[Marburg virus disease in travellers]. / Maladie à virus Marburg chez les voyageurs.

Marburg virus disease (MVD) is a dreadful but exceptional disease. Formerly mainly identified in Uganda, Angola and the Democratic Republic of Congo, it has recently appeared in the Republic of Guinea, Ghana, Equatorial Guinea and Tanzania, adding West Africa to the affected regions. Humans become infected through exposure to bats Roussettus aegyptiacus or during unprotected care of infected people. Five cases are linked to travellers, the last one dates to 2008 and involved a visit to caves colonized by bats. At present, there is no specific treatment or vaccine. Despite its rarity, adventurous travelers should be aware of the risks of exposure and avoid entering places inhabited by bats.

La maladie à virus Marburg est une maladie redoutable mais exceptionnelle. Autrefois identifiée en Ouganda, Angola et République démocratique du Congo, elle a récemment fait son apparition en République de Guinée, au Ghana, en Guinée équatoriale et en Tanzanie, ajoutant l'Afrique de l'Ouest aux régions touchées. Les humains s'infectent lors d'une exposition avec les chauves-souris roussettes d'Égypte ou lors de la prise en charge sans protection de personnes infectées. Cinq cas sont liés à des voyageurs, le dernier remonte à 2008 et était associé à la visite de grottes colonisées par des roussettes d'Égypte. Actuellement, il n'existe aucun traitement spécifique ni vaccin. Malgré sa rareté, les voyageurs aventureux doivent être informés des risques d'exposition et éviter de pénétrer dans des lieux habités par des chauves-souris.

[Mpox, 40 years after smallpox eradication]. / Mpox, 40 ans après l'éradication de la variole humaine.

In 2022, mpox - a neglected tropical zoonosis - emerged to the world stage. From 1980, the disease was periodically noted, with increasing frequency, in endemic regions of Africa. In 2017, a large outbreak in Nigeria marks a turning point in the evolution of mpox and seems to be at the origin of the 2022 pandemic. The factors for mpox emergence are complex and include loss of cross-protection conferred by smallpox vaccination, increased exposure to the animal reservoir, and increased human-to-human transmission due to behavioral factors. While the current epidemic seems under control, an evolution towards a more transmissible or more virulent virus is not excluded. The 2022 pandemic is an opportunity to initiate and strengthen mpox surveillance, prevention and care management among all affected populations.

En 2022, le mpox ­ une zoonose tropicale négligée ­ a émergé sur la scène mondiale. Depuis 1980, la maladie a été notifiée avec une fréquence croissante dans les régions endémiques d'Afrique. En 2017, une large épidémie au Nigeria marque un tournant dans l'évolution du mpox et semble à l'origine de la pandémie 2022. Les facteurs d'émergence du mpox sont complexes et incluent la perte de la protection croisée conférée par la vaccination antivariolique, une exposition accrue au réservoir animal et une augmentation de la transmission interhumaine due à des facteurs comportementaux. Alors que l'épidémie actuelle semble sous contrôle, une évolution vers un virus plus transmissible ou plus virulent n'est pas exclue. La pandémie 2022 est une opportunité pour initier et renforcer la surveillance, la prévention et la prise en charge clinique du mpox auprès de toutes les populations affectées.

A Case of Mpox Reinfection.

A healthy young man first diagnosed with mpox in May 2022 presented again in November 2022 with anal proctitis and a positive polymerase chain reaction on a rectal swab for Monkeypox virus after a recent trip to Brazil, where he engaged in condomless sexual intercourse with multiple male partners.

Analytical Sensitivity of Eight Different SARS-CoV-2 Antigen-Detecting Rapid Tests for Omicron-BA.1 Variant.

The emergence of each novel SARS-CoV-2 variant of concern (VOC) requires investigation of its potential impact on the performance of diagnostic tests in use, including antigen-detecting rapid diagnostic tests (Ag-RDTs). Although anecdotal reports have been circulating that the newly emerged Omicron-BA.1 variant is in principle detectable by Ag-RDTs, few data on sensitivity are available. We have performed (i) analytical sensitivity testing with cultured virus in eight Ag-RDTs and (ii) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron-BA.1 (n = 59) or Delta (n = 54) breakthrough infection on seven Ag-RDTs. Overall, in our analytical study we have found heterogenicity between Ag-RDTs for detecting Omicron-BA.1. When using cultured virus, we observed a trend toward lower endpoint sensitivity for Omicron-BA.1 detection than for earlier circulating SARS-CoV-2 and the other VOCs. In our retrospective study, the detection of Delta and Omicron-BA.1 was assessed in a comparable set of stored clinical samples using seven Ag-RDTs. Four hundred ninety-seven of all 826 tests (60.17%) performed on Omicron-BA.1 samples were positive, compared to 489/756 (64.68%) for Delta samples. In the analytical study, the sensitivity for both Omicron-BA.1 and Delta between the Ag-RDTs was variable. All seven Ag-RDTs showed comparable sensitivities to detect Omicron-BA.1 and Delta in the retrospective study. IMPORTANCE Sensitivity for detecting Omicron-BA.1 shows high heterogenicity between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. Analytical and retrospective testing is a proxy and timely solution to generate rapid performance data, but it is not a replacement for clinical evaluations, which are urgently needed. Biological and technical reasons for detection failure by some Ag-RDTs need to be further investigated.

