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Introduction Nous avons précédemment montré que le vaccin monovalent (souche B1.351) à protéine recombinante avec adjuvant AS03 (MVB.1.351, Sanofi/GSK), administré en 1ère dose de rappel chez des adultes préalablement vaccinés par 2 doses du vaccin BNT162b2 (Pfizer-BioNTech), induit une meilleure réponse immunitaire qu'une 3ème dose de vaccin BNT162b2 à 15 jours du rappel, tant sur la souche sauvage que sur les 3 variants testés (Delta, Beta et Omicron BA.1). Nous montrons ici la persistance d'anticorps neutralisants contre Omicron BA.5, jusqu'à 6 mois post vaccination. Matériels et méthodes Dans le cadre d'un essai multicentrique, randomisé en simple aveugle selon le ratio 1.1.1, les participants ont reçu l'un des trois vaccins suivants en 1ère dose de rappel: les vaccins à protéine recombinante MV B.1.351 ou MVD614 (Sanofi/ GSK) ou le vaccin BNT162b2. La persistance des anticorps neutralisants contre la souche sauvage et divers variants du SARS-CoV2, y compris Omicron BA.1 et BA.5, jusqu'à 6 mois après le rappel, a été évaluée à l'aide d'un test de microneutralisation. L'analyse de la population per-protocole inclut les participants sans infection par le SRAS CoV-2 (sérologie anti-nucléocapside négative ou test de confirmation pour le SRAS CoV-2) entre le 28e jour et le 6e mois (M6) après le rappel. Résultats Parmi les 247 participants randomisés, 99 participants ont été inclus dans l'analyse per protocole à M6 (32 dans le groupe MVD614, 35 dans le groupe MVB.1.351 et 32 dans le groupe BNT162b2) Pour l'ensemble de la population étudiée, le vaccin MVB.1.351 a induit des titres d'anticorps neutralisants plus élevés contre la souche sauvage et les variants testés y compris Omicron BA.1 et BA.5 jusqu'à 6 mois après la dose de rappel comparés aux vaccins MVD614 et BNT162b2. À 6 mois post vaccination, la moyenne géométrique des titres (MGT) d'anticorps neutralisants contre la souche sauvage, Beta, Delta, Omicron BA.1 et Omicron BA.5 était respectivement de: 599.7 (CI 95%: 398.7 – 902.1), 221.4 (CI 95%: 133.8 – 366.4), 515.4 (CI 95%: 328.3 – 808.9), 48.6 (CI 95%: 30.5 – 77.6) et 37.5 (CI 95%: 26.3 – 53.5) pour MVD614;764.9 (CI 95%: 505.7 – 1156.9), 475.5 (CI 95%: 328.1 – 689.2), 706.6 (CI 95%: 497.0 – 1004.7), 97.5 (CI 95%: 64.7 –147.0) et 71.0 (CI95%: 49.9 – 101.2) pour MVB.1.531;252.2 (CI95%: 174.5 – 364.3);113.1 (CI95%: 77.7 – 164.7), 221.4 (CI95%: 149.7 – 327.4), 24.8 (CI95%: 17.9 – 34.4) et 23.3 (CI95%: 17.1 -31.7) pour BNT162b2 Conclusion Les titres d'anticorps neutralisants induits par le vaccin MVB.1.531 (Sanofi/GSK), administré en 1ère dose de rappel après 2 doses du vaccin BNT162b2, restent plus élevés et durables contre la souche sauvage et les variants du SRAS-COV-2 incluant Omicron BA.1 et BA.5, jusqu'à 6 mois post vaccination par rapport à une 3ème dose du vaccin BNT162b2. Ceci pourrait constituer une option intéressante pour un schéma de vaccination hétérologue. Liens d'intérêts déclarés O.L. Recherches/essais cliniques: en qualité d'investigateur principal, coodonnateur, MSD, Sanofi Pasteur, Janssen, Pfizer • Advisory Boards/DSMB: Sanofi Pasteur, Janssen, Pfizer • Cours, formations: Pfizer, MSD, Sanofi Pasteur
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Background: We compared the 12-month post primary vaccination humoral immune response to mRNA COVID-19 vaccines in PLHIV and controls. Method(s): PLHIV and HIV-negative healthy controls included in the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-POPART were analyzed. Percentage (95% CI) of responders (positive anti- Spike SARS-CoV-2 IgG antibodies) and geometric means titers (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (BAU/mL) were assessed at 1 month and 6 months (M) after the 2nd dose of the primary vaccination and at 12 months in those who received a booster dose. Specific neutralizing antibodies (nAbs) (in vitro neutralization assay against original, Delta and Omicron BA.1 strains) were estimated in a subset of participants. Serological tests (ELISA Euroimmun) and seroneutralization were performed centrally. Result(s): Overall, 858 PLHIV and 1156 controls were included. PLHIV were older than controls: 55.2 years, (49.6-60.6) vs 46.6 years (36.3-56.6) and more frequently