Identification of a measles variant displaying mutations impacting molecular diagnostics, Geneva, Switzerland, 2023.

Real-time PCR is one of the most widely used techniques to diagnose measles cases. Here we report measles virus variants with three genetic mutations in the reverse primer annealing site of a widely used PCR. The mutations result in a slight loss of the PCR sensitivity. Variants bearing the three mutations presently circulate in different countries since at least the end of 2021. Our findings highlight the usefulness of molecular surveillance in monitoring if oligonucleotides in diagnostic tests remain adequate.

Prevalence of Post-Coronavirus Disease Condition 12 Weeks After Omicron Infection Compared With Negative Controls and Association With Vaccination Status.

BACKGROUND: Post-coronovirus disease (COVID) symptoms can persist several months after severe acute respiratory syndrome coronavirus 2 infection. Little is known, however, about the prevalence of post-COVID condition following infections from Omicron variants and how this varies according to vaccination status. This study evaluates the prevalence of symptoms and functional impairment 12 weeks after an infection by Omicron variants (BA.1 and BA.2) compared with negative controls tested during the same period. METHODS: Outpatient individuals who tested positive or negative for COVID-19 infection between December 2021 and February 2022 at the Geneva University Hospitals were followed 12 weeks after their test date. RESULTS: Overall, 11.7% of Omicron cases had symptoms 12 weeks after the infection compared with 10.4% of individuals who tested negative during the same period (P < .001), and symptoms were much less common in vaccinated versus nonvaccinated individuals with Omicron infection (9.7% vs 18.1%; P < .001). There were no significant differences in functional impairment at 12 weeks between Omicron cases and negative controls, even after adjusting for multiple potential confounders. CONCLUSIONS: The differential prevalence of post-COVID symptoms and functional impairment attributed to Omicron BA.1 and BA.2 infection is low when compared with negative controls. Vaccination is associated with lower prevalence of post-COVID symptoms.

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV.

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.

Risk of Reinfection After Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Population-based Propensity-score Matched Cohort Study.

BACKGROUND: Serological assays detecting anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are being widely deployed in studies and clinical practice. However, the duration and effectiveness of the protection conferred by the immune response remains to be assessed in population-based samples. To estimate the incidence of newly acquired SARS-CoV-2 infections in seropositive individuals as compared to seronegative controls, we conducted a retrospective longitudinal matched study. METHODS: A seroprevalence survey including a representative sample of the population was conducted in Geneva, Switzerland, between April and June 2020, immediately after the first pandemic wave. Seropositive participants were matched one-to-two to seronegative controls, using a propensity-score including age, gender, immunodeficiency, body mass index (BMI), smoking status, and education level. Each individual was linked to a state-registry of SARS-CoV-2 infections. Our primary outcome was confirmed infections occurring from serological status assessment to the end of the second pandemic wave (January 2021). RESULTS: Among 8344 serosurvey participants, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow-up of 35.6 (standard deviation [SD] 3.2) weeks, 7 out of 498 (1.4%) seropositive subjects had a positive SARS-CoV-2 test, of whom 5 (1.0%) were classified as reinfections. In contrast, the infection rate was higher in seronegative individuals (15.5%, 154/996) during a similar follow-up period (mean 34.7 [SD 3.2] weeks), corresponding to a 94% (95% confidence interval [CI]: 86%- 98%, P < .001) reduction in the hazard of having a positive SARS-CoV-2 test for seropositives. CONCLUSIONS: Seroconversion after SARS-CoV-2 infection confers protection against reinfection lasting at least 8 months. These findings could help global health authorities establishing priority for vaccine allocation.

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.

[Specificities of SARS-CoV-2 infection in elderly patients]. / Spécificités de l'infection à SARS-CoV-2 chez les patients âgés.

COVID-19 has strongly impacted the elderly population with a particularly high mortality rate due to several reasons: sometimes difficult and delayed diagnosis, multimorbidity, immunosenescence, frailty, which seems to be a better prognostic marker than age. Treatment includes both therapies specifically directed against SARS CoV-2 (monoclonal antibodies, systemic corticosteroids, tocilizumab, remdesivir) and symptomatic and palliative treatments. Vaccination, especially the booster, is essential to reduce the risk of infection and severe forms. The emergence of variants is a challenge because of their impact on vaccine and treatment efficacy. Specific studies in the elderly are needed to improve their management.

