PURPOSE OF REVIEW:Flaviviruses are an increasing public health concern, responsible for a broad spectrum of human disease ranging from asymptomatic or mild febrile illness to severe neuroinvasive infections such as encephalitis. Flavivirus encephalitis is associated with substantial mortality and long-term neurological sequelae, yet no specific antiviral therapy is currently available. Diagnosis remains challenging because of transient viremia and serological cross-reactivity, and preventive strategies are unevenly implemented. This review summarizes recent advances in the diagnosis, prognostic assessment, treatment, and prevention of flavivirus-associated encephalitis. RECENT FINDINGS:Recent studies have reshaped diagnostic strategies through improved viral detection, including multimatrix molecular testing and metagenomic approaches, alongside better characterization of host-response markers in cerebrospinal fluid. Recent work has substantially refined understanding of host susceptibility, highlighting preexisting antitype I interferon autoantibodies as a major driver of severe disease across neurotropic flaviviruses, and identifying several biomarkers with potential prognostic value. Neuroimaging work has refined MRI pattern recognition across flaviviral encephalitis, with limited but evolving prognostic implications. While management remains largely supportive, the therapeutic pipeline is increasingly diverse, with growing interest in host-directed strategies. SUMMARY:Flavivirus encephalitis represents a major clinical challenge driven by host vulnerability, diagnostic complexity, and the absence of validated therapies. Integrating recent advances in diagnostics, risk stratification, and prevention is essential, while ongoing therapeutic development offers cautious optimism for future management.

This narrative review aims to provide an overview of current knowledge on mpox, emphasizing updated epidemiology and recent advances in treatment and prevention strategies, in light of the latest outbreaks. We searched PubMed and Google Scholar for publications on ‘Mpox’ and ‘Monkeypox’ up to June 5, 2025. Grey literature from governmental and health agencies was also accessed for outbreak reports and guidelines where published evidence was unavailable. Recent outbreaks have redefined mpox epidemiology. Whereas previous regional outbreaks were mainly driven by zoonotic spillover with limited household transmission and often affecting children, more recent outbreaks have involved sustained human-to-human transmission. Such transmission has occurred among men who have sex with men for clade IIb and within heterosexual networks for clade Ib outbreaks, and more recently clade Ia outbreaks, primarily through sexual contact. Clinical features have also shifted toward more localized lesions, prominently in the anogenital area. While mpox is usually self-limited, severe cases may occur in pregnant women, young children, and immunocompromised individuals. Mpox management primarily relies on supportive care. In patients with severe mpox, or at risk of, tecovirimat was widely recognized as the first-line therapy, although it has failed to demonstrate its effectiveness in recent randomized controlled trials. The Modified Vaccinia Ankara vaccine (two-dose regimen) has shown a favorable safety profile and promising efficacy data in preventing clade IIb mpox, including immunocompromised individuals. Mpox has transitioned from a neglected zoonosis to a re-emerging global health threat. Sustained surveillance, robust and targeted public health interventions, and equitable access to diagnostics, vaccines, and antiviral treatments are critical to managing potential future mpox outbreaks.

Chikungunya virus (CHIKV) is known to circulate in Africa, but there is little evidence of CHIKV transmission in Côte d’Ivoire. Using genomic data, we linked CHIKV cases imported in France from Côte d’Ivoire to a lineage from the West African genotype, likely been circulating in the country since July 2021.

IntroductionInflammation related to influenza virus infection can lead to multiple neurological presentations. Encephalitis is one of them, mostly accompanied by seizures, with different profiles depending on the epidemics and previous medical conditions.Materials and MethodsAll children presenting neurological symptoms and positive for influenza virus RNA detection in a respiratory sample between November 2018 and April 2023, hospitalized in the Department of Paediatric Neurology of Toulouse Children’s Hospital, were retrospectively analysed.ResultsAmong the 1,277 children diagnosed with influenza in our centre, 131 (10.3%) were hospitalized for neurological features. The year 2020-2021 was marked by zero incidence of positive influenza tests, associated with the COVID-19 pandemic. Among the 131 patients included, 71.6% were under 5 years old. Most of them (80.9%) were infected by influenza A virus. The first neurological symptoms were mainly seizures in 73.3% of patients. Possible or confirmed encephalitis was observed in 29% of cases, including one acute necrotizing encephalopathy. Few children (6.1%) presented with acute myositis. Twenty-seven patients (20.6%) had a personal history of significant previous neurological disorders. Most patients (88.5%) displayed a rapid favourable outcome, marked by the disappearance of their neurological symptoms within the first 2 days. Anti-epileptic drugs were introduced in 1.5% of cases, and adapted in 16.8%, mainly in patients with febrile status epilepticus and an abnormal EEG.ConclusionNeurological features were frequently associated with influenza infection in children; most were transient. Effects on long-term neurodevelopmental outcomes need to be clarified as our follow-up was limited, especially in children with pre-existing neurological conditions.

BackgroundSevere acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019, affects multiple organs. The virus enters cells through angiotensin-converting enzyme-2 and host factors present in genital organs, leading to concern over virus shedding in semen and reproductive function.ObjectivesTo investigate severe acute respiratory syndrome coronavirus 2 in semen from patients with a mild infection, identify the seminal infected cells, and explore the effect of the infection on sex hormones and semen parameters.Materials and methodsProspective study of 54 men with mild severe acute respiratory syndrome coronavirus 2 infection. Semen was collected at 7, 15, 30, 60, 90, 180, and 365 days after symptom onset, and severe acute respiratory syndrome coronavirus 2 RNA was measured in serum, saliva, urine, and semen. The presence of infectious severe acute respiratory syndrome coronavirus 2 in semen was assessed using Vero cell culture. Infected semen cells were identified using immunofluorescence against severe acute respiratory syndrome coronavirus 2 nucleoprotein antigen and cell markers. Semen characteristics as well as testosterone, inhibin B, luteinizing hormone, and follicle-stimulating hormone levels were determined.Results11% of patients had at least one severe acute respiratory syndrome coronavirus 2 RNA-positive semen. One patient had viral semen shedding up to day 90 after infection onset, with replication-competent virus isolated from semen and 40% cell fraction at day 7. After sperm preparation, 90% fraction was severe acute respiratory syndrome coronavirus 2 RNA-positive at days 7 and 15. The swim-up fraction was positive only on day 7. In semen, nucleoprotein antigen was detected mainly in exfoliated epithelial cells and less frequently in Sertoli cells. Sperm count and motile sperm count were lower at day 30 than at day 7. Round cells in semen were increased during the acute phase. At days 7 and 15, sperm count and motile sperm count were lower in severe acute respiratory syndrome coronavirus 2 RNA-positive semen compared with negative semen, while semen volume and follicle-stimulating hormone levels were increased. Long-term follow-up shows no evidence of a detrimental effect on hormonal or semen characteristics.Discussion and conclusion11% of patients with mild coronavirus disease 2019 who were not hospitalized had severe acute respiratory syndrome coronavirus 2 excretions in semen, which persisted for up to 90 days in one patient. No germ cells appeared infected by the virus, but the detection of nucleoprotein antigen-positive epithelial semen cells and Sertoli cells suggests genital tract infection. Albeit infrequent, semen may contain the replication-competent virus during the acute phase with potential risk of severe acute respiratory syndrome coronavirus 2 transmissions during sexual contact and assisted reproduction procedures. The effect of mild coronavirus disease 2019 on spermatogenesis and reproductive hormones was moderate and reversible.

