21 research outputs found
Update of Perinatal Human Immunodeficiency Virus Type 1 Transmission in France: Zero Transmission for 5482 Mothers on Continuous Antiretroviral Therapy From Conception and With Undetectable Viral Load at Delivery
No full textInternational audienceBACKGROUND: Antiretroviral therapy (ART) is remarkably effective in preventing perinatal transmission (PT) of HIV-1. We evaluated the PT rate in a population of women with widespread access to ART before conception. METHODS: The analysis included 14 630 women with HIV-1 who delivered from 2000 to 2017 at centers participating in the nationwide prospective multicenter French Perinatal Cohort (ANRS-EPF). PT was analyzed according to time period, timing of ART initiation, maternal plasma viral load (pVL), and gestational age at birth. No infants were breastfed, and all received neonatal prophylaxis. RESULTS: PT decreased between 3 periods, from 1.1% in 2000-2005 (58/5123) to 0.7% in 2006-2010 (30/4600) and to 0.2% in 2011-2017 (10/4907; P < .001). Restriction of the analysis to the 6316/14 630 (43%) women on ART at conception, PT decreased from 0.42% (6/1434) in 2000-2005 to 0.03% (1/3117) in 2011-2017 (P = .007). Among women treated at conception, if maternal pVL was undetectable near delivery, no PT was observed regardless of the ART combination [95%CI 0-0.07] (0/5482). Among women who started ART during pregnancy and with undetectable pVL near delivery, PT was 0.57% [95%CI 0.37-0.83] (26/4596). Among women treated at conception but with a detectable pVL near delivery, PT was 1.08% [95%CI 0.49-2.04] (9/834). We also qualitatively described 10 cases of transmission that occurred during the 2011-2017 period. CONCLUSIONS: In a setting with free access to ART, monthly pVL assessment, infant ART prophylaxis, and in the absence of breastfeeding, suppressive ART initiated before pregnancy and continued throughout pregnancy can reduce PT of HIV to almost zero
Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study
No full textInternational audienceBackground: The early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8TN), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).Methods: The ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.Results: At the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability.Conclusion: In children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
No full textInterindividual clinical vari-ability is vast in humans infected withsevere acute respiratory syndrome corona-virus 2 (SARS-CoV-2), ranging from silent in-fection to rapid death. Three risk factors forlife-threatening coronavirus disease 2019(COVID-19) pneumonia have been identified—being male, being elderly, or having othermedical conditions—but these risk factorscannot explain why critical disease remainsrelatively rare in any given epidemiologicalgroup. Given the rising toll of the COVID-19pandemic in terms of morbidity and mortality,understanding the causes and mechanisms oflife-threatening COVID-19 is crucial.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANRS-COV05), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Institut Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. Samples from San Raffaele Hospital were obtained through the Covid-BioB project and by healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical laboratory and clinical research unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort Study Group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Milieu Intérieur Consortium was supported by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Milieu Intérieur grant (ANR-10-LABX-69-01) (primary investigators: L.Q.-M. and D.Du.). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (primary investigator: G.G.). S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia and a COVID19 Rapid Response Grant awarded by UNSW Sydney. C.R.-G. and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE) and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). S.T.-A. and A.B. were supported by ANR-20-COVI-0064 (primary investigator: A.Be.). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013,” by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and by a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir program FIGHT-HF (reference no. ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence” (reference no. ANR-15-IDEX-04-LUE) (45); and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology; by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to F.R.-L.); and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1; a George Mason University Fast Grant; and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants from the Amsterdam Corona Research Fund, the Dr. C.J. Vaillant Fund, and the Netherlands Organization for Health Research and Development [ZonMw; NWO-Vici-Grant (grant no. 918·19·627 to D.v.d.B.)]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. J.H. holds an Institut Imagine M.D.-Ph.D. fellowship from the Fondation Bettencourt Schueller. J.R. is supported by the INSERM Ph.D. program (“poste d’accueil Inserm”). P.Ba. was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the M.D.-Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K.K. was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (contract no. HHSN316201300006W/HHSN27200002 to MSC, Inc.), the Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data, and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support. Biomedical Advanced Research and Development Authority was supported under contract no. HHSO10201600031C (to J.H.). Financial support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) K08AI135091; the Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; and the American Academy of Allergy, Asthma, and Immunology
