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2.
Kidney Int Rep ; 2022 Mar 26.
Article in English | MEDLINE | ID: covidwho-1757313

ABSTRACT

Kidney transplant recipients (KTRs) are prone to develop severe coronavirus disease 2019 (Covid-19) and are less well protected by vaccine than immunocompetent subjects. Thus, the use of neutralizing monoclonal anti-SARS-CoV-2 antibody (MoAb) to confer a passive immunity appears attractive in KTRs. METHODS: We performed a French nation-wide study to compare Covid-19-related hospitalization, 30-days-admission to intensive care unit (ICU) and 30-days-death between KTRs who received an early infusion of MoAb (MoAb group) and KTRs who did not (control group). Controls were identified from the COVID-SFT registry (NCT04360707) using a propensity score matching with the following covariates: age, sex, delay between transplantation and infection, induction and maintenance immunosuppressive therapy, initial symptoms and comorbidities. RESULTS: Eighty KTRs received MoAb between February and June 2021. They were matched to 155 controls. Covid-19-related hospitalization, 30-days-admission to intensive care unit (ICU) and 30-days-death were less frequently observed in MoAb group (35.0% vs 49.7%, p=0.032; 2.5% vs 15.5%, p=0.002, 1.25% vs 11.6%, p=0.005, respectively). No patients required mechanical ventilation in MoAb group. The number of patients to treat to prevent one death was 9.7. CONCLUSION: The early use of MoAb in KTRs with a mild form of Covid-19 largely improved outcomes in KTRs.

3.
EClinicalMedicine ; 46: 101362, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1757291

ABSTRACT

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

4.
Nephrol Dial Transplant ; 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1662128

ABSTRACT

BACKGROUND: Patients on maintenance hemodialysis have an increased risk of severe COVID-19 and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population. METHODS: Following a COVID-19 outbreak among vaccinated patients in a hemodialysis unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded. RESULTS: Among fifty-three patients present in the dialysis room, fourteen were infected by SARS-CoV-2 alpha variant (COVID_Pos) and 39 were not. In comparison to uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50% vs 21%, p = 0.046), and were more often scheduled on the Monday-Wednesday-Friday (MWF) shift (86% vs 39%, p = 0.002). Moreover, COVID_pos had lower anti-Spike IgG titers than uninfected patients (24 BAU/ml [3-1163] vs 435 BAU/mL [99-2555], p = 0.001) and lower neutralization titers (108 [17-224] vs 2483 [481-43 908], p = 0.007). Anti-Spike and neutralization antibody titers are correlated (r = 0.92, p < 0.001). In multivariable analysis, MWF schedule (OR = 10.74 (1.9-93.5), p = 0.014) and anti-spike IgG titers one month before the outbreak (<205 BAU/ml: OR = 0.046 (0.002-0.29), p = 0.006) were independently associated with COVID-19 infection. None of the patients with anti-Spike IgG above 284 BAU/mL got infected. Ten out of fourteen COVID_Pos patients were treated with Casirivimab and Imdevimab. No patient developed severe disease. CONCLUSIONS: Anti-spike IgG titer measured prior to exposure correlates to protection from SARS-CoV-2 infection in hemodialysis patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.

5.
Clin Microbiol Infect ; 27(10): 1520.e1-1520.e5, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1260695

ABSTRACT

OBJECTIVES: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalization and fatality rates in residents of homeless shelters run by Samusocial of Paris. METHODS: We conducted a retrospective serological study between July and August 2020 on all residents and staff members of three homeless shelters run by Samusocial of Paris: two centres providing healthcare accommodation (HCA) and one a women's dormitory. We included all adults present in the shelters or who died of a proven SARS-CoV-2 infection during the first wave (March-May). SARS-CoV-2 antibodies were detected in serum samples using the SARS-CoV-2 IgG Architect (Abbott) test. Any participant with a positive PCR or serology was defined as a confirmed SARS-CoV-2 case. RESULTS: We included 100 residents and 83 staff members. The confirmed SARS-CoV-2 rate by PCR or serology was 72/100 (72.0%) for residents and 17/83 (20.5%) for staff members. Women accommodated in the dormitory had the highest infection rate (90.6%). The hospitalization rate in residents was 17/72 (23.6%) and the death rate 4/72 (5.6%). All hospitalizations and deaths occurred among HCA residents. Among the residents of HCA shelters, 34/68 (50%) presented at least two comorbidity factors associated with being at high risk for severe SARS-CoV-2 infection. CONCLUSION: The SARS-CoV-2 infection rate was high in residents of these homeless shelters (10.6% seroprevalence in the Île-de-France region during the first wave). Severe SARS-CoV-2 infection was highly associated with the prevalence of comorbidities. This population should be considered as a priority in vaccination campaigns and in access to individual housing units when at risk.


Subject(s)
COVID-19/epidemiology , Homeless Persons/statistics & numerical data , Adult , COVID-19/blood , COVID-19/mortality , Female , France/epidemiology , Hospitalization , Humans , Incidence , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
6.
Open Forum Infect Dis ; 8(3): ofab054, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1135879

ABSTRACT

In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with coronavirus disease 2019 (COVID-19) patients or with colleagues were associated with infection with severe acute respiratory syndrome coronavirus 2, whereas working in a COVID-dedicated unit and having children kept in childcare facilities were not.

8.
Blood ; 136(20): 2290-2295, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-950941

ABSTRACT

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/pathology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immune Sera/administration & dosage , Lymphopenia/therapy , Pneumonia, Viral/immunology , Adult , Aged , B-Lymphocytes/immunology , Blood Component Transfusion , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , France , Hematologic Neoplasms/complications , Humans , Immunization, Passive , Lymphopenia/etiology , Lymphopenia/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , SARS-CoV-2
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