High seroconversion rate and SARS-CoV-2 Delta neutralization in people with HIV vaccinated with BNT162b2.

OBJECTIVES: To assess humoral responses to SARS-CoV-2 Delta-variant in people with HIV (PWH) after BNT162b2-vaccination. DESIGN: Multicenter cohort study of PWH with CD4 + cell count less than 500 cells/µl and viral load less than 50 copies/ml on stable antiretroviral therapy for at least 3 months. METHODS: Anti-SARS-CoV-2 receptor-binding-domain IgG antibodies (anti-RBD IgG) were quantified and neutralization capacity was evaluated by ELISA/GenScript and virus-neutralization-test against the D614G-strain, beta and delta variants before vaccination (day 0) and 1 month after complete schedule (M1). RESULTS: We enrolled 97 PWH, 85 received two vaccine shots. The seroconversion rate for anti-RBD IgG was 97% [95% confidence interval (CI) 90-100%] at M1. Median (IQR) anti-RBD IgG titer was 0.97 (0.97-5.3) BAU/ml at D0 and 1219 (602-1929) at M1. Neutralization capacity improved between D0 (15%; 50% CI 8-23%) and M1 (94%; 95% CI 87-98%) ( P  < 0.0001). At M1, NAbs against the D614G strain, beta and delta variants were present in 82, 77, and 84% PWH, respectively. The seroconversion rate and median anti-RBD-IgG level were 91% and 852 BAU/ml, respectively, in PWH with CD4 + cell count less than 250 ( n  = 13) and 98% and 1270 BAU/ml for CD4 + greater than 250 ( n  = 64) ( P  = 0.3994). NAbs were present in 73% of PWH with CD4 + less than 250 and 97% of those with CD4 + cell count greater than 250 ( P  = 0.0130). NAbs against beta variant were elicited in 50% in PWH with CD4 + cell count less than 250 and in 81% of those with CD4 + cell count greater than 250 ( P  = 0.0292). CD4 + and CD8 + T-cell counts were unchanged, whereas CD19 + B-cell counts decreased after vaccination(208 ±â€Š124 at D0 vs. 188 ±â€Š112 at M1, P  < 0.01). No notable adverse effects or COVID-19 cases were reported. CONCLUSION: Seroconversion rates were high, with delta-neutralization rates similar to those for the D61G strain, after a two-dose BNT162b2 vaccination in PWH.

In utero exposure to antiretroviral drugs and pregnancy outcomes: Analysis of the French ANRS pharmacovigilance database.

AIMS: In 2018, 1.07 million pregnant women received antiretroviral drugs, raising whether this affects pregnancy outcomes. We assessed the adverse pregnancy outcomes associated with prenatal antiretroviral drug exposure, notified to the French ANRS pharmacovigilance system. METHODS: An exhaustive case report series has been performed using the ANRS pharmacovigilance database. All ANRS-sponsored HIV clinical research studies using antiretroviral drugs either in pregnant women or women of childbearing age were eligible from 2004 to 2019. We analysed the following pregnancy outcomes: abortion, ectopic pregnancy, stillbirth, prematurity (<37 weeks of gestational age), low birth weight (<2500 g) and congenital abnormalities. A logistic regression was performed to assess the odds ratio (OR) for each outcome separately (if occurrence >50) compared to the outcome observed when exposed to non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based regimen as the reference. RESULTS: Among the 34 studies selected, 918 deliveries occurred, of whom 88% had pregnancy outcomes documented. Pregnant women were mainly exposed to PI (n = 387, 48.6%), NNRTI (n = 331, 41.5%) and INI-based combinations (n = 40, 5.0%, 18 on dolutegravir). Compared to NNRTI-based combinations, there was no significant association observed with exposure to other antiretroviral combination for spontaneous abortion, prematurity or low birth weight, except an increased risk of low birth weight in new-born exposed to exclusive nucleoside-reverse-transcriptase-inhibitor (NRTI) combinations (n = 4; OR 7.50 [1.49-37.83]). CONCLUSIONS: Our study, mainly based on protease inhibitor (PI) and NNRTI-based regimens, is overall reassuring on the risk of adverse pregnancy outcomes, except for NRTI which should be interpreted cautiously (small number, indication bias). In this study, the number of integrase inhibitor (INI)-based combinations was too low to draw any conclusions.

Les formes prolongées de la COVID-19 ou COVID long : formes cliniques et prise en charge Long COVID : clinical forms and management

Au décours d'un épisode aigu de COVID-19 symptomatique, plus de 30 % des patients adultes ont encore des symptômes à 1-2 mois et 10 à 15 % à 6-8 mois. Il peut s'agir de symptômes persistants ou de nouveaux symptômes. Si les plus fréquents sont une fatigue sévère, une dyspnée et des signes neurocognitifs, de nombreux autres organes peuvent être atteints. Ces symptômes évoluent en général de façon fluctuante et sont souvent majorés par l'effort physique ou intellectuel. Avec le temps, ils évoluent de façon lente vers l'amélioration. L'absence de documentation virologique de l’épisode aïgu (la PCR n'ayant pu être faite et/ou la sérologie étant négative) n'exclut pas ce diagnostic. L'origine de ces symptômes n'est pas encore élucidée et certaines hypothèses sont en cours d'exploration, comme par exemple une persistance virale qui a été démontrée dans certains cas, une réponse inflammatoire notamment mastocytaire excessive, ou bien un défaut de l'immunité innée ou adaptative. Des facteurs génétiques et hormonaux sont possiblement associés. La prise en charge des patients doit être initiée dès le premier recours aux soins. Suite à une analyse approfondie des symptômes, des diagnostics seront portés et feront l'objet d'une prise en charge multidisciplinaire où les traitements symptomatiques et la rééducation tiennent une place importante. Si le recours à l'hospitalisation est rare, ces formes prolongées, maintenant appelées « COVID long », vont avoir un impact sociétal majeur nécessitant la mise en place de politiques publiques adaptées.

