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.

COVID-19 epidemic in Switzerland: on the importance of testing, contact tracing and isolation.

Switzerland is among the countries with the highest number of coronavirus disease-2019 (COVID-19) cases per capita in the world. There are likely many people with undetected SARS-CoV-2 infection because testing efforts are currently not detecting all infected people, including some with clinical disease compatible with COVID-19. Testing on its own will not stop the spread of SARS-CoV-2. Testing is part of a strategy. The World Health Organization recommends a combination of measures: rapid diagnosis and immediate isolation of cases, rigorous tracking and precautionary self-isolation of close contacts. In this article, we explain why the testing strategy in Switzerland should be strengthened urgently, as a core component of a combination approach to control COVID-19.

Metagenomic Next-Generation Sequencing of Plasma for Diagnosis of COVID-19-Associated Pulmonary Aspergillosis.

Timely diagnosis remains an unmet need in non-neutropenic patients at risk for aspergillosis, including those with COVID-19-associated pulmonary aspergillosis (CAPA), which in its early stages is characterized by tissue-invasive growth of the lungs with limited angioinvasion. Currently available mycological tests show limited sensitivity when testing blood specimens. Metagenomic next-generation sequencing (mNGS) to detect microbial cell-free DNA (mcfDNA) in plasma might overcome some of the limitations of conventional diagnostics. A two-center cohort study involving 114 COVID-19 intensive care unit patients evaluated the performance of plasma mcfDNA sequencing for the diagnosis of CAPA. Classification of CAPA was performed using the European Confederation for Medical Mycology (ECMM)/International Society for Human and Animal Mycoses (ISHAM) criteria. A total of 218 plasma samples were collected between April 2020 and June 2021 and tested for mcfDNA (Karius test). Only 6 patients were classified as probable CAPA, and 2 were classified as possible, while 106 patients did not fulfill CAPA criteria. The Karius test detected DNA of mold pathogens in 12 samples from 8 patients, including Aspergillus fumigatus in 10 samples from 6 patients. Mold pathogen DNA was detected in 5 of 6 (83% sensitivity) cases with probable CAPA (A. fumigatus in 8 samples from 4 patients and Rhizopus microsporus in 1 sample), while the test did not detect molds in 103 of 106 (97% specificity) cases without CAPA. The Karius test showed promising performance for diagnosis of CAPA when testing plasma, being highly specific. The test detected molds in all but one patient with probable CAPA, including cases where other mycological tests from blood resulted continuously negative, outlining the need for validation in larger studies.

Race and ethnicity: Risk factors for fungal infections?

Racial and ethnic identities, largely understood as social rather than biologic constructs, may impact risk for acquiring infectious diseases, including fungal infections. Risk factors may include genetic and immunologic differences such as aberrations in host immune response, host polymorphisms, and epigenomic factors stemming from environmental exposures and underlying social determinants of health. In addition, certain racial and ethnic groups may be predisposed to diseases that increase risk for fungal infections, as well as disparities in healthcare access and health insurance. In this review, we analyzed racial and ethnic identities as risk factors for acquiring fungal infections, as well as race and ethnicity as they relate to risk for severe disease from fungal infections. Risk factors for invasive mold infections such as aspergillosis largely appear related to environmental differences and underlying social determinants of health, although immunologic aberrations and genetic polymorphisms may contribute in some circumstances. Although black and African American individuals appear to be at high risk for superficial and invasive Candida infections and cryptococcosis, the reasons for this are unclear and may be related to underling social determinants of health, disparities in access to healthcare, and other socioeconomic disparities. Risk factors for all the endemic fungi are likely largely related to underlying social determinants of health, socioeconomic, and health disparities, although immunologic mechanisms likely play a role as well, particularly in disseminated coccidioidomycosis.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland.

