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The genetic encephalopathy Aicardi–Goutières syndrome is thought to be due to misidentification of self-derived nucleic acids and the induction of a type I interferon–mediated response. Administration of three reverse-transcriptase inhibitors reduced interferon signaling and serum levels of interferon in patients with the syndrome.

We describe an unvaccinated child at risk for life-threatening COVID-19 due to an inherited deficiency of IRF9, which governs ISGF-3–dependent responses to type I and III interferons (IFN). She was admitted, with a high nasal SARS-CoV-2 load on day 1 of upper respiratory tract infection. She was viremic on day 2 and received casirivimab and imdevimab. Her clinical manifestations and viremia disappeared on days 3 and 4, respectively. Circulating SARS-CoV-2 virus induced the expression of IFN-stimulated genes in leukocytes on day 1, whereas the secretion of blood type I IFNs, which peaked on day 4, did not. Antibody-mediated SARS-CoV-2 neutralization is, therefore, sufficient to overcome a deficiency of antiviral IFNs.

Anal cancer, usually driven by an oncogenic Human Papillomavirus, remains a leading cause of morbidity in men who have sex with men (MSM) living with HIV, despite combined antiretroviral therapy. Various recommendations advocate to perform regular examination and proctologist-performed samples to anticipate this risk and treat locally before cancer occurrence, an efficient strategy which has the drawback of requiring the proctologist's availability. This study evaluates the acceptability, feasibility, and efficiency of self-performed samples to screen for HPV-infection and HPV-related anal dysplasia among MSM living with HIV followed in Hôtel-Dieu Hospital. Between February 2015 and June 2015, MSM living with HIV and referred to the day-care hospital were offered to perform an anal self-sampling for cytologic and virologic evaluation. A self-sampling kit was provided, and a tutorial video was shown. A subset of participants had a proctology appointment after they did the self-sampling, and thus had a clinical examination and an anal swab sampling performed by the proctologist, using the same sampling material. Anal self-sampling was offered to 103 patients, and 100 accepted. Sixty-three samples were interpretable, of which 36 (57%) were normal and 27 (43%) showed abnormal results. Virologic analysis was performed for 60 (95%) interpretable samples: 50/60 (83%) of them were positive for HPV. Among HPV-carrier patients, 42/50 (84%) were infected with at least one HR-HPV. Twenty patients had a proctologist consultation. All clinician-performed samples were interpretable and 14 (70%) self-samples were interpretable. This study highlights the acceptable accuracy of self-sampling screening method among MSM living with HIV and try out its acceptability and feasibility as a secondary prevention device. Although it cannot replace a proctologist consultation for high risk patients, self-sampling should be studied further as one of the ways of screening for anal cancer among low-risk outpatients.

Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1-infected individuals. Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-α/β and -λ antiviral responses. HSE can result from a single-gene immunodeficiency that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious diseases may also reflect monogenic disorders of immunity.

[...]we assessed diagnostic performance of a point-of-care serology test for SARS-CoV-2 in 99 patients hospitalized in ICU with a definite SARS-Cov-2 and found a 91.9% sensitivity, confounded by younger age and shorter delay since symptoms onset. [...]we thank Biosynex which freely provided point-of-care serology tests. Jean-Paul Mira View author publications You can also search for this author in PubMed Google Scholar Contributions LSN designed the study, participated to data collection, wrote the manuscript and performed statistical analyses. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

