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1.
Support Care Cancer ; 31(7): 376, 2023 Jun 05.
Article in English | MEDLINE | ID: covidwho-20240047

ABSTRACT

PURPOSE: This study aimed to explore the challenges of access to treatment and quality of life in female cancer survivors living in rural areas of Iran within the global pandemic context (COVID-19). METHODS: We conducted a qualitative exploratory study where we recruited nine female-identifying individuals diagnosed with cancer, 23 family members, and five healthcare providers from a hospital affiliated with the Birjand University of Medical Sciences in Iran. Data was collected using semi-structured interviews and analyzed using Braun and Clarke's reflective thematic analysis. RESULTS: The three themes constructed were lack of strength from fighting on two fronts (subthemes: (i) fear related to longevity and life span, (ii) disruption of emotional relationships and family functioning, (iii) loneliness and fear of the future, (iv) village culture and double whammy, and (v) isolation and rejection in a rural community); changes during treatment (subthemes: (i) confusion related to treatment and (ii) the hope found during treatment "bottlenecks"); and spiritual growth and clarifying values (subthemes: (i) patience and resilience and (ii) clarifying life values and opportunities when facing uncertainty about the future). CONCLUSION: This study highlights the importance of further evaluating interventions to mitigate barriers to supportive care for female cancer survivors living in rural areas with low-resource contexts during the COVID-19 pandemic.


Subject(s)
COVID-19 , Neoplasms , Humans , Female , Pandemics , Quality of Life , Iran , Neoplasms/therapy , Qualitative Research
2.
Clin Infect Dis ; 2022 Oct 05.
Article in English | MEDLINE | ID: covidwho-2240690

ABSTRACT

BACKGROUND: People with HIV on antiretroviral therapy with good CD4 T cell counts make effective immune responses following vaccination against SARS-CoV-2. There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed twelve months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µl. Immune responses to the ancestral strain and variants of concern were measured by anti-spike IgG ELISA, MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, Activation Induced Marker (AIM) assay and T cell proliferation. FINDINGS: 54 participants received two doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) one year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titres (MSD), ACE-2 inhibition and IgG ELISA results were significantly higher compared to Day 182 titres (P < 0.0001 for all three). SARS-CoV-2 specific CD4+ T cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4 + and CD8+ T cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs.

3.
Lancet Microbe ; 3(1): e21-e31, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1915218

ABSTRACT

BACKGROUND: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA vaccine. METHODS: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3-4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. FINDINGS: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232-285). At 28 days (IQR 27-33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150-461] vs 55 [IQR 24-132] spot-forming units [SFUs] per 106 PBMCs; p<0·0001). With cryopreserved PBMCs, the T-cell response in previously infected individuals (n=52) after one vaccine dose was equivalent to that of infection-naive individuals (n=19) after receiving two vaccine doses (median 152 [IQR 119-275] vs 162 [104-258] SFUs/106 PBMCs; p=1·00). Anti-spike IgG antibody responses following a single dose in 142 previously infected health-care workers (median 270 373 [IQR 203 461-535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099-55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221-242 467] AU/mL; p<0·0001). INTERPRETATION: A single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern. Future studies should determine the additional benefit of a second dose on the magnitude and durability of immune responses in individuals vaccinated following infection, alongside evaluation of the impact of extending the interval between vaccine doses. FUNDING: UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antibody Formation , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Leukocytes, Mononuclear , Prospective Studies , T-Lymphocytes , United Kingdom/epidemiology , Vaccines, Synthetic , mRNA Vaccines
4.
PLoS One ; 17(5): e0268302, 2022.
Article in English | MEDLINE | ID: covidwho-1910642