The pandemic toll and post-acute sequelae of SARS-CoV-2 in healthcare workers at a Swiss University Hospital.

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population. The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models. Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76-2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59-5.60). Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2.

Infectious viral load (VL) expelled as droplets and aerosols by infected individuals partly determines transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RNA VL measured by qRT-PCR is only a weak proxy for infectiousness. Studies on the kinetics of infectious VL are important to understand the mechanisms behind the different transmissibility of SARS-CoV-2 variants and the effect of vaccination on transmission, which allows guidance of public health measures. In this study, we quantified infectious VL in individuals infected with SARS-CoV-2 during the first five symptomatic days by in vitro culturability assay in unvaccinated or vaccinated individuals infected with pre-variant of concern (pre-VOC) SARS-CoV-2, Delta or Omicron BA.1. Unvaccinated individuals infected with pre-VOC SARS-CoV-2 had lower infectious VL than Delta-infected unvaccinated individuals. Full vaccination (defined as >2 weeks after receipt of the second dose during the primary vaccination series) significantly reduced infectious VL for Delta breakthrough cases compared to unvaccinated individuals. For Omicron BA.1 breakthrough cases, reduced infectious VL was observed only in boosted but not in fully vaccinated individuals compared to unvaccinated individuals. In addition, infectious VL was lower in fully vaccinated Omicron BA.1-infected individuals compared to fully vaccinated Delta-infected individuals, suggesting that mechanisms other than increased infectious VL contribute to the high infectiousness of SARS-CoV-2 Omicron BA.1. Our findings indicate that vaccines may lower transmission risk and, therefore, have a public health benefit beyond the individual protection from severe disease.

Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial.

BACKGROUND: Since the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19. METHODS: We conducted a pragmatic open-label, parallel, cluster-randomised superiority trial in four sites in Switzerland and Brazil between March 2020 to March 2021. Clusters were randomised to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). Exposure to SARS-CoV-2 was defined as a close contact of >15 minutes in <2 metres distance or having shared a closed space for ≥2 hours with a person with confirmed SARS-CoV-2 infection. The primary outcome is the occurrence of COVID-19 defined by a SARS-CoV-2 infection (positive oropharyngeal SARS-CoV-2 PCR and/or a seroconversion) and ≥1 compatible symptom within 21 days post-enrolment. ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732. FINDINGS: Of 318 participants, 157 (49.4%) were women; median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomised to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76-2.73). In the primary endpoint analysis, which was adjuted for baseline imbalance, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.60 (95% CI, 0.29-1.26; p =0.18). INTERPRETATION: The role of LPV/r as PEP for COVID-19 remains unanswered. Although LPV/r over 5 days did not significantly reduce the incidence of COVID-19 in exposed individuals, we observed a change in the directionality of the effect in favour of LPV/r after adjusting for baseline imbalance. LPV/r for this indication merits further testing against SARS-CoV-2 in clinical trials. FUNDING: Swiss National Science Foundation (project no.: 33IC30_166819) and the Private Foundation of Geneva University Hospitals (Edmond Rothschild (Suisse) SA, Union Bancaire Privée and the Fondation pour la recherche et le traitement médical).

Negative Association Between Smoking and Positive SARS-CoV-2 Testing: Results From a Swiss Outpatient Sample Population.

To date, most of the evidence suggests that smoking is negatively associated with testing positive for SARS-CoV-2. However, evidence has several methodological limitations. Using an outpatient sample population, we analyzed the association of testing positive for SARS-CoV-2 and smoking considering comorbidities, socioeconomic and demographic factors. Baseline data were obtained from a cohort during the first wave of the pandemic in Geneva, Switzerland (March-April 2020). RT-PCR tests were carried out on individuals suspected of having SARS-CoV-2 according to the testing strategy at that time. Logistic regressions were performed to test the association of smoking and testing positive for SARS-CoV-2 and further adjusted for comorbidities, socioeconomic and demographic factors. The sample included 5,169 participants; 60% were women and the mean age was 41 years. The unadjusted OR for testing positive for SARS-CoV-2 was 0.46 (CI: 0.38-0.54). After adjustment for comorbidities, socioeconomic and demographic factors, smoking was still negatively associated with testing positive for SARS-CoV-2 (OR: 0.44; CI: 0.35-0.77). Women (OR: 0.79; CI: 0.69-0.91), higher postal income (OR: 0.97; CI: 0.95-0.99), having respiratory (OR: 0.68; CI: 0.55-0.84) and immunosuppressive disorders (OR: 0.63; CI: 0.44-0.88) also showed independent negative associations with a positive test for SARS-CoV-2. Smoking was negatively associated with a positive test for SARS-CoV-2 independently of comorbidities, socioeconomic and demographic factors. Since having respiratory or immunosuppressive conditions and being females and healthcare workers were similarly negatively associated with SARS-CoV-2 positive testing, we hypothesize that risk factor-related protective or testing behaviors could have induced a negative association with SARS-CoV-2.

