COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

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.

Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variants BA.2, BA.5 and BQ.1.1 in critically ill patients with COVID-19: a prospective, multicenter cohort study.

BACKGROUND: Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. RESULTS: The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as "BA.2" (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as "BA.4/BA.5", and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as "BQ.1.1". The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. CONCLUSIONS: Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.

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.

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.

Clinical phenotypes and outcomes associated with SARS-CoV-2 variant Omicron in critically ill French patients with COVID-19.

Infection with SARS-CoV-2 variant Omicron is considered to be less severe than infection with variant Delta, with rarer occurrence of severe disease requiring intensive care. Little information is available on comorbid factors, clinical conditions and specific viral mutational patterns associated with the severity of variant Omicron infection. In this multicenter prospective cohort study, patients consecutively admitted for severe COVID-19 in 20 intensive care units in France between December 7th 2021 and May 1st 2022 were included. Among 259 patients, we show that the clinical phenotype of patients infected with variant Omicron (n = 148) is different from that in those infected with variant Delta (n = 111). We observe no significant relationship between Delta and Omicron variant lineages/sublineages and 28-day mortality (adjusted odds ratio [95% confidence interval] = 0.68 [0.35-1.32]; p = 0.253). Among Omicron-infected patients, 43.2% are immunocompromised, most of whom have received two doses of vaccine or more (85.9%) but display a poor humoral response to vaccination. The mortality rate of immunocompromised patients infected with variant Omicron is significantly higher than that of non-immunocompromised patients (46.9% vs 26.2%; p = 0.009). In patients infected with variant Omicron, there is no association between specific sublineages (BA.1/BA.1.1 (n = 109) and BA.2 (n = 21)) or any viral genome polymorphisms/mutational profile and 28-day mortality.

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.

SARS-CoV-2 infection long time after full vaccination is related to a lack of neutralizing antibodies.

SARS-CoV-2 infections after COVID-19 vaccination are not unexpected, but those occurring more than 14 days after second vaccine dose need to be investigated. We describe a well-characterized infection which occurred almost 2 months after full vaccination, and provide the evidence of a link with a lack of anti-SARS-CoV-2 neutralizing antibodies.

Serological diagnosis of Toxoplasma gondii: analysis of false-positive IgG results and implications.

BACKGROUND: Primary infection by Toxoplasma gondii in pregnant women can result in serious outcomes for the foetus. A false-positive IgG result during pregnancy can lead to a misdiagnosis of past infection and to stopping preventive measures. We collected 189 sera with positive Architect® Toxo IgG assay (Abbott Laboratories) and negative IgG results with at least two other serological tests, in order to find an explanation for the suspected false-positive IgG results. We used the recomLine Toxoplasma IgG® immunoblot (Mikrogen Diagnostik) to search for specific antigenic reactivities of the sera, and the LDBio Toxo II IgG® immunoblot (LDBio Diagnostics) as a confirmatory test. RESULTS: The bands GRA8 and/or GRA7 were positive for 148 samples (78.3%). GRA8 was the most frequent band, appearing in 133 patterns (70.4%), whereas GRA7 was present for 49 samples (25.9%). Of the 81 samples tested with LDBio®, 23 (28.4%) turned out to be positive. Of the 58 negative LDBio® tests (71.6%) (real false-positive Architect® IgG), 23 samples (39.6%) did not show either a GRA8 or p30 band by recomLine®. Their false positivity with Architect® remains unexplained since Abbott uses these two recombinant antigens for their assay. CONCLUSIONS: The Architect® IgG false positivity for T. gondii seems to be due to reactivity against GRA8 for the majority of the sera and GRA7 to a lesser extent. The hypothesis of past contact with parasites genetically close to T. gondii such as Hammondia hammondi or Neospora caninum seems promising and should be assessed further.

