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1.
Front Immunol ; 13: 790334, 2022.
Article in English | MEDLINE | ID: covidwho-1715001

ABSTRACT

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.


Subject(s)
Betacoronavirus/physiology , COVID-19/immunology , Common Cold/immunology , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2/physiology , Aged , Aged, 80 and over , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antigens, Viral/immunology , COVID-19/mortality , COVID-19/therapy , Cross Reactions , Female , Humans , Immunity, Heterologous , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Immunologic Memory , Male , Middle Aged , Survival Analysis
2.
Clin Infect Dis ; 74(4): 707-710, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703814

ABSTRACT

There are concerns about neutralizing antibodies' (NAbs') potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Health Personnel , Humans , SARS-CoV-2/genetics , United Kingdom/epidemiology
4.
Crit Care ; 26(1): 48, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1703362

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS. METHODS: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 106 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO2/FiO2)-ratio change between baseline (day (D) 0) and D7. RESULTS: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO2/FiO2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. CONCLUSIONS: D0-to-D7 PaO2/FiO2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context. TRIAL REGISTRATION: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Double-Blind Method , Humans , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Treatment Outcome
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315970

ABSTRACT

Background: Data on incidence, clinical presentation and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. Methods: . Case series of patients with COVID-19 pneumonia admitted to a single ICU in France. All consecutive patients requiring MV with RT-PCR–confirmed SARS-CoV-2 infection between March 12th and April 24 th , 2020 were included. Frequency, clinical characteristics, responsible pathogens and outcomes of VAP were assessed, and compared to an historical cohort of patients with severe influenza-associated pneumonia requiring MV admitted to the same ICU during the preceding three winter seasons. Results: : Among 54 consecutive patients with Covid-19–associated acute respiratory failure requiring MV included (median (IQR) age 48 (42-58) years;74% male;93% requiring venovenous-extracorporeal membrane oxygenation), 46 (85%) developed VAP (median (IQR) MV duration before the first episode, 11 (8-16) days). VAP-causative pathogens were predominantly Enterobacteriaceae (72%), particularly inducible AmpC-cephalosporinase producers (41%), followed by Pseudomonas aeruginosa (35%). VAP recurred in 46 (85%) patients and 17 (31%) died. Most recurrences were relapses (ie, infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Despite a high P. aeruginosa -VAP rate in patients with influenza-associated ARDS, the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups. Conclusions: : Patients with severe Covid-19–associated acute respiratory failure requiring MV had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase–producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

6.
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.
Euro Surveill ; 27(6)2022 Feb.
Article in English | MEDLINE | ID: covidwho-1686391

ABSTRACT

BackgroundThe COVID-19 pandemic has led to an unprecedented daily use of RT-PCR tests. These tests are interpreted qualitatively for diagnosis, and the relevance of the test result intensity, i.e. the number of quantification cycles (Cq), is debated because of strong potential biases.AimWe explored the possibility to use Cq values from SARS-CoV-2 screening tests to better understand the spread of an epidemic and to better understand the biology of the infection.MethodsWe used linear regression models to analyse a large database of 793,479 Cq values from tests performed on more than 2 million samples between 21 January and 30 November 2020, i.e. the first two pandemic waves. We performed time series analysis using autoregressive integrated moving average (ARIMA) models to estimate whether Cq data information improves short-term predictions of epidemiological dynamics.ResultsAlthough we found that the Cq values varied depending on the testing laboratory or the assay used, we detected strong significant trends associated with patient age, number of days after symptoms onset or the state of the epidemic (the temporal reproduction number) at the time of the test. Furthermore, knowing the quartiles of the Cq distribution greatly reduced the error in predicting the temporal reproduction number of the COVID-19 epidemic.ConclusionOur results suggest that Cq values of screening tests performed in the general population generate testable hypotheses and help improve short-term predictions for epidemic surveillance.


