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1.
Lancet Rheumatol ; 4(1): e42-e52, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1595648

ABSTRACT

BACKGROUND: COVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. Here, we aimed to assess immune responses following the second dose. METHODS: In this longitudinal cohort study, we recruited individuals with psoriasis who were receiving methotrexate or targeted biological monotherapy (ie, tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South-East England. The healthy control cohort were volunteers without psoriasis, not receiving immunosuppression. Immunogenicity was evaluated immediately before, on day 28 after the first BNT162b2 vaccination and on day 14 after the second dose (administered according to an extended interval regimen). Here, we report immune responses following the second dose. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as titres of total spike-specific IgG and of neutralising antibody to wild-type, alpha (B.1.1.7), and delta (B.1.617.2) SARS-CoV-2 variants, and cellular immunity defined as spike-specific T-cell responses (including numbers of cells producing interferon-γ, IL-2, IL-21). FINDINGS: Between Jan 14 and April 4, 2021, 121 individuals were recruited, and data were available for 82 participants after the second vaccination. The study population included patients with psoriasis receiving methotrexate (n=14), TNF inhibitors (n=19), IL-17 inhibitors (n=14), IL-23 inhibitors (n=20), and 15 healthy controls, who had received both vaccine doses. The median age of the study population was 44 years (IQR 33-52), with 43 (52%) males and 71 (87%) participants of White ethnicity. All participants had detectable spike-specific antibodies following the second dose, and all groups (methotrexate, targeted biologics, and healthy controls) demonstrated similar neutralising antibody titres against wild-type, alpha, and delta variants. By contrast, a lower proportion of participants on methotrexate (eight [62%] of 13, 95% CI 32-86) and targeted biologics (37 [74%] of 50, 60-85; p=0·38) had detectable T-cell responses following the second vaccine dose, compared with controls (14 [100%] of 14, 77-100; p=0·022). There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 106 cells 160 [IQR 10-625]), targeted biologics (169 [25-503], p=0·56), and controls (185 [133-328], p=0·41). INTERPRETATION: Functional humoral immunity (ie, neutralising antibody responses) at 14 days following a second dose of BNT162b2 was not impaired by methotrexate or targeted biologics. A proportion of patients on immunosuppression did not have detectable T-cell responses following the second dose. The longevity of vaccine-elicited antibody responses is unknown in this population. FUNDING: NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London; The Psoriasis Association.

3.
Clinical Medicine ; 21:S55-S56, 2021.
Article in English | ProQuest Central | ID: covidwho-1380300

ABSTRACT

Introduction Continuous positive airway pressure (CPAP) therapy had been previously shown to reduce the need for invasive mechanical ventilation (IMV) in cardiogenic pulmonary oedema, but evidence of its efficacy in viral-induced respiratory failure is limited and is a subject of debate.1,2 An early intubation strategy without trial of non-invasive ventilation (NIV) had been previously suggested, while others have argued for timely, but not premature, intubation.3 We retrospectively evaluated the efficacy of CPAP in patients with COVID-19 at a single centre. Exclusion criteria were <16 years old, pregnancy, acute-on-chronic hypercapnic respiratory failure and acute respiratory failure from an alternative diagnosis to SARS-CoV-2. Early intubation strategy was previously fiercely advocated due to concerns of exceedingly high NIV failure rate in MERS, infection transmission risks and poorer outcomes with delayed intubation.4-6 In a non-SARS-CoV-2 population, the LUNGSAFE study showed higher ICU mortality with NIV use in patients with PaO2/FiO2 <150 mmHg compared with early intubation.6 Data in SARS-CoV-2 are not available.

4.
Lancet Rheumatol ; 3(9): e627-e637, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1301109

ABSTRACT

BACKGROUND: Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose. METHODS: In this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination. FINDINGS: Between Jan 14 and April 4, 2021, 84 patients with psoriasis (17 on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors) and 17 healthy controls were included. The study population had a median age of 43 years (IQR 31-52), with 56 (55%) males, 45 (45%) females, and 85 (84%) participants of White ethnicity. Seroconversion rates were lower in patients receiving immunosuppressants (60 [78%; 95% CI 67-87] of 77) than in controls (17 [100%; 80-100] of 17), with the lowest rate in those receiving methotrexate (seven [47%; 21-73] of 15). Neutralising activity against wild-type SARS-CoV-2 was significantly lower in patients receiving methotrexate (median 50% inhibitory dilution 129 [IQR 40-236]) than in controls (317 [213-487], p=0·0032), but was preserved in those receiving targeted biologics (269 [141-418]). Neutralising titres against the B.1.1.7 variant were similarly low in all participants. Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls. INTERPRETATION: Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved. Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness. FUNDING: UK National Institute for Health Research.

6.
J Racial Ethn Health Disparities ; 8(6): 1563-1572, 2021 12.
Article in English | MEDLINE | ID: covidwho-920070

ABSTRACT

OBJECTIVES: This article evaluates if ethnicity is an independent poor prognostic factor in COVID-19 disease. METHODS: MEDLINE, EMBASE, Cochrane, WHO COVID-19 databases from inception to 15/06/2020 and medRxiv. No language restriction. Newcastle-Ottawa Scale (NOS) and GRADE framework were utilised to assess the risk of bias and certainty of evidence. PROSPERO CRD42020188421. RESULTS: Seventy-two articles (59 cohort studies with 17,950,989 participants, 13 ecological studies; 54 US-based, 15 UK-based; 41 peer-reviewed) were included for systematic review and 45 for meta-analyses. Risk of bias was low: median NOS 7 of 9 (interquartile range 6-8). Compared to White ethnicity, unadjusted all-cause mortality was similar in Black (RR: 0.96 [95% CI: 0.83-1.08]) and Asian (RR: 0.99 [0.85-1.16]) but reduced in Hispanic ethnicity (RR: 0.69 [0.57-0.84]). Age- and sex-adjusted risks were significantly elevated for Black (HR: 1.38 [1.09-1.75]) and Asian (HR: 1.42 [1.15-1.75]), but not for Hispanic (RR: 1.14 [0.93-1.40]). Further adjusting for comorbidities attenuated these associations to non-significance: Black (HR: 0.95 [0.72-1.25]); Asian (HR: 1.17 [0.84-1.63]); Hispanic (HR: 0.94 [0.63-1.44]). Subgroup analyses showed a trend towards greater disparity in outcomes for UK ethnic minorities, especially hospitalisation risk. CONCLUSIONS: This review could not confirm a certain ethnicity as an independent poor prognostic factor for COVID-19. Racial disparities in COVID-19 outcomes may be partially attributed to higher comorbidity rates in certain ethnicity.


Subject(s)
COVID-19/ethnology , Patient Acuity , COVID-19/therapy , Humans , Prognosis , Risk Factors
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