Long-term neurological symptoms after acute COVID-19 illness requiring hospitalization in adult patients: insights from the ISARIC-COVID-19 follow-up study
No full textin this study we aimed to characterize the type and prevalence of neurological symptoms related to neurological long-COVID-19 from a large international multicenter cohort of adults after discharge from hospital for acute COVID-19
Long Covid: a global health issue – a prospective, cohort study set in four continents
No full textIntroduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium’s Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities.Results Of 11 860 participants (median age: 52 (IQR: 41–62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively.Conclusion Our data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all
Initiating antiretroviral treatment early in infancy has long-term benefits on the HIV reservoir in late childhood and adolescence
No full textInternational audienceBackgroundEarly combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study aims to compare HIV reservoirs in children (5-12 years) and adolescents (13-17 years) who started cART before 6 months (early (E-)group) or after 2 years old (late (L-)group). MethodsThe ANRS-EP59-CLEAC study prospectively enrolled 76 HIV-1 perinatally-infected patients who reached HIV-RNA<400 copies/mL less than 24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cells (PBMCs) stimulation.ResultsTotal HIV-DNA levels were lower in early- than late-treated patients (Children: 2.14 vs 2.87 log cp/million PBMCs, p<0.0001; Adolescents: 2.25 vs 2.74log, p<0.0001). Low reservoir was independently associated with treatment precocity, protective HLA and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than the other patients (4 vs 54 months, p=0.03). In those with sustained virological control, transitional memory and effector memory CD4+T cells were less infected in the E-group than in the L-group (p=0.03 and 0.02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between the groups.ConclusionsEarly cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies
The value of open-source clinical science in pandemic response: lessons from ISARIC
No full textInternational audienc
Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms
No full textBackground: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders
Sex differences in post-acute neurological sequelae of SARS-CoV-2 and symptom resolution in adults after coronavirus disease 2019 hospitalization: an international multi-centre prospective observational study
No full text: Although it is known that coronavirus disease 2019 can present with a range of neurological manifestations and in-hospital complications, sparse data exist on whether these initial neurological symptoms of coronavirus disease 2019 are closely associated with post-acute neurological sequelae of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; PANSC) and whether female versus male sex impacts symptom resolution. In this international, multi-centre, prospective, observational study across 407 sites from 15 countries (30 January 2020 to 30 April 2022), we report the prevalence and risk factors of PANSC among hospitalized adults and investigate the differences between males and females on neurological symptom resolution over time. PANSC symptoms included altered consciousness/confusion, fatigue/malaise, anosmia, dysgeusia and muscle ache/joint pain, on which information was collected at index hospitalization and during follow-up assessments. The analysis considered a time to the resolution of individual and all neurological symptoms. The resulting times were modelled by Weibull regression, assuming mixed-case interval censoring, with sex and age included as covariates. The model results were summarized as cumulative probability functions and age-adjusted and sex-adjusted median times to resolution. We included 6862 hospitalized adults with coronavirus disease 2019, who had follow-up assessments. The median age of the participants was 57 years (39.2% females). Males and females had similar baseline characteristics, except that more males (versus females) were admitted to the intensive care unit (30.5 versus 20.3%) and received mechanical ventilation (17.2 versus 11.8%). Approximately 70% of patients had multiple neurological symptoms at the first follow-up (median = 102 days). Fatigue (49.9%) and myalgia/arthralgia (45.2%) were the most prevalent symptoms of PANSC at the initial follow-up. The reported prevalence in females was generally higher (versus males) for all symptoms. At 12 months, anosmia and dysgeusia were resolved in most patients, although fatigue, altered consciousness and myalgia remained unresolved in >10% of the cohort. Females had a longer time to the resolution (5.2 versus 3.4 months) of neurological symptoms at follow-up for those with more than one neurological symptom. In the multivariable analysis, males were associated with a shorter time to the resolution of symptoms (hazard ratio = 1.53; 95% confidence interval = 1.39-1.69). Intensive care unit admission was associated with a longer time to the resolution of symptoms (hazard ratio = 0.68; 95% confidence interval = 0.60-0.77). Post-discharge stroke was uncommon (0.3% in females and 0.5% in males). Despite the methodological challenges involved in the collection of survey data, this international multi-centre prospective cohort study demonstrated that PANSC following index hospitalization was high. Symptom prevalence was higher and took longer to resolve in females than in males. This supported the fact that while males were sicker during acute illness, females were disproportionately affected by PANSC
COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
No full textBackground: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