The direct and indirect impact of the COVID-19 pandemic on population-level mortality is of concern to public health but challenging to quantify. Using data for 2011-2019, we applied Bayesian models to predict the expected number of deaths in Switzerland and compared them with laboratory-confirmed COVID-19 deaths from February 2020 to April 2022 (study period). We estimated that COVID-19-related mortality was underestimated by a factor of 0.72 (95% credible interval [CrI]: 0.46-0.78). After accounting for COVID-19 deaths, the observed mortality was -4% (95% CrI: -8 to 0) lower than expected. The deficit in mortality was concentrated in age groups 40-59 (-12%, 95%CrI: -19 to -5) and 60-69 (-8%, 95%CrI: -15 to -2). Although COVID-19 control measures may have negative effects, after subtracting COVID-19 deaths, there were fewer deaths in Switzerland during the pandemic than expected, suggesting that any negative effects of control measures were offset by the positive effects. These results have important implications for the ongoing debate about the appropriateness of COVID-19 control measures.

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.

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.

HIV suppression was maintained during the COVID-19 pandemic in Malawi: a program-level cohort study.

BACKGROUND AND OBJECTIVES: Measures introduced to reduce the spread of SARS-CoV-2 by the Malawi government and the national HIV care program might have compromised treatment outcomes of patients living with HIV on antiretroviral therapy (ART). We studied viral load (VL) outcomes before and during the COVID-19 epidemic in Malawi. METHODS: In this population-based cohort study, we included all routine VL measurements collected from July 2019 to December 2020 in about 650 ART clinics in Malawi. We examined differences between pandemic periods (before/during COVID-19) for i) VL monitoring, and ii) VL suppression (VLS: <1,000 copies/ml). For i) we studied the number of VL measurements over time and assessed predictors of missed measurements before and during COVID-19 in logistic regression models. For ii) we estimated the odds of VLS before and during the COVID-19 epidemic stratified by treatment regimen using generalized estimation equations adjusted for age, sex, time on ART, and type of biological sample. We imputed missing treatment regimens by population-calibrated multiple imputation. RESULTS: We included 607,894 routine VL samples from 556,281 patients. VL testing declined during COVID-19 (243,729; 40%) compared to before COVID-19 (365,265; 60%), but predictors of missing tests were similar in the two periods. VLS rates increased slightly from 93% before to 94% during COVID-19. Compared to before COVID-19, the odds of VLS increased during COVID-19 for patients on protease inhibitor-based (PI) regimens (adjusted odds ratio [aOR] 1.22, 95% CI: 0.99-1.49) and for patients on integrase strand transfer inhibitor-based (INSTI) regimens (aOR 1.10, 95% CI: 1.03-1.17). There was no difference in VLS between the two periods among patients on nonnucleoside reverse transcriptase inhibitor-based (NNRTI) regimens. VLS varied by age, sex, regimen, and duration on ART, ranging from 45.1% (95% CI 40.3-50.0%) to 97.2% (95% CI 96.9-97.4%). CONCLUSION: There was a significant decline in VL monitoring during COVID-19, but we did not find clear evidence that the pandemic reduced VL suppression rates. Routine scheduled VL monitoring, targeted adherence support, and timely regimen switches for patients with treatment failure remain critical to improving VLS.

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

AIMS: The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. METHODS: We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020. RESULTS: 710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). CONCLUSIONS: Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning.

Alpha variant coronavirus outbreak in a nursing home despite high vaccination coverage: molecular, epidemiological and immunological studies.

