المؤلفون: Clayton Faua, Axel Ursenbach, Anne Fuchs, Stéphanie Caspar, Frédéric Jegou, Yvon Ruch, Baptiste Hoellinger, Elodie Laugel, Aurélie Velay, David Rey, Samira Fafi-Kremer, Pierre Gantner

المصدر: Pathogens and Immunity, Vol 8, Iss 2 (2024)

مصطلحات موضوعية: AIDS, recent infection, productively infected cells, phenotype, exhaustion, Pathology, RB1-214, Immunologic diseases. Allergy, RC581-607

الوصف: Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage. Methods: Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively. Results: The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4low, HLA-ABClow, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, TTD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1. Conclusions: In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection.

وصف الملف: electronic resource

Relation: https://www.paijournal.com/index.php/paijournal/article/view/638; https://doaj.org/toc/2469-2964

URL الوصول: https://doaj.org/article/ead386184e6940d585c10e1297ad700d

المؤلفون: Aurélie Velay, Ralf Janssen-Langenstein, Stéphane Kremer, Elodie Laugel, Maximilian Lutz, Anne Laure Pierson, Marie-Josée Wendling, Francis Schneider, Samira Fafi-Kremer

المصدر: Emerging Infectious Diseases, Vol 29, Iss 3, Pp 669-671 (2023)

مصطلحات موضوعية: tick-borne encephalitis, tick-borne encephalitis virus, TBEV, pregnant woman, long-term sequelae, intensive care, Medicine, Infectious and parasitic diseases, RC109-216

الوصف: We report a case of severe tick-borne encephalitis in a pregnant woman, leading to a prolonged stay in the intensive care unit. She showed minor clinical improvement >6 months after her presumed infection. The patient was not vaccinated, although an effective vaccine is available and not contraindicated during pregnancy.

وصف الملف: electronic resource

Relation: https://wwwnc.cdc.gov/eid/article/29/3/22-1328_article; https://doaj.org/toc/1080-6040; https://doaj.org/toc/1080-6059

URL الوصول: https://doaj.org/article/21426b91f4b84b02a377ab55026d1101

المؤلفون: Clayton Faua, Samira Fafi-Kremer, Pierre Gantner

المصدر: Journal of Virus Eradication, Vol 9, Iss 2, Pp 100329- (2023)

مصطلحات موضوعية: HIV, Antigen-specificity, Productive infection, Latent infection, Memory CD4+ T cells, Persistence, Microbiology, QR1-502, Public aspects of medicine, RA1-1270

الوصف: Antigen-experienced memory CD4+ T cells are the major target of HIV infection and support both productive and latent infections, thus playing a key role in HIV dissemination and persistence, respectively. Here, we reviewed studies that have shown direct association between HIV infection and antigen specificity. During untreated infection, some HIV-specific cells host productive infection, while other pathogen-specific cells such as cytomegalovirus (CMV) and Mycobacterium tuberculosis also contribute to viral persistence on antiretroviral therapy (ART). These patterns could be explained by phenotypic features differing between these pathogen-specific cells. Mechanisms involved in these preferential infection and selection processes include HIV entry and restriction, cell exhaustion, survival, self-renewal and immune escape. For instance, MIP-1β expressing cells such as CMV-specific memory cells were shown to resist infection by HIV CCR5 coreceptor downregulation/inhibition. Conversely, HIV-infected CMV-specific cells undergo clonal expansion during ART. We have identified several research areas that need further focus such as the role of other pathogens, viral genome intactness, inducibility and phenotypic features. However, given the sheer diversity of both the CD4+ T cell repertoire and antigenic history of each individual, studying HIV-infected, antigen-experienced cells still imposes numerous challenges.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S2055664023000158; https://doaj.org/toc/2055-6640

URL الوصول: https://doaj.org/article/32e0a7109ce748e0abf677709953b323

المؤلفون: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-12 (2022)

مصطلحات موضوعية: Science

الوصف: SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/dd637bc719eb47f4af62af55e665cafc