male (75.1% vs 48.9%). Among PLHIV at inclusion, 97.3% were under antiretroviral therapy, 95.6% had an undetectable viral load and 71.8% had CD4 counts above 500 cells/mm3. Participants had namely received BNT162b2 as the primary vaccination (93% in PLWHIV vs 84% in controls) and 53.1% had received a booster dose (57.2% in PLHIV (median time after the 2nd dose: 6.1 M [5.9-6.7]) and 50.1% in controls (median time 6.0 M [5.5-6.2])). Percentage of responders after the 2nd dose was lower in PLHIV than controls ((98.7% [97.7;99.3] vs 99.9% [99.5;99.9], p=0.0001)). PLHIV had significantly lower levels of anti-Spike antibodies at 1 M ((1188 [650;2067] vs 1506 [950;2507] BAU/mL, p< 0.0001)) and 6 M (149 [95;235] vs 194 [124;314] BAU/mL, p=< 0.0001) but similar levels at 12 M (520 [269;1198] vs 427 [259;1087] BAU/mL, p=0.3387) (Figure A). PLHIV had significantly lower nAbs against original, Delta and Omicron BA.1 strains at 1, 6 and 12 M after primary vaccination compared to controls. The booster dose significantly increased the titers of nAbs against original and Delta strains and, to a lower extent, against Omicron (Figure B). Conclusion(s): PLHIV had high response rates to mRNA COVID-19 vaccines but lower titers of antibodies and nAbs at 1 and 6 M after primary vaccination than controls. One mRNA booster dose increased SARS-CoV-2 IgG antibodies titers to similar levels to controls but neutralizing activity especially against Omicron remained lower. (Figure Presented).
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Background. New adjuvanted recombinant protein vaccines against coronavirus disease 2019 (COVID-19) as heterologous boosters could maximize the benefits of vaccination against SARS CoV-2. Methods. In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3-7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a >= 10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between D0 and D15. Results. The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor >= 10 between Day 0 and Day 15 was 55.3% (95% CI 43.4-66.7) in MV(D614) group (n=76), 76.1% (64.5-85.4) in MV(Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV(Beta) vaccine compared to the other vaccines. Comparable reactogenicity profile was observed the three vaccines. Conclusion. All three vaccines boosted antibodies and neutralizing response after BNT162b2 initial course. Heterologous boosting with the Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein vaccine B.1.351 (Beta formulation) provided higher neutralizing antibodies response rates against variants, including Omicron BA.1, compared with the mRNA BNT162b2 vaccine.
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Background: COVID-19 convalescent plasma (CCP) contains neutralizing anti-SARS- CoV- 2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Aim(s): Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients. Method(s): CCP (n = 766) were compared to control non-convalescent plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralizing auto-Ab to type I IFNs, and reported adverse events in the recipients. Result(s): CCP exhibited significantly higher IL-6 and TNF-alpha (0.531+/-0.04 vs 0.271+/-0.04;p = 0.0061 and 0.900+/-0.07 vs 0.283+/-0.07 pg/ml;p < 0.0001), respectively) and lower IL-10 (0.731+/-0.07 vs 1.22+/-0.19 pg/ ml, p = 0.0034) levels than control plasma. Other inflammatory markers as well as ex-vivo bioactivity did not differ significantly between CCP and control plasma. Neutralizing auto-Abs against type I IFNs were detected in 14/766 (1.8 %) CCP. They were not associated with reported adverse events when transfused (n = 14). Inflammatory markers and bioactivity in CCP with or without auto-Ab, or in CCP associated or not with adverse events in transfused patients, did not differ significantly. Overall, CCP exhibited moderately increased inflammatory markers compared to control plasma with no discernable differences in ex-vivo bioactivity. Auto-Ab to type I IFNs, detected in a small fraction of CCP, were not associated with reported adverse events or differences in inflammatory markers. Conclusion(s): Further defining the clinical relevance of these findings will require further studies including careful clinical evaluation of patients treated with CCP.
