ORCID Profile
0000-0001-8906-805X
Current Organisations
Newcastle University
,
University College London
,
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 17-08-2020
DOI: 10.1038/S41591-020-1038-6
Abstract: Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, in idual traits within this signature may collectively and in idually guide treatment options offer insights into COVID-19 pathogenesis and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Cold Spring Harbor Laboratory
Date: 17-03-2021
DOI: 10.1101/2021.03.17.21253131
Abstract: The efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer diagnosis were hitherto excluded from trials of the vaccines currently in clinical use. This study presents data on the safety and immune efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in 54 healthy controls and 151 mostly elderly patients with solid and haematological malignancies, respectively, and compares results for patients who were boosted with BNT162b2 at 3 weeks versus those who were not. Immune efficacy was measured as antibody seroconversion, T cell responses, and neutralisation of SARS-CoV-2 Wuhan strain and of a variant of concern (VOC) (B.1.1.7). We also collected safety data for the BNT162b2 vaccine up to 5 weeks following first dose. The vaccine was largely well tolerated. However, in contrast to its very high performance in healthy controls ( % efficacious), immune efficacy of a single inoculum in solid cancer patients was strikingly low (below 40%) and very low in haematological cancer patients (below 15%). Of note, efficacy in solid cancer patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer patients were boosted for clear conclusions to be drawn. Delayed boosting potentially leaves most solid and haematological cancer patients wholly or partially unprotected, with implications for their own health their environment and the evolution of VOC strains. Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients. Some cancer patients have been shown to exhibit sustained immune dysregulation, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, their exclusion and, in particular, the exclusion of patients receiving systemic anti-cancer therapies, from the registry trials of the 5 approved COVID-19 vaccines raises questions about the efficacy and safety of SARS-CoV-2 vaccination in this patient population. In addition, whilst the change in the UK’s dosing interval to 12-weeks aimed to maximise population coverage, it is unclear whether this strategy is appropriate for cancer patients and those on systemic anti-cancer therapies. We report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer patients was well tolerated, and we provide first insights into both antibody and T cell responses to the vaccine in an immunocompromised patient population. In cancer patients, one dose of 30ug of BNT162b2 yields poor vaccine efficacy, as measured by seroconversion rates, viral neutralisation capacity and T cell responses, at 3- and 5-weeks following the first inoculum. Patients with solid cancers exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of ‘ring vaccination’, and careful follow-up should be prioritised.
Publisher: Cold Spring Harbor Laboratory
Date: 09-06-2020
DOI: 10.1101/2020.06.08.20125112
Abstract: Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because of its potential to cause life-threatening Covid-19 disease. By comparison to paucisymptomatic virus clearance by most in iduals, Covid-19 has been proposed to reflect insufficient and/or pathologically exaggerated immune responses. Here we identify a consensus peripheral blood immune signature across 63 hospital-treated Covid-19 patients who were otherwise highly heterogeneous. The core signature conspicuously blended adaptive B cell responses typical of virus infection or vaccination with discrete traits hitherto associated with sepsis, including monocyte and dendritic cell d ening, and hyperactivation and depletion of discrete T cell subsets. This blending of immuno-protective and immuno-pathogenic potentials was exemplified by near-universal CXCL10/IP10 upregulation, as occurred in SARS1 and MERS. Moreover, specific parameters including CXCL10/IP10 over-expression, T cell proliferation, and basophil and plasmacytoid dendritic cell depletion correlated, often prognostically, with Covid-19 progression, collectively composing a resource to inform SARS-CoV-2 pathobiology and risk-based patient stratification.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Irene del Molino del Barrio.