BackgroundNecrotizing pneumonia (NP) is a serious and rare disease in children. Pediatric data on NP are limited and the impact of the 13-valent pneumococcal conjugate vaccine has been very poorly evaluated.Patients and methodsWe conducted a retrospective study at Toulouse University Hospital between 2008 and 2018. Children who presented with thin-walled cavities in the areas of parenchymal consolidation on imaging were included in the study.ResultsThe incidence of NP did not decrease during this period. Bacterial identification occurred in 56% of cases (14/25) and included six cases of Streptococcus pneumoniae, five of Staphylococcus aureus, two of Streptococcus pyogenes, and one of Streptococcus viridans. Streptococcus pneumoniae NP are more frequently associated with empyema/parapneumonic effusion compared to S. aureus NP (p = 0.02). Patients with S. pyogenes NP more often required volume expansion than did S. pneumoniae cases (p = 0.03). When comparing children born before and after implementation of the 13-valent pneumococcal conjugate vaccine, we identified a relative modification of the bacterial epidemiology, with an increase in the proportion of S. pyogenes NP and S. aureus NP and a decrease in the proportion of NP caused by S. pneumoniae.ConclusionFuture studies are needed to assess the epidemiology of NP in children. Continued surveillance of identified pneumococcal serotypes is essential to document epidemiological changes in the coming years.

INTRODUCTION:As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking.METHODS:We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily.RESULTS:Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes.CONCLUSION:No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.

We used variant typing polymerase chain reaction to describe the evolution of severe acute respiratory syndrome coronavirus 2 Omicron sublineages between December 2021 and mid-March 2022. The selective advantage of the BA.2 variant over BA.1 is not due to greater nasopharyngeal viral loads.

The Omicron variant differs from earlier strains of SARS-CoV-2 in the way it enters host cells and grows in vitro. We therefore reevaluated its diagnosis using saliva, nasopharyngeal swab (NPs), and anterior nasal swab (ANs) specimens from 202 individuals (64.9% symptomatic) tested at the Toulouse University Hospital SARS-CoV-2 drive-through testing center. All tests were done with the Thermo Fisher TaqPath COVID-19 reverse transcription-PCR (RT-PCR) kit. Overall, 92 subjects (45.5%) had one or more positive specimens. Global sensitivities of saliva, NPs, and ANs were 94.6%, 90.2%, and 82.6%, respectively. Saliva provided significantly greater sensitivity among symptomatic patients tested within 5 days of symptom onset (100%) than did ANs (83.1%) or NPs (89.8%). We obtained follow-up samples for 7/20 individuals with discordant results. Among them, 5 symptomatic patients were diagnosed positive on saliva sample only, soon after symptom onset; NPs and ANs became positive only later. Thus, saliva samples are effective tools for the detection of the Omicron variant. In addition to its many advantages, such as improved patient acceptance and reduced cost, saliva sampling could help limit viral spread through earlier viral detection. IMPORTANCE Diagnostic testing for SARS-CoV-2 is an essential component of the global strategy for the prevention and control of COVID-19. Since the beginning of the pandemic, numerous studies have evaluated the diagnostic sensitivity of different respiratory and oral specimens for SARS-CoV-2 detection. The pandemic has been since dominated by the emergence of new variants, the latest being the Omicron variant characterized by numerous mutations and changes in host tropism in vitro that might affect the diagnostic performance of tests depending on the sampling location. In this prospective study, we evaluated the clinical performance of NPs, ANs, and saliva for SARS-CoV-2 diagnosis during the Omicron wave. Our results highlight the effectiveness of saliva-based RT-PCR for the early detection of the Omicron variant. These findings may help to refine guidelines and support the use of a highly sensitive diagnostic method that allows earlier diagnosis, when transmission is the most critical.

Objective: To describe the contribution of the rapid antigen diagnostic testing (RDT) to the management strategy of the COVID-19 pandemic. Methodologies: The protein chain reaction (PCR) and the RDT have been performed on each COVID-19 suspected workers from December 2020 to September 2021. Results: A total of 286 people tested. A positivity rate of 38.1% was recorded. The average time to obtain PCR results was 8.3 days. 54.8% (n = 142) of the RDT were followed by a PCR for confirmation or invalidation and 100% of positive cases with Ag-RDT were confirmed by the PCR. We have noticed a 58.3% reduction of lost work days due to COVID-19, since the use of the Ag-RDT. Conclusion: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid diagnostic tests are efficient. They have enabled early treatment of COVID-19 patients, helped hold back the spread of the disease in a high-risk professional environment, and reduced the impact of the pandemic on a vital sector in developing countries.