Network Analysis of Outpatients to Identify Predictive Symptoms and Combinations of Symptoms Associated With Positive/Negative SARS-CoV-2 Nasopharyngeal Swabs.

Background: Limited data exist on early predictive clinical symptoms or combinations of symptoms that could be included in the case definition of coronavirus disease 2019 (COVID-19), particularly for mild-to-moderate disease in an outpatient setting. Methods: A cohort study of individuals presenting with clinical symptoms to one of the largest dedicated networks of COVID-19 test centers in Geneva, Switzerland, between March 2 and April 23, 2020. Individuals completed a symptom questionnaire, received a nurse-led check-up, and nasopharyngeal swabs were obtained. An analysis of clinical features predicting the positivity and negativity of the SARS-CoV-2 RT-PCR test was performed to determine the relationship between symptoms and their combinations. Results: Of 3,248 patients included (mean age, 42.2 years; 1,504 [46.3%] male), 713 (22%) had a positive RT-PCR; 1,351 (41.6%) consulted within 3 days of symptom onset. The strongest predictor of a positive SARS-CoV-2 RT-PCR was anosmia, particularly in early disease, followed by fever, myalgia, and cough. Symptoms predictive of a negative test were breathing difficulties, abdominal symptoms, thoracic pain and runny nose. Three distinct networks of symptoms were identified, but did not occur together: respiratory symptoms; systemic symptoms related to fever; and other systemic symptoms related to anosmia. Conclusions: Symptoms and networks of symptoms associated with a positive/negative SARS-CoV-2 RT-PCR are emerging and may help to guide targeted testing. Identification of early COVID-19-related symptoms alone or in combination can contribute to establish a clinical case definition and provide a basis for clinicians and public health authorities to distinguish it from other respiratory viruses early in the course of the disease, particularly in the outpatient setting.

Equity in access to COVID-19 testing for undocumented migrants and homeless persons during the initial phase of the pandemic.

INTRODUCTION: The COVID-19 pandemic has excessively affected socially and economically deprived groups of population. There is a dearth of empirical evidence about the effect of policies regulating access to care for such groups. This study aims to document the impact of an equity-based strategy to facilitate access to COVID-19 testing during the initial phase of the pandemic. MATERIALS AND METHODS: This cross-sectional study included all outpatients presenting at the Geneva University Hospital for COVID-19 testing in March and April 2020. We compared the testing program uptake, and the proportions of positive tests and of complicated clinical course between undocumented migrants and homeless persons and the general population. RESULTS: Underserved patients represented 215 (6.5%) of the 3299 participants. There was no significant difference in the time-lag between the first COVID-19 evocative symptoms and the testing, the number of symptoms at presentation, and the participation to the program during its first month of implementation. The proportion of positive tests was significantly higher (32.1% vs. 23.6%, p=.005) among undeserved while the proportion of complicated clinical course was comparable. CONCLUSIONS: Equity-based policies can mitigate disparities in access to care during the pandemic and reduce the spread of COVID-19 in the community by early detection of infective cases. The high proportion of positive test in underserved patients highlight the need to include such groups into future COVID-19 immunization program. More globally, this study highlights the opportunity to reinforce healthcare systems to adapt to new threats and to contribute to a better protection of the whole of society.

Vulnerable patients forgo health care during the first wave of the Covid-19 pandemic.

During the first wave of the Covid-19 pandemic, access to health care was limited, and patients encountered important delays for scheduled appointments and care. Empirical data relying on patients' reports of forgoing health care are scarce. This study investigated Covid-19-related self-reports of forgoing health care in a sample of vulnerable outpatients in Geneva, Switzerland. We collected data from 1167 adult outpatients, including clinically vulnerable patients (with chronic diseases), geriatric patients (involved in a health care network for people aged 60 or older), and socially vulnerable patients (involved in a migrant health program or a mobile outpatient community care center) in June 2020. Data on sociodemographic factors, forgoing health care, and anti-SARS-CoV-2 antibodies were collected. Of the patients, 38.5% reported forgoing health care. Forgoing health care was more frequent for younger patients, women, patients with a low level of education, and patients with a chronic disease (p < .001). There was no significant association between the presence of anti-SARS-CoV-2 antibodies and forgoing health care (p = .983). As the decrease in routine management of patients might have important and unpredictable adverse health consequences, avoiding delayed health care is crucial.