المؤلفون: Kamil Demircan, Thilo Samson Chillon, Tommy Bracken, Ilaria Bulgarelli, Irene Campi, Gijs Du Laing, Samira Fafi-Kremer, Laura Fugazzola, Alejandro Abner Garcia, Raban Heller, David J. Hughes, Louis Ide, Georg Jochen Klingenberg, Pawel Komarnicki, Zbigniew Krasinski, Alain Lescure, Patrick Mallon, Arash Moghaddam, Luca Persani, Mirko Petrovic, Marek Ruchala, Morgane Solis, Linos Vandekerckhove, Lutz Schomburg

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: trace elements, SARS-CoV-2, mortality, biomarker, nutrition, Immunologic diseases. Allergy, RC581-607

الوصف: IntroductionCertain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe.MethodsSerum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory.ResultsMedian levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769).DiscussionThe data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1022673/full; https://doaj.org/toc/1664-3224

URL الوصول: https://doaj.org/article/37b22a6c4a434d8e9b71bf2f8d0a1db5

المؤلفون: Maxence Meyer, Thomas Vogel, Anita Meyer, Florentin Constancias, Louise F. Porter, Georges Kaltenbach, Elise Schmitt, Saïd Chayer, Floriane Zeyons, Marianne Riou, Samira Fafi‐Kremer, Aurélie Velay, Soraya El Ghannudi

المصدر: ESC Heart Failure, Vol 8, Iss 5, Pp 4307-4312 (2021)

مصطلحات موضوعية: COVID‐19, SARS‐CoV‐2, Myocarditis, Myocardial injury, 6 month follow‐up, Long‐term sequelae, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Abstract Here, we present the case of an 81‐year‐old male patient, who was hospitalized for a severe form of COVID‐19. Transthoracic echocardiogram (TTE) performed 1 month after symptom onset was normal. Respiratory evolution was favourable, and the patient was discharged at Day 78. At 6 months, despite a good functional recovery, he presented pulmonary sequelae, and the TTE revealed a clear reduction of left ventricular ejection fraction (LVEF) and mild LV dilatation without cardiac symptoms. The cardiac magnetic resonance (CMR) using Lake Louise Criteria (LLC), T1 and T2 mapping showed focal infero‐basal LV wall oedema, elevated T1 and T2 myocardial relaxation times especially in basal inferior and infero‐lateral LV walls, and sub‐epicardial late gadolinium enhancement in those LV walls. The diagnosis of active myocarditis was raised especially based on TTE abnormalities and CMR LLC, T1 and T2 mapping. Currently, we are not aware of published reports of a 6 month post‐COVID‐19 active myocarditis.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2055-5822

URL الوصول: https://doaj.org/article/d03c60a4c42e46d49edc99a63c3aa7fc

المؤلفون: Floriane Gallais, Pierre Gantner, Delphine Planas, Morgane Solis, Timothée Bruel, Florian Pierre, Eric Soulier, Paola Rossolillo, Slim Fourati, Jean Sibilia, Olivier Schwartz, Samira Fafi-Kremer

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: SARS-CoV-2, variant of concern, vaccine, immune evasion, breakthrough infection, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundSARS-CoV-2 breakthrough infections after complete vaccination are increasing whereas their determinants remain uncharacterized.MethodsWe analyzed two cases of post-vaccination SARS-CoV-2 infections by α and β variants, respectively. For each participant both humoral (binding and neutralizing antibodies) and cellular (activation markers and cytokine expression) immune responses were characterized longitudinally.ResultsThe first participant (P1) was infected by an α variant and displayed an extended and short period of viral excretion and symptom. Analysis of cellular and humoral response 72 h post-symptom onset revealed that P1 failed at developing neutralizing antibodies and a potent CD4 memory response (lack of SARS-CoV-2 specific CD4+IL-2+ cells) and CD8 effector response (CD8+IFNγ+ cells). The second participant (P2) developed post-vaccination SARS-CoV-2 infection by a β variant, associated with a short period of viral excretion and symptoms. Despite displaying initially high levels and polyfunctional T cell responses, P2 lacked initial β-directed neutralizing antibodies. Both participants developed and/or increased their neutralization activity and cellular responses against all variants, namely, β and δ variants that lasts up to 3 months after breakthrough infection.ConclusionsAn analysis of cellular and humoral response suggests two possible mechanisms of breakthrough infection: a poor immune response to vaccine and viral evasion to neutralizing antibodies.