Dear Editor, Recent studies indicated that the strong immune evasion potential of the most recent SARS-CoV-2 variant, Omicron, results in more frequent reinfections and breakthrough infections despite the widespread delivery of mRNA vaccine booster doses .1Kuhlmann C. Konstanze Mayer C. Claassen M. Maponga T. Burgers W.A. Keeton R. Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose.The Lancet. 2022 Jan 18; https://doi.org/10.1016/S0140-6736(22)00090-3Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,2Lu L. Mok B.W. Chen L.L. Chan J.M. Tsang O.T. Lam B.H. et al.Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients.Clin Infect Dis. 2021 Dec 16; : ciab1041https://doi.org/10.1093/cid/ciab1041Crossref PubMed Google Scholar Antispike antibody titers greater than 141 binding antibody units (BAU) per milliliter are correlated with the presence of neutralizing antibodies (the most widely accepted marker of protection) against wild-type virus and the Alpha variant,3Dimeglio C. Herin F. Martin-Blondel G. Miedougé M. Izopet J. Antibody titers and protection against a SARS-CoV-2 infection.J Infect. 2021 Sep 21; (00483-7): S0163-S4453https://doi.org/10.1016/j.jinf.2021.09.013Abstract Full Text Full Text PDF Scopus (5) Google Scholar but neutralization of the Delta and Omicron variants probably requires higher antibody titers. Recent results showed that there was evidence of significant waning of antibody reactivity against Delta and Omicron six months after the second dose of vaccine.4Faustini S. Shields A. Banham G. Wall N. Al-Taei S. Tanner C. et al.Cross reactivity of spike glycoprotein induced antibody against delta and omicron variants before and after third SARS-CoV-2 vaccine dose in healthy and immunocompromised individuals.J Infect. 2022 Jan 10; (00002-0): S0163-S4453https://doi.org/10.1016/j.jinf.2022.01.002Abstract Full Text Full Text PDF PubMed Google Scholar In this complementary study, we compared the concentrations of binding antibodies before breakthrough infections with Delta or Omicron SARS-CoV-2 variants. We measured the antibody titers in 1169 vaccinated individuals shortly before their breakthrough infection with the Omicron SARS-CoV-2 variant (1 November – 31 December 2021). Total SARS-CoV-2 antibodies were measured with a quantitative enzyme-linked immunosorbent assay (ELISA) (Wantai Biological Pharmacy Enterprise Co., Ltd, China).5Chapuy-Regaud S. Miédougé M. Abravanel F. Da Silva I. Porcheron M. Fillaux J. et al.Evaluation of three quantitative anti-SARS-CoV-2 antibody immunoassays.Microbiol Spectr. 2021 Dec 22; 9e0137621https://doi.org/10.1128/spectrum.01376-21Crossref PubMed Google Scholar Symptomatic and asymptomatic infections were detected between 15 November 2021 and 12 January 2022 using a nucleic-acid amplification method (Aptima™ SARS-CoV-2 assay, Panther™ system, Hologic, USA).6Trémeaux P. Lhomme S. Abravanel F. et al.Evaluation of the Aptima™ transcription-mediated amplification assay (Hologic®) for detecting SARS-CoV-2 in clinical specimens.J Clin Virol. 2020; 129 (Aug)104541https://doi.org/10.1016/j.jcv.2020.104541Crossref PubMed Scopus (19) Google Scholar Viral genotyping was performed using Pacific Biosciences Technology.7Lhomme S. Latour J. Jeanne N. Trémeaux P. Ranger N. Migueres M. et al.Prediction of SARS-CoV-2 variant lineages using the S1-encoding region sequence obtained by pacbio single-molecule real-time sequencing.Viruses. 2021 Dec 18; 13: 2544https://doi.org/10.3390/v13122544Crossref PubMed Scopus (0) Google Scholar We matched for age, gender and vaccination status (1, 2 or 3 doses) each Omicron-infected individual with a person infected with the Delta variant identified between September 1 and December 1, 2021 for whom we had a total antibody titer 15 days to 2 months before infection. The antibody concentrations at the time of infection were estimated with an exponential decay model.8Dimeglio C. Herin F. Da-Silva I. Porcheron M. Martin-Blondel G. Chapuy-Regaud S. Izopet J. Post-vaccination SARS-CoV-2 antibody kinetics and protection duration.Clin Infect Dis. 2021 Nov 27; : ciab984https://doi.org/10.1093/cid/ciab984Crossref PubMed Google Scholar These analyses were part of the national SARS-CoV-2 surveillance. French law (CSP Art.L1121–1.1) does not require institutional review board approval for anonymous non-interventional studies. The median age of the 1169 individuals (602; 51.5 males) was 45 years (interquartile range [IQR] 29–71). 258 (22.1%) had been given one, 859 (73.5%) two, and 52 (4.4%) three doses of mRNA vaccine. The ELISA analyses indicated that 90% of the Omicron infections occurred in people whose total antibody concentration was less than or equal to 6967 BAU/ml. In contrast, 90% of the Delta infections involved people with binding antibody concentrations below 2905 BAU/ml (Fig. 1, p<0.01, Wilcoxon signed rank test). These figures suggest that infections with the Omicron SARS-CoV-2 variant can occur despite high binding antibody concentrations, even at concentrations 2.4 higher than infections with the Delta SARS-CoV-2 variant. This is consistent with a recent study indicating that a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 6 - 23 times lower against Omicron than those against Delta.9Planas D. Saunders N. Maes P. Guivel-Benhassine F. Planchais C. Buchrieser J. Bolland W.H. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2021 Dec 23; https://doi.org/10.1038/s41586-021-04389-zCrossref Scopus (13) Google Scholar This is also consistent with another study showing that the neutralization titers of anti-Omicron antibodies in the serum of plasma donors were 17 to 22 times lower than they are against the Delta variant.10Aggarwal, A. et al. SARS-Cov-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. medRxiv. doi: https://doi.org/10.1101/2021.12.14.21267772Google Scholar The antibody thresholds found in our study should be compared to those obtained in further studies on other populations. The authors declare no conflict of interest

