[Motivational factors for early option choice by laboratory medicine residents in France]. / Facteurs de motivation pour le choix d'option précoce par les internes de biologie médicale en France.

In France, both students from medicine and pharmacy background can have access to the residency in laboratory medicine (LM). The current curriculum of LM residency includes an early choice of option after the first two years of residency, which subsequently guides the rest of the training. This study aimed to analyze these choice and motivational factors, since its implementation in 2017. A national survey was conducted among LM residents and former residents who underwent the early option choice process. A questionnaire was developed and sent to residents via Google Forms. Several groups of items corresponding to potential motivational factors were included and rated on a 5-point Likert scale. A psychometric analysis allowed to identify the main motivational factors. A total of 178 responses from 24 residency regions were recorded. The median age was 28 years, with a slight female predominance (52%), and three-quarters of the participants had a pharmacy training background. The "hematology and immunology" option was the most chosen (35%). The psychometric analysis enabled to identify 7 motivational factors, and the most important is the training during the residency, which weights approximately 21 % in the choice. Several associations have been observed between the motivational factors and the background training, origin, the chosen option and the planned career. Several factors influence the choice of early option among LM residents, and some of these factors are associated with the background training, origin, chosen option and planned career.

Comparison of two automated commercial assays for routine detection of anti-hepatitis E Virus IgM antibodies in clinical samples.

Diagnosis of hepatitis E virus (HEV) infection relies first on detection of IgM antibodies (Ab), sometimes completed with HEV RNA detection. This study aimed to compare the performance of two automated anti-HEV IgM Ab assays. Correlation between Virclia® (Vircell) and Liaison® (Diasorin) assays was carried out on 178 routine clinical samples. Both assays were run on 67 samples from HEV RT-PCR (Altona) screened patients, and 52 Wantai® EIA (Euroimmun) tested samples. An excellent correlation was observed between both assays with an overall agreement of 96.6% (172/178), and a kappa coefficient at 0.93. In HEV RNA positive group (n=43), IgM detection rate was 93.3% (14/15) in immunocompetent patients, with both assays. In immunocompromised patients, detection rate was 75% (21/28) and 71.4% (20/28) using Virclia® and Liaison XL® assays, respectively. Virclia® and Liaison® anti-HEV IgM assays have similar performance for the detection of anti-HEV IgM Ab.

Antibody-dependent enhancement and neutralization against CVB4 investigated in vitro and in silico through an agent-based model.

The infection with coxsackievirus B4 (CVB4) can be enhanced in vitro by antibodies directed against the viral capsid protein VP4. In peripheral blood mononuclear cells, antibody-dependent enhancement (ADE) of CVB4 infection leads to the production of interferon alpha (IFN-α). To investigate ADE of CVB4-induced production of IFN-α, an agent-based model was constructed with enhancing and neutralizing antibodies. The model recapitulates viral neutralization and ADE in silico. The enhancing and neutralizing activities of serum samples were evaluated in vitro to confront the model predictions with experimental results. Increasing the incubation time of CVB4 with serum samples improves virus neutralization in silico as well as in vitro. It also results in ADE at lower antibody numbers in silico, which is confirmed in vitro with IFN-α production at lower serum concentrations. Furthermore, incubation of CVB4 with serum at a low temperature does not induce IFN-α production in vitro. Thus, taken together our results suggest that enhancing antibodies bind cryptic epitopes, more accessible with longer incubation time and at higher temperature due to changes in capsid conformation, consistent with previous results indicating that enhancing antibodies are anti-VP4 antibodies.

Frequency and burden of disease for SARS-CoV-2 and other viral respiratory tract infections in children under the age of 2 months.

