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  1. Article ; Online: Genetic and Environmental Contributors for Celiac Disease.

    Serena, Gloria / Lima, Rosiane / Fasano, Alessio

    Current allergy and asthma reports

    2019  Volume 19, Issue 9, Page(s) 40

    Abstract: Purpose of review: Celiac disease (CD) is an autoimmune enteropathy triggered by gluten. The purpose of this review is to examine the major genetic and environmental factors that contribute to CD pathogenesis.: Recent findings: We reviewed the ... ...

    Abstract Purpose of review: Celiac disease (CD) is an autoimmune enteropathy triggered by gluten. The purpose of this review is to examine the major genetic and environmental factors that contribute to CD pathogenesis.
    Recent findings: We reviewed the current state of knowledge on the genetic and environmental components that play a role in CD onset. A genome-wide association study (GWAS) analysis has highlighted several genes other than HLA involved in CD. Recent studies have shown that HLA haplotype influences the microbiome composition in infants and that dysbiosis in the intestinal microflora, in turn, contributes to loss of tolerance to gluten. Recently, observational studies have discussed the hypothesis stating that breast-feeding had a protective role against CD onset. CD etiology is influenced by genetic and environmental factors. A better understanding of these components would deepen our knowledge on the mechanisms that lead to loss of tolerance and could help in developing a more "personalized medicine."
    MeSH term(s) Breast Feeding ; Celiac Disease/etiology ; Celiac Disease/genetics ; Celiac Disease/prevention & control ; Dysbiosis/complications ; Gastrointestinal Microbiome ; Genome-Wide Association Study ; Glutens/adverse effects ; HLA Antigens/genetics ; Humans ; Infant ; Major Histocompatibility Complex/genetics
    Chemical Substances HLA Antigens ; Glutens (8002-80-0)
    Language English
    Publishing date 2019-07-18
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057370-4
    ISSN 1534-6315 ; 1529-7322
    ISSN (online) 1534-6315
    ISSN 1529-7322
    DOI 10.1007/s11882-019-0871-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pediatric Nonceliac Gluten Sensitivity: A Gluten-related Disorder Treatment Center Experience.

    Camhi, Stephanie S / Sangal, Kajal / Kenyon, Victoria / Lima, Rosiane / Fasano, Alessio / Leonard, Maureen M

    Journal of pediatric gastroenterology and nutrition

    2019  Volume 69, Issue 2, Page(s) 200–205

    Abstract: Objective: The aim of the study was to identify the prevalence and clinical characteristics of children with nonceliac gluten sensitivity (NCGS) presenting to a tertiary care center specialized for evaluation of gluten-related disorders.: Methods: ... ...

    Abstract Objective: The aim of the study was to identify the prevalence and clinical characteristics of children with nonceliac gluten sensitivity (NCGS) presenting to a tertiary care center specialized for evaluation of gluten-related disorders.
    Methods: The medical records of all patients aged 0 to 18 years who presented to our center over a 4-year period (July 2013-June 2018) and consented to participate in our research registry were reviewed. Patients meeting the clinical criteria for NCGS were reviewed in detail.
    Results: Among 500 pediatric patients who volunteered to participate in the registry during the study period, we identified 26 (5.2%) with NCGS. Both gastrointestinal and extraintestinal symptoms associated with gluten ingestion were common with abdominal pain (57.7%), bloating (53.9%), rash (53.9%), diarrhea/loose stool (42.3%), and emotional/behavioral issues (42.3%) emerging as the predominant complaints. In addition, children with NCGS demonstrated a high personal history (61.5%) and family history (61.5%) of concomitant allergic/atopic disease.
    Conclusions: Even within our highly specialized population of patients with a suspected gluten-related disorder, pediatric NCGS is relatively uncommon. The estimated prevalence and clinical features mirror those previously reported in a similarly highly selective population of adults. In the absence of celiac disease, clinical suspicion for NCGS should arise in a child with gastrointestinal and/or extraintestinal complaints alleviated with gluten removal and considered in symptomatic patients with associated allergic/atopic disease. Proper and adequate exclusion of celiac disease and other potential causes of the clinical complaints is essential to justify adoption of the gluten-free diet according to an appropriate stringency and with dietitian supervision to avoid nutritional deficiencies.
    MeSH term(s) Adolescent ; Child ; Child, Preschool ; Diet, Gluten-Free ; Female ; Food Hypersensitivity/diagnosis ; Food Hypersensitivity/diet therapy ; Food Hypersensitivity/epidemiology ; Glutens/adverse effects ; Humans ; Male ; Massachusetts/epidemiology ; Medical Records ; Prevalence ; Tertiary Care Centers
    Chemical Substances Glutens (8002-80-0)
    Language English
    Publishing date 2019-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 603201-1
    ISSN 1536-4801 ; 0277-2116
    ISSN (online) 1536-4801
    ISSN 0277-2116
    DOI 10.1097/MPG.0000000000002335
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study.