ABSTRACT

Early public health strategies to prevent the spread of COVID-19 in the United States relied on non-pharmaceutical interventions (NPIs) as vaccines and therapeutic treatments were not yet available. Implementation of NPIs, primarily social distancing and mask wearing, varied widely between communities within the US due to variable government mandates, as well as differences in attitudes and opinions. To understand the interplay of trust, risk perception, behavioral intention, and disease burden, we developed a survey instrument to study attitudes concerning COVID-19 and pandemic behavioral change in three states: Idaho, Texas, and Vermont. We designed our survey (n = 1034) to detect whether these relationships were significantly different in rural populations. The best fitting structural equation models show that trust indirectly affects protective pandemic behaviors via health and economic risk perception. We explore two different variations of this social cognitive model: the first assumes behavioral intention affects future disease burden while the second assumes that observed disease burden affects behavioral intention. In our models we include several exogenous variables to control for demographic and geographic effects. Notably, political ideology is the only exogenous variable which significantly affects all aspects of the social cognitive model (trust, risk perception, and behavioral intention). While there is a direct negative effect associated with rurality on disease burden, likely due to the protective effect of low population density in the early pandemic waves, we found a marginally significant, positive, indirect effect of rurality on disease burden via decreased trust (p = 0.095). This trust deficit creates additional vulnerabilities to COVID-19 in rural communities which also have reduced healthcare capacity. Increasing trust by methods such as in-group messaging could potentially remove some of the disparities inferred by our models and increase NPI effectiveness.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Cost of Illness , Health Behavior , Humans , Perception , SARS-CoV-2 , Trust , United States/epidemiology
5.
Intern Med J ; 52(8): 1322-1329, 2022 08.
Article in English | MEDLINE | ID: covidwho-1861359

ABSTRACT

BACKGROUND: COVID-19 has caused a global shift in healthcare-seeking behaviour; however, presentation rates with serious conditions, such as stroke in low COVID-19-prevalence cities, has received less attention. AIMS: To determine if there was a significant reduction in stroke admissions, delivery of acute reperfusion therapies, or increased delays to presentation during the first wave of the COVID-19 pandemic. METHODS: A multicentre, retrospective, observational cohort study was performed across three tertiary hospitals in Brisbane, Australia. Cases were identified using ICD-10 codes and then individually reviewed for eligibility using prespecified inclusion and exclusion criteria. All metrics were compared over 3 months from 1 March to 31 May 2020 with two corresponding 3-month periods in 2018 and 2019. RESULTS: There was a mean of 2.15 (95% CI 1.87-2.48) stroke admissions per day in the examined pandemic months compared with 2.13 (95% CI 1.85-2.45) and 2.26 (95% CI 1.97-2.59) in March to May 2018 and 2019 respectively, with no significant difference found (P = 0.81). There was also no difference in rates of intravenous thrombolysis (P = 0.82), endovascular thrombectomy (P = 0.93) and time from last known well to presentation (P = 0.54). Conversely, daily emergency department presentations (including non-stroke presentations) significantly reduced (P < 0.0001). CONCLUSIONS: During the early months of the COVID-19 pandemic there was no significant reduction in stroke presentations, use of acute reperfusion therapies or delays to presentation, despite a reduction in ED presentations for any cause. Our results differ from the global experience, with possible explanations, including differences in public health messaging and healthcare infrastructure.


Subject(s)
COVID-19 , Stroke , COVID-19/epidemiology , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Stroke/diagnosis , Stroke/epidemiology , Stroke/therapy , Tertiary Care Centers
6.
Stroke Vasc Neurol ; 7(2): 158-165, 2022 04.
Article in English | MEDLINE | ID: covidwho-1832554

ABSTRACT

RATIONALE: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. METHODS AND DESIGN: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. HYPOTHESIS: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. SAMPLE SIZE ESTIMATES: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. INTERVENTION: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. PRIMARY EFFICACY MEASURE: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. DISCUSSION: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.


Subject(s)
Cerebral Hemorrhage , Tranexamic Acid , Antifibrinolytic Agents/adverse effects , Antifibrinolytic Agents/therapeutic use , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/drug therapy , Clinical Trials, Phase II as Topic , Hematoma/etiology , Hematoma/prevention & control , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Stroke/therapy , Time Factors , Tranexamic Acid/adverse effects , Tranexamic Acid/therapeutic use
7.
Trials ; 23(1): 263, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1779666

ABSTRACT

BACKGROUND: Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. METHODS: RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. DISCUSSION: The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. TRIAL REGISTRATION: The protocol is registered on Clinical. TRIALS: gov and EudraCT and has approval from UK Ethics and MHRA.