We read with interest the letter published recently by Costa et al. in the journal of Infection. They analyzed the difference between the viral loads of the SARS-CoV-2 Alpha and Delta variants using the parameters of clinical presentation, time to testing from symptoms onset, age and vaccination status.1Rosa C. Beatriz O. Alma B.M. Eliseo A. de Michelena Paula M.C.C. et al.RNA viral loads of SARS-CoV-2 Alpha and Delta variants in nasopharyngeal specimens at diagnosis stratified by age, clinical presentation and vaccination status.J Infect. 2021; (S0163-4453(21)00641-1)https://doi.org/10.1016/j.jinf.2021.12.018Abstract Full Text Full Text PDF Scopus (4) Google Scholar A new variant of concern (VOC), the Omicron variant (B.1.1.529), emerged in South Africa in November 2021, and rapidly spread throughout the world.2Weekly Epidemiological Update: Omicron Variant of Concern (VOC) – Week 1 (Data as of 7 January 2022) EU/EEA. European Centre for Disease Prevention and Control, 2022https://www.ecdc.europa.eu/en/news-events/weekly-epidemiological-update-omicron-variant-concern-voc-week-1-data-7-january-2022Google Scholar Recent data suggest that this variant is more transmissible,3L.F. Plesner, M.L. Hvas, J. Denwood Matthew, C.L. Engbo, M.C. Holten, S.R. Leo, et al. SARS-CoV-2 Omicron VOC transmission in Danish households. medRxiv 2021:2021.12.27.21268278. doi:10.1101/2021.12.27.21268278.Google Scholar less sensitive to vaccination,4Delphine P. Nell S. Piet M. Florence G.B. Cyril P. Julian B. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2021; : 1-7https://doi.org/10.1038/s41586-021-04389-zCrossref Scopus (655) Google Scholar and causes less severe outcomes than the Delta variant.5Caroline M. Richard F. Mande T. Anchen L. Teshlin A. Boniswa K. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves.JAMA. 2021; https://doi.org/10.1001/jama.2021.24868Crossref Scopus (238) Google Scholar In vitro studies have demonstrated changes in cell entry and cellular tropism with the Omicron variant that might explain its greater transmissibility and reduced severity.6Hanjun Z. Lu L. Zheng P. Lin-Lei C. Xinjin M. Chuyuan Z. et al.SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with delta variant in TMPRSS2-expressed cells.Emerg Microbes Infect. 2021; : 1-18https://doi.org/10.1080/22221751.2021.2023329Crossref PubMed Scopus (177) Google Scholar,7HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung. Available at https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection. Accessed January 13, 2022, n.d.Google Scholar However, clinical data comparing Delta and Omicron infections remain scarce, especially for ambulatory patients. We therefore examined the virological features of these two variants found in patients attending testing center. All positive specimens detected at the Toulouse University Hospital drive-through testing center between December 15 and 31, 2021 were screened for SARS-CoV-2 variant. We used the Thermo Fisher® TaqPath™ COVID-19 CE-IVD RT-PCR kit (TaqPath) for SARS-CoV-2 detection and variant screening. A deletion at position 69-70 in the spike (S) gene of Omicron variant leads to a loss of detection of this target in the TaqPath assay and allows the discrimination with the Delta variant (Omicron: S-/ Delta: S+) .8Anthony Li Allison M. Megan C. Hugh Guan T. Omicron and S-gene target failure cases in the highest COVID-19 case rate region in Canada - December 2021.J Med Virol. 2021; https://doi.org/10.1002/jmv.27562Crossref Scopus (22) Google Scholar The TaqPath profiles and whole genome sequences (PacBio technology) of a subset of 560 positive specimens were 100% concordant. Viral loads (log10 copies/ml) were determined using a calibration curve obtained with the TaqPath N gene Ct values and digital droplet RT-PCR (RT-ddPCR) (BioRad, Hercules, CA). Data on patient symptomatology and vaccination status were collected at sampling. Among the 12 949 tests performed during this period, 975 Delta variant infections (median age= 31[20–42]; 52.7% men) and 1578 Omicron infections (median age= 28[22–38]; 49.2% men) have been diagnosed. The Omicron variant was detected in 10% of SARS-CoV-2 infections between December 15 and December 19, 55% of infections during December 20–26, and in 82% of infections during December 27–31. The patients' characteristics are shown in the Supplementary Table. In bivariate analysis, the nasopharyngeal (NP) viral loads of patients infected with the Omicron variant were lower than those of Delta-infected patients (p = 0.04), although the Omicron-infected patients had more mild symptoms (63.2% [60.7%−79.8%]) than those infected with the Delta variant (51.8% [48.6%−55.0%]; p < 0.01). The proportion of infections in vaccinated patients (2 or 3 doses) was higher with the Omicron variant (68.7% [66.3%−82.5%]) than with the Delta variant (52.6% [49.4%−55.7%]; p < 0.01). Multivariate analysis identified several characteristics that were independently associated with Omicron infections (Table 1). Omicron infections resulted in more symptomatic cases (OR=1.24; p < 0.01), were more frequent in vaccinated patients (OR=1.48; p < 0.01), and in young patients (OR=0.99; p < 0.01) (Table 1). The nasopharyngeal viral loads of Delta and Omicron infections were not significantly different, after adjustment for age, sex, symptoms and vaccination status (Table 1, Fig. 1). After stratification on age (interactions with vaccination and symptoms, p < 0.01), our final model showed that Omicron infections were more frequent than Delta infections in vaccinated patients. This was true for all age categories (<22 years (OR= 1.85; p < 0.0.01); 22–39 years (OR=1.32; p < 0.01); ≥40 years (OR=1.39; p < 0.01)) (Table 1). Omicron infections were associated with more symptomatic forms only in 22–39 year-old patients (OR=1.29; p < 0.01).Table 1Multivariate analysis of the factors associated with Omicron variant infections.Delta (ref) /OmicronInitial and final analysesAge-dependent analyses (final)< 22 years22–39 years≥ 40 yearsOR95% CIP valueOR95% CIP valueOR95% CIP valueOR95% CIP valueAge0.99[0.98;0.99]<0.01Not ApplicableNot ApplicableNot ApplicableGender (Female)1.11[0.95;−1.31]nsVaccination*compared to unvaccinated patients.1.48[1.37;1.61]<0.011.85[1.55;2.21]<0.011.32[1.17;1.49]<0.011.39[1.19;1.61]<0.01Symptoms⁎⁎compared to asymptomatic patients.1.24[1.08;1.42]<0.011.29[1.05;1.58]0.01Nasopharyngeal RNA viral load0.98[0.91;1.05]ns compared to unvaccinated patients. compared to asymptomatic patients. Open table in a new tab The SARS-CoV-2 pandemic has evolved since its beginning in late 2019, with the continuous emergence of new variants. Those with the highest transmissibility became prevalent and responsible for epidemic waves. The Omicron variant is no exception and outcompeted the Delta variant in many countries within a few weeks.2Weekly Epidemiological Update: Omicron Variant of Concern (VOC) – Week 1 (Data as of 7 January 2022) EU/EEA. European Centre for Disease Prevention and Control, 2022https://www.ecdc.europa.eu/en/news-events/weekly-epidemiological-update-omicron-variant-concern-voc-week-1-data-7-january-2022Google Scholar The emergence of these variants challenges the effectiveness of our current vaccines and monoclonal antibodies. In vitro studies indicate that monoclonal antibodies and antibody-enriched plasma are much less effective against the Omicron variant .4Delphine P. Nell S. Piet M. Florence G.B. Cyril P. Julian B. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2021; : 1-7https://doi.org/10.1038/s41586-021-04389-zCrossref Scopus (655) Google Scholar Our data provide clinical evidence that the Omicron variant is responsible for a greater proportion of vaccine breakthrough infections than is the Delta variant. The transmissibility of the Alpha and Delta variants has been linked to higher NP viral loads.1Rosa C. Beatriz O. Alma B.M. Eliseo A. de Michelena Paula M.C.C. et al.RNA viral loads of SARS-CoV-2 Alpha and Delta variants in nasopharyngeal specimens at diagnosis stratified by age, clinical presentation and vaccination status.J Infect. 2021; (S0163-4453(21)00641-1)https://doi.org/10.1016/j.jinf.2021.12.018Abstract Full Text Full Text PDF Scopus (4) Google Scholar,9Rosa C. Felipe B. Estela G. Alma B. Eliseo A. Diego C. et al.Initial viral load and decay kinetics of SARS-CoV-2 lineage B.1.1.7 in the upper respiratory tract of adults and children.J Infect. 2021; 83: 496-522https://doi.org/10.1016/j.jinf.2021.08.015Abstract Full Text Full Text PDF Scopus (6) Google Scholar However, our data demonstrate that the increased transmissibility of the Omicron variant is not explained by higher nasopharyngeal viral load. Danish data also found similar nasopharyngeal viral load between Delta and Omicron infections.3L.F. Plesner, M.L. Hvas, J. Denwood Matthew, C.L. Engbo, M.C. Holten, S.R. Leo, et al. SARS-CoV-2 Omicron VOC transmission in Danish households. medRxiv 2021:2021.12.27.21268278. doi:10.1101/2021.12.27.21268278.Google Scholar Whether higher viral loads can be found in more superficial samples such as saliva and nasal specimens as suggested by some should be further investigated.10M. Gert, H. Nei-yuan, I. Arash, D. Deelan, E. Annabel, C. Chun-yat, et al. Saliva swabs are the preferred sample for Omicron detection. MedRxiv 2021:2021.12.22.21268246. doi:10.1101/2021.12.22.21268246.Google Scholar Ex-vivo studies on cultures of human bronchus and lung explants found that Omicron replicated faster in bronchial tissue than did Delta but that it replicated less efficiently in lungs .7HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung. Available at https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection. Accessed January 13, 2022, n.d.Google Scholar Perhaps the reduced severity of Omicron infections is due to a change in host cell tropism and faster replication in the upper respiratory tract. Our study suggests that the Omicron variant is more contagious mainly because of vaccine escape resulting from the spike mutation that alters virus neutralization rather than because of greater virus shedding in the nasopharynx. Although we did no follow-up and collected no detailed clinical data, a strength of our study is that the specimens were collected from unselected individuals in a homogeneous population, all within a short time frame. We believe our findings will help identify the factors underlying the spread of the Omicron variant and the measures needed to control the pandemic. No specific funding.