    Tran, Tina / Senger, Stefania / Baldassarre, Mariella / Brosnan, Rachel A / Cristofori, Fernanda / Crocco, Marco / De Santis, Stefania / Elli, Luca / Faherty, Christina S / Francavilla, Ruggero / Goodchild-Michelman, Isabella / Kenyon, Victoria A / Leonard, Maureen M / Lima, Rosiane S / Malerba, Federica / Montuori, Monica / Morelli, Annalisa / Norsa, Lorenzo / Passaro, Tiziana /
    Piemontese, Pasqua / Reed, James C / Sansotta, Naire / Valitutti, Francesco / Zomorrodi, Ali R / Fasano, Alessio

    Pediatric research

    2024  Volume 95, Issue 5, Page(s) 1254–1264

    Abstract: Background and aims: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the ... ...

    Abstract Background and aims: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions.
    Methods: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS).
    Results: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS.
    Conclusions: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming.
    Impact: Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.
    Language English
    Publishing date 2024-01-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/s41390-023-02960-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children.

    Burns, Madeleine D / Boribong, Brittany P / Bartsch, Yannic C / Loiselle, Maggie / Davis, Jameson P / Lima, Rosiane / Edlow, Andrea G / Fasano, Alessio / Alter, Galit / Yonker, Lael M

    medRxiv : the preprint server for health sciences

    2022  

    Abstract: Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for ... ...

    Abstract Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. We tested the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the SARS-CoV-2 wild type and Omicron antigens. Serum from 77 adolescents showed that anti-Spike antibodies wane significantly over 6 months. After completion of a two-vaccine series, cross-reactivity against Omicron-specific receptor-binding domain (RBD) was seen. Evidence of waning mRNA-induced vaccine immunity underscores vulnerabilities in long-term pediatric protection against SARS-CoV-2 infection, while cross-reactivity highlights the additional benefits of vaccination. Characterization of adolescent immune signatures post-vaccination will inform guidance on vaccine platforms and timelines, and ultimately optimize immunoprotection of children.
    Language English
    Publishing date 2022-02-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.01.05.22268617
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease.

    Serena, Gloria / Huynh, Daniel / Lima, Rosiane S / Vise, Luciana M / Freire, Rachel / Ingano, Laura / Leonard, Maureen M / Senger, Stefania / Fasano, Alessio

    Frontiers in nutrition

    2019  Volume 6, Page(s) 167

    Abstract: Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about ... ...

    Abstract Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or maintenance of the disease. Macrophages are extremely plastic immune cells that can be directed toward a pro- or anti-inflammatory phenotype by the surrounding microenvironment. Of note, gliadin, the most prominent causative agent of the disease, has been reported to trigger the production of pro-inflammatory cytokines in this cell population. In the present study, we aimed at investigating how the intestinal milieu and more specifically the epithelium can shape the macrophage response to gliadin. Using patient-derived organoids we showed that the intestinal epithelium derived from celiac disease donors releases anti-inflammatory factors that curb the macrophage response to gliadin. Furthermore, we uncovered that the celiac macrophages were better responders than macrophages derived from non-celiac controls. Finally, we demonstrated that IFNγ released by the epithelium is in part responsible of the observed anti-inflammatory effect. Our data shed light on the cross-talk between the immune system and the epithelium and its critical role in the intestinal homeostasis. Furthermore, we provide more evidence how alterations in the innate immune machinery in celiac patients may contribute to the onset of the disease.
    Language English
    Publishing date 2019-11-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2019.00167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Durability and Cross-Reactivity of SARS-CoV-2 mRNA Vaccine in Adolescent Children.

    Burns, Madeleine D / Boribong, Brittany P / Bartsch, Yannic C / Loiselle, Maggie / St Denis, Kerri J / Sheehan, Maegan L / Chen, Jessica W / Davis, Jameson P / Lima, Rosiane / Edlow, Andrea G / Fasano, Alessio / Balazs, Alejandro B / Alter, Galit / Yonker, Lael M

    Vaccines

    2022  Volume 10, Issue 4

    Abstract: Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for ... ...