BACKGROUND: Vaccination may control the 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 vaccination uptake of mRNA vaccines against SARS-CoV-2 was 82% among residents as of Jan 21/2021. After a vaccinated symptomatic HCW was diagnosed with COVID-19 on Feb 22, we did an outbreak investigations in house A (47 residents, 37 HCWs) using SARS-CoV-2-specific PCR in nasopharyngeal swabs. We performed whole-genome sequencing of SARS-CoV-2 and serological analyses. RESULTS: We identified 17 individuals with positive PCR tests; ten residents (five vaccinated) and seven HCWs (three vaccinated). Median age among residents was 86 years (interquartile range [IQR] 70-90) and 49 years (IQR 29-59) among HCWs. Among the five vaccinated residents, 60% had mild disease and had 40% no symptoms, whereas all five unvaccinated residents had mild to severe disease and two died. The vaccine effectiveness for the prevention of infection among the residents was 73.0% (95% Cl 24.7-90.1). The 12 available genomes were all alpha variants. Neutralizing titers were significantly higher in vaccinated individuals upon re-exposure (>1 week after diagnosis) than in vaccinated, unexposed HCWs (p=0.012). Transmission networks indicated four 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.

Survival among people hospitalized with COVID-19 in Switzerland: a nationwide population-based analysis.

BACKGROUND: Increasing age, male sex, and pre-existing comorbidities are associated with lower survival from SARS-CoV-2 infection. The interplay between different comorbidities, age, and sex is not fully understood, and it remains unclear if survival decreases linearly with higher ICU occupancy or if there is a threshold beyond which survival falls. METHOD: This national population-based study included 22,648 people who tested positive for SARS-CoV-2 infection and were hospitalized in Switzerland between February 24, 2020, and March 01, 2021. Bayesian survival models were used to estimate survival after positive SARS-CoV-2 test among people hospitalized with COVID-19 by epidemic wave, age, sex, comorbidities, and ICU occupancy. Two-way interactions between age, sex, and comorbidities were included to assess the differential risk of death across strata. ICU occupancy was modeled using restricted cubic splines to allow for a non-linear association with survival. RESULTS: Of 22,648 people hospitalized with COVID-19, 4785 (21.1%) died. The survival was lower during the first epidemic wave than in the second (predicted survival at 40 days after positive test 76.1 versus 80.5%). During the second epidemic wave, occupancy among all available ICU beds in Switzerland varied between 51.7 and 78.8%. The estimated survival was stable at approximately 81.5% when ICU occupancy was below 70%, but worse when ICU occupancy exceeded this threshold (survival at 80% ICU occupancy: 78.2%; 95% credible interval [CrI] 76.1 to 80.1%). Periods with higher ICU occupancy (>70 vs 70%) were associated with an estimated number of 137 (95% CrI 27 to 242) excess deaths. Comorbid conditions reduced survival more in younger people than in older people. Among comorbid conditions, hypertension and obesity were not associated with poorer survival. Hypertension appeared to decrease survival in combination with cardiovascular disease. CONCLUSIONS: Survival after hospitalization with COVID-19 has improved over time, consistent with improved management of severe COVID-19. The decreased survival above 70% national ICU occupancy supports the need to introduce measures for prevention and control of SARS-CoV-2 transmission in the population well before ICUs are full.

Prevalence of COVID-19-Associated Pulmonary Aspergillosis: Critical Review and Conclusions.

First reports of cases and case series of COVID-19-associated pulmonary aspergillosis (CAPA) emerged during the first months of the pandemic. Prevalence rates varied widely due to the fact that CAPA was, and still remains, challenging to diagnose in patients with COVID-19-associated acute respiratory failure (ARF). The clinical picture and radiological findings of CAPA are unspecific and can resemble those of severe COVID-19. Hence, mycological evidence became a key component in establishing a diagnosis. However, blood tests lack sensitivity in early treatable phases of CAPA and once positive, mortality has been shown to exceed 80% despite systemic antifungal therapy. The primarily airway invasive growth in non-neutropenic patients and the late occurrence of angioinvasion in the course of disease may mainly account for these diagnostic obstacles. Testing of bronchoalveolar lavage (BAL) is therefore crucial in the diagnostic process, but was rarely performed during the early phase of the pandemic, which potentially interfered with the accuracy of reported prevalence. Current guidelines recommend treatment of CAPA during its early airway invasive phase, which may result in some overtreatment (i.e., treatment in patients that may not develop angioinvasive infection) and adverse drug events, yet there is no viable alternative approach. Timely treatment of cases needs to be ensured for patients with mycological evidence of CAPA in the lower respiratory tract given the independent contribution of CAPA to devastating mortality rates of around 50% that have been shown in multiple studies. Here, we review the evolution of reported CAPA prevalence and the role of CAPA as an important opportunistic infection affecting COVID-19 patients in intensive care units (ICUs).

