Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many ...countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with ...COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9-11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine.
•There is an urgent need for independent validation of available antigen-detecting rapid diagnostic tests designed for direct detection of SARS-CoV-2 viral proteins produced by replicating virus in ...respiratory secretions.•The SIENNA™ COVID-19 Antigen test demonstrates excellent analytical performances for viral loads ≤33 Ct, corresponding to situations of symptomatic COVID-19 and/or proven contagiousness.•The SIENNA™ COVID-19 Antigen test can be recommended for routine clinical use in most diagnostic indications of SARS-CoV-2 infection.
We herein assessed the analytical performances of the antigen-rapid diagnostic test (Ag-RDT) SIENNA™ COVID-19 Antigen Rapid Test Cassette (Nasopharyngeal Swab) (Salofa Oy, Salo, Finland), targeting the SARS-CoV-2 N nucleocapsid protein, for the diagnosis of COVID-19 in hospitalized patients with suspected SARS-CoV-2 infection, by reference to real-time RT-PCR (rRT-PCR).
Nasopharyngeal swabs were collected from patients with COVID-19-like illness during the second epidemic wave in Paris, France, among which 100 and 50 were positive and negative for SARS-CoV-2 RNA, respectively.
Overall, the Ag-RDT showed high sensitivity, specificity, positive and negative predictive values of 90.0%, 100.0%, 100.0% and 98.1%, respectively, as well as high or almost perfect agreement (93.3%), reliability assessed by Cohen’s κ coefficient (0.86), and accuracy assessed by Youden’s J index (90%) to detect SARS-CoV-2. The analytical performances of the Ag-RDT remained high in the event of significant viral excretion (i.e., N gene Ct values ≤33 by reference rtRT-PCR), while the sensitivity of the Ag-RDT dropped to 69.6% with low or very low viral shedding (Ct > 33).
The SIENNA™ Ag-RDT presents excellent analytical performances for viral loads ≤33 Ct, classically corresponding to situations of symptomatic COVID-19 and/or proven contagiousness.
Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16-positive metastasis were ...retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.
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.
We read with a great interest the meta-analysis of Gilbert D.C. et al. recently published in British Journal of Cancer1 and contributing to the evaluation of the potential risk of HPV-related second ...cancer in patients with a history of a primary HPV-related cancer in the same or an independent mucosal site.
Cervical cancer associated with high risk-human papillomavirus (HR-HPV) infection is becoming the one of the most common female cancer in many sub-Saharan African countries. First-generation ...immigrant African women living in Europe are at-risk for cervical cancer, in a context of social vulnerability, with frequent lack of cervical cancer screening and HPV vaccination.
Our objective was to address immunologically the issue of catch-up prophylactic HPV vaccination in first-generation African immigrant women living in France.
IgG immune responses and cross-reactivities to α7 (HPV-18, -45 and -68) and α9 (HPV-16, -31, -33, -35, -52 and -58) HPV types, including 7 HR-HPV targeted by the Gardasil-9® prophylactic vaccine, were evaluated in paired serum and cervicovaginal secretions (CVS) by HPV L1-virus-like particles-based ELISA. Genital HPV were detected by multiplex real time PCR (Seegene, Seoul, South Korea).
Fifty-one immigrant women (mean age, 41.7 years; 72.5% HIV-infected) were prospectively included. More than two-third (68.6%) of them carried genital HPV (group I) while 31.4% were negative (group II). The majority (90.2%) exhibited serum IgG to at least one α7/α9 HR-HPV. Serum HPV-specific IgG were more frequently detected in group I than group II (100% versus 68.7%; P = 0.002). The distribution of serum and genital HPV-specific IgG was similar, but mean number of IgG reactivities to α7/α9 HR-HPV was higher in serum than CVS (5.6 IgG per woman in serum versus 3.2 in CVS; P<0.001). Rates of IgG cross-reactivities against HPV different from detected cervicovaginal HPV were higher in serum and CVS in group I than group II. Finally, the majority of groups I and II women (68.6% and 68.7%, respectively) exhibited serum or cervicovaginal IgG to Gardasil-9® HR-HPV, with higher mean rates in group I than group II (6.1 Gardasil-9® HR-HPV per woman versus 1.4; P<0.01). One-third (31.2%) of group II women did not show any serum and genital HPV-specific IgG.
Around two-third of first-generation African immigrant women living in France showed frequent ongoing genital HPV infection and high rates of circulating and genital IgG to α7/α9 HPV, generally cross-reacting, avoiding the possibility of catch-up vaccination. Nevertheless, about one-third of women had no evidence of previous HPV infection, or showed only low levels of genital and circulating HR-HPV-specific IgG and could therefore be eligible for catch-up vaccination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human papillomavirus (HPV)-related cervical lesions in first-generation immigrant African women in France should reflect the epidemiology of high-risk (HR)-human papillomavirus (HPV) infection in ...sub-Saharan Africa. First-generation immigrant African women attending the
Centre Hospitalier Régional
of Orléans, France, were prospectively subjected to endocervical swabs for HPV DNA PCR and Pap smear. Fifty women (mean age, 41.7 years) living in France (mean stay, 10.7 years) were enrolled, including 26.0% of HIV-negative women from general population and 74.0% of women with known HIV infection. Cervical HPV prevalence was 68.0%, with 56.0% of HR-HPV. HR-HPV -68 and -58 were the predominant genotypes (20.0% and 14.0%, respectively). HR-HPV-16 and HR-HPV-18 were infrequently detected. HIV-infected women showed a trend to be more frequently infected by HPV than HIV-negative women (70.3%
versus
61.5%). Most women (84.0%) showed normal cytology, while the remaining (16.0%) exhibited cervical abnormalities and were frequently HIV-infected (87.5%). These observations highlight the unsuspected high burden of cervical HR-HPV infections mostly associated with atypical genotypes, HIV infection and cervical abnormalities in first-generation immigrant African women living in France.