OBJECTIVE: To evaluate the frequency and burden of disease of SARS-CoV-2 and other respiratory viruses in children under the age of 2 months. METHODS: A retrospective, cross-sectional, single-center study was conducted between March 2021 and February 2022. All children under the age of 2 months and tested for SARS-CoV-2 were included. The frequency of SARS-CoV-2, of other respiratory viruses and the burden of disease caused by SARS-CoV-2 and other respiratory viruses were evaluated. RESULTS: Seven hundred and twenty-seven children with an RT-PCR test for SARS-CoV-2 were included (mean age: 0.9 months (±0.6); boys: 57%); 514 (71%) in the emergency room and 213 (29%) in hospital. Among them, 62 (8.5%) had a positive RT-PCR test for SARS-CoV-2, more often in the Omicron period (23%) than in the Alpha period (4%). Of the 565 (78%) with a multiplex RT-PCR test for other viruses, 325 (58%) were positive. Children with a positive SARS-CoV-2 were less likely to have required respiratory support (p = 0.001), enteral nutrition (p = 0.03), or intensive care admission (p = 0.01) and had a shorter hospital stay than children with other respiratory viruses (5 days vs. 7 days, p = 0.007). CONCLUSION: In this young population of children, SARS-CoV-2 infection was less frequent and less severe than other viral respiratory infections.

Four complete genomes of human parvovirus B19 from amniotic fluid specimens.

We report the sequences of four complete genomes of parvovirus B19, extracted from human amniotic fluid specimens collected from pregnant women with abnormal ultrasound features in France. The genome sequences are 5,596 nucleotides long and include long terminal repeats. Several amino acid substitutions were observed in nonstructural protein (NS1).

Absence of association between persistent skin lesion and virological replication in severe disseminated monkeypox infection in solid organ transplant recipient.

The Monkeypox (mpox) virus outbreak has been controlled worldwide. We report the case of a combined pancreas-kidney transplant recipient who presented a severe and prolonged cutaneous infection with onset of 3 successive rashes while receiving tecovirimat therapy. During follow-up, skin lesions, blood and throat samples were collected. Viral culture and mpox PCR were performed. No positive viral culture was obtained from blood and throat. The lowest mpox CT-values were obtained early after onset of skin lesions and were more likely to be associated with positive viral cultures. Furthermore, we observed persistent skin lesions up to 3 months. On these persistent lesions, mpox PCR positives were obtained but were not associated with positive viral culture after 23 days. In this immunocompromised host, who was receiving tecovirimat, in accordance with existing recommendations a 21-day isolation period appeared to be adapted. That said, isolation should not be systematically extended if complete healing of skin lesions has not been achieved.

Viruses and Endocrine Diseases.

Viral infections have been frequently associated with physiological and pathological changes in the endocrine system for many years. The numerous early and late endocrine complications reported during the current pandemic of coronavirus disease 2019 (COVID-19) reinforce the relevance of improving our understanding of the impact of viral infections on the endocrine system. Several viruses have been shown to infect endocrine cells and induce endocrine system disturbances through the direct damage of these cells or through indirect mechanisms, especially the activation of the host antiviral immune response, which may lead to the development of local or systemic inflammation or organ-specific autoimmunity. In addition, endocrine disorders may also affect susceptibility to viral infections since endocrine hormones have immunoregulatory functions. This review provides a brief overview of the impact of viral infections on the human endocrine system in order to provide new avenues for the control of endocrine diseases.

Secondary syphilis in a 14-month-old girl and child-to-mother transmission.

Syphilis cases in childhood are usually associated with congenital transmission. Acquired transmission is uncommon, and primarily related to sexual abuse or close contact/nursing with infected family members. We here describe a case of syphilis in a 14-month-old girl resulting from intrafamilial infection, with a subsequent transmission to her mother.

Respiratory virus detection in returning travelers and pilgrims from the Middle East.

BACKGROUND: Pilgrims travelling to Saudi Arabia are commonly infected with respiratory viruses. Since the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012, patients with acute respiratory symptoms returning from an endemic area can be suspected to be infected by this virus. METHODS: 98 patients suspected to have MERS-CoV infection from 2014 to 2019 were included in this retrospective cohort study. Upper and lower respiratory tract samples were tested by real-time RT-PCR for the detection of MERS-CoV and other respiratory viruses. Routine microbiological analyses were also performed. Patient data were retrieved from laboratory and hospital databases retrospectively. RESULTS: All patients with suspected MERS-CoV infection travelled before their hospitalization. Most frequent symptoms were cough (94.4%) and fever (69.4%). 98 specimens were tested for MERS-CoV RNA and none of them was positive. Most frequently detected viruses were Enterovirus/Rhinovirus (40/83; 48.2%), Influenzavirus A (34/90; 37.8%) and B (11/90; 12.2%), H-CoV (229E and OC43 10/83; 12% and 7/83; 8.4%, respectively). CONCLUSION: From 2014 to 2019, none of 98 patients returning from endemic areas was MERS-CoV infected. However, infections with other respiratory viruses were frequent, especially with Enterovirus/Rhinoviruses and Influenzaviruses.