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Background: The efficacy of COVID-19 convalescent plasma (CCP) as passive immunotherapy in hospitalized COVID-19 patients remains uncertain. The transfusion of a large volume of high titre CCP in recently hospitalized patients may be beneficial. Aims: To evaluate the ability CCP transfusion to improve early outcome in patients with moderate to severe COVID-19 pneumonia. Methods: The CORIPLASM study was a multicentric, open-label, Bayesian randomized, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalized with COVID-19 in 14 French centers, requiring at least 3 L/min of oxygen but without mechanic ventilation assistance and a WHO Clinical progression scale [CPS, 1 to 10] of 4 or 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomization list stratified on center, to receive usual care plus 4 units of CCP (2 units/day over 2 days) (CCP group) or usual care alone (usual care group) on day 1 and 2 post-enrollment. Primary outcomes were the proportion of patients withWHO CPS greater than 5 on the 10-point scale on day 4 and survival without ventilation or additional immunomodulatory treatment by day 14. Results: One hundred and twenty patients were recruited from April 16th 2020 and April 21th 2021 and randomly assigned to the CCP group (n = 60) and to the usual care group (n = 60) and followed up for 28 days. Immunosuppressed patients comprised 43% (26/60) and 50% (30/60) of patients in the CCP and usual care groups, respectively. Median time from symptoms onset to randomization (days) was 7.0 [interquartile range (IQR): 5.0-9.0] in the CCP group and 7.0 [IQR: 4.0- 8.5] in the usual care group. Thirteen (22%) patients in the CCP group had a WHO CPS greater than 5 at day 4 versus 8 (13%) in the usual care group (adjusted odds ratio (OR): 1.88 [95% CI: 0.71 to 5.24]. By day 14, 19 (31.6%) patients in the CCP and 20 (33.3%) patients in the usual care group had needed ventilation, additional immunomodulatory treatment or had died (adjusted HR: 1.04 [95% CI: 0.55 to 1.97]). The cumulative incidence of death was 3 (5%) in the CCP group and 8 (13%) in the usual care group at day 14 (adjusted HR: 0.40 [95% CI: 0.10 to 1.53]), and 7 (12%) in the CCP group and 12 (20%) in the usual care group at day 28 (adjusted HR: 0.51 [95% CI: 0.20 to 1.32]). Frequency of severe adverse events did not differ significantly between both treatment arms. Subgroup analysis revealed that mortality at day 28 was mostly observed in the immunosuppressed patients (15/56 vs. 4/64) and that CCP was associated with less mortality in these patients (4/26 in the CCP group vs. 11/30 in the usual care group)(HR: 0.36 [95% CI: 0.14-0.97]). Summary/Conclusions: CCP treatment did not improve early outcome in patients with moderate-to-severe COVID-19 pneumonia. CCP-associated early respiratory worsening as well as CCP-associated reduced D14 and D28 mortality were observed, while not reaching statistical significance. CCP treatment was associated with reduced D28 mortality in immunosuppressed patients.