Subject(s)
COVID-19 , HIV Infections , HIV-1 , Broadly Neutralizing Antibodies , Clinical Trials, Phase II as Topic , Community Participation , HIV Antibodies , HIV Infections/diagnosis , HIV Infections/drug therapy , Humans , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
8.
Nat Commun ; 13(1): 1251, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1740439

ABSTRACT

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Antiviral Agents , Humans , Longitudinal Studies , Spike Glycoprotein, Coronavirus
9.
BMJ Case Rep ; 15(2)2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1714384

ABSTRACT

We present a case study of a 38-year-old man who developed arterial and venous thrombi, resulting in multiterritorial strokes, a pulmonary embolus and a cerebral venous sinus thrombosis in the setting of spontaneous heparin-induced thrombocytopaenia syndrome.


Subject(s)
Stroke , Thrombocytopenia , Thrombosis , Adult , Heparin/adverse effects , Humans , Male , Thrombocytopenia/chemically induced
10.
JCI Insight ; 7(7)2022 04 08.
Article in English | MEDLINE | ID: covidwho-1702851

ABSTRACT

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/µL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.


Subject(s)
COVID-19 , HIV Infections , COVID-19/prevention & control , ChAdOx1 nCoV-19 , HIV Infections/drug therapy , Humans , Male , SARS-CoV-2 , Vaccination
11.
J Sports Sci ; 40(8): 899-907, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1642109

ABSTRACT

This study examined adolescent muscle-strengthening exercise (MSE) participation at home and associated socioecological correlates during Australia's initial COVID-19 lockdown restrictions. Adolescents (N = 731, Mage = 16.3, SD = 1.2 years, 73% female) self-reported their MSE participation in February 2020 (pre-lockdown; at a gym or at home) and April/May (during lockdown; at home only as gyms were closed). They also reported a range of potential individual, family, and home environment correlates. Remoteness and area-level socioeconomic disadvantage were also considered. Logistic regression models examined potential correlates of participation in any MSE and MSE engagement ≥3 times/week during April/May. Fewer adolescents participated in MSE during April/May (48%) than February (54%), however, the proportions that engaged in MSE ≥3 times/week were the same (30%). Prioritising being active every day (OR = 2.43, 95% CI = 1.52, 3.90), being active with sibling/s ≥ 5 days/week (OR = 2.24, 95% CI = 1.00, 5.00) and access to weights at home (OR = 2.98, 95% CI = 1.94, 4.57) were associated with higher odds of any MSE participation at home during April/May. These variables were also positively associated with MSE participation at home ≥3 times/week. Understanding how to support adolescents to prioritise being active, engage in MSE with siblings, and provide equipment may assist adolescents to engage in home-based MSE.


Subject(s)
COVID-19 , Adolescent , Communicable Disease Control , Exercise , Female , Humans , Male , Muscles , Self Report
12.
J Sci Med Sport ; 25(3): 235-241, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1525863

