drugs was available at 9 (31%) clinics. MDR-TB treatment was delivered on-site at 15 (52%) clinics, with 10 individualizing treatment based on DST results and five using standardized regimens alone. Bedaquiline was routinely available at 5 (17%) clinics and delamanid at 3 (10%) clinics. Although most ART clinics reported having integrated HIV and TB services, few had fully integrated MDR-TB services. There is a continued need for increased access to diagnostic and treatment options for MDR-TB patients and better integration of MDR-TB services into the HIV care continuum.

Losing ground at the wrong time: trends in self-reported influenza vaccination uptake in Switzerland, Swiss Health Survey 2007-2017.

OBJECTIVES: We studied time trends in seasonal influenza vaccination and associations with socioeconomic and health-related determinants in Switzerland, overall and in people aged ≥65 years. DESIGN: Three cross-sectional surveys. PARTICIPANTS: Individuals who participated in the Swiss Health Surveys 2007, 2012 and 2017. We calculated the proportion reporting influenza vaccination in the last 12 months, and performed multivariable logistic regression analyses. RESULTS: We included 51 582 individuals in this analysis. The median age was 49 years (IQR 25-64), and 27 518 were women (53.3%). The proportion of reporting a history of influenza vaccination overall was 31.9% (95% CI 31.4 to 32.4); and dropped from 34.5% in 2007 to 28.8% in 2017. The uptake of vaccination within the past 12 months was 16% in 2007 and similar in 2012 and 2017 (around 14%). In people with chronic disease, uptake dropped from 43.8% in 2007 to 37.1% in 2012 and to 31.6% in 2017 (p<0.001). In people aged ≥65 years, uptake dropped from 47.8% in 2007 to 38.5% in 2012 to 36.2% in 2017 (p<0.001). In logistic regression, self-reported vaccination coverage decreased in the 65-75 years old (adjusted OR (aOR) 0.56, 95% CI 0.48 to 0.66 between 2007 and 2012; aOR 0.89, 95% CI 0.77 to 1.03 between 2012 and 2017). Uptake was positively associated with the ≥65 age group, living in French-speaking and urban areas, history of smoking, bad self-reported health status, private/semiprivate health insurance, having a medical profession and having any underlying chronic disease. CONCLUSION: Influenza vaccination coverage was low in older and chronically ill persons. Significant efforts are required in preparing for the influenza season 2020/2021 to reduce the double burden of COVID-19 and seasonal influenza. These efforts should include campaigns but also novel approaches using social media.