وصف الملف: electronic resource

Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2022.790212/full; https://doaj.org/toc/1664-3224

URL الوصول: https://doaj.org/article/d4500e13332842ab9db6c5f1eb035ba4

المؤلفون: Floriane Gallais, Aurélie Velay, Charlotte Nazon, Marie-Josée Wendling, Marialuisa Partisani, Jean Sibilia, Sophie Candon, Samira Fafi-Kremer

المصدر: Emerging Infectious Diseases, Vol 27, Iss 1, Pp 113-121 (2021)

مصطلحات موضوعية: antibodies, coronavirus disease, coronavirus symptoms, COVID-19, household exposure, IgA, Medicine, Infectious and parasitic diseases, RC109-216

الوصف: We investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies and T-cell responses against SARS-CoV-2 and human coronavirus (HCoV) 229E and OC43 in 11 SARS-CoV-2 serodiscordant couples in Strasbourg, France, in which 1 partner had evidence of mild coronavirus disease (COVID-19) and in 10 unexposed healthy controls. Patients with confirmed COVID-19 were considered index patients and their partners close contacts. All index patients displayed positive SARS-CoV-2–specific antibody and T-cell responses that lasted up to 102 days after symptom onset. All contacts remained seronegative for SARS-CoV-2; however, 6 reported COVID-19 symptoms within a median of 7 days after their partners, and 4 of those showed a positive SARS-CoV-2–specific T-cell response against 3 or 4 SARS-CoV-2 antigens that lasted up to 93 days after symptom onset. The 11 couples and controls displayed positive T-cell responses against HCoV-229E or HCoV-OC43. These data suggest that exposure to SARS-CoV-2 can induce virus-specific T-cell responses without seroconversion.

وصف الملف: electronic resource

Relation: https://wwwnc.cdc.gov/eid/article/27/1/20-3611_article; https://doaj.org/toc/1080-6040; https://doaj.org/toc/1080-6059

URL الوصول: https://doaj.org/article/5bf83613af004008bec216fc7186bdb1

المؤلفون: Nicolas de Prost, Etienne Audureau, Nicholas Heming, Elyanne Gault, Tài Pham, Amal Chaghouri, Nina de Montmollin, Guillaume Voiriot, Laurence Morand-Joubert, Adrien Joseph, Marie-Laure Chaix, Sébastien Préau, Raphaël Favory, Aurélie Guigon, Charles-Edouard Luyt, Sonia Burrel, Julien Mayaux, Stéphane Marot, Damien Roux, Diane Descamps, Sylvie Meireles, Frédéric Pène, Flore Rozenberg, Damien Contou, Amandine Henry, Stéphane Gaudry, Ségolène Brichler, Jean-François Timsit, Antoine Kimmoun, Cédric Hartard, Louise-Marie Jandeaux, Samira Fafi-Kremer, Paul Gabarre, Malo Emery, Claudio Garcia-Sanchez, Sébastien Jochmans, Aurélia Pitsch, Djillali Annane, Elie Azoulay, Armand Mekontso Dessap, Christophe Rodriguez, Jean-Michel Pawlotsky, Slim Fourati

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-1 (2022)

مصطلحات موضوعية: Science

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/b162254b4a2c409dac5066889a655216

المؤلفون: Julie Helms, Stéphane Kremer, Hamid Merdji, Malika Schenck, François Severac, Raphaël Clere-Jehl, Antoine Studer, Mirjana Radosavljevic, Christine Kummerlen, Alexandra Monnier, Clotilde Boulay, Samira Fafi-Kremer, Vincent Castelain, Mickaël Ohana, Mathieu Anheim, Francis Schneider, Ferhat Meziani

المصدر: Critical Care, Vol 24, Iss 1, Pp 1-11 (2020)

مصطلحات موضوعية: COVID-19, Delirium, Encephalopathy, ICU, MRI, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9

الوصف: Abstract Background Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients. Methods We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms. Results The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2. Conclusions and relevance Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources. Trial registration NA.

وصف الملف: electronic resource

Relation: http://link.springer.com/article/10.1186/s13054-020-03200-1; https://doaj.org/toc/1364-8535

URL الوصول: https://doaj.org/article/c3b40ded9ce74b01a0041ff44ed7094e