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  1. Article ; Online: Airway oscillometry parameters in baseline lung allograft dysfunction: Associations from a multicenter study.

    Darley, David Ross / Nilsen, Kris / Vazirani, Jaideep / Borg, Brigitte M / Levvey, Bronwyn / Snell, G / Plit, Marshall Lawrence / Tonga, Katrina O

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2023  Volume 42, Issue 6, Page(s) 767–777

    Abstract: Background: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry ... ...

    Abstract Background: Baseline lung allograft dysfunction (BLAD), the failure to achieve ≥80%-predicted spirometry after lung transplant (LTx), is associated with impaired survival. Physiologic abnormalities in BLAD are poorly understood. Airway oscillometry measures respiratory system mechanics and may provide insight into understanding the mechanisms of BLAD.
    Objectives: This study aims to describe and measure the association between airway oscillometry parameters [Reactance (X
    Methods: A multi-center cross-sectional study was performed including bilateral LTx between January 2020 and June 2021. Participants performed concurrent airway oscillometry and spirometry. Multivariable logistic regression was performed to measure the association between oscillometry parameters and BLAD.
    Results: A total of 404 LTx recipients performed oscillometry and 253 were included for analysis. Stable allograft function was confirmed in 149 (50.2%) recipients (92 (61.7%) achieving normal spirometry and 57 (38.3%) with BLAD). Among stable LTx recipients, lower X
    Conclusions: Oscillometry provides novel physiologic insights into mechanisms of BLAD. The independent association between X
    MeSH term(s) Humans ; Oscillometry ; Cross-Sectional Studies ; Lung ; Respiratory Function Tests ; Lung Transplantation ; Spirometry ; Allografts
    Language English
    Publishing date 2023-01-06
    Publishing country United States
    Document type Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2022.12.026
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  2. Article: Limited recovery from post-acute sequelae of SARS-CoV-2 at 8 months in a prospective cohort.

    Darley, David Ross / Dore, Gregory John / Byrne, Anthony Luke / Plit, Marshall Lawrence / Brew, Bruce James / Kelleher, Anthony / Matthews, Gail Veronica

    ERJ open research

    2021  Volume 7, Issue 4

    Abstract: In a longitudinal cohort, a significant proportion of patients had persistent symptoms 8 months after initial #COVID19 infection. There was no significant improvement in symptoms or health-related quality of life between 4- and 8-month assessments. ...

    Abstract In a longitudinal cohort, a significant proportion of patients had persistent symptoms 8 months after initial #COVID19 infection. There was no significant improvement in symptoms or health-related quality of life between 4- and 8-month assessments.
    Language English
    Publishing date 2021-11-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2827830-6
    ISSN 2312-0541
    ISSN 2312-0541
    DOI 10.1183/23120541.00384-2021
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  3. Article ; Online: Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study.

    Darley, David Ross / Ma, Jin / Huszti, Ella / Ghany, Rasheed / Hutcheon, Michael / Chow, Chung-Wai / Tikkanen, Jussi / Keshavjee, Shaf / Singer, Lianne Gail / Martinu, Tereza

    The European respiratory journal

    2022  Volume 59, Issue 1

    Abstract: Rationale: The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (: Objectives: To determine the prognostic significance of the : Methods: A retrospective analysis was conducted of all bilateral lung transplant ... ...

    Abstract Rationale: The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (
    Objectives: To determine the prognostic significance of the
    Methods: A retrospective analysis was conducted of all bilateral lung transplant recipients at a single centre, between January 1998 and January 2018, with one or more
    Results: 1259 out of 1492 lung transplant recipients were included. The median (range) time to peak
    Conclusion: Low baseline
    MeSH term(s) Carbon Monoxide ; Humans ; Longitudinal Studies ; Lung ; Lung Transplantation ; Primary Graft Dysfunction ; Retrospective Studies
    Chemical Substances Carbon Monoxide (7U1EE4V452)
    Language English
    Publishing date 2022-01-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.03639-2020
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    Zs.MO 292: Show issues

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  4. Article ; Online: Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study

    Cysique, Lucette Adeline / Jakabek, David / Bracken, Sophia G / Allen-Davidian, Yasmin / Heng, Benjamin / Chow, Sharron / Dehhaghi, Mona / Staats-Pires, Ananda / Darley, David Ross / Byrne, Anthony / Phetsouphanh, Chansavath / Kelleher, Anthony / Dore, Gregory / Matthews, Gail V / Guillemin, Gilles / Brew, Bruce J

    medRxiv

    Abstract: Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung ...

    Abstract Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12-months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p<.001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p<.001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.
    Keywords covid19
    Language English
    Publishing date 2022-06-07
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.06.07.22276020
    Database COVID19

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  5. Article ; Online: SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern.