Les formes prolongées de la COVID-19 ou COVID long : formes cliniques et prise en charge

Résumé Au décours d'un épisode aigu de COVID-19 symptomatique, plus de 30 % des patients adultes ont encore des symptômes à 1-2 mois et 10 à 15 % à 6-8 mois. Il peut s'agir de symptômes persistants ou de nouveaux symptômes. Si les plus fréquents sont une fatigue sévère, une dyspnée et des signes neurocognitifs, de nombreux autres organes peuvent être atteints. Ces symptômes évoluent en général de façon fluctuante et sont souvent majorés par l'effort physique ou intellectuel. Avec le temps, ils évoluent de façon lente vers l'amélioration. L'absence de documentation virologique de l’épisode aïgu (la PCR n'ayant pu être faite et/ou la sérologie étant négative) n'exclut pas ce diagnostic. L'origine de ces symptômes n'est pas encore élucidée et certaines hypothèses sont en cours d'exploration, comme par exemple une persistance virale qui a été démontrée dans certains cas, une réponse inflammatoire notamment mastocytaire excessive, ou bien un défaut de l'immunité innée ou adaptative. Des facteurs génétiques et hormonaux sont possiblement associés. La prise en charge des patients doit être initiée dès le premier recours aux soins. Suite à une analyse approfondie des symptômes, des diagnostics seront portés et feront l'objet d'une prise en charge multidisciplinaire où les traitements symptomatiques et la rééducation tiennent une place importante. Si le recours à l'hospitalisation est rare, ces formes prolongées, maintenant appelées « COVID long », vont avoir un impact sociétal majeur nécessitant la mise en place de politiques publiques adaptées. As a result of an acute symptomatic COVID-19 episode, more than 30% of adult patients still have symptoms at 1-2 months and 10-15% at 6-8 months. These may be persistent symptoms or new symptoms. If the most common are severe fatigue, dyspnea and neurocognitive signs, many other organs may be affected. These symptoms generally evolve in a fluctuating manner and are often aggravated by physical or intellectual effort. Over time they evolve slowly towards improvement. The lack of virological documentation (PCR could not be made at the initial episode and/or serology is negative) does not exclude this diagnosis. The origin of these symptoms is not yet clear: a viral persistence has been demonstrated in some cases, an inflammatory response including excessive mastocyte activation, a defect of innate or adaptive immunity are hypotheses being explored. Genetic and hormonal factors may be associated. Patient management must be initiated at the first point of care. Based on a thorough analysis of the symptoms, diagnoses will be made which leads to a multidisciplinary management where symptomatic treatments and rehabilitation are important. While hospitalization is rare, these protracted forms, now known as” long COVID”, will have a major societal impact requiring the implementation of appropriate public policies.

Household transmission of SARS-CoV-2 infection in the Paris/Ile-de-France area.

This st udy aims to evaluate the prevalence of SARS-CoV-2 antibodies in locked-down family households to determine viral dynamics and immunity acquisition. COVID-19 individuals and their households in lockdown under the same roof during early spring 2020 were interviewed and tested using rapid immunochromatographic lateral flow antibodies assays (LFA) between July and September 2020. Outcomes were secondary infection rate (SIR) among contacts, household infection rate, and predictors of transmission. We enrolled 87 households including 87 COVID-19 index cases (female 78.2%; median age: 47.0 years, IQR: 42.0-51.5) and 255 contacts (males: 52.9%; median age: 19.0 years, IQR: 11.0-43.5) consisting of their children (42%) or spouses/partners (28.2%). A total of 95/255 contacts were SARS-CoV-2 antibody positive leading to a SIR of 37.3% (95% confidence interval (CI): 31.3-43.5%). Viral transmission was observed in 54 households (62%). SARS-CoV-2 infection was asymptomatic in 33/95 (34.7%) of SARS-CoV-2-positive contacts. Independent predictors of virus transmission from index to contacts were housing surface area < 60 m2 (OR: 5.6 [1.1; 28.2] and a four-member family compared to five (OR: 3.6 [1.2; 10.3]). Households represent a high-risk setting for SARS-CoV-2 transmission through close contact within the family amplified by the number of family members and the housing surface area.

Compassionate Use of Hydroxychloroquine in Clinical Practice for Patients With Mild to Severe COVID-19 in a French University Hospital.

BACKGROUND: Data from nonrandomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against coronavirus disease 2019 (COVID-19). METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe COVID-19 in a French university hospital. Patients who received hydroxychloroquine (200 mg 3 times daily dosage for 10 days) on a compassionate basis in addition to standard of care (SOC) were compared with patients without contraindications to hydroxychloroquine who received SOC alone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, obesity, National Early Warning Score 2 (NEWS2) score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed COVID-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOC alone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxychloroquine was not associated with a significantly reduced risk of unfavorable outcome (hazard ratio, 0.90 [95% confidence interval, .38-2.1], P = .81). Overall survival was not significantly different between the 2 groups (hazard ratio, 0.89 [0.23; 3.47], P = 1). CONCLUSION: In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC. Unmeasured confounders may have persisted however, despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of COVID-19. In hospitalized adults with COVID-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to SOC.