ABSTRACT

OBJECTIVES: To examine the effects of COVID-19 related 'lockdown restrictions' on Australian's (5-75 years) physical activity recommendation achievement and active recreation participation. DESIGN: Cross-sectional online survey with self and proxy-report items (where the participant was a parent). METHODS: Adults (n = 1360) and adolescents (n = 1292) reported the frequency they performed 30- or 60-min of moderate-to-vigorous physical activity (MVPA), muscle-strengthening exercises, and participation in 11 active recreation behaviours in February 2020 (pre-COVID-19) and in April/May (during lockdown restrictions). Parents also proxy-reported activity for their child (n = 147, 5-12 years). Mixed effects logistic regressions or a logistic regression (with robust sandwich estimation for variance) assessed recall differences pre- and during lockdown, and interaction by sex. RESULTS: Compared to February, in April/May children were less likely to meet MVPA recommendations (OR = 0.27, 95%CI = 0.12-0.64); adolescents males, but not females, were less likely to meet MVPA (OR = 0.71, 95%CI 0.43, 1.17) and both recommendations (OR = 0.12, 95%CI = 0.02, 0.79); and adults were more likely to meet MVPA (OR = 1.26, 95%CI = 1.01, 1.57) but less likely to meet muscle-strengthening exercise recommendations (OR = 0.76, 9%CI = 0.65, 0.89). Across age groups more participants reported walking, muscle strengthening exercises at home, and yoga/Pilates/stretching at home, and fewer performed informal sport practice and play, and recreational activities. CONCLUSIONS: Lockdown restrictions had different effects on physical activity and active recreation among age groups and by sex. Physical activity promotion strategies that target children and adolescents, at home physical activity options, active neighbourhoods, and (re)engagement in informal sport and recreational activities post-COVID-19 are critical for (re)engaging Australians in health-enhancing behaviours.


Subject(s)
COVID-19 , Sports , Adolescent , Adult , Australia , Child , Communicable Disease Control , Cross-Sectional Studies , Exercise/physiology , Humans , Male , Recreation , SARS-CoV-2
13.
Nat Commun ; 12(1): 5061, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361634

ABSTRACT

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Monoclonal/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/isolation & purification , Antibodies, Neutralizing/metabolism , Antibodies, Viral/blood , Antibodies, Viral/immunology , Carrier Proteins , Epitopes , Humans , Immunity , SARS-CoV-2/drug effects , T-Lymphocytes/immunology
14.
J R Coll Physicians Edinb ; 51(S1): S20-S25, 2021 06.
Article in English | MEDLINE | ID: covidwho-1286975

ABSTRACT

BACKGROUND: To manage the public health risk posed by COVID-19 and assess the impact of interventions, policymakers must be able to closely monitor the epidemic's trajectory. METHODS: Here we present a simple methodology based on basic surveillance metrics for monitoring the spread of COVID-19 and its burden on health services in Scotland. RESULTS: We examine how the dynamics of the epidemic have changed over time and assess the similarities and differences between metrics. DISCUSSION: We illustrate how our method has been used throughout the epidemic in Scotland, explore potential biases and conclude that our method has proven to be an effective tool for monitoring the epidemic's trajectory.


Subject(s)
COVID-19 , Epidemics , Humans , Public Health , SARS-CoV-2 , Scotland/epidemiology
15.
Lancet HIV ; 8(8): e474-e485, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275800

ABSTRACT

BACKGROUND: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV. METHODS: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per µL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4-6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing. FINDINGS: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2-49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per µL (IQR 573·5-859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704-2728]; n=50) and were sustained until day 56 (median 941 EUs [531-1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses). INTERPRETATION: In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , HIV Infections/immunology , SARS-CoV-2/immunology , Adult , CD4 Lymphocyte Count , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , HIV Infections/drug therapy , Humans , Male , Middle Aged , Vaccination
16.
Nat Commun ; 12(1): 2055, 2021 04 06.
Article in English | MEDLINE | ID: covidwho-1171493

ABSTRACT

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/immunology , COVID-19/virology , Cross Reactions/immunology , Immunoassay/methods , SARS-CoV-2/physiology , T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/epidemiology , Cell Proliferation , Cytokines/metabolism , HEK293 Cells , Health Personnel , Humans , Immunoglobulin G/immunology , Immunologic Memory , Interferon-gamma/metabolism , Pandemics , Peptides/metabolism , SARS-CoV-2/drug effects
17.
J Med Internet Res ; 23(2): e23389, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1058354