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Background: Several studies have evaluated COVID-19 convalescent plasma (CCP)'s safety and effectiveness in the prevention of severe COVID-19's worsening. Some of these studies have shown a trend for its efficacy in immunosuppressed patients and that CCP was safe. These studies were performed before the emergence of Omicron variant of SARS-CoV-2, which appeared in December 2021 in France. Aims: All CCP transfusions in France have been performed in a monitored use protocol allowed by the national agency of drug and blood components safety (ANSM). After giving their consent to be transfused, patients were followed to assess this compassionate therapy. All CCPs were qualified with a high titre of antibody, either by seroneutralization (SN) or an ELISA based surrogate for SN. We describe results of this follow-up with a focus on omicron infection. Methods: Consultative multidisciplinary meeting validated the indication for CCP and the order of a medical prescription of CCP. All CCP demands were sent to the EFS medical department to be pseudonymized. Initial and follow-up data of cases were recorded as requested for an assessment. Variables were analysed in relation with the last available follow-up. Results: From May 2020 to the end of February 2022, 1539 patients had received CCP, of whom 455 had an available follow-up more than 24 h after the last CCP transfusion. Most of them (99.8%) have got a comorbidity: 62.6% have a malignant hemopathy and 19.3% an auto-immune pathology. Among the At the time of CCP request, majority of patients (76.9%) were hospitalized without mechanical ventilation (MV), 18.2% were intubated and a few were not hospitalized for COVID-19 (1.3%) but for another reason. At the last available follow-up, 26.2% were dead but the majority (40.9%) have left the hospital, 23.7% were hospitalized without MV and 9.2% were intubated. Variables associated with a decreased percentage of death were: • The young age (p < 0.0001;N = 455) and the female gender (p = 0.0177;N = 455). • The better state at the time of CCP request (p < 0.0001;N = 439). • The longer delay between the beginning of symptoms and the transfusion (p = 0.0023;N = 445). • A trend was observed for immunosuppression, but it did not reach statistical significance (p = 0.0548;N = 346). There were no difference between Infection due to Omicron variant compared to other variants (p = 0.1560;N = 443). However, follow-up was available in only 33 patients infected with omicron (32.7% of transfused patients infected with omicron) while it was available in 410 patients infected with others SARS-CoV-2 variants (94.4%). Among all transfused patients, 75 adverse events (AE) were reported in 1539 patients (4.8%). Imputability was excluded for 11. Allergy was the most frequent (N = 26;34.6% of AE) always scored as not severe, TACO have occurred in 8 patients, with possible or likely imputability, and TRALI have occurred in 3 patients with possible imputability in 2 cases and non evaluable in one case. Summary/Conclusions: CCP transfusion was more effective when the patient were in better state at the time of CCP request and in immunocompromised than in immunocompetent patients, but this was not statistically significant. Due to the low number of patients infected with omicron with an available follow-up at this day, no conclusion can be drawn on survival of these patients versus patients infected with previous variants.
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Background: High effectiveness of COVID-19 vaccines was demonstrated. In people living with HIV (PLWHIV), immunogenicity and efficacy of COVID-19 vaccines might be lower. We evaluated the humoral immune response to COVID-19 vaccines in PLWHIV compared to controls without specific comorbidities. Methods: PLWHIV and controls from the French national multi-center prospective COVID 19 vaccine cohort study ANRS0001S COV-PopART were included. Participants with pre-vaccination positive SARS CoV-2 antibodies, history of SARS CoV-2 infection, or positive SARS CoV-2 anti-nucleocapsid (NCP) antibodies were excluded. Percentage (95% confidence interval (CI)) of responders, geometric means (95% CI) of anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were estimated one month after the second vaccine dose. Serological tests (ELISA Euroimmun) with tests limits and seroneutralization for the original SARS-CoV-2 strain were performed centrally. Results: Among the 6089 participants included, 2625 were PLWHIV or controls;1212 had serological measures available one month after their second dose and 1133 had negative anti-NCP antibodies: 591 PLWHIV and 542 controls. PLWHIV were older than controls: 56.5 years, (51.2-62.2) vs 52.1 years (42.1-62.6) and more frequently male (78.7% vs 52.1%). All PLWHIV were under antiretroviral therapy, 76% had an undetectable viral load and 70.6% had CD4 counts above 500 cells/mm3. Participants had primarily received BNT162b2 (92.4% in PLWHIV vs 88.2% in controls). Proportions of participants who developed anti-Spike IgG (98.5% [97.1;99.3] vs 100.0% [99.3;100.0], p<0.01) and neutralizing antibodies (96.8% [95.0;98.1] vs 99.8 [99.0;100.0], p<0.01) were significantly lower in PLWHIV compared to controls. Of the nine non-responding PLWHIV, all were in CDC stage C, two had detectable HIV viral load and seven had CD4 cell counts below 200/mm3. PLWHIV had similar levels of anti-Spike antibodies (1149.0 [1066.6;1237.8] vs 1299.3 [1208.7;1396.6] BAU/mL, p=0.27) but lower seroneutralization titers (156.8 [141.9;173.2] vs 279.8 [256.1;305.6] IU/mL, p<0.01) than controls (figure). Conclusion: PLWHIV under ARV treatment had high response rates one month after two doses of COVID-19 vaccination. Nonetheless, seroneutralization titers were lower, and non-responders in PLWHIV had a more advanced disease stage. Longer follow-up is needed to gain a better insight into the humoral response after COVID-19 vaccination in PLWHIV.
