Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
Preprint in English | medRxiv | ID: ppmedrxiv-22278636

ABSTRACT

BackgroundAlthough France was one of the most affected European countries by the COVID-19 pandemic in 2020, the dynamics of SARS-CoV-2 transmissions within France, Europe and worldwide remain only partially characterized during the first year of the pandemic. MethodsHere, we analyzed GISAID deposited sequences from January to December 2020 (n = 638,706 sequences). To tackle the huge number of sequences without the bias of analyzing a single sequence subset, we produced 100 independent and randomly selected sequence datasets and related phylogenetic trees for different geographic scales (worldwide, European countries and French administrative regions) and time periods (first and second half of 2020). We applied a maximum likelihood discrete trait phylogeographic method to date transmission events and to estimate the geographic spread of SARS-CoV-2 to, from and within France, Europe and worldwide. ResultsThe results unraveled two different patterns of inter- and intra-territory transmission events between the first and second half of 2020. Throughout the year, Europe was systematically associated with most of the intercontinental transmissions, for which France has played a pivotal role. SARS-CoV-2 transmissions with France were concentrated with North America and Europe (mainly Italy, Spain, United Kingdom, Belgium and Germany) during the first wave, and were limited to neighboring countries without strong intercontinental transmission during the second one. Regarding French administrative regions, the Paris area was the main source of transmissions during the first wave. But, for the second epidemic wave, it equally contributed to virus spread with Lyon and Marseille area, the two other most densely populated cities in France. ConclusionBy enabling the inclusion of tens of thousands of viral sequences, this original phylogenetic strategy enabled us to robustly depict SARS-CoV-2 transmissions through France, Europe and worldwide in 2020.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-21261806

ABSTRACT

HypothesisCoronavirus disease 2019 (COVID-19) resulted in a 30% mortality rate in thoracic cancer patients. Given that cancer patients were excluded from serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine registration trials, it is still unknown whether they would develop a protective anti-spike antibody response following vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to SARS-CoV2 vaccine in thoracic cancer patients. MethodsSARS-CoV2-spike antibodies were measured using Abbot ARCHITECT SARS-CoV-2 IgG immunoassay, prior to first injection of BNT162b2 mRNA vaccine, as well as at Week 4, and two-to-sixteen weeks after second vaccine dose. The factors associated with antibody response were analyzed. ResultsOverall, 306 patients, with a median age of 67.0 years (IQR=58-74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After 4.7-month median follow-up, seven patients (2.3%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of 269 serological results available beyond Day 14 post-second vaccine dose, 17 (6.3%) were still negative (<50 AU/mL) (arbitrary units/mL), while 34 (11%) were <300 AU/mL (12.5th percentile). In multivariate analysis, only age and chronic corticosteroid treatment were significantly associated with a lack of immunization. Thirty patients received a third vaccine dose, with only three patients showing persistent negative serology thereafter, whereas the others demonstrated clear seroconversion. ConclusionSARS-CoV2 vaccines were shown to be efficient in thoracic cancer patients, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in a 88% immunization rate.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21253498

ABSTRACT

The 501Y.V2 and the 501Y.V1 SARS-CoV-2 variants emerged and spread rapidly into the world. We analysed the RT-PCR cycle threshold values of 643 nasopharyngeal samples of COVID-19 patients at diagnosis and found that the 501Y.V2 variant presented an intermediate viral load between the 501Y.V1 and the historical variants.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-20194860