ABSTRACT

BACKGROUND: Government responses to managing the COVID-19 pandemic may have impacted the way individuals were able to engage in physical activity. Digital platforms are a promising way to support physical activity levels and may have provided an alternative for people to maintain their activity while at home. OBJECTIVE: This study aimed to examine associations between the use of digital platforms and adherence to the physical activity guidelines among Australian adults and adolescents during the COVID-19 stay-at-home restrictions in April and May 2020. METHODS: A national online survey was distributed in May 2020. Participants included 1188 adults (mean age 37.4 years, SD 15.1; 980/1188, 82.5% female) and 963 adolescents (mean age 16.2 years, SD 1.2; 685/963, 71.1% female). Participants reported demographic characteristics, use of digital platforms for physical activity over the previous month, and adherence to moderate- to vigorous-intensity physical activity (MVPA) and muscle-strengthening exercise (MSE) guidelines. Multilevel logistic regression models examined differences in guideline adherence between those who used digital platforms (ie, users) to support their physical activity compared to those who did not (ie, nonusers). RESULTS: Digital platforms include streaming services for exercise (eg, YouTube, Instagram, and Facebook); subscriber fitness programs, via an app or online (eg, Centr and MyFitnessPal); facilitated online live or recorded classes, via platforms such as Zoom (eg, dance, sport training, and fitness class); sport- or activity-specific apps designed by sporting organizations for participants to keep up their skills (eg, TeamBuildr); active electronic games (eg, Xbox Kinect); and/or online or digital training or racing platforms (eg, Zwift, FullGaz, and Rouvy). Overall, 39.5% (469/1188) of adults and 26.5% (255/963) of adolescents reported using digital platforms for physical activity. Among adults, MVPA (odds ratio [OR] 2.0, 95% CI 1.5-2.7), MSE (OR 3.3, 95% CI 2.5-4.5), and combined (OR 2.7, 95% CI 2.0-3.8) guideline adherence were higher among digital platform users relative to nonusers. Adolescents' MVPA (OR 2.4, 95% CI 1.3-4.3), MSE (OR 3.1, 95% CI 2.1-4.4), and combined (OR 4.3, 95% CI 2.1-9.0) guideline adherence were also higher among users of digital platforms relative to nonusers. CONCLUSIONS: Digital platform users were more likely than nonusers to meet MVPA and MSE guidelines during the COVID-19 stay-at-home restrictions in April and May 2020. Digital platforms may play a critical role in helping to support physical activity engagement when access to facilities or opportunities for physical activity outside the home are restricted.


Subject(s)
COVID-19 , Exercise , Guideline Adherence , Resistance Training , Social Media , Video Games , Webcasts as Topic , Adolescent , Adult , Australia , Female , Humans , Logistic Models , Male , Middle Aged , Mobile Applications , Multilevel Analysis , Pandemics , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
18.
J Pain Symptom Manage ; 62(1): 141-148.e2, 2021 07.
Article in English | MEDLINE | ID: covidwho-949880

ABSTRACT

CONTEXT: In response to the COVID-19 pandemic, NHS England prohibited people visiting acute hospital trusts. An end-of-life companion scheme was introduced to support the delivery of care for seriously unwell and dying patients during this time. OBJECTIVES: This study aims to capture the companions' experience and activities, including qualitative feedback, as well as outline recommendations for this role in future services and training. METHODS: The companions' service comprised Allied Healthcare Professionals working for the trust who volunteered for the role following a reduction in their normal workload due to COVID-19. They worked in shifts covering a 12-hour period every day of the week with patients identified by the palliative care team. Companions completed questionnaires containing a 4 domains mixture of Likert scale and free text responses before and after their experience. Details of the visits were recorded in daily spreadsheets. RESULTS: The majority of companions were from the physiotherapy team with a range of experience working in the NHS. In total, 64 patients were seen over 382 visits. The companions often carried out more than one activity per visit including communication with the patient and next of kin, personal care, literature, and spirituality. Data showed a statistically significant association between experience as a companion and reduced anxiety around spending time with dying people. CONCLUSION: This study highlights an interesting approach to changing job roles for health-care professionals during the COVID-19 pandemic as well as recognizing the importance of allied health professionals in the multidisciplinary approach to palliative and end-of-life care.


Subject(s)
COVID-19 , Pandemics , Death , Delivery of Health Care , Empathy , England/epidemiology , Humans , SARS-CoV-2
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