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1.
Microbiol Res ; 263: 127133, 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1956271

ABSTRACT

OBJECTIVES: Despite the quick implementation of infection prevention and control procedures and the use of personal protective equipment within healthcare facilities, many cases of nosocomial COVID-19 transmission have been reported. We aimed to estimate the frequency and impact of healthcare-associated COVID-19 (HA-COVID-19) and evaluate the contribution of whole-genome sequencing (WGS) in cluster investigation. METHODS: We estimated the frequency and mortality of HA-COVID-19 infections from September 1 to November 30, 2020, with a focus on the evolution of hospitalized community-associated COVID-19 (CA-COVID-19) cases and cases detected among healthcare workers (HCWs) within the Sorbonne University Hospital Group (Paris, France). We thoroughly examined 12 clusters through epidemiological investigations and WGS. RESULTS: Overall, 209 cases of HA-COVID-19 were reported. Evolution of HA-COVID-19 incidence closely correlated with the incidence of CA-COVID-19 and COVID-19 among HCWs. During the study period, 13.9 % of hospitalized patients with COVID-19 were infected in the hospital and the 30-day mortality rate of HA-COVID-19 was 31.5 %. Nosocomial transmission of SARS-CoV-2 led to clusters involving both patients and HCWs. WGS allowed the exclusion of one-third of cases initially assigned to a cluster. CONCLUSIONS: WGS analysis combined with comprehensive epidemiological investigations is essential to understand transmission routes and adapt the IPC response to protect both patients and HCWs.

2.
Viruses ; 14(7)2022 07 13.
Article in English | MEDLINE | ID: covidwho-1939016

ABSTRACT

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3-8] vs. 3 [2-4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Adult , Critical Illness , Genomics , Humans , Prospective Studies , SARS-CoV-2/genetics
3.
Sci Rep ; 12(1): 9502, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1886229

ABSTRACT

The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30-4.41] vs. 9.53 [2.56-19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.


Subject(s)
COVID-19 , Biomarkers , Bronchoalveolar Lavage Fluid , Critical Illness , Humans , Prospective Studies , SARS-CoV-2
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310346

ABSTRACT

Background: The virus responsible of severe acute respiratory syndrome named SARS-CoV-2 and causing the new coronavirus disease (COVID-19) has gone global within three months. The current gold standard technique used to detect SARS-CoV-2 is real-time reverse transcription-polymerase chain reaction (rRT-PCR) from naso-pharyngeal swabs but it may be negative in up to 30% of COVID-19 patients. Detection of specific antibodies against SARS-CoV-2 may therefore enhance sensitivity of the current biological diagnosis, as well as monitor the extent of the epidemics in global or specific population, such as health-care worker. Many serological assays are currently available, but their clinical performances are still to be evaluated.Material and Method: A total of 2,594 serum samples collected from patients with SARS-CoV-2 infection documented by a positive rRT-PCR were enrolled in this study. They were tested for IgM/IgG/IgA against SARS-CoV-2 using 31 commercial assays. Antibody response was assessed depending on the onset of symptoms. In addition, 1,996 pre-epidemic serum samples expected to be negative were tested to assess specificity.Results: Rapid tests for qualitative detection of anti-SARS-CoV-2 antibodies (RDTs) achieved 77.4-100%, and ELISA/CLIA (ELISA) assays 58.8-100% for SARS-CoV-2-specific total antibodies (TAb) specificity. From 15 days after onset of symptoms, 13/18 RDT and 8/13 ELISA reached sensitivity > 90%. However, only 4 RDT and 3 ELISA assays fitted both sensitivity (> 90%) and specificity (> 98%) criteria according to French recommendations.Conclusions: Serology may offer valuable information during the course of COVID-19 pandemic, at the condition that commercial assays give reliable results. Contrasted performances were observed among the 31 commercial assays we evaluated, which underlines the importance of independent evaluation before clinical implementation.Funding Statement: This study was funded by the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS, AC43)".Declaration of Interests: JM Pawlotsky has served as an advisor and/or a speaker for Abbvie, Gilead, GlaxoSmithKline, Merck, Regulus and Siemens Healthcare. C Vauloup-Fellous served as un expert (rubella and CMV serology) for Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare and DiaSorin. No other authors have any competing interests to declare.Ethics Approval Statement: The study was carried out in accordance with the Declaration of Helsinki. This work was a retrospective non-interventional study with no addition to standard care procedures. Reclassification of biological remnants into research material after completion of the ordered virological tests was approved by the local interventional review board of hospital. According to the French Public Health Code (CSP Article L.1121-1.1) such protocols are exempted from individual informed consent.

7.
Blood Cancer J ; 11(8): 142, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1351934

ABSTRACT

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Hematologic Neoplasms/complications , Hematologic Neoplasms/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adaptive Immunity , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/administration & dosage , Comorbidity , Female , Host-Pathogen Interactions/immunology , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Risk Factors , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Young Adult
9.
Infect Dis Now ; 51(6): 556-559, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1230513

ABSTRACT

A broad-based SARS-CoV-2 testing program for all symptomatic healthcare workers (HCWs) was implemented in Tenon hospital, Paris, France. From February 26 to April 22, 2020, 701 symptomatic HCWs were screened, of whom 247 (35.2%) tested positive for SARS-Cov-2. Myalgia, fever, anosmia and ageusia were associated with RT-PCR positivity. Testing of HCWs is an essential step toward control of the epidemic. Further studies could establish clinical algorithms for SARS-CoV-2 diagnosis to compensate for RT-PCR test and chest CT limits or unavailability.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Health Personnel , Hospitals , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Ageusia/epidemiology , Anosmia/epidemiology , COVID-19/epidemiology , Female , Fever/epidemiology , France , Humans , Infection Control/methods , Male , Middle Aged , Myalgia/epidemiology , Paris , Primary Health Care , Risk Factors , Young Adult
11.
Eur J Clin Microbiol Infect Dis ; 40(10): 2235-2241, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1156953

ABSTRACT

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Immunoassay/methods , SARS-CoV-2/immunology , COVID-19/virology , Humans , Immunoassay/economics , Immunoglobulin M/blood , Reagent Kits, Diagnostic , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
12.
Diagn Microbiol Infect Dis ; 100(3): 115366, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1116562

ABSTRACT

RT-PCR is the reference method for diagnosis of a Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infection. During the setting up of 6 SARS-CoV-2 RT-PCR assays in our laboratory, comparative evaluations were systematically undertaken and allowed to evidence major discrepancies on cycle threshold RT-PCR results between techniques. These tendencies were confirmed in routine application when analyzing sequential samples from the same patients. Our aim was to examine the impact of the technique among factors influencing RT-PCR result, a far surrogate of 'viral load' in the heterogeneous environment of respiratory specimens.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19/virology , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing/methods , Datasets as Topic , Diagnostic Tests, Routine , Genome, Viral , Humans , Nasopharynx/virology , RNA, Viral/genetics , SARS-CoV-2/genetics , Viral Load
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