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  1. Article: Retrospective and prospective studies evaluating the performance of the SARS-Cov-2 "AQ+ COVID-19 Ag Rapid Test" from InTec on symptomatic and non-symptomatic patients.

    Prazuck, Thierry / Serreau, Raphael / Theillay, Aurelie / Pallay, Sandra / Pires-Roteia, Daniela / Prazuck, Fanny / Lesne, Fabien

    Heliyon

    2023  Volume 9, Issue 7, Page(s) e18088

    Abstract: For the last two years, the SARS-CoV-2 virus spread all around the world and led to the COVID-19 pandemic. The need of methods to control the pandemic and to propose rapid and efficient diagnostic tools has emerged. In this perspective, SARS-CoV-2 rapid ... ...

    Abstract For the last two years, the SARS-CoV-2 virus spread all around the world and led to the COVID-19 pandemic. The need of methods to control the pandemic and to propose rapid and efficient diagnostic tools has emerged. In this perspective, SARS-CoV-2 rapid antigen detection tests (RADT) have been developed. We performed a retrospective study on 638 collected nasopharyngeal samples used for reference RT-qPCR diagnosis to compare the AQ + COVID-19 Ag Rapid Test" from InTec (AQ + InTec test) performance with other commercially available RADT (Abbott Panbio, Roche SDBiosensor and Siemens Clinitest). We analysed the sensitivity and specificity of the different tests and showed a better overall performance of the AQ + InTec test, which was confirmed on the SARS-Cov-2 Omicron variant. We then conducted a prospective study on 844patients, to evaluate the sensitivity and specificity of the AQ + InTec test on nasal and nasopharyngeal samples in a point of care setting. We showed that sensitivity and specificity reach acceptable criteria (respectively 94.4% and 99.6% on nasal samples) regarding the official recommendations of the MDCG 2021-21 in both symptomatic and asymptomatic patients. Overall, the results of these two studies confirm that the AQ + InTec test is a valuable tool for testing in a pandemic context with a high proportion of asymptomatic patients who are potential carriers for the SARS-CoV-2 virus and is performant on the most current circulating variant Omicron.
    Language English
    Publishing date 2023-07-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e18088
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Diagnostic accuracy of a rapid antigen triple test (SARS-CoV-2, respiratory syncytial virus, and influenza) using anterior nasal swabs versus multiplex RT-PCR in children in an emergency department.

    Ferrani, Salim / Prazuck, Thierry / Béchet, Stéphane / Lesne, Fabien / Cohen, Robert / Levy, Corinne

    Infectious diseases now

    2023  Volume 53, Issue 7, Page(s) 104769

    Abstract: Background: In children, respiratory infections such as SARS-CoV-2, respiratory syncytial virus (RSV), and influenza share similar clinical signs and symptoms. Here we compared the performance of a rapid antigen diagnostic test using a self-collected ... ...

    Abstract Background: In children, respiratory infections such as SARS-CoV-2, respiratory syncytial virus (RSV), and influenza share similar clinical signs and symptoms. Here we compared the performance of a rapid antigen diagnostic test using a self-collected anterior nasal swab (COVID-VIRO ALL IN TRIPLEX) and multiplex RT-PCR.
    Methods: From October to December 2022, in the emergency pediatrics unit of Orleans Hospital, France, we evaluated the diagnostic accuracy of the triplex test.
    Results: For the 263 children, sensitivity of the test was 88.9% (95%CI 51.8-99.7), 79.1% (95%CI 64.0-90.0), and 91.6% (95%CI 84.1-96.3), for SARS-CoV-2, RSV, and influenza, respectively. Specificity was 100% for each virus. For RT-PCR with cycle threshold < 32, sensitivity was 100.0% [95%CI 59.0-100.0], 87.2% [95%CI 72.6-95.7] and 92.3% [95%CI 84.896.9] for SARS-CoV-2, RSV, and influenza respectively.
    Conclusions: This easy-to-perform triplex test is a considerable advance, allowing clinicians to obtain an accurate diagnosis in most cases of respiratory infection. More data are needed to validate this test in different contexts and across several seasons.
    MeSH term(s) Humans ; Child ; Influenza, Human/diagnosis ; SARS-CoV-2 ; Reverse Transcriptase Polymerase Chain Reaction ; COVID-19/diagnosis ; Sensitivity and Specificity ; Respiratory Syncytial Virus, Human/genetics ; Respiratory Tract Infections ; COVID-19 Testing
    Language English
    Publishing date 2023-08-10
    Publishing country France
    Document type Journal Article
    ISSN 2666-9919
    ISSN (online) 2666-9919
    DOI 10.1016/j.idnow.2023.104769
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Lectin Analysis of SARS-CoV-2-Positive Nasopharyngeal Samples Using GLYcoPROFILE