Background and Aims Direct virological diagnosis of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infectionis based on either viral antigen or viral genome detection. These methods, in addition to the dedicated reagents and transport packaging, require the use of quantities of plastic that may individually appear negligible but which, in the context of a pandemic, are very high. The aim was to estimate the amount of plastic involved in a diagnostic assay whether molecular or antigenic. Methods We weighed the plastics used to obtain a diagnostic assay result for SARS-CoV-2 infection in our hospital. Results Each ready-to-use antigen assay requires about 20 g of plastic whereas the PCR assay implies the use of 30 g. This unit mass, when compared to our laboratory's SARS-CoV-2 genomic screening activity,represents more than 10 tons of plastic for 2021. At our region level (#6.10 inhabitants), more than 350 tons of plastic were used to carry out more than 7 million declared PCR assays and as many antigenic assays. Conclusions The virologic diagnostic activityl inked to the SARS-CoV-2 pandemic has highlighted once more our dependance for plastic use. We must already think about a more environmentally virtuous diagnostic activity by integrating a reasonned use of diagnostic tools and a higher use of ecological friendly material. Parallel the notion of waste management must also be addressed in order to limit their environmental impact.

We investigated the effects of dengue virus (DENV) on semen using samples collected 7, 15, 30, 60, and 90 days after symptom onset from 10 infected volunteers on Réunion Island. We assessed characteristics of semen and reproductive hormones and isolated motile spermatozoa from semen. We assayed semen for DENV using reverse transcription PCR and searched for DENV RNA by virus isolation in Vero E6 cell cultures. Four volunteers had >1 DENV RNA-positive semen samples; 2 volunteers had DENV RNA–positive semen at day 15 and 1 at day 30. No motile sperm were DENV positive. After exposure to positive semen, few Vero E6 cells stained positive for DENV antigens, indicating low levels of replicative virus. We found DENV had shorter duration in semen than in blood. These findings support the possibilities that DENV is sexually transmissible for a short period after acute dengue illness and that acute dengue induces reversible alterations in sperm.

Studies comparing SARS-CoV-2 nasopharyngeal (NP) viral load (VL) according to virus variant and host vaccination status have yielded inconsistent results. We conducted a single center prospective study between July and September 2021 at the drive-through testing center of the Toulouse University Hospital. We compared the NP VL of 3775 patients infected by the Delta (n = 3637) and Alpha (n = 138) variants, respectively. Patient’s symptoms and vaccination status (2619 unvaccinated, 636 one dose and 520 two doses) were recorded. SARS-CoV-2 RNA testing and variant screening were assessed by using Thermo Fisher® TaqPath™ COVID-19 and ID solutions® ID™ SARS-CoV-2/VOC evolution Pentaplex assays. Delta SARS-CoV-2 infections were associated with higher VL than Alpha (coef = 0.68; p ≤ 0.01) independently of patient’s vaccination status, symptoms, age and sex. This difference was higher for patients diagnosed late after symptom onset (coef = 0.88; p = 0.01) than for those diagnosed early (coef = 0.43; p = 0.03). Infections in vaccinated patients were associated with lower VL (coef = −0.18; p ≤ 0.01) independently of virus variant, symptom, age and sex. Our results suggest that Delta infections could lead to higher VL and for a longer period compared to Alpha infections. By effectively reducing the NP VL, vaccination could allow for limiting viral spread, even with the Delta variant.

A patient aged 28 years who is immunocompromised and living with HIV/AIDS became infected with the monkeypox virus (MPXV). His clinical condition deteriorated for 37 days, with fever, skin lesions, and diarrhea before going to the infectious diseases department, where his severe, protracted infection was treated with tecovirimat for 14 days. His condition rapidly improved, and the skin lesions decreased, as did the MPXV loads, with no adverse events. This case indicates that tecovirimat might be effective for treating patients who are immunocompromised and are infected with MPXV.