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Background: The emergence of SARS-CoV-2 variants is a major concern. As the Delta variant became dominant worldwide, obtaining specific data on the humoral and cellular responses after BNT162b2 vaccination against this variant of concern in PLWHIV is crucial. Methods: Multicenter cohort study of PLWHIV, with a CD4 cell count <500/mm3 and a viral load <50 copies/ml on stable antiretroviral therapy for at least 3 months, to explore humoral and cellular responses to BNT162b2 vaccination. IgG antibodies (Ab) to the Receptor Binding Domain (RBD) of the spike protein and their neutralization capacity, assessed by an ELISA (Genscript) and a virus neutralization test (VNT), against historical strain, Beta and Delta variants were performed before vaccination (day 0) and one month after a complete vaccination schedule (M1). Results: 97 patients were enrolled in the study (table 1. baseline characteristics). Among them, 85 patients received 2 shots (11 previous COVID-19 and 1 premature exit). The median time between the 2 shots was 28 [IQR 28-29] days. 90 patients could be evaluated at M1. The seroconversion rate in anti-RBD IgG was 97% CI95%[90%;100%] at M1. Median (IQR) anti-RBD Ab titer was 0.97 (0.97-5.3) BAU/ml at D0 and 1219 (602-1929) at M1. Neutralizing Ab capacity improved between D0 (15% CI95%[8%;23%]) and M1 (94% CI95%[87%;98%]) with the Genscript assay. Neutralizing Ab with the VNT were present at M1 for historical strain, Beta and Delta variants in 82%, 77% and 84% patients respectively. Planned subgroups analysis at M1 showed that seroconversion rate and median anti-RBD Ab titer were 91% and 852 BAU/ml in patients with CD4<250/mm3 (n=13) and 98% and 1270 BAU/ml in patients with CD4>250/mm3 (n=64) (difference of change between D0 and M1 between subgroups p=0.8224). 73% of patients with CD4<250/mm3 had neutralizing Ab and 97% of those with CD4>250/mm3 (p=0.0130). The neutralization capacity of beta variant was 50% in CD4<250/mm3 and 81% in CD4>250/mm3 (p=0.0292). No change in CD4+ or CD8+ T cells count was observed while a decrease of CD19+ B cells count was observed (208 ±124/mm3 at D0 vs 188 ±112/mm3 at M1, p<0.01). Tolerance was very good and no COVID-19 was reported until M1. Conclusion: These results show a high seroconversion rate with a Delta neutralization in PLWHIV patients after a complete BNT162b2 vaccination schedule. However, patients with CD4<250/mm3 had a decrease neutralizing Ab capacity mainly against Beta than Delta variant.