Le Covid-19 a fortement impacté la population âgée avec un taux de mortalité particulièrement élevé dû à plusieurs raisons: diag nostic parfois difficile et retardé, multimorbidité, immunosénescence, fragilité, qui semble d'ailleurs être un meilleur marqueur pronostique que l'âge. Le traitement inclut autant des thérapies spécifiquement dirigées contre le SARS CoV-2 (anticorps monoclonaux, corticothérapie systémique, tocilizumab, remdésivir) que des traitements symptomatiques et palliatifs. La vaccination, notamment le rappel, est primordiale pour diminuer le risque infectieux et les formes graves. L'apparition de variants représente un défi en raison de leur impact sur l'efficacité du vaccin et des traitements. Des études réalisées spécifiquement chez les sujets âgés sont nécessaires pour améliorer leur prise en charge.

Puumala Virus Infection in Family, Switzerland.

We report 3 cases of Puumala virus infection in a family in Switzerland in January 2019. Clinical manifestations of the infection ranged from mild influenza-like illness to fatal disease. This cluster illustrates the wide range of clinical manifestations of Old World hantavirus infections and the challenge of diagnosing travel-related hemorrhagic fevers.

[Treatment of SARS-CoV-2 in paediatrics : what is the evidence to date?] / Traitement du SARS-CoV-2 en pédiatrie : quelles évidences et quelle utilité ?

Although SARS-CoV-2 infects individuals of all ages, children show less severe symptoms. Nevertheless, the very rare COVID-19 severe cases in paediatrics require our full attention. Much research has been conducted and is still ongoing on effective treatments. On the antiviral front, no molecule has been proven effective yet and the results of several studies on the benefit of monoclonal antibodies and convalescent plasma are pending. On the side of immunomodulators, the benefit of steroids has been demonstrated for patients severely ill. Other molecules are being investigated. However, all these studies focused on adults and paediatric data are warranted.

Bien que le SARS-CoV-2 infecte des individus de tout âge, les enfants montrent des symptômes moins sévères. Les cas de Covid-19 graves sont exceptionnels en pédiatrie mais nécessitent néanmoins toute notre attention. De nombreuses études ont été menées et sont encore en cours à la recherche de traitements efficaces. Sur le plan antiviral, aucune molécule n'a fait ses preuves à l'heure actuelle. Les résultats de plusieurs travaux sur le bénéfice des anticorps monoclonaux et du plasma convalescent sont attendus avec impatience. Du côté des immunomodulateurs, le bénéfice des stéroïdes a pu être démontré chez les patients présentant une infection pulmonaire sévère. D'autres molécules sont à l'étude. Cependant, toutes ces études s'intéressent aux adultes et les données pédiatriques sont quasiment inexistantes.

Maladies infectieuses.

What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project «â€…PIRATE ¼ indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.

Que dire des nouveautés en maladies infectieuses en 2020 ? L'année a été marquée évidemment par la pandémie du Covid-19, motivant une revue dans cet article, des connaissances actuelles sur le SARS-CoV-2 et de sa prise en charge. Les résultats du projet suisse PIRATE ont montré une non-infériorité pour les bactériémies Gram négatif entre une antibiothérapie de 7 jours ou guidée par la CRP face à une durée de 14 jours. Une étude mongolienne n'a pas permis de montrer le bénéfice d'une substitution en vitamine D chez les enfants sur l'incidence de la tuberculose. Le baloxavir, un nouvel antiviral contre la grippe, a été approuvé par Swissmedic. Et enfin, des nouvelles recommandations américaines sur le monitoring thérapeutique de la vancomycine et sur le dépistage universel de l'hépatite C ont été publiées.

[Ebola : an uncontrolled outbreak despite vaccines and new treatments]. / Ebola : vaccin et traitements efficaces mais épidémie persistante.

The Ebola virus disease outbreak raging in the North-Kivu and Ituri provinces of Democratic Republic of the Congo already accounts for more than 3400 cases, from which 2200 died. Major progress have been achieved since the 2014-2016 West Africa outbreak. A vaccine is now approved by the European Medicine Agency and has been administered to more than 250 000 volunteers in the field. New specific antiviral treatments are now available. Ebola virus disease shifted from a deadly disease to a preventable, curable one. However, the long-lasting conflict and repeated attacks of civilians and health workers hampers the control of the outbreak.

L'épidémie de maladie à virus Ebola (MVE) qui sévit dans les provinces du Nord-Kivu et de l'Ituri en République démocratique du Congo dans le nord-est du pays a déjà touché plus de 3400 personnes dont plus de 2200 sont décédées. Depuis la grande épidémie d'Afrique de l'Ouest en 2014-2016, d'énormes progrès ont été faits en termes de prise en charge et de prévention de la maladie. Il existe maintenant un vaccin homologué en Europe et d'autres sont en développement. L'efficacité des traitements spécifiques permet de modifier le devenir des patients infectés. De mortelle, la MVE est devenue évitable et guérissable. L'insé- curité de la région, zone de conflit depuis plus de 30 ans, rend cependant le contrôle de l'épidémie difficile.