Vaccination willingness for COVID-19 among healthcare workers: a cross-sectional survey in a Swiss canton.

AIMS OF THE STUDY: Vaccination is regarded as the most promising response to the COVID-19 pandemic. We assessed opinions about COVID-19 vaccination, willingness to be vaccinated, and reasons for vaccination hesitancy among healthcare workers. METHODS: We conducted a cross-sectional, web-based survey among 3,793 healthcare workers in December 2020 in the Canton of Solothurn, Switzerland, before the start of the national COVID-19 vaccination campaign. RESULTS: Median age was 43 years (interquartile range [IQR] 31-53), 2,841 were female (74.9%). A total of 1,511 healthcare workers (39.8%) reported willingness to accept vaccination, whereas 1,114 (29.4%) were unsure and 1,168 (30.8%) would decline vaccination. Among medical doctors, 76.1% were willing, whereas only 27.8% of nurses expressed willingness. Among the 1,168 healthcare workers who would decline vaccination, 1,073 (91.9%) expressed concerns about vaccine safety and side effects. The willingness of healthcare workers to be vaccinated was associated with older age (adjusted odds ratio [aOR] 1.97, 95% confidence interval [Cl] 1.71-2.27) and having been vaccinated for influenza this year (aOR 2.70, 95% Cl 2.20-3.31). Healthcare workers who reported a lack of confidence in government were less likely to be willing to be vaccinated (aOR 0.58, 95% Cl 0.40-0.84), and women were less willing to be vaccinated than men (OR 0.33, 95% CI 0.28-0.38). CONCLUSION: Less than half of healthcare workers reported willingness to be vaccinated before the campaign start, but proportions varied greatly depending on profession and workplace. Strategies with clear and objective messages that particularly address the concerns of healthcare workers are needed if their willingness to be vaccinated against COVID-19 is to be further increased.

Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.

The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.

Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA): a Multicenter Study.

This multicenter study evaluated the IMMY Aspergillus Galactomannan Lateral Flow Assay (LFA) with automated reader for diagnosis of pulmonary aspergillosis in patients with COVID-19-associated acute respiratory failure (ARF) requiring intensive care unit (ICU) admission between 03/2020 and 04/2021. A total of 196 respiratory samples and 148 serum samples (n = 344) from 238 patients were retrospectively included, with a maximum of one of each sample type per patient. Cases were retrospectively classified for COVID-19-associated pulmonary aspergillosis (CAPA) status following the 2020 consensus criteria, with the exclusion of LFA results as a mycological criterion. At the 1.0 cutoff, sensitivity of LFA for CAPA (proven/probable/possible) was 52%, 80% and 81%, and specificity was 98%, 88% and 67%, for bronchoalveolar lavage fluid (BALF), nondirected bronchoalveolar lavage (NBL), and tracheal aspiration (TA), respectively. At the 0.5 manufacturer's cutoff, sensitivity was 72%, 90% and 100%, and specificity was 79%, 83% and 44%, for BALF, NBL and TA, respectively. When combining all respiratory samples, the receiver operating characteristic (ROC) area under the curve (AUC) was 0.823, versus 0.754, 0.890 and 0.814 for BALF, NBL and TA, respectively. Sensitivity and specificity of serum LFA were 20% and 93%, respectively, at the 0.5 ODI cutoff. Overall, the Aspergillus Galactomannan LFA showed good performances for CAPA diagnosis, when used from respiratory samples at the 1.0 cutoff, while sensitivity from serum was limited, linked to weak invasiveness during CAPA. As some false-positive results can occur, isolated results slightly above the recommended cutoff should lead to further mycological investigations.