During winter, after excluding obvious sites of infection, the most important diagnoses of isolated fever or influenza-like illness (ILI) to rule out are listeriosis and influenza, because of their severe potential outcomes and the straightforward management available for each. While awaiting laboratory results, the recommended management strategy is usually hospitalization for intravenous antibiotic therapy against potential listeria. This study sought to assess the effect of the use of a rapid test on hospitalization and antibiotic therapy rates. The study included all pregnant women who consulted for ILI or isolated fever after clinical and laboratory investigations and had a molecular diagnostic assay for influenza during two time periods, both during influenza epidemics: before introduction of the rapid molecular assay use (period 1) and after this (period 2). The study included 38 women during period 1 and 124 during period 2. The influenza diagnosis was confirmed for 24 of 38 (63.2%) women during period 1 and 65 of 124 (52.4%) women during period 2 (P = 0.24). The hospitalization rate fell significantly from period 1 to period 2, both in the total population (71.0% versus 44.3%, P = 0.004) and among women with confirmed influenza (83.3% versus 38.5%, P<0.001), as did the antibiotic therapy rate in both groups (respectively, 86.8% versus 56.1%, P = 0.001 and 91.7% versus 44.7%, P<0.001). The use of a rapid molecular assay for the diagnosis of influenza improved the management of pregnant women with an isolated fever or ILI by reducing the rates of unnecessary hospitalization and antibiotic therapy.

We report the case of an HIV-1-infected patient, treated with anti-CD20 monoclonal antibody for a B-cell lymphoma previously treated by autologous stem cell transplant. He suffered from chronic COVID19 and we monitored by plasma SARS-CoV-2 RNA by highly sensitive droplet-based digital PCR technology (ddPCR). Under tocilizumab therapy and despite a first clinical improvement biologically associated with decreasing inflammatory markers, a slight increase of SARS-CoV-2 RNAaemia quantified by ddPCR was highlighted, confirming the absence of viral efficacy of this treatment and predicting the subsequent observed deterioration. As expected, his complete recovery, finally achieved after COVID-19 convalescent plasmatherapy, strictly paralleled plasma SARS-CoV-2 RNA clearance. With these results, we confirmed the interest of SARS-CoV-2 RNAaemia monitoring by ddPCR in COVID-19 patients, particularly during treatment, and firstly showed that this new and specific biomarker could be helpful to select eligible patient for anti-IL6 receptors therapy considering the variable levels of efficacy recently observed with such therapy.

Merkel Cell Polyomavirus (MCPyV) is associated with Merkel Cell carcinoma (MCC), a rare, aggressive skin cancer with neuroendocrine features. The causal role of MCPyV is highly suggested by monoclonal integration of its genome and expression of the viral large T (LT) antigen in MCC cells. We investigated and characterized MCPyV molecular features in MCC, respiratory, urine and blood samples from 33 patients by quantitative PCR, sequencing and detection of integrated viral DNA. We examined associations between either MCPyV viral load in primary MCC or MCPyV DNAemia and survival. Results were interpreted with respect to the viral molecular signature in each compartment. Patients with MCC containing more than 1 viral genome copy per cell had a longer period in complete remission than patients with less than 1 copy per cell (34 vs 10 months, P = 0.037). Peripheral blood mononuclear cells (PBMC) contained MCPyV more frequently in patients sampled with disease than in patients in complete remission (60% vs 11%, P = 0.00083). Moreover, the detection of MCPyV in at least one PBMC sample during follow-up was associated with a shorter overall survival (P = 0.003). Sequencing of viral DNA from MCC and non MCC samples characterized common single nucleotide polymorphisms defining 8 patient specific strains. However, specific molecular signatures truncating MCPyV LT were observed in 8/12 MCC cases but not in respiratory and urinary samples from 15 patients. New integration sites were identified in 4 MCC cases. Finally, mutated-integrated forms of MCPyV were detected in PBMC of two patients with disseminated MCC disease, indicating circulation of metastatic cells. We conclude that MCPyV molecular features in primary MCC tumour and PBMC may help to predict the course of the disease.

Background VZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown. Methods This is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta. Results Seventy‐two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty‐two patients completed follow‐up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd‐ratio (OR) 3.1 [1.4–8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4–181] p = .001, OR 6.2 [1.3–33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta. Conclusions Neurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively. Neurological complications of varicella zoster virus reactivation can involve the central and peripheral nervous systems. Central nervous system involvement was associated with a higher mortality and peripheral involvement with higher sequelae. Higher age and Rankin scale prior to infection were associated with a poorer prognosis.