Abstract Background High-risk human papillomavirus (HR-HPV) anal infection is a major problem among men who have sex with men (MSM) living in sub-Saharan Africa. The prevalence of anal HR-HPV ...infection and associated risk factors were estimated in a cross-sectional study in MSM living in Bamako, Mali. Methods MSM consulting at sexual health center of the National NGO Soutoura, Bamako, were prospectively included. Sociodemographic and clinical-biological data were collected. HPV detection and genotyping were performed from anal swabs using multiplex real-time PCR. Risk factors associated with anal HPV infection were assessed by logistic regression analysis. Results Fifty MSM (mean age, 24.2 years; range, 18–35) of which 32.0% were infected with HIV-1, were prospectively included. The overall prevalence of anal HPV infection of any genotypes was 70.0% (35/50) with 80.0% (28/35) of swabs positive for HR-HPV. HR-HPV-58 was the most detected genotype 13/35 (37.1%), followed by HR-HPV-16 and low-risk (LR)-HPV-6 12/35 (34.2%), LR-HPV-40 10/35 (28.6%), LR-HPV-11 9/35 (25.7%), HR-HPV-51 8/35 (22.8%), HR-HPV types 18 and 39 7/35 (20.0%) and LR-HPV-43 6/35 (17.1%). HR-HPV-52 and LR-HPV-44 were detected in lower proportions 5/35 (14.3%) and 4/35 (11.4%), respectively. LR-HPV-42, LR-HPV-54, HR-HPV-31 and HR-HPV-35 were detected in very low proportions 3/35 (8.5%). Multiple HR-HPV infections were diagnosed in one-third of anal samples 16/50 (32.0%), including around half of HR-HPV-positive anal swabs 16/35 (45.7%). More than half 27/50 (54.0%) swabs were infected by at least one of HPV genotypes targeted by Gardasil-9® vaccine, including a majority of vaccine HR-HPV 22/50 (44.0%). In multivariate analysis, participation to sex in group was associated with anal infection by multiple HPV (aOR: 4.5, 95% CI: 1.1–18.1%; P = 0.032), and HIV-1 infection was associated with anal shedding of multiple HR-HPV (aOR: 5.5, 95% CI: 1.3–24.5%; P = 0.024). Conclusions These observations indicate that the MSM community living in Bamako is at high-risk for HR-HPV anal infections, with a unique epidemiological HPV genotypes profile and high prevalence of anal HPV covered by the Gardasil-9® vaccine. Scaling up prevention strategies against HPV infection and related cancers adapted to this highly vulnerable MSM community should be urgently prioritized with innovative interventions.
Abstract
Background
Little is known about targeted (antiviral or monoclonal antibody) anti-SARS-CoV-2 treatment in immunocompromised patients with COVID-19.
Objectives
To assess the real-life ...efficacy and tolerance of targeted treatment of COVID-19 in immunocompromised patients.
Patients and methods
Single-centre retrospective case series of immunocompromised patients with COVID-19 between December 2021 and March 2022. We recorded all cases of COVID-19 among immunocompromised patients treatment between 20 December 2021 and 15 March 2022. Choice of treatment was left to the physician’s decision, according to internal treatment protocol, treatment availability and circulating variants. Main outcome was death from COVID-19 after no treatment or targeted treatment.
Results
Sixty-seven immunocompromised patients 38 male; median (IQR) age, 53 (43–63) years, with a median (IQR) follow-up of 60 (47–80) days. Ten patients did not receive any targeted treatment. Targeted treatment consisted of IV curative remdesivir (n = 22), sotrovimab (n = 16), tixagevimab/cilgavimab (n = 13) and casirivimab/imdevimab (n = 1). Ten patients (15%) presented severe COVID-19 and 2 (3%) died from Omicron COVID-19. Comparing patients who received targeted anti-SARS-CoV-2 treatment and no prophylaxis, (n = 42; 81%) with those who did not (n = 10; 19%), death rate was significantly lower in treated patients n = 0 (0%) versus n = 2 (20%); P = 0.034. No severe adverse events were reported among treated patients. Among 15 patients who received tixagevimab/cilgavimab as pre-exposure prophylaxis, 6 received an additional curative treatment and none died from COVID-19.
Conclusions
Our results suggest that targeted COVID-19 treatment, including direct antivirals or monoclonal antibodies, is safe and efficient and could be proposed in high-risk immunocompromised patients.
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