    Aggarwal, Anupriya / Akerman, Anouschka / Milogiannakis, Vanessa / Ruiz Silva, Mariana / Walker, Gregory J / Kindinger, Andrea / Angelovich, Thomas / Churchill, Melissa / Waring, Emily / Amatayakul-Chantler, Supavadee / Roth, Nathan / Coppola, Germano / Yeang, Malinna / Jean, Tyra / Foster, Charles S.P. / Carey Hoppe, Alexandra / Munier, Mee Ling / Christ, Daniel / Darley, David Ross /
    Matthews, Gail / Rawlinson, William D / Kelleher, Anthony D / Turville, Stuart G

    medRxiv

    Abstract: Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and ... ...

    Abstract Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, the Omicron BA.1 variant emerged, with significant genetic differences and clinical effects from other variants of concern (VOC). This variant demonstrated higher numbers of polymorphisms in the gene encoding the Spike (S) protein, and there has been displacement of the dominant Delta variant. Shortly after dominating global spread in early 2022, BA.1 was supplanted by the genetically distinct Omicron lineage BA.2. A sub-lineage of BA.2, designated BA.5 has now started to dominate globally, with the potential to supplant BA.2. To address the relative threat of BA.5, we determined infectivity to particle ratios in primary nasopharyngeal samples and expanded low passage isolates in a well characterised, genetically engineered ACE2/TMPRSS2 cell line. We then assessed the impact of BA.5 infection on humoral neutralisation in vitro, in vaccinated and convalescent cohorts, using concentrated human IgG pooled from thousands of plasma donors, and licensed monoclonal antibody therapies. The infectivity of virus in primary swabs and expanded isolates revealed whilst BA.1 and BA.2 are attenuated through ACE2/TMPRSS2, BA.5 infectivity is equivalent to that of an early 2020 circulating clade and has greater sensitivity to the TMPRSS2 inhibitor Nafamostat. As with BA.1, we observed BA.5 to significantly reduce neutralisation titres across all donors. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 7-fold with BA.5. Of all therapeutic antibodies tested, we observed a 14.3-fold reduction using Evusheld and 16.8 reduction using Sotrovimab when neutralising a Clade A versus BA.5 isolate. These results have implications for ongoing tracking and management of Omicron waves globally.
    Keywords covid19
    Language English
    Publishing date 2022-07-10
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.07.07.22277128
    Database COVID19

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  6. Article ; Online: SARS-CoV-2 Omicron: reduction of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

    Aggarwal, Anupriya / Ospina Stella, Alberto / Walker, Gregory / Akerman, Anoushka / Milogiannakis, Vanessa / Hoppe, Alexandra Carey / Mathivanan, Vennila / Fichter, Christina / McAllery, Samantha / Amatayakul-Chantler, Supavadee / Roth, Nathan / Coppola, Germano / Munier, Mee Ling / Darley, David Ross / Khoury, David S / Foster, Charles S.P. / Lu, Yonghui / Schofield, Peter / Jackson, Jennifer /
    Henry, Jake / Mazigi, Ohan / Jaeck, Hans-Martin / Langles, David / Cromer, Deborah / Davenport, Miles Philip / Christ, Daniel / Matthews, Gail / Rawlinson, William / Kelleher, Anthony Dominic / Turville, Stuart G

    medRxiv

    Abstract: From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses resulted in significant global vaccine rollouts that have now significantly lowered Covid-19 hospitalisation and mortality ... ...

    Abstract From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses resulted in significant global vaccine rollouts that have now significantly lowered Covid-19 hospitalisation and mortality rates in the developed world. Unfortunately, in late 2021, the variant Omicron (B.1.1.529) emerged and it eclipsed the other variants of concern (VOC) in its number of Spike polymorphisms, and its ability to compete with and displacement of the dominant VOC Delta. Herein we accessed the impact of Omicron to humoral neutralisation in vaccinated, convalescent cohorts, in concentrated human IgG from thousands of plasma donors and also alongside many clinically used monoclonal antibodies. Overall, we observed a 17 to 22 fold drop in neutralisation titres across all donors that reached a titre to Omicron. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth but was still reduced by 16-fold. In all therapeutic antibodies tested, significant neutralization was only observed for Sotrovimab, with other monoclonals unable to neutralize B.1.1.529.
    Keywords covid19
    Language English
    Publishing date 2021-12-15
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.12.14.21267772
    Database COVID19

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  7. Article ; Online: SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants

    Tea, Fiona / Ospina Stella, Alberto / Aggarwal, Anupriya / Darley, David Ross / Pilli, Deepti / Vitale, Daniele / Merheb, Vera / Lee, Fiona X. Z. / Cunningham, Philip / Walker, Gregory J / Brown, David A / Rawlinson, William D / Isaacs, Sonia R / Mathivanan, Vennila / Hoffman, Markus / Poehlmann, Stefan / Dwyer, Dominic E / Rockett, Rebecca / Sintchenko, Vitali /
    Hoad, Veronica C / Irving, David O / Dore, Gregory J / Gosbell, Iain B / Kelleher, Anthony D / Matthews, Gail V / Brilot, Fabienne / Turville, Stuart G

    medRxiv

    Abstract: The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 ... ...

    Abstract The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of high responders maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.
    Keywords covid19
    Language English
    Publishing date 2020-12-22
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2020.12.19.20248567
    Database COVID19

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