Dear Editor,The B.1.1.529 SARS-CoV-2 lineage, named Omicron, was recently divided into three lineages (BA.1, BA.2 and BA.3). BA.1 and BA.2 are much more dominant than BA.3. BA.1 could cause breakthrough infections in highly immune populations [1Kuhlmann C. Mayer C.K. Claassen M. Maponga T. Burgers W.A. Keeton R. Riou C. Sutherland A.D. Suliman T. Shaw M.L. Preiser W. Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose.Lancet. 2022 Feb 12; 399: 625-626https://doi.org/10.1016/S0140-6736(22)00090-3Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar]. Preliminary studies indicate that BA.2 can readily overcome the immunity provided by vaccination and/or infection with an earlier variant. We used data for the French city of Toulouse to evaluate the impact of the proportions of the BA.1 and BA.2 variants in positive-testing samples and the impact of vaccination on SARS-CoV-2 proliferation.Our discretized version of a susceptible infectious and recovered (SIR)-type model has been shown well suited to studies on the spread of SARS-CoV-2 [2Dimeglio C. Milhes M. Loubes J.M. Ranger N. Mansuy J.M. Trémeaux P. Jeanne N. Latour J. Nicot F. Donnadieu C. Izopet J Influence of SARS-CoV-2 variant B.1.1.7, vaccination, and public health measures on the spread of SARS-CoV-2.Viruses. 2021 May 12; 13: 898https://doi.org/10.3390/v13050898Crossref PubMed Scopus (3) Google Scholar,3Dimeglio C. Loubes J.M. Mansuy J.M. Izopet J. Quantifying the impact of public health protection measures on the spread of SARS-CoV-2.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (3) Google Scholar].The model includes a diffusion/transmission coefficient R0 that varies with the likelihood of contagion, and two reduction coefficients c^and q^ that describe the impact of public health measures on virus transmission. Values of c^ and q^ were estimated in previous studies [2Dimeglio C. Milhes M. Loubes J.M. Ranger N. Mansuy J.M. Trémeaux P. Jeanne N. Latour J. Nicot F. Donnadieu C. Izopet J Influence of SARS-CoV-2 variant B.1.1.7, vaccination, and public health measures on the spread of SARS-CoV-2.Viruses. 2021 May 12; 13: 898https://doi.org/10.3390/v13050898Crossref PubMed Scopus (3) Google Scholar,3Dimeglio C. Loubes J.M. Mansuy J.M. Izopet J. Quantifying the impact of public health protection measures on the spread of SARS-CoV-2.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (3) Google Scholar]. It also takes into account a parameter p1 describing the proportion of the BA1 variant in urban Toulouse, and a similar parameter p2 for the BA2 variant; there are also vaccine/immunity efficacy coefficients i1^ and i2^ indicating the weight of each variant in the number of new infections. The model predicts how the SARS-CoV-2 virus would have evolved and projects the daily percentage of new positive cases (see Supplementary materials S1).We setR0(D)=5.9 for the Delta variant at its peak, based on WHO international data [4Campbell F. Archer B. Laurenson-Schafer H. Jinnai Y. Konings F. Batra N. Pavlin B. Vandemaele K. Van Kerkhove M.D. Jombart T. Morgan O. le Polain de Waroux O. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021.Euro Surveill. 2021; 262100509https://doi.org/10.2807/1560-7917.ES.2021.26.24.2100509Crossref Scopus (327) Google Scholar]. First elements showed that R0(BA1) could reach 10 [5Burki T.K. Omicron variant and booster COVID-19 vaccines.Lancet Respir Med. 2022; 10: e17https://doi.org/10.1016/S2213-2600(21)00559-2Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. We estimated the initial model settings using data collected by Toulouse Virology Laboratory (Table 1).Table 1.Model initial parameters.Weeks 2021Weeks 202236373839404142434445464748495051521234567Variant (%)Delta98.591.887.510010010010010098.610086.997.499.599.490.145.117.92.31.20.20.20.100BA.10000000000000.20.69.954.782.197.49797.994.387.777.360.1BA.2000000000000000000.31.81.95.512.322.739.9Non Delta/ Non Omicron1.58.212.5000001.4013.12.60.2000.200000000TestsTotal number1535136111079478771025125015561573170915842565352642924778550666648998762260493794236816191921Positive (%)5.9%4.8%4.1%4.8%2.0%2.9%3.4%3.4%5.3%5.1%7.1%14.5%16.7%16.5%14.3%21.8%33.1%38.4%42.1%47.5%41.6%32.1%27.7%19.6% Open table in a new tab The nucleic acids in nasopharyngeal swab samples collected at Toulouse University Hospital were extracted with the MGI extraction system and tested using the ThermoFisher TaqPath RT-PCR assay. All positive nasopharyngeal samples with a cycle threshold (Ct) value below 30 (N gene) were tested using the ID solutions screening system for mutations K417N, L452R and E484K. The Omicron BA.1 variant was identified based on TaqPath S gene target failure (SGTF) or S gene target late (SGTL) detection profiles plus the presence of the K417N mutation. The Omicron BA.2 variant was identified based on TaqPath non-SGTF/SGTL detection profiles plus the presence of the K417N mutation. The results for a subset of 1080 positive specimens tested with our VOC screening strategy and those obtained by genome sequencing using Pacific Biosciences Technology [6Lhomme S. Latour J. Jeanne N. Trémeaux P. Ranger N. Migueres M. Salin G. Donnadieu C. Izopet J Prediction of SARS-CoV-2 variant lineages using the S1-encoding region sequence obtained by PacBio Single-Molecule Real-Time Sequencing.Viruses. 2021; 13: 2544https://doi.org/10.3390/v13122544Crossref PubMed Scopus (5) Google Scholar] were 100% concordant.In addition to barrier measures, the local authorities decided to make mask wearing compulsory in the Toulouse area from November 24, 2021 (week 47) as this protective measure had been shown to reduce SARS-CoV-2 circulation among Toulouse inhabitants by 27% [3Dimeglio C. Loubes J.M. Mansuy J.M. Izopet J. Quantifying the impact of public health protection measures on the spread of SARS-CoV-2.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (3) Google Scholar]. The BA.1 variant was the major variant (> 90%) in the Toulouse area from January 1 to February 1 (weeks 1–4, Table 1). The parameters of its R0 (see Methods; R0=10) predicted that the percentage of new positive cases during this period would be 20.9% if 69.8% of the fully vaccinated population was as protected against BA.1 infection as they were against Delta: <88% [7Torgovnick J. Effectiveness of Covid-19 vaccines against the B.1.617.2 (delta) variant.N Engl J Med. 2021 Dec 16; 385: e92https://doi.org/10.1056/NEJMc2113090Crossref PubMed Scopus (1) Google Scholar] (Fig. 1A). The vaccine/immunity efficacy coefficient i1^ was about 23% after correction based on the observed data (Equation 1, Supplementary S1) (Fig. 1C). The proportion, p2, of BA.2 variant increased from 5.5% at the end of January 2022 to 39.9% on February 21, 2022 (Table 1). The rate of positive RT-PCR tests should have doubled between February 1 and 21 if the vaccine/immunity efficacy for BA.2 is close to 23%, the same as that for BA.1 (Fig. 1B). However the percentage of positive RT-PCR tests decreased from 44% on February 4 to 19.6% on February 21 (weeks 5–7, Table 1). Correcting the model parameters to bring the predicted data in line with the observed data (Equation 2, Supplementary S1) gave a vaccine/immunity coefficient of 92.8% (Fig. 1C).The rapid proliferation of BA.1 was different from that of the Delta variant, which became the dominant strain in the summer months, when health measures were relaxed and vaccination coverage lower. This indicates the great capacity of the BA.1 variant to evade antibodies produced in response to infection with an earlier strain of virus and antibodies generated by vaccination. We showed that the Omicron BA.1 variant was more contagious than the Delta variant because of vaccine escape resulting from the spike mutations that alter virus neutralization rather than because of greater virus shedding in the nasopharynx [8Migueres M. Dimeglio C. Trémeaux P. Abravanel F. Raymond S. Lhomme S. Mansuy J.M. Izopet J. Influence of immune escape and nasopharyngeal virus load on the spread of SARS-CoV-2 Omicron variant.J Infect. 