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Introduction L' incidence de la tuberculose est à la hausse en Ile-de-France, avec une augmentation de 23,4 % à Paris. Les données de l'INVS pré-COVID rapportent un pourcentage de traitement mené à son terme de 73,2 %. Parmi ces cas, 20,2 % avaient une issue potentiellement défavorable dont 45 % de perdus de vue. Sur notre établissement, les données de Santé Publique France retrouvent sur la période pré-COVID et pré-ETP un traitement non complété dans 45 % des cas.L'objectif de cette étude est d'évaluer l'impact d'une prise en charge ETP sur les issues de traitements antituberculeux pendant la période COVID et pré-COVID. Matériels et méthodes Recueil des principales données cliniques descriptives des patients avec un diagnostic de tuberculose documentée entre 2019 et 2021. Description des outils utilisés;Description des principales difficultés rencontrées.Evolution du nombre de patients ayant complété l'intégralité du traitement selon qu ils aient ou non bénéficier d'un accompagnement en ETP. Résultats Entre le 1er janvier 2019 et le 31 décembre 2021, 80 patients ont été notifiés par le laboratoire de microbiologie avec un diagnostic de tuberculose et pris en charge dans le service des maladies infectieuses . La répartition sur les 3 années de l'étude étaient, respectivement de 29 patients (2019), 26 (2020) et 25 (2021) . Le sexe ratio était de 4 hommes pour une femme, l'âge moyen de 35 ans. Dans 2/3 des cas, les patients étaient originaires d'Afrique Sub-Saharienne et arrivés en France depuis moins de 5 ans. Pendant cette période 26/29 patients (2019),18/26 (2020) et 21/25 (2021) ont pu bénéficier d'un accompagnement en ETP. Les outils utilisés étaient un questionnaire sur les connaissances de la maladie, les outils permettant l'appropriation des traitements, l'étoile des 5 santés, un jeu interactif type Tuber plan. Une évaluation sociale était systématiquement réalisée ainsi qu'une évaluation psychologique et diététique si nécessaire. En moyenne les patients ont bénéficié de 5 consultations ETP au cours du suivi de leur tuberculose en 2019, 8 en 2020 et 5 en 2021. . Les issues de traitement favorables (définies par la guérison de la tuberculose et la prise du traitement jusqu'à son terme) ont été respectivement de 25/26, 18/18 et 19/21 pour les années 2019, 2020 et 2021 soit un taux global de 95 %;pour les patients pris en charge en ETP;Pour ceux n'en ayant pas bénéficié sur les 3 ans 10/15 sont en succès soit 66 %. Conclusion La mise en place et la poursuite d'un accompagnement ETP au cours de la tuberculose permettent d'augmenter significativement les issues de traitement favorable au cours de la tuberculose et d'atteindre les objectifs de l'OMS (90 % d'issue de traitement favorable) Le % de succès pour les patients n'ayant pas bénéficiés d'un accompagnement en ETP est comparable aux chiffres de Santé Publique France. Ces éléments nous ont conduit à réaliser un PRI, en élargissant cette prise en charge à l'ensemble des services prenant en charge des patients atteints de tuberculose afin d'atteindre les objectifs de l'OMS. Aucun lien d'intérêt
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Introduction L'efficacité de la vaccination Covid-19 est diminuée chez les personnes immunodéprimées. La réponse en anticorps anti-Spike est hétérogène dans ces populations mais la plupart des études publiées sont de taille limitée sans groupe contrôle. Matériels et méthodes COV-POPART est une cohorte nationale prospective multicentrique ayant inclus, entre le 25 mars et le 31 décembre 2021, des participants adultes dans 11 populations particulières (cancer solide, transplantés organe solide (TOS), greffés cellules souches hématopoïétiques (GCSH), insuffisants rénaux chroniques (IRC), maladies auto-immunes et systémiques (MAIS), rhumatismes inflammatoires chroniques (RIC), Sclérose En Plaques et maladies du spectre de la neuromyélite optique (SEP), hypogammaglobulinémie, diabète (1 et 2), obésité sans diabète, Personnes Vivant avec le VIH-1 (PVVIH)) et 2 groupes contrôles (18-74 ans et > 74 ans) indemnes des affections suscitées. Les participants ayant à l'inclusion des anticorps anti-nucléocapside (NCP) positifs ont été exclus. La proportion de participants avec des anticorps IgG anti-Spike (ELISA Euroimmun) (=répondeurs) et des anticorps neutralisants spécifiques (test de neutralisation in vitro sur la souche originale) a été évaluée de manière standardisée et centralisée un mois après la deuxième dose de vaccin. Résultats Parmi les 6612 participants