TITLE: Diagnostic sérologique de Toxoplasma gondii : analyse des IgG faux positifs et implications. ABSTRACT: Contexte : La primo-infection à Toxoplasma gondii chez la femme enceinte peut avoir de graves conséquences pour le fœtus. Un résultat IgG faussement positif pendant la grossesse peut mener à un diagnostic erroné d'infection ancienne et à stopper les mesures préventives. Nous avons collecté 189 sérums présentant un résultat Architect® Toxo IgG (Abbott Laboratories) positif ainsi qu'un résultat IgG négatif par au moins deux autres tests sérologiques, dans le but de trouver une explication aux résultats IgG suspectés faux positifs. Nous avons utilisé l'immunoblot recomLine Toxoplasma IgG® (Mikrogen Diagnostik) pour chercher certaines réactivités antigéniques spécifiques des sérums et l'immunoblot LDBio Toxo II IgG® (LDBio Diagnostics) comme test de confirmation. Résultats : Les bandes GRA8 et/ou GRA7 étaient positives pour 148 (78,3 %) échantillons. GRA8 était la bande la plus fréquente, apparaissant dans 133 (70,4 %) profils alors que GRA7 était présente pour 49 (25,9 %) échantillons. Sur les 81 échantillons testés en LDBio®, 23 (28,4 %) se sont révélés positifs. Sur les 58 (71,6 %) tests LDBio® négatifs (réels faux positifs IgG Architect®), 23 (39,6 %) échantillons n'ont montré ni bande GRA8 ni bande p30 en recomLine® et leur fausse positivité reste donc inexpliquée puisque Abbott utilise ces deux antigènes recombinants dans son test. Conclusions : La fausse positivité IgG Architect® pour T. gondii semble être due à une réactivité envers la protéine GRA8 pour la majorité des sérums et envers GRA7 dans une moindre mesure. L'hypothèse d'un contact passé avec des parasites génétiquement proches de T. gondii comme Hammondia hammondi ou Neospora caninum semble prometteuse et devrait être approfondie.

Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma.

Background: HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Methods: Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm. Results: Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL < 1.7 log 10 copies/mL). The CSF VL was lower (median 2.8 versus 4.0 log 10 copies/mL; P < 0.001) and the CD4 cell count was higher (median 476 versus 214 cells/mm 3 ; P < 0.001) in the group of patients with VL < 1.7 log 10 copies/mL in plasma compared with patients with plasma VL > 1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Conclusions: Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.

Reliability of the INSTI® rapid test for the diagnosis of HIV-1 non-B subtypes and recombinant variants.

Data regarding the efficacy of Rapid HIV tests (RHTs) in detecting non-B subtype HIV-1 are limited. We evaluated the sensitivity of the INSTI® test for the detection of HIV-1 antibodies for the diagnosis of HIV-1 non-B subtypes and recombinant variants. We identified adults with HIV-1 infection due to non-B subtypes and recombinant variants. The participants were re-tested with INSTI® test. We included 258 patients. Overall, the INSTI® test sensitivity was 98.4% (95%CI: 96.9-99.9%). For the major CRF_02AG subtype, the sensitivity was 99.0% (95%CI: 97.1-100%). The HIV INSTI® test is reliable for the detection of various non-B HIV-1 antibodies.

Risk Factors and Outcomes for Intestinal Carriage of AmpC-Hyperproducing Enterobacteriaceae in Intensive Care Unit Patients.

In a cohort of 1,209 intensive care unit (ICU) patients, the prevalence of intestinal colonization with high-level expressed AmpC cephalosporinase-producing Enterobacteriaceae (HLAC-PE) rose steadily from 2% at admission to 30% in patients with lengths of stay (LOS) exceeding 4 weeks. In multivariate analysis, LOS was the main predictor of carriage acquisition after adjustment on antimicrobial exposure. HLAC-PE infection occurred in 15% of carriers. Carriage and infection were associated with a marked increase in carbapenem consumption.

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma.

OBJECTIVES: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. METHODS: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. RESULTS: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P=0.0455) and T215Y (P=0.0455). CONCLUSIONS: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.

Finger-stick whole blood HIV-1/-2 home-use tests are more sensitive than oral fluid-based in-home HIV tests.