Serum neutralization of SARS coronavirus 2 Omicron sublineages BA.1 and BA.2 and cellular immune responses 3 months after booster vaccination.

OBJECTIVES: We investigated serum neutralizing activity against BA.1 and BA.2 Omicron sublineages and T cell response before and 3 months after administration of the booster vaccine in healthcare workers (HCWs). METHODS: HCWs aged 18-65 years who were vaccinated and received booster doses of the BNT162b2 vaccine were included. Anti-SARS coronavirus 2 IgG levels and cellular response (through interferon γ ELISpot assay) were evaluated in all participants, and neutralizing antibodies against Delta, BA.1, and BA.2 were evaluated in participants with at least one follow-up visit 1 or 3 months after the administration of the booster dose. RESULTS: Among 118 HCWs who received the booster dose, 102 and 84 participants attended the 1-month and 3-month visits, respectively. Before the booster vaccine dose, a low serum neutralizing activity against Delta, BA.1, and BA.2 was detectable in only 39/102 (38.2%), 8/102 (7.8%), and 12/102 (11.8%) participants, respectively. At 3 months, neutralizing antibodies against Delta, BA.1, and BA.2 were detected in 84/84 (100%), 79/84 (94%), and 77/84 (92%) participants, respectively. Geometric mean titres of neutralizing antibodies against BA.1 and BA.2 were 2.2-fold and 2.8-fold reduced compared with those for Delta. From 1 to 3 months after the administration of the booster dose, participants with a recent history of SARS coronavirus 2 infection (n = 21/84) had persistent levels of S1 reactive specific T cells and neutralizing antibodies against Delta and BA.2 and 2.2-fold increase in neutralizing antibodies against BA.1 (p 0.014). Conversely, neutralizing antibody titres against Delta (2.5-fold decrease, p < 0.0001), BA.1 (1.5-fold, p 0.02), and BA.2 (2-fold, p < 0.0001) declined from 1 to 3 months after the administration of the booster dose in individuals without any recent infection. DISCUSSION: The booster vaccine dose provided significant and similar response against BA.1 and BA.2 Omicron sublineages; however, the immune response declined in the absence of recent infection.

Oropharyngeal samples versus lesion specimens at diagnosis in patients infected with monkeypox virus in Northern France.

The ongoing outbreak of monkeypox virus (MPXV) is the largest one in historically non-endemic countries. Early reports described atypical epidemiological and clinical presentations. We investigated MPXV DNA detection in oropharyngeal samples (OPS), and compared the viral load to that in lesion samples at diagnosis in patients infected with MPXV. We retrospectively included patients suspected to have monkeypox in Northern France, who underwent a MPXV PCR in the Virology Laboratory, University Hospital of Lille, from May 23 to August 18, 2022. Overall, a total of 228 patients (376 samples) were included. A positive result in at least one sample was found in 138 patients (60.5%). We compared PCR results between OPS and lesion samples (i.e., cutaneous or anal/rectal samples) in patients with both samples. A positive result in OPS was observed in 54 out of 60 patients (90%). The viral load in OPS (median Ct value = 29.5; interquartile range [IQR] = 24.7-34) was significantly lower than that in lesion samples (median Ct  value = 17.8; IQR = 16.3 and 19.7) (p < 0.0001). This report shows that pharyngeal sampling does not bring additional information for the initial diagnosis in patients presenting with typical lesions.

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients.