The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.

Seroprevalence of SARS-CoV-2 in healthcare workers from outpatient facilities and retirement or nursing homes in a Swiss canton.

BACKGROUND: Healthcare workers are more frequently exposed to SARS-CoV-2 than the general population. Little is known about healthcare settings outside of hospitals. We studied the seroprevalence of SARS-CoV-2 among healthcare workers in outpatient facilities and retirement or nursing homes in the Canton of Solothurn, Switzerland in the first wave of the COVID-19 pandemic. METHODS: Longitudinal seroprevalence study among healthcare workers with examinations at baseline and 2 months between June and September 2020. The Abbott SARS-CoV-2 IgG and Liaison/Diasorin SARS-CoV-2 S1/S2 IgG assay were used to detect antibodies against SARS-CoV-2. All participants provided demographic information. We report descriptive statistics and calculated the seroprevalence with 95% confidence intervals. RESULTS: We included 357 healthcare workers; their median age was 43 years (interquartile range 29-54), and 315 (88.2%) were female. Forty-nine (13.7%) were physicians, 87 (24.4%) practice assistants and 221 (61.9%) nurses. Overall seroprevalence among healthcare workers in outpatient facilities and retirement or nursing homes was 3.4% (12/357). The 12 seropositive healthcare workers were all nurses (12/221, 5.5%); 11 worked at retirement or nursing homes and one at the hospital's outpatient clinic. Symptoms such as loss of smell or taste, shortness of breath, and fever were more prevalent among seropositive healthcare workers than seronegative healthcare workers. No close contact had detectable antibodies against SARS-CoV-2. CONCLUSIONS: Seroprevalence among healthcare workers was low, but higher among nursing staff of retirement or nursing homes. Healthcare workers at private practices were able to protect themselves well during the first wave of the COVID-19 pandemic.

Symptoms of common mental disorders and adherence to antiretroviral therapy among adults living with HIV in rural Zimbabwe: a cross-sectional study.

OBJECTIVES: To examine the proportion of people living with HIV who screen positive for common mental disorders (CMD) and the associations between CMD and self-reported adherence to antiretroviral therapy (ART). SETTING: Sixteen government-funded health facilities in the rural Bikita district of Zimbabwe. DESIGN: Cross-sectional study. PARTICIPANTS: HIV-positive non-pregnant adults, aged 18 years or older, who lived in Bikita district and had received ART for at least 6 months. OUTCOME MEASURES: The primary outcome was the proportion of participants screening positive for CMD defined as a Shona Symptoms Questionnaire score of 9 or greater. Secondary outcomes were the proportion of participants reporting suicidal ideation, perceptual symptoms and suboptimal ART adherence and adjusted prevalence ratios (aPR) for factors associated with CMD, suicidal ideation, perceptual symptoms and suboptimal ART adherence. RESULTS: Out of 3480 adults, 18.8% (95% CI 14.8% to 23.7%) screened positive for CMD, 2.7% (95% CI 1.5% to 4.7%) reported suicidal ideations, and 1.5% (95% CI 0.9% to 2.6%) reported perceptual symptoms. Positive CMD screens were more common in women (aPR 1.67, 95% CI 1.19 to 2.35) than in men and were more common in adults aged 40-49 years (aPR 1.47, 95% CI 1.16 to 1.85) or aged 50-59 years (aPR 1.51, 95% CI 1.05 to 2.17) than in those 60 years or older. Positive CMD screen was associated with suboptimal adherence (aPR 1.53; 95% CI 1.37 to 1.70). CONCLUSIONS: A substantial proportion of people living with HIV in rural Zimbabwe are affected by CMD. There is a need to integrate mental health services and HIV programmes in rural Zimbabwe. TRIAL REGISTRATION NUMBER: NCT03704805.