BACKGROUND: Several countries have recently recommended the expansion of anti-human immunodeficiency virus (HIV) antibody testing, including self-testing with rapid tests using oral fluid (OF). Several tests have been proposed for at-home use, but their diagnostic accuracy has not been fully evaluated. OBJECTIVE: To evaluate the performance of 5 rapid diagnostic tests for the detection of anti-HIV-1/2 antibodies, with 4 testing OF and 1 testing whole blood. METHODS: Prospective multi-center study in France. HIV-infected adults and HIV-uninfected controls were systematically screened with 5 at-home HIV tests using either OF or finger-stick blood (FSB) specimens. Four OF tests (OraQuick Advance Rapid HIV-1/2, Chembio DPP HIV 1/2 Assay, test A, and test B) and one FSB test (Chembio Sure Check HIV1/2 Assay) were performed by trained health workers and compared with laboratory tests. RESULTS: In total, 179 HIV-infected patients (M/F sex ratio: 1.3) and 60 controls were included. Among the HIV-infected patients, 67.6% had an undetectable HIV viral load in their plasma due to antiretroviral therapy. Overall, the sensitivities of the OF tests were 87.2%, 88.3%, 58.9%, and 28% (for OraQuick, DPP, test A, and test B, respectively) compared with 100% for the FSB test Sure Check (p<0.0001 for all comparisons). The OraQuick and DPP OF tests' sensitivities were significantly lower than that of the FSB-based Sure Check (p<0.05). The sensitivities of the OF tests increased among the patients with a detectable HIV viral load (>50 copies/mL), reaching 94.8%, 96.5%, 90%, and 53.1% (for OraQuick, DPP, test A, and test B, respectively). The specificities of the four OF tests were 98.3%, 100%, 100%, and 87.5%, respectively, compared with 100% for the FSB test. CONCLUSION: An evaluation of candidates for HIV self-testing revealed unexpected differences in performance of the rapid tests: the FSB test showed a far greater reliability than OF tests.

Epidemiological and molecular features of dengue virus type-1 in New Caledonia, South Pacific, 2001-2013.

BACKGROUND: The epidemiology of dengue in the South Pacific has been characterized by transmission of a single dominant serotype for 3-5 years, with subsequent replacement by another serotype. From 2001 to 2008 only DENV-1 was reported in the Pacific. In 2008, DENV-4 emerged and quickly displaced DENV-1 in the Pacific, except in New Caledonia (NC) where DENV-1 and DENV-4 co-circulated in 2008-2009. During 2012-2013, another DENV-1 outbreak occurred in NC, the third DENV-1 outbreak in a decade. Given that dengue is a serotype-specific immunizing infection, the recurrent outbreaks of a single serotype within a 10-year period was unexpected. FINDINGS: This study aimed to inform this phenomenon by examining the phylogenetic characteristics of the DENV-1 viruses in NC and other Pacific islands between 2001 and 2013. As a result, we have demonstrated that NC experienced introductions of viruses from both the Pacific (genotype IV) and South-east Asia (genotype I). Moreover, whereas genotype IV and I were co-circulating at the beginning of 2012, we observed that from the second half of 2012, i.e. during the major DENV-1 outbreak, all analyzed viruses were genotype I suggesting that a genotype switch occurred. CONCLUSIONS: Repeated outbreaks of the same dengue serotype, as observed in NC, is uncommon in the Pacific islands. Why the earlier DENV-1 outbreaks did not induce sufficient herd immunity is unclear, and likely multifactorial, but the robust vector control program may have played a role by limiting transmission and thus maintaining a large susceptible pool in the population.

Usefulness in clinical practice of a point-of-care rapid test for simultaneous detection of nontreponemal and Treponema pallidum-specific antibodies in patients suffering from documented syphilis.

The usefulness of a point-of-care immunochromatographic dual test for the simultaneous detection of both nontreponemal and Treponema pallidum-specific antibodies (Chembio Diagnostics Systems Inc., Medford, NY, USA) was assessed in various situations related to syphilis, by reference to conventional syphilis serology. Thawed sera were obtained from 100 adults including 36 primary syphilis, 6 secondary syphilis, 6 re-infection, 9 recently-treated syphilis, and 43 old syphilis. Doubtful reactivities for the treponemal line were considered positive; doubtful reactivities for the nontreponemal line were considered positive only when the treponemal line was present. The sensitivity, the specificity, and its concordance to gold standard serology of treponemal line were high, around 90%. The sensitivity of nontreponemal line was 96.3%, its specificity 76.7%, and its concordance 83.4%. In conclusion, the dual rapid test from Chembio Diagnostics Systems Inc. is useful for rapid point-of-care diagnosis in the various situations encountered with patients suffering from syphilis.

HIV-DNA in the genital tract of women on long-term effective therapy is associated to residual viremia and previous AIDS-defining illnesses.

OBJECTIVES: To assess the impact of long-term combined antiretroviral therapy (cART) on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL); to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission. METHODS: Women with undetectable PVL (<50 copies/mL) for >6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL). Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated. RESULTS: Eighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%). There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08). In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2-61) and current residual viremia (20