de la cohorte, 3301 avaient des résultats disponibles au 17/02/2022 et 3127 des anticorps anti-NCP négatifs : 2271 participants de populations particulières (156 cancers solides, 135 TOS, 47 GCSH, 81 IRC, 124 MAI, 129 RIC, 321 SEP, 50 hypogammaglobulinémies, 320 diabétiques, 623 obèses non diabétiques et 777 VIH) et 856 contrôles (831 : 18-74 ans et 25 : >74 ans). La majorité des participants (86,7%) a reçu deux doses de BNT162b2. Dans le groupe contrôle, 99,9% (IC95% 99,3 ;100,0) des personnes âgées de 18 à 74 ans et 96,0% (79.6 ;99,9) des personnes âgées de plus de 75 ans ont développé des anticorps IgG anti-Spike. Chez les patients obèses et les PVVIH, les pourcentages de répondeurs étaient de 88,9 % (86,2 ;91,3) et 97.3 % (95,9 ;98,3). Les pourcentages de répondeurs étaient plus faibles chez les SEP (73,8 % [68,7 ;78,6]), GCSH (61,7 % [46,4 ;75,5]) ou TOS (31,1 % [23,4 ;39,6]). La fréquence des anticorps neutralisants était similaire à celle des anticorps anti-Spike dans les groupes contrôles. Les obèses et PVVIH (85,8 % [82,8 ;88,5] et 95,6 % [93,9 ;96,9]) présentaient plus fréquemment des anticorps neutralisants contrairement aux participants SEP, GSCH et TOS (69,8 % [64,4 ;74,8], 57,4 % [42,2 ;71,7] et 27,4 % [20,1 ;35,7]). Conclusion Les résultats préliminaires de la cohorte COV-POPART montrent, à 1 mois de la fin du schéma vaccinal standard de primo-vaccination Covid-19, une réponse humorale hétérogène dans les populations particulières. Cette réponse est plus faible chez les patients atteints de SEP, GSCH ou TOS. Aucun lien d'intérêt
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Introduction Treatment of B-lineage lymphoma with B-cell depleting immunotherapy causes B-cell aplasia and impairs immune response. Case studies have reported patients treated with anti-CD20 therapy who suffered from persistent Covid-19. We aimed to assess the incidence, risk factors and long-term outcomes of persistent Covid-19 in patients with lymphoma. Patients and methods This retrospective multicentric study was conducted in 16 French hospitals. All adult patients with lymphoma who were admitted for Covid-19 in March and April 2020 were included. Persistent Covid-19 was defined as persisting severe Covid-19 symptoms requiring in-hospital stay for >30 days. Patients who re-experienced severe Covid-19 symptoms after initial improvement, requiring repeated hospitalizations for a total in-hospital length of stay >30 days were added to the persistent Covid-19 cases. Results One hundred eleven patients were included. Thirty days after admission for Covid-19, 24 patients had died, 55 had been definitively discharged from hospital, 31 were still hospitalized and 1 was later rehospitalized for Covid-19 recurrence. The incidence of persistent Covid-19 was 32/111 (29%). Patients with persistent Covid-19 had a median age of 64 years (range, 43-87) and 63% were male. Twenty-two patients (69%) had at least one significant comorbidity. None of the patients with T-cell (n=8) lymphoma or classical Hodgkin's disease (n=8) experienced persistent Covid-19. In the 32 patients with persistent Covid-19, the median time between first admission and final discharge was 58 days (range, 31-235) and the median duration of Covid-19 symptoms was 83 days (range, 32-237). Eight patients received corticosteroids and 9 convalescent plasma: all patients recovered from their symptoms, except one. Overall, 9 patients with persistent Covid-19 died (27%). After a median follow-up of 191 days (range, 3-260), the 6-month overall survival was 69% (95% CI 60-78%) for the whole cohort. In multivariate analysis, administration of anti-CD20 monoclonal antibody within 12 months before admission to hospital for Covid-19 was both associated with decreased overall survival (HR 2.13, 95% CI 1.03-4.44, p = 0.043) and prolonged in-hospital stay (HR 1.97, 95% CI 1.24-3.13, p = 0.004). The two other significant factors associated with decreased overall survival and prolonged in-hospital stay: age ≥ 70 years and refractory or relapsed lymphoma. Conclusion Patients with B-cell non-Hodgkin lymphoma hospitalized for Covid-19 have a high incidence of prolonged evolution of SARS-CoV-2 infection. Administration of anti-CD20 therapy within the last 12 months is one of the main risk factors for longer in-hospital stay and death of Covid-19. The risk of persistent Covid-19 was also higher in patients older than 70 years or with refractory or relapsed disease. These findings may contribute to guide the management of lymphoma patients during the Covid-19 pandemic.