Clinical Management of Ebola Virus Disease in the United States and Europe.

BACKGROUND: Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS: We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015. RESULTS: A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%. CONCLUSIONS: Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived.

Ebola Virus Shedding and Transmission: Review of Current Evidence.

BACKGROUND: The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community. METHODS: We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission. FINDINGS: Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission.

Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone.

BACKGROUND: Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone. METHODS: A survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors. RESULTS: A total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness. CONCLUSIONS: Post-EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness.

[Infections disease update: 2014 is viral]. / Infectiologie en 2014: une année virale.

Chikungunya's phenomenal dissemination imposes now infection suspicion when returning from endemic areas. Colorectal cancer screening may be dependent of the microbiome. Even a small amount of E. coli in catheter sampled urine is predictive for a urinary infection. Prevention of pharyngitis suppurated late complications doesn't justify systematic antimicrobial therapy. A bitherapy is probably better for severe community acquired pneumonias. Due to epidemiology and resistances, management of gonorrhoea has changed. Enterovirus 68 is particular because of its almost exclusive lung tropism in children. The question is no longer how to treat hepatitis C but which patients to treat and when. Pritelivir clearly improves herpes genitalis symptoms. The first confirmed case of Ebola has reach our contry.

Hepatitis E Virus Infection Epidemiology in Recipients of Allogeneic Hematopoietic Cell Transplant.

Among 292 recipients of allogeneic hematopoietic cell transplant (2018-2022), 64 (21.9%) tested positive for anti-hepatitis E virus (HEV) immunoglobulin G. Among 208 recipients tested by plasma/serum HEV polymerase chain reaction (2012-2022), 3 (1.4%) primary HEV infections were diagnosed; in 1 patient, plasma HEV polymerase chain reaction relapsed positive for 100 days. HEV infection remains rare albeit associated with persistent viral replication.

Trends in management and outcomes of COVID patients admitted to a Swiss tertiary care hospital.

Two successive COVID-19 flares occurred in Switzerland in spring and autumn 2020. During these periods, therapeutic strategies have been constantly adapted based on emerging evidence. We aimed to describe these adaptations and evaluate their association with patient outcomes in a cohort of COVID-19 patients admitted to the hospital. Consecutive patients admitted to the Geneva Hospitals during two successive COVID-19 flares were included. Characteristics of patients admitted during these two periods were compared as well as therapeutic management including medications, respiratory support strategies and admission to the ICU and intermediate care unit (IMCU). A mutivariable model was computed to compare outcomes across the two successive waves adjusted for demographic characteristics, co-morbidities and severity at baseline. The main outcome was in-hospital mortality. Secondary outcomes included ICU admission, Intermediate care (IMCU) admission, and length of hospital stay. A total of 2'983 patients were included. Of these, 165 patients (16.3%, n = 1014) died during the first wave and 314 (16.0%, n = 1969) during the second (p = 0.819). The proportion of patients admitted to the ICU was lower in second wave compared to first (7.4 vs. 13.9%, p < 0.001) but their mortality was increased (33.6% vs. 25.5%, p < 0.001). Conversely, a greater proportion of patients was admitted to the IMCU in second wave compared to first (26.6% vs. 22.3%, p = 0.011). A third of patients received lopinavir (30.7%) or hydroxychloroquine (33.1%) during the first wave and none during second wave, while corticosteroids were mainly prescribed during second wave (58.1% vs. 9.1%, p < 0.001). In the multivariable analysis, a 25% reduction of mortality was observed during the second wave (HR 0.75; 95% confidence interval 0.59 to 0.96). Among deceased patients, 82.3% (78.2% during first wave and 84.4% during second wave) died without beeing admitted to the ICU. The proportion of patients with therapeutic limitations regarding ICU admission increased during the second wave (48.6% vs. 38.7%, p < 0.001). Adaptation of therapeutic strategies including corticosteroids therapy and higher admission to the IMCU to receive non-invasive respiratory support was associated with a reduction of hospital mortality in multivariable analysis, ICU admission and LOS during the second wave of COVID-19 despite an increased number of admitted patients. More patients had medical decisions restraining ICU admission during the second wave which may reflect better patient selection or implicit triaging.

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.

Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs.

Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.