    Seničar, Mateja / Roubinet, Benoît / Daniellou, Richard / Prazuck, Thierry / Landemarre, Ludovic

    Diagnostics (Basel, Switzerland)

    2022  Volume 12, Issue 11

    Abstract: Nasopharyngeal samples are currently accepted as the standard diagnostic samples for nucleic acid amplification testing and antigenic testing for the SARS-CoV-2 virus. In addition to the diagnostic capacity of SARS-CoV-2-positive crude nasopharyngeal ... ...

    Abstract Nasopharyngeal samples are currently accepted as the standard diagnostic samples for nucleic acid amplification testing and antigenic testing for the SARS-CoV-2 virus. In addition to the diagnostic capacity of SARS-CoV-2-positive crude nasopharyngeal samples, their qualitative potential for direct glycan-specific analysis, in order to uncover unique glycol profiles, was assessed. In this study we provide glycan characterization of SARS-CoV-2-positive and -negative nasopharyngeal samples directly from lectin interactions. Although with limited throughput, this study evaluated the clinical sensitivity and specificity of the GLYcoPROFILE® technology platformon45crude nasopharyngeal samples collected between November 2020 and April 2022. Each GLYcoPROFILE® of 39 SARS-CoV-2-positive samples was compared toglycoprofiling on a panel of 10 selected lectins and the results were paralleled with SARS-CoV-2-negative samples’ results. The GLYcoPROFILE® showed a clear distinction between positive and negative samples with WFA, GSL-II, PHA-L (GlcNAc-specific) and BPA (GalNAc-specific) highlighted as relevant lectins in SARS-CoV-2-positive samples. In addition, a significant, positive statistical correlation was found for these lectins (p < 0.01).
    Language English
    Publishing date 2022-11-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics12112860
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Retrospective and prospective studies evaluating the performance of the SARS-Cov-2 “AQ+ COVID-19 Ag Rapid Test” from InTec on symptomatic and non-symptomatic patients

    Thierry Prazuck / Raphael Serreau / Aurelie Theillay / Sandra Pallay / Daniela Pires-Roteia / Fanny Prazuck / Fabien Lesne

    Heliyon, Vol 9, Iss 7, Pp e18088- (2023)

    2023  

    Abstract: For the last two years, the SARS-CoV-2 virus spread all around the world and led to the COVID-19 pandemic. The need of methods to control the pandemic and to propose rapid and efficient diagnostic tools has emerged. In this perspective, SARS-CoV-2 rapid ... ...

    Abstract For the last two years, the SARS-CoV-2 virus spread all around the world and led to the COVID-19 pandemic. The need of methods to control the pandemic and to propose rapid and efficient diagnostic tools has emerged. In this perspective, SARS-CoV-2 rapid antigen detection tests (RADT) have been developed. We performed a retrospective study on 638 collected nasopharyngeal samples used for reference RT-qPCR diagnosis to compare the AQ + COVID-19 Ag Rapid Test” from InTec (AQ + InTec test) performance with other commercially available RADT (Abbott Panbio, Roche SDBiosensor and Siemens Clinitest). We analysed the sensitivity and specificity of the different tests and showed a better overall performance of the AQ + InTec test, which was confirmed on the SARS-Cov-2 Omicron variant. We then conducted a prospective study on 844patients, to evaluate the sensitivity and specificity of the AQ + InTec test on nasal and nasopharyngeal samples in a point of care setting. We showed that sensitivity and specificity reach acceptable criteria (respectively 94.4% and 99.6% on nasal samples) regarding the official recommendations of the MDCG 2021-21 in both symptomatic and asymptomatic patients. Overall, the results of these two studies confirm that the AQ + InTec test is a valuable tool for testing in a pandemic context with a high proportion of asymptomatic patients who are potential carriers for the SARS-CoV-2 virus and is performant on the most current circulating variant Omicron.
    Keywords Covid-19 ; SARS-CoV-2 ; Diagnostic testing ; Antigen testing ; Nasopharyngeal sampling ; Nasal sampling ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Subject code 150
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Maternal-Fetal Implications of SARS CoV-2 Infection during Pregnancy, Viral, Serological Analyses of Placenta and Cord Blood.