ABSTRACT
Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits antibodies (Abs) that bind several viral proteins such as the spike entry protein and the abundant nucleocapsid (N) protein. We examined convalescent sera collected through 6 months (~24wks) post-SARS-CoV-2 infection in children to evaluate changes in neutralization potency and N-binding. Methods. Outpatient, hospitalized, and community recruited volunteers < 18 years with COVID-19 were enrolled in a longitudinal study at Seattle Children's Hospital. Analysis includes symptomatic and asymptomatic children with laboratory-confirmed SARS-CoV-2 infection who provided blood samples at approximately 4wks (range: 2-18wks, IQR:4-8wks) and 24 wks (range: 23-35wks, IQR:25-27wks) after diagnosis. We measured neutralizing Ab using an in-house pseudoneutralization assay and anti-N binding Ab using the Abbott Architect assay. Results. Of 32 children enrolled between April 2020 and January 2021, 27 had no underlying immunocompromised state and 25 of these 27 children had symptomatic disease. Ten of 27 had a > 2-fold decrease neutralization titers between 4 and 24wks (most were < 10-fold);12 had < 2-fold change;and 5 had neutralization titers that increased > 2-fold over time (Fig. 1A). All but one of these 27 children had detectable neutralizing activity at 24wks. Anti-N Abs were assessed for 25 children at 4wks and 17 children at 24wks (data pending for 14 samples);all children with paired samples had a > 1.75-fold Abbott index reduction at 24wks, and 5 children had no detectable anti-N Abs by 24wks (Fig. 2A). An additional 5 children with symptomatic disease had complicating immunosuppression or multiple blood transfusions;2 had decreasing neutralizing titers, 2 increased, and 1 had no change (Fig. 1B). Anti-N Abs were undetectable for one child by 24wks (data pending for 4 samples) (Fig. 2B). No participants received COVID-19 vaccine. Conclusion. We show neutralizing Abs wane to a small degree over 24wks post-SARS-CoV-2 infection and remain detectable in most children. In contrast, anti-N Abs decreased, becoming undetectable in some children by 24wks. These findings add to understanding of the natural history of SARS-CoV-2 immunity in children.
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COVID-19 , Adult , Humans , SARS-CoV-2 , Severity of Illness Index , Syndrome , Systemic Inflammatory Response Syndrome/etiologyABSTRACT
OBJECTIVES: Diagnosis of COVID-19 is essential to prevent the spread of SARS-CoV-2. Nasopharyngeal swabs (NPS) remain the gold standard in screening, although associated with false negative results (up to 30%). We developed a 3D simulator of the nasal and pharyngeal cavities for the learning and improvement of NPS collection. PATIENTS AND METHODS: Simulator training sessions were carried out in 11 centers in France. A questionnaire assessing the simulator was administered at the end of the sessions. The study population included both healthcare workers (HCW) and volunteers from the general population. RESULTS: Out of 589 participants, overall satisfaction was scored 9.0 [8.9-9.1] on a scale of 0 to 10 with excellent results in the 16 evaluation items of each category (HCWs and general population, NPS novices and experienced). The simulator was considered very realistic (95%), easy to use (97%), useful to understand the anatomy (89%) and NPS sampling technique (93%). This educational tool was considered essential (93%). Participants felt their future NPS would be more reliable (72%), less painful (70%), easier to perform (88%) and that they would be carried out more serenely (90%). The mean number of NPS conducted on the simulator to feel at ease was two; technical fluency with the simulator can thus be acquired quickly. CONCLUSION: Our simulator, whose 3D printing can be reproduced freely using a permanent open access link, is an essential educational tool to standardize the learning and improvement of NPS collection. It should enhance virus detection and thus contribute to better pandemic control.