ABSTRACT

Objective: We aimed to estimate the risk of infection in Healthcare workers (HCWs) following a high-risk exposure without personal protective equipment (PPE). Methods: We conducted a prospective cohort in HCWs who had a high-risk exposure to SARS-CoV-2-infected subject without PPE. Daily symptoms were self-reported for 30 days, nasopharyngeal swabs for SARS-CoV-2 RT-PCR were performed at inclusion and at days 3, 5, 7 and 12, SARS-CoV-2 serology was assessed at inclusion and at day 30. Confirmed infection was defined by positive RT-PCR or seroconversion, and possible infection by one general and one specific symptom for two consecutive days. Results: Between February 5th and May 30th, 2020, 154 HCWs were enrolled within 14 days following one high-risk exposure to either a hospital patient (70/154; 46.1%) and/or a colleague (95/154; 62.5%). At day 30, 25.0% had a confirmed infection (37/148; 95%CI, 18.4%; 32.9%), and 43.9% (65/148; 95%CI, 35.9%; 52.3%) had a confirmed or possible infection. Factors independently associated with confirmed or possible SARS-CoV-2 infection were being a pharmacist or administrative assistant rather than being from medical staff (adjusted OR (aOR)=3.8, CI95%=1.3;11.2, p=0.01), and exposure to a SARS-CoV-2-infected patient rather than exposure to a SARS-CoV-2-infected colleague (aOR=2.6, CI95%=1.2;5.9, p=0.02). Among the 26 HCWs with a SARS-CoV-2-positive nasopharyngeal swab, 7 (26.9%) had no symptom at the time of the RT-PCR positivity. Conclusions: The proportion of HCWs with confirmed or possible SARS-CoV-2 infection was high. There were less occurrences of high-risk exposure with patients than with colleagues, but those were associated with an increased risk of infection.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-20191759

ABSTRACT

Background. Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. Despite massive worldwide efforts, the high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the performances of a new ELISA microplate assay quantifying SARS-CoV-2 nucleocapsid antigen (N-antigen) in serum or plasma. Methods. The specificity of the assay, determined on 63 non-COVID patients, was 98.4% (95% confidence interval [CI], 85.3 to 100). Performances were determined on 227 serum samples from 165 patients with RT-PCR confirmed SARS-CoV-2 infection included in the French COVID and CoV-CONTACT cohorts. Findings. Sensitivity was 132/142, 93.0% (95% CI, 84.7 to 100), within the first two weeks after symptoms onset. A subset of 73 COVID-19 patients had a serum collected within 24 hours following or preceding a positive nasopharyngeal swab. Among patients with high nasopharyngeal viral loads, Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among patients with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia. The lower respiratory tract was explored for 6/8 patients, showing positive PCR in 5 cases. Interpretation. This is the first demonstration of the N-antigen antigenemia during COVID-19. Its detection presented a robust sensitivity, especially within the first 14 days after symptoms onset and high nasopharyngeal viral loads. These findings have to be confirmed with higher representation of outpatients. This approach could provide a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-20185082

ABSTRACT

Immune system dysfunction is paramount in Coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in a cohort of 182 patients including patients at various stages of disease activity. A profound decrease of MAIT cell counts in blood of critically ill patients was observed. These cells showed a strongly activated and cytotoxic phenotype that positively correlated with circulating pro-inflammatory cytokines, notably IL-18. MAIT cell alterations markedly correlated with disease severity and patient mortality. SARS-CoV-2-infected macrophages activated MAIT cells in a cytokine-dependent manner involving an IFN-dependent early phase and an IL-18-induced later phase. Therefore, altered MAIT cell phenotypes represent valuable biomarkers of disease severity and their therapeutic manipulation might prevent the inflammatory phase involved in COVID-19 aggravation.

7.
Preprint in English | bioRxiv | ID: ppbiorxiv-179184

ABSTRACT

BackgroundRT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas(R) (Roche) and the RealStar(R) assay (Altona). MethodsAssessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas(R) assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMerieux). ResultsOverall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas(R) minus RealStar(R)) was + 3.3 Ct, with a SD of + 2.3 Ct. ConclusionsIn this comparison, both RealStar(R) and Cobas(R) assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar(R) assay, probably due to a low viral load close to the detection limit of both assays.

8.
Preprint in English | medRxiv | ID: ppmedrxiv-20068858

ABSTRACT

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre-epidemic individuals, 51 patients from Hopital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C-terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV-2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.

9.
Preprint in English | medRxiv | ID: ppmedrxiv-20038059

ABSTRACT

A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.

SELECTION OF CITATIONS
SEARCH DETAIL