    Alouini, Souhail / Guinard, Jerôme / Belin, Olivier / Mesnard, Louis / Werner, Evelyne / Prazuck, Thierry / Pichon, Chantal

    International journal of environmental research and public health

    2022  Volume 19, Issue 4

    Abstract: Objective: There are few data on the maternal-fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns' samples ... ...

    Abstract Objective: There are few data on the maternal-fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns' samples and search antibodies in cord blood.
    Methods: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers' blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications.
    Results: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers' samples. IgM was negative in the 23 cord blood samples.
    Conclusions: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood samples of newborns. They are possibly of maternal origin, suggesting a probable mechanism of fetal protection against SARS-CoV-2 infection. No SARS-CoV-2 IgM was found in the cord blood samples. Detection of SARS-CoV-2 in placenta is rare.
    MeSH term(s) COVID-19/epidemiology ; Cesarean Section ; Child ; Female ; Fetal Blood ; Humans ; Immunoglobulin M ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology ; Pregnancy Outcome ; Prospective Studies ; SARS-CoV-2/genetics
    Chemical Substances Immunoglobulin M
    Language English
    Publishing date 2022-02-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph19042105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: COVID-19 seroprevalence among local authority workers from Orléans Métropole, the Community of Communes of the Terres du Val de Loire, the local public service management centre of the Loiret department and the Region Centre Val de Loire: a prospective epidemiological study.

    Hanane, Guerrout / Amine, Zaouia / Roomila, Naeck / Prazuck, Thierry / Amirouche, Ammar / Olivier, Vernay / Benyamina, Amine / Serreau, Raphaël

    BMJ open

    2023  Volume 13, Issue 5, Page(s) e066504

    Abstract: Objective: To evaluate the SARS-CoV-2 seroprevalence among local authority workers, depending on their position and potential interaction with the public.: Methods: A cohort of volunteer participants was recruited among local authority workers of the ...

    Abstract Objective: To evaluate the SARS-CoV-2 seroprevalence among local authority workers, depending on their position and potential interaction with the public.
    Methods: A cohort of volunteer participants was recruited among local authority workers of the Centre Val de Loire region in France, to be tested using a rapid serological test (COVID-PRESTO). The collected data were analysed by comparing different parameters including, gender, age, position held, and contact or not with the public. The study was carried out from August to December 2020 and included 3228 participants (n=3228), from 18 to 65 years old.
    Results: The seroprevalence of SARS-CoV-2 among local authority workers was estimated at 3.04%. No significant difference could be observed according to the position held by the workers and whether they were or not in contact with the public. Nevertheless, a significant difference was observed between the different investigating centres, in correlation with the geographical location.
    Conclusion: Contact with members of the public was not a critical parameter for SARS-CoV-2 seroprevalence as long as protective measures are applied. Among the population included in the study, childcare workers were more at risk of getting infected by the virus.
    Trial registration number: NCT04387968.
    MeSH term(s) Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; COVID-19/epidemiology ; SARS-CoV-2 ; Seroepidemiologic Studies ; Prospective Studies ; Antibodies, Viral ; Health Personnel
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2023-05-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2022-066504
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  7. Article ; Online: Modeling the kinetics of the neutralizing antibody response against SARS-CoV-2 variants after several administrations of Bnt162b2.

    Clairon, Quentin / Prague, Mélanie / Planas, Delphine / Bruel, Timothée / Hocqueloux, Laurent / Prazuck, Thierry / Schwartz, Olivier / Thiébaut, Rodolphe / Guedj, Jérémie

    PLoS computational biology

    2023  Volume 19, Issue 8, Page(s) e1011282

    Abstract: Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concern (VoC)s. That is why the measure of the ... ...