2022 Feb 7; (S0163-4453): 00054-00058https://doi.org/10.1016/j.jinf.2022.01.036Abstract Full Text Full Text PDF Scopus (11) Google Scholar]. The "BA.1 wave" seems to induce significant natural immunity against the BA.2 variant. The slowdown in the spread of the SARS-CoV-2 virus could also be due to the vaccine booster campaign that started at the beginning of January 2022 when about 76% of those who were primo-vaccinated had been given 3 doses by mid-February 2022. We could not distinguish between the influence of a booster vaccination and the immunity conferred by a BA.1 infection on the spread of BA.2, because the two events were confounded. These results agree with those showing that BA.2 and BA.1 are similarly able to resist the neutralizing antibodies of people who had been vaccinated or previously infected [9Iketani S. Liu L. Guo Y. Liu L. Huang Y. Wang M. Iketani S. Liu L. Guo Y. Liu L. Chan J.F. Huang Y. Wang M. Luo Y. Yu J. Chu H. Chik K.K. Yuen T.T. Yin M.T. Sobieszczyk M.E. Huang Y. Yuen K.Y. Wang H.H. Sheng Z. Ho D.D. Antibody evasion properties of SARS-CoV-2 Omicron sublineages.Nature. 2022 Mar 3; https://doi.org/10.1038/s41586-022-04594-4Crossref Scopus (176) Google Scholar]. A slight difference in neutralizing capacity against Omicron BA.1 and BA.2 of natural or vaccine antibodies could explain a growth advantage of BA.2 over BA.1. In a Danish study, unvaccinated individuals, like vaccinated individuals, were more susceptible to BA.2 infection than to BA.1 infection indicating that viral properties other than immune evasion could also play a role in the growth advantage of BA.2 [10Lyngse F.P. Kirkeby C.T. Denwood M. Christiansen L.E. Mølbak K. Møller C.H. et al.Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: evidence from Danish Households.medRXiv. 2022; (Preprint at) (01.28.22270044; doi: https://doi.org/)https://doi.org/10.1101/2022.01.28.22270044Crossref Scopus (0) Google Scholar].We conclude that the increase in the proportion of BA.2 has not led to a faster spread of the virus; which seems to indicate that the immunity induced by BA.1 infection is effective against BA.2. Further studies are needed to determine the contributions of the vaccine booster and a BA.1 infection to protection against BA.2. Dear Editor, The B.1.1.529 SARS-CoV-2 lineage, named Omicron, was recently divided into three lineages (BA.1, BA.2 and BA.3). BA.1 and BA.2 are much more dominant than BA.3. BA.1 could cause breakthrough infections in highly immune populations [1Kuhlmann C. Mayer C.K. Claassen M. Maponga T. Burgers W.A. Keeton R. Riou C. Sutherland A.D. Suliman T. Shaw M.L. Preiser W. Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose.Lancet. 2022 Feb 12; 399: 625-626https://doi.org/10.1016/S0140-6736(22)00090-3Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar]. Preliminary studies indicate that BA.2 can readily overcome the immunity provided by vaccination and/or infection with an earlier variant. We used data for the French city of Toulouse to evaluate the impact of the proportions of the BA.1 and BA.2 variants in positive-testing samples and the impact of vaccination on SARS-CoV-2 proliferation. Our discretized version of a susceptible infectious and recovered (SIR)-type model has been shown well suited to studies on the spread of SARS-CoV-2 [2Dimeglio C. Milhes M. Loubes J.M. Ranger N. Mansuy J.M. Trémeaux P. Jeanne N. Latour J. Nicot F. Donnadieu C. Izopet J Influence of SARS-CoV-2 variant B.1.1.7, vaccination, and public health measures on the spread of SARS-CoV-2.Viruses. 2021 May 12; 13: 898https://doi.org/10.3390/v13050898Crossref PubMed Scopus (3) Google Scholar,3Dimeglio C. Loubes J.M. Mansuy J.M. Izopet J. Quantifying the impact of public health protection measures on the spread of SARS-CoV-2.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (3) Google Scholar]. The model includes a diffusion/transmission coefficient R0 that varies with the likelihood of contagion, and two reduction coefficients c^and q^ that describe the impact of public health measures on virus transmission. Values of c^ and q^ were estimated in previous studies [2Dimeglio C. Milhes M. Loubes J.M. Ranger N. Mansuy J.M. Trémeaux P. Jeanne N. Latour J. Nicot F. Donnadieu C. Izopet J Influence of SARS-CoV-2 variant B.1.1.7, vaccination, and public health measures on the spread of SARS-CoV-2.Viruses. 2021 May 12; 13: 898https://doi.org/10.3390/v13050898Crossref PubMed Scopus (3) Google Scholar,3Dimeglio C. Loubes J.M. Mansuy J.M. Izopet J. Quantifying the impact of public health protection measures on the spread of SARS-CoV-2.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (3) Google Scholar]. It also takes into account a parameter p1 describing the proportion of the BA1 variant in urban Toulouse, and a similar parameter p2 for the BA2 variant; there are also vaccine/immunity efficacy coefficients i1^ and i2^ indicating the weight of each variant in the number of new infections. The model predicts how the SARS-CoV-2 virus would have evolved and projects the daily percentage of new positive cases (see Supplementary materials S1). We setR0(D)=5.9 for the Delta variant at its peak, based on WHO international data [4Campbell F. Archer B. Laurenson-Schafer H. Jinnai Y. Konings F. Batra N. Pavlin B. Vandemaele K. Van Kerkhove M.D. Jombart T. Morgan O. le Polain de Waroux O. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021.Euro Surveill. 2021; 262100509https://doi.org/10.2807/1560-7917.ES.2021.26.24.2100509Crossref Scopus (327) Google Scholar]. First elements showed that R0(BA1) could reach 10 [5Burki T.K. Omicron variant and booster COVID-19 vaccines.Lancet Respir Med. 2022; 10: e17https://doi.org/10.1016/S2213-2600(21)00559-2Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar]. We estimated the initial model settings using data collected by Toulouse Virology Laboratory (Table 1). The nucleic acids in nasopharyngeal swab samples collected at Toulouse University Hospital were extracted with the MGI extraction system and tested using the ThermoFisher TaqPath RT-PCR assay. All positive nasopharyngeal samples with a cycle threshold (Ct) value below 30 (N gene) were tested using the ID solutions screening system for mutations K417N, L452R and E484K. The Omicron BA.1 variant was identified based on TaqPath S gene target failure (SGTF) or S gene target late (SGTL) detection profiles plus the presence of the K417N mutation. The Omicron BA.2 variant was identified based on TaqPath non-SGTF/SGTL detection profiles plus the presence of the K417N mutation. The results for a subset of 1080 positive specimens tested with our VOC screening strategy and those obtained by genome sequencing using Pacific Biosciences Technology [6Lhomme S. Latour J. Jeanne N. Trémeaux P. Ranger N. Migueres M. Salin G. Donnadieu C. Izopet J Prediction of SARS-CoV-2 variant lineages using the S1-encoding region sequence obtained by PacBio Single-Molecule Real-Time Sequencing.Viruses. 