Letermovir is the first approved drug for cytomegalovirus (CMV) infection prophylaxis in adult patients who are CMV positive undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Because CMV infection risk varies from patient to patient, we evaluated whether a risk-based strategy could be effective. In this single-center study, all consecutive adult patients who were CMV positive and underwent allo-HCT between 2015 and 2021 were included. During period 1 (2015-2017), letermovir was not used, whereas during period 2 (2018-2021), letermovir was used in patients at high risk but not in patients at low risk, except in those receiving corticosteroids. In patients at high risk, the incidence of clinically significant CMV infection (csCMVi) in period 2 was lower than that in period 1 (P < .001) by week 14 (10.5% vs 51.6%) and week 24 (16.9% vs 52.7%). In patients at low risk, although only 28.6% of patients received letermovir in period 2, csCMVi incidence was also significantly lower (P = .003) by week 14 (7.9% vs 29.0%) and week 24 (11.2% vs 33.3%). Among patients at low risk who did not receive letermovir (n = 45), 23 patients (51.1%) experienced transient positive CMV DNA without csCMVi, whereas 17 patients (37.8%) experienced negative results. In both risk groups, the 2 periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and nonrelapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in patients at high risk but allows some patients at low risk to not use letermovir.

Combating coxsackievirus B infections.

Coxsackieviruses B (CVB) are small, non-enveloped, single-stranded RNA viruses belonging to the Enterovirus genus of the Picornaviridae family. They are common worldwide and cause a wide variety of human diseases ranging from those having relatively mild symptoms to severe acute and chronic pathologies such as cardiomyopathy and type 1 diabetes. The development of safe and effective strategies to combat these viruses remains a challenge. The present review outlines current approaches to control CVB infections and associated diseases. Various drugs targeting viral or host proteins involved in viral replication as well as vaccines have been developed and shown potential to prevent or combat CVB infections in vitro and in vivo in animal models. Repurposed drugs and alternative strategies targeting miRNAs or based on plant extracts and probiotics and their derivatives have also shown antiviral effects against CVB. In addition, clinical trials with vaccines and drugs are underway and offer hope for the prevention or treatment of CVB-induced diseases.

[Coxsackievirus B infection and pathogenesis of type 1 diabetes]. / Infection à coxsackievirus B et pathogenèse du diabète de type 1.

Epidemiological and experimental studies suggest that enteroviruses (EV) and particularly coxsackieviruses B (CVB) are likely to trigger or accelerate the onset of islet autoimmunity and the development of type 1 diabetes (T1D) in genetically susceptible individuals. Several mutually non-exclusive mechanisms have been proposed to explain the involvement of CVB in the pathogenesis of T1D. CVB can infect and persist in the intestine, thymic cells, monocytes/macrophages, ductal cells and pancreatic ß-cells, which leads to structural or functional alterations of these cells. A chronic inflammatory response and disruption of tolerance towards ß-cells due to CVB infections are able to promote the recruitment and activation of pre-existing autoreactive T-cells and the destruction of ß-cells. Vaccine or therapeutic strategies to control EV infections have been developed and open perspectives for the prevention or treatment of T1D.

Evaluation of a rapid semiquantitative lateral flow assay for the prediction of serum neutralizing activity against SARS-CoV-2 variants.

BACKGROUND: Neutralizing antibodies (NAbs) against SARS-CoV-2 have been shown to correlate with protection against infection. Simple tools such as lateral flow assays (LFA) that can accurately measure NAbs may be useful for monitoring anti-SARS-CoV-2 immunity in the future. OBJECTIVES: We assessed the performance of the ichroma™ COVID-19 nAb test, a rapid semiquantitative LFA, for the prediction of serum neutralizing activity against SARS-CoV-2 variants. STUDY DESIGN: Serum samples were collected from COVID-19 recovered patients and vaccinated individuals. The result of the ichroma assay was provided as inhibition rate, and was compared to anti-SARS-CoV-2 IgG levels, and NAbs against Alpha, Delta and Omicron variants. RESULTS: A total of 90 sera from recovered unvaccinated patients and 209 sera from the vaccine cohort were included in this study. In post-infection samples, the ichroma inhbition rate was found to be correlated with IgG levels (ρ = 0.83), and with anti-Alpha NAbs levels (ρ = 0.78). In the vaccine cohort, a good correlation was also observed between the ichroma inhibition rate and IgG levels (ρ = 0.84), as well as NAbs against Alpha (ρ = 0.62), Delta (ρ = 0.88) and Omicron (ρ = 0.74). An ichroma inhbition rate of 77.2%, 90.8% and 99.6% accurately predicted neutralization against Alpha, Delta and Omicron variants respectively. CONCLUSIONS: The ichroma™ COVID-19 nAb assay, with appropriate variant cut-offs, can be useful for the monitoring of anti-SARS-CoV-2 immunization and may provide a rapid prediction of protection, especially in individuals with significant levels of NAbs.