    Abstract Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. We tested the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the SARS-CoV-2 D614G ("wild type") and Omicron antigens. Serum from 77 adolescents showed that anti-Spike antibodies wane significantly over six months. After completion of a two-vaccine series, cross-reactivity against Omicron-specific receptor-binding domain (RBD) was seen. Functional humoral activation against wild type and Omicron SARS-CoV-2 also declines over time in vaccinated adolescent children. Evidence of waning mRNA-induced vaccine immunity underscores vulnerabilities in long-term pediatric protection against SARS-CoV-2 infection, while cross-reactivity highlights the additional benefits of vaccination. Characterization of adolescent immune signatures post-vaccination will inform guidance on vaccine platforms and timelines, and ultimately optimize immunoprotection of children.
    Language English
    Publishing date 2022-03-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10040492
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: COVID-19 booster dose induces robust antibody response in pregnant, lactating, and nonpregnant women.

    Atyeo, Caroline / Shook, Lydia L / Nziza, Nadege / Deriso, Elizabeth A / Muir, Cordelia / Baez, Arantxa Medina / Lima, Rosiane S / Demidkin, Stepan / Brigida, Sara / De Guzman, Rose M / Burns, Madeleine D / Balazs, Alejandro B / Fasano, Alessio / Yonker, Lael M / Gray, Kathryn J / Alter, Galit / Edlow, Andrea G

    American journal of obstetrics and gynecology

    2022  Volume 228, Issue 1, Page(s) 68.e1–68.e12

    Abstract: Background: Although emerging data during the SARS-CoV-2 pandemic have demonstrated robust messenger RNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and ... ...

    Abstract Background: Although emerging data during the SARS-CoV-2 pandemic have demonstrated robust messenger RNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of messenger RNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known.
    Objective: This study aimed to profile the humoral immune response to a COVID-19 messenger RNA booster dose in a cohort of pregnant, lactating, and nonpregnant age-matched women.
    Study design: This study characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating, and 20 nonpregnant age-matched controls who received a BNT162b2 or messenger RNA-1273 booster dose after primary COVID-19 vaccination. In addition, this study examined the vaccine-induced antibody profiles of 15 maternal-to-cord dyads at delivery.
    Results: Receiving a booster dose during pregnancy resulted in increased immunoglobulin G1 levels against Omicron Spike (postprimary vaccination vs postbooster dose; P=.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total immunoglobulin G1, immunoglobulin M, and immunoglobulin A levels and neutralizing titers against Omicron compared with nonpregnant women. Subtle differences in Fc receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant vs nonpregnant individuals. The analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific immunoglobulin G1 in maternal and cord blood, yet higher Spike-specific FcγR3a-binding antibodies in the cord relative to maternal blood (P=.002), consistent with the preferential transfer of highly functional immunoglobulin. Spike-specific immunoglobulin G1 levels in the cord were positively correlated with the time elapsed since receiving the booster dose (Spearman R, .574; P=.035).
    Conclusion: Study data suggested that receiving a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester of pregnancy, higher Spike-specific cord immunoglobulin G1 levels are achieved with greater time elapsed between receiving the booster and delivery. Receiving a booster dose has the potential to augment maternal and neonatal immunity.
    MeSH term(s) Infant, Newborn ; Pregnancy ; Female ; Humans ; Antibody Formation ; COVID-19 ; BNT162 Vaccine ; COVID-19 Vaccines ; Lactation ; SARS-CoV-2 ; Immunoglobulin G ; Antibodies, Viral
    Chemical Substances BNT162 Vaccine ; COVID-19 Vaccines ; Immunoglobulin G ; Antibodies, Viral
    Language English
    Publishing date 2022-07-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80016-8
    ISSN 1097-6868 ; 0002-9378
    ISSN (online) 1097-6868
    ISSN 0002-9378
    DOI 10.1016/j.ajog.2022.07.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: A Versatile Human Intestinal Organoid-Derived Epithelial Monolayer Model for the Study of Enteric Pathogens.

    Nickerson, Kourtney P / Llanos-Chea, Alejandro / Ingano, Laura / Serena, Gloria / Miranda-Ribera, Alba / Perlman, Meryl / Lima, Rosiane / Sztein, Marcelo B / Fasano, Alessio / Senger, Stefania / Faherty, Christina S

    Microbiology spectrum

    2021  Volume 9, Issue 1, Page(s) e0000321

    Abstract: Gastrointestinal infections cause significant morbidity and mortality worldwide. The complexity of human biology and limited insights into host-specific infection mechanisms are key barriers to current therapeutic development. Here, we demonstrate that ... ...