2021; 13: 2544https://doi.org/10.3390/v13122544Crossref PubMed Scopus (5) Google Scholar] were 100% concordant. In addition to barrier measures, the local authorities decided to make mask wearing compulsory in the Toulouse area from November 24, 2021 (week 47) as this protective measure had been shown to reduce SARS-CoV-2 circulation among Toulouse inhabitants by 27% [3Dimeglio C. Loubes J.M. Mansuy J.M. Izopet J. Quantifying the impact of public health protection measures on the spread of SARS-CoV-2.J Infect. 2020; Abstract Full Text Full Text PDF Scopus (3) Google Scholar]. The BA.1 variant was the major variant (> 90%) in the Toulouse area from January 1 to February 1 (weeks 1–4, Table 1). The parameters of its R0 (see Methods; R0=10) predicted that the percentage of new positive cases during this period would be 20.9% if 69.8% of the fully vaccinated population was as protected against BA.1 infection as they were against Delta: <88% [7Torgovnick J. Effectiveness of Covid-19 vaccines against the B.1.617.2 (delta) variant.N Engl J Med. 2021 Dec 16; 385: e92https://doi.org/10.1056/NEJMc2113090Crossref PubMed Scopus (1) Google Scholar] (Fig. 1A). The vaccine/immunity efficacy coefficient i1^ was about 23% after correction based on the observed data (Equation 1, Supplementary S1) (Fig. 1C). The proportion, p2, of BA.2 variant increased from 5.5% at the end of January 2022 to 39.9% on February 21, 2022 (Table 1). The rate of positive RT-PCR tests should have doubled between February 1 and 21 if the vaccine/immunity efficacy for BA.2 is close to 23%, the same as that for BA.1 (Fig. 1B). However the percentage of positive RT-PCR tests decreased from 44% on February 4 to 19.6% on February 21 (weeks 5–7, Table 1). Correcting the model parameters to bring the predicted data in line with the observed data (Equation 2, Supplementary S1) gave a vaccine/immunity coefficient of 92.8% (Fig. 1C). The rapid proliferation of BA.1 was different from that of the Delta variant, which became the dominant strain in the summer months, when health measures were relaxed and vaccination coverage lower. This indicates the great capacity of the BA.1 variant to evade antibodies produced in response to infection with an earlier strain of virus and antibodies generated by vaccination. We showed that the Omicron BA.1 variant was more contagious than the Delta variant because of vaccine escape resulting from the spike mutations that alter virus neutralization rather than because of greater virus shedding in the nasopharynx [8Migueres M. Dimeglio C. Trémeaux P. Abravanel F. Raymond S. Lhomme S. Mansuy J.M. Izopet J. Influence of immune escape and nasopharyngeal virus load on the spread of SARS-CoV-2 Omicron variant.J Infect. 2022 Feb 7; (S0163-4453): 00054-00058https://doi.org/10.1016/j.jinf.2022.01.036Abstract Full Text Full Text PDF Scopus (11) Google Scholar]. The "BA.1 wave" seems to induce significant natural immunity against the BA.2 variant. The slowdown in the spread of the SARS-CoV-2 virus could also be due to the vaccine booster campaign that started at the beginning of January 2022 when about 76% of those who were primo-vaccinated had been given 3 doses by mid-February 2022. We could not distinguish between the influence of a booster vaccination and the immunity conferred by a BA.1 infection on the spread of BA.2, because the two events were confounded. These results agree with those showing that BA.2 and BA.1 are similarly able to resist the neutralizing antibodies of people who had been vaccinated or previously infected [9Iketani S. Liu L. Guo Y. Liu L. Huang Y. Wang M. Iketani S. Liu L. Guo Y. Liu L. Chan J.F. Huang Y. Wang M. Luo Y. Yu J. Chu H. Chik K.K. Yuen T.T. Yin M.T. Sobieszczyk M.E. Huang Y. Yuen K.Y. Wang H.H. Sheng Z. Ho D.D. Antibody evasion properties of SARS-CoV-2 Omicron sublineages.Nature. 2022 Mar 3; https://doi.org/10.1038/s41586-022-04594-4Crossref Scopus (176) Google Scholar]. A slight difference in neutralizing capacity against Omicron BA.1 and BA.2 of natural or vaccine antibodies could explain a growth advantage of BA.2 over BA.1. In a Danish study, unvaccinated individuals, like vaccinated individuals, were more susceptible to BA.2 infection than to BA.1 infection indicating that viral properties other than immune evasion could also play a role in the growth advantage of BA.2 [10Lyngse F.P. Kirkeby C.T. Denwood M. Christiansen L.E. Mølbak K. Møller C.H. et al.Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: evidence from Danish Households.medRXiv. 2022; (Preprint at) (01.28.22270044; doi: https://doi.org/)https://doi.org/10.1101/2022.01.28.22270044Crossref Scopus (0) Google Scholar]. We conclude that the increase in the proportion of BA.2 has not led to a faster spread of the virus; which seems to indicate that the immunity induced by BA.1 infection is effective against BA.2. Further studies are needed to determine the contributions of the vaccine booster and a BA.1 infection to protection against BA.2. The authors have no conflict of interest to declare. The English text was edited by Dr Owen Parkes. Appendix. Supplementary materials Download .docx (.02 MB) Help with docx files Download .docx (.02 MB) Help with docx files

Although placental small extracellular vesicles (sEVs) are extensively studied in the context of pregnancy, little is known about their role during viral congenital infection, especially at the beginning of pregnancy. In this study, we examined the consequences of human cytomegalovirus (hCMV) infection on sEVs production, composition, and function using an immortalized human cytotrophoblast cell line derived from first trimester placenta. By combining complementary approaches of biochemistry, electron microscopy, and quantitative proteomic analysis, we showed that hCMV infection increases the yield of sEVs produced by cytotrophoblasts and modifies their protein content towards a potential proviral phenotype. We further demonstrate that sEVs secreted by hCMV-infected cytotrophoblasts potentiate infection in naive recipient cells of fetal origin, including human neural stem cells. Importantly, these functional consequences are also observed with sEVs prepared from an ex vivo model of infected histocultures from early placenta. Based on these findings, we propose that placental sEVs could be important actors favoring viral dissemination to the fetal brain during hCMV congenital infection.