Rapid syndromic testing for respiratory viral infections in children attending the emergency department during COVID-19 pandemic in Lille, France, 2021-2022.

OBJECTIVES: Viral respiratory infections are common in children, and usually associated with non-specific symptoms. Respiratory panel-based testing was implemented during the COVID-19 pandemic, for the rapid differentiation between SARS-CoV-2 and other viral infections, in children attending the emergency department (ED) of the teaching hospital of Lille, northern France, between February 2021 and January 2022. METHODS: Samples were collected using nasopharyngeal swabs. Syndromic respiratory testing was performed with two rapid multiplex molecular assays: the BioFire® Respiratory Panel 2.1 - plus (RP2.1 plus) or the QIAstat-Dx Respiratory SARS-CoV-2 Panel. SARS-CoV-2 variant was screened using mutation-specific PCR-based assays and genome sequencing. RESULTS: A total of 3517 children were included in the study. SARS-CoV-2 was detected in samples from 265 children (7.5%). SARS-CoV-2 infected patients were younger than those without SARS-CoV-2 infection (median age: 6 versus 12 months, p < 0.0001). The majority of infections (61.5%) were associated with the Omicron variant. The median weekly SARS-CoV-2 positivity rate ranged from 1.76% during the Alpha variant wave to 24.5% with the emergence of the Omicron variant. Most children (70.2%) were treated as outpatients, and seventeen patients were admitted to the intensive care unit. Other respiratory viruses were more frequently detected in SARS-CoV-2 negative children than in positive ones (82.1% versus 37.4%, p < 0.0001). Human rhinovirus/enterovirus and respiratory syncytial virus were the most prevalent in both groups. CONCLUSIONS: We observed a low prevalence of SARS-CoV-2 infection in children attending pediatric ED, despite the significant increase due to Delta and Omicron variants, and an important circulation of other respiratory viruses. Severe disease was overall rare in children.

A comparison of high-throughput SARS-CoV-2 sequencing methods from nasopharyngeal samples.

The COVID-19 pandemic caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten public health and burden healthcare systems worldwide. Whole SARS-CoV-2 genome sequencing has become essential for epidemiological monitoring and identification of new variants, which could represent a risk of increased transmissibility, virulence, or resistance to vaccines or treatment. Different next-generation sequencing approaches are used in SARS-CoV-2 sequencing, although with different ability to provide whole genome coverage without gaps and to reliably detect new variants. In this study, we compared the performance of three target enrichment methods (two multiplex amplification methods and one hybridization capture) using nasopharyngeal swabs from infected individuals. We applied these target enrichment methods to the same set of nasopharyngeal samples (N = 93) in high-throughput mode. SARS-CoV-2 genome was obtained using short-read next-generation sequencing. We observed that each method has some advantages, such as high mapping rate (CleanPlex and COVIDSeq) or absence of systematic variant calling error (SureSelect) as well as their limitations such as suboptimal uniformity of coverage (CleanPlex), high cost (SureSelect) or supply shortages (COVIDSeq). Nevertheless, each of the three target enrichment kits tested in this study yielded acceptable results of whole SARS-CoV-2 genome sequencing and either of them can therefore be used in prospective programs of genomic surveillance of SARS-CoV-2. Genomic surveillance will be crucial to overcoming the ongoing pandemic of COVID-19, despite its successive waves and continually emerging variants.