    Abstract Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity of antibodies initially targeting the historical strain against emerging Variants of Concern (VoC)s. That is why the measure of the protection conferred by vaccination cannot solely rely on the antibody levels, but also requires to measure their neutralization capacity. Here we used a mathematical model to follow the humoral response in 26 individuals that received up to three vaccination doses of Bnt162b2 vaccine, and for whom both anti-S IgG and neutralization capacity was measured longitudinally against all main VoCs. Our model could identify two independent mechanisms that led to a marked increase in measured humoral response over the successive vaccination doses. In addition to the already known increase in IgG levels after each dose, we identified that the neutralization capacity was significantly increased after the third vaccine administration against all VoCs, despite large inter-individual variability. Consequently, the model projects that the mean duration of detectable neutralizing capacity against non-Omicron VoC is between 348 days (Beta variant, 95% Prediction Intervals PI [307; 389]) and 587 days (Alpha variant, 95% PI [537; 636]). Despite the low neutralization levels after three doses, the mean duration of detectable neutralizing capacity against Omicron variants varies between 173 days (BA.5 variant, 95% PI [142; 200]) and 256 days (BA.1 variant, 95% PI [227; 286]). Our model shows the benefit of incorporating the neutralization capacity in the follow-up of patients to better inform on their level of protection against the different SARS-CoV-2 variants. Trial registration: This clinical trial is registered with ClinicalTrials.gov, Trial IDs NCT04750720 and NCT05315583.
    MeSH term(s) Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; Immunoglobulin G ; SARS-CoV-2/genetics ; Vaccination
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; Immunoglobulin G
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1011282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: HIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria.

    Planchais, Cyril / Molinos-Albert, Luis M / Rosenbaum, Pierre / Hieu, Thierry / Kanyavuz, Alexia / Clermont, Dominique / Prazuck, Thierry / Lefrou, Laurent / Dimitrov, Jordan D / Hüe, Sophie / Hocqueloux, Laurent / Mouquet, Hugo

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 6326

    Abstract: HIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1- ... ...

    Abstract HIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1-infected humans. We show that only class-switched memory B cells markedly differ between subjects treated during the acute and chronic phases of infection. Intestinal memory B-cell monoclonal antibodies show more prevalent polyreactive and commensal bacteria-reactive clones in late- compared to early-treated individuals. Mirroring this, serum IgA polyreactivity and commensal-reactivity are strongly increased in late-treated individuals and correlate with intestinal permeability and systemic inflammatory markers. Polyreactive blood IgA memory B cells, many of which egressed from the gut, are also substantially enriched in late-treated individuals. Our data establish gut and systemic B-cell polyreactivity to commensal bacteria as hallmarks of chronic HIV-1 infection and suggest that initiating treatment early may limit intestinal B-cell abnormalities compromising HIV-1 humoral response.
    MeSH term(s) Humans ; Memory B Cells ; HIV-1 ; B-Lymphocytes ; Bacteria ; HIV Infections/drug therapy ; Immunoglobulin A ; Intestinal Mucosa/microbiology
    Chemical Substances Immunoglobulin A
    Language English
    Publishing date 2023-10-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-42027-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Maternal-Fetal Implications of SARS CoV-2 Infection during Pregnancy, Viral, Serological Analyses of Placenta and Cord Blood

    Souhail Alouini / Jerôme Guinard / Olivier Belin / Louis Mesnard / Evelyne Werner / Thierry Prazuck / Chantal Pichon

    International Journal of Environmental Research and Public Health, Vol 19, Iss 2105, p

    2022  Volume 2105

    Abstract: Objective: There are few data on the maternal–fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns’ samples ... ...

    Abstract Objective: There are few data on the maternal–fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns’ samples and search antibodies in cord blood. Methods: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers’ blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications. Results: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers’ samples. IgM was negative in the 23 cord blood samples. Conclusions: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood ...
    Keywords COVID-19 ; SARS-CoV-2 ; SARS-CoV-2 antibodies ; coronavirus ; cord blood ; pregnancy ; Medicine ; R
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: A case of erythema multiforme major with multiple mucosal involvements in COVID-19 infection.

    Binois, Raphaëlle / Colin, Mathilda / Rzepecki, Vincent / Prazuck, Thierry / Esteve, Eric / Hocqueloux, Laurent

    International journal of dermatology

    2020  Volume 60, Issue 1, Page(s) 117–118

    MeSH term(s) COVID-19/complications ; Erythema Multiforme/etiology ; Humans ; Male ; Middle Aged ; Mucous Membrane
    Language English
    Publishing date 2020-11-23
    Publishing country England
    Document type Case Reports ; Letter
    ZDB-ID 412254-9
    ISSN 1365-4632 ; 0011-9059 ; 1461-1244
    ISSN (online) 1365-4632
    ISSN 0011-9059 ; 1461-1244
    DOI 10.1111/ijd.15158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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