Subject(s)
COVID-19 , SARS-CoV-2 , France/epidemiology , Humans , Pandemics , Reverse Transcriptase Polymerase Chain Reaction
9.
Diagnostics (Basel) ; 12(1)2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1613661

ABSTRACT

SARS-CoV-2 viral antigen detection may be an interesting alternative to RT-PCR for the diagnosis of SARS-CoV-2 infection as a less laborious or expensive method but requires validation. This study aimed to compare the performance of the DiaSorin™ LiaisonXL automated quantitative antigen test (QAT) and the AAZ™ rapid antigen test (RAT) to the DiaSorin™ MDX RT-PCR assay. A total of 242 nasopharyngeal samples were tested at La Pitié-Salpêtrière University Hospital (Paris, France). Performances for the detection of variants of SARS-CoV-2 were further investigated. RATs were visually read for qualitative results and band intensity was determined. Overall sensitivity was 63.2% for QAT and 58.6% for RAT. For RT-PCR Ct value 25, sensitivity was 89.8% for both tests. Both tests showed comparable sensitivity for detection of variants. There was a strong relationship between antigen concentration and band positivity. On the same set of samples these tests share similar performances.

10.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295413

ABSTRACT

ABSTRACT There are concerns about neutralizing antibodies (NAb) potency against the newly emerged VOC202012/01 (UK) and 501Y.V2 (SA) SARS-CoV-2 variants in mRNA-vaccinated subjects and in recovered COVID-19 patients. We used a viral neutralization test with a strict 100% neutralizing criterion on UK and SA clinical isolates in comparison with a globally distributed D614G SARS-CoV-2 strain. In two doses BNT162b2-vaccinated healthcare workers (HCW), despite heterogeneity in neutralizing capacity against the three SARS-CoV-2 strains, most of the sera harbored at least a NAb titer ≥ 1:10 suggesting a certain humoral protection activity either on UK or SA variants. However, six months after mild forms of COVID-19, an important proportion of HCW displayed no neutralizing activity against SA strain. This result supports strong recommendations for vaccination of previously infected subjects.

11.
Int J Infect Dis ; 113: 12-14, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1446701

ABSTRACT

SARS-CoV-2 variants raise concern regarding the mortality caused by COVID-19 epidemics. We analyse 88,375 cycle amplification (Ct) values from variant-specific RT-PCR tests performed between January 26 and March 13, 2021. We estimate that on March 12, nearly 85% of the infections were caused by the Alpha variant and that its transmission advantage over wild type strains was between 38 and 44%. We also find that tests positive for Alpha and Beta/Gamma variants exhibit significantly lower cycle threshold (Ct) values.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Reverse Transcriptase Polymerase Chain Reaction
14.
J Allergy Clin Immunol ; 147(6): 2098-2107, 2021 06.
Article in English | MEDLINE | ID: covidwho-1269289

ABSTRACT

BACKGROUND: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. METHODS: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). RESULTS: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-ß was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. CONCLUSIONS: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.


Subject(s)
COVID-19 , Cytokines/immunology , Respiration, Artificial , SARS-CoV-2/immunology , Severity of Illness Index , Adult , Aged , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Female , Humans , Male , Middle Aged
15.
Clin Infect Dis ; 74(4): 707-710, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1246701

ABSTRACT

There are concerns about neutralizing antibodies' (NAbs') potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Health Personnel , Humans , SARS-CoV-2/genetics , United Kingdom/epidemiology
17.
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
18.
Euro Surveill ; 26(9)2021 03.
Article in English | MEDLINE | ID: covidwho-1154191

ABSTRACT

The emergence of SARS-CoV-2 variant 20I/501Y.V1 (VOC-202012/1 or GR/501Y.V1) is concerning given its increased transmissibility. We reanalysed 11,916 PCR-positive tests (41% of all positive tests) performed on 7-8 January 2021 in France. The prevalence of 20I/501Y.V1 was 3.3% among positive tests nationwide and 6.9% in the Paris region. Analysing the recent rise in the prevalence of 20I/501Y.V1, we estimate that, in the French context, 20I/501Y.V1 is 52-69% more transmissible than the previously circulating lineages, depending on modelling assumptions.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , France/epidemiology , Humans , Paris
19.
J Clin Immunol ; 41(3): 536-544, 2021 04.
Article in English | MEDLINE | ID: covidwho-1092712

ABSTRACT

PURPOSE: To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. METHODS: Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. RESULTS: Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. CONCLUSIONS: PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study.


Subject(s)
Autoantibodies/blood , COVID-19/therapy , Interferon Type I/immunology , Plasma Exchange , SARS-CoV-2 , Adult , Aged , Autoantibodies/isolation & purification , COVID-19/immunology , Female , Humans , Male , Prospective Studies
20.
Nat Commun ; 12(1): 844, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1069105

ABSTRACT

There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , Binding Sites/immunology , COVID-19/virology , Cell Line, Tumor , Female , Humans , Immunoglobulin A/immunology , Male , Middle Aged , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Time Factors
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