    Abstract Gastrointestinal infections cause significant morbidity and mortality worldwide. The complexity of human biology and limited insights into host-specific infection mechanisms are key barriers to current therapeutic development. Here, we demonstrate that two-dimensional epithelial monolayers derived from human intestinal organoids, combined with
    MeSH term(s) Cell Culture Techniques/methods ; Enterobacteriaceae/genetics ; Enterobacteriaceae/pathogenicity ; Enterobacteriaceae/physiology ; Enterobacteriaceae Infections/microbiology ; Enterocytes/microbiology ; Epithelial Cells/cytology ; Epithelial Cells/microbiology ; Epithelium/microbiology ; Gastrointestinal Tract/cytology ; Gastrointestinal Tract/microbiology ; Humans ; Organoids/cytology ; Organoids/microbiology ; Virulence
    Language English
    Publishing date 2021-06-09
    Publishing country United States
    Document type Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/Spectrum.00003-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: COVID-19 booster dose antibody response in pregnant, lactating, and nonpregnant women

    Atyeo, Caroline / Shook, Lydia L / Nziza, Nadege / DeRiso, Elizabeth A / Muir, Cordelia / Medina Baez, Arantxa / Lima, Rosiane S / Demidkin, Stepan / Brigida, Sara / De Guzman, Rose M / Burns, Madeleine D / Balazs, Alejandro B / Fasano, Alessio / Yonker, Lael M / Gray, Kathryn J / Alter, Galit / Edlow, Andrea G

    medRxiv

    Abstract: BACKGROUND: While emerging data during the SARS-CoV-2 pandemic have demonstrated robust mRNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence ... ...

    Abstract BACKGROUND: While emerging data during the SARS-CoV-2 pandemic have demonstrated robust mRNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of mRNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known. OBJECTIVE: We sought to profile the humoral immune response to a COVID-19 mRNA booster dose in a cohort of pregnant, lactating, and age-matched nonpregnant women. STUDY DESIGN: We characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating and 20 nonpregnant age-matched controls who received a BNT162b2 or mRNA-1273 booster dose after primary COVID-19 vaccination. We also examined the vaccine-induced antibody profiles of 15 maternal:cord dyads at delivery. RESULTS: Receipt of a booster dose during pregnancy resulted in increased IgG1 against Omicron Spike (post-primary vaccination vs post-booster, p = 0.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total IgG1, IgM and IgA levels and neutralizing titers against Omicron compared to nonpregnant women. Subtle differences in Fc-receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant compared to nonpregnant individuals. Analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific IgG1 in maternal and cord blood, yet higher Spike-specific Fc-gamma-R3a-binding antibodies in the cord relative to maternal blood (p = 0.002), consistent with preferential transfer of highly functional IgG. Spike-specific IgG1 levels in the cord were positively correlated with time elapsed since receipt of the booster dose (Spearman R 0.574, p = 0.035). CONCLUSIONS: These data suggest that receipt of a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester, higher Spike-specific cord IgG1 levels are achieved with greater time elapsed between receipt of the booster and delivery. Receipt of a booster dose has the potential to augment maternal and neonatal immunity.
    Keywords covid19
    Language English
    Publishing date 2022-05-19
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.05.17.22275154
    Database COVID19

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  10. Article: Establishment of a Pediatric COVID-19 Biorepository: Unique Considerations and Opportunities for Studying the Impact of the COVID-19 Pandemic on Children.

    Lima, Rosiane / Gootkind, Elizabeth / Flor, Denis De La / Yockey, Laura / Bordt, Evan / D'Avino, Paolo / Ning, Shen / Heath, Katerina / Harding, Katherine / Zois, Jaclyn / Park, Grace / Hardcastle, Margot / Grinke, Kathleen A / Grimmel, Sheila / Forde, Pamela J / Davidson, Susan P / Hall, Kathryn E / Neilan, Anne / Matute, Juan D /
    Lerou, Paul H / Fasano, Alessio / Shui, Jessica E / Edlow, Andrea G / Yonker, Lael M

    Research square

    2020  

    Abstract: ... ...

    Abstract Background
    Keywords covid19
    Language English
    Publishing date 2020-08-10
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-42030/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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