ABSTRACT
Background: Adults living with HIV may have higher risk of SARS-CoV- 2 infection than HIV negative adults. There are no published data on seroprevalence of SARS-CoV-2 in children and adolescents living with HIV (CALWHIV). Method(s): We did a repeat SARS-CoV-2 seroprevalence study in 7 paediatric HIV observational cohorts in 5 countries in the European Pregnancy & Paediatric Infections Cohort Collaboration (EPPICC;Belgium, Greece, Spain, Ukraine, United Kingdom (UK)) and also the Cape Town Adolescent Antiretroviral Cohort (CTAAC), South Africa (SA) (CALWHIV and HIV negative adolescents). Participants gave 2 blood samples for SARS-CoV-2 antibody testing ~6 months apart during routine visits between May 2020 and July 2022, and completed questionnaires on SARS-CoV-2 exposure/infection and vaccine status. Clinical and demographic data were extracted from clinic records. Result(s): Of 906 participants, 53%(477) were female, 89%(803) CALWHIV, median [IQR] age at first visit 17[15-19] years. Most were enrolled in SA (45%, 410/906), UK (23%, 205/906) or Ukraine (18%, 160/906). 85%(767/906) had 2 blood samples and the rest a single sample. For CALWHIV, at time of first sample, 99%(761/765) were on antiretroviral therapy, median CD4 count was 666[478-858] cells/mL, 70%(535/764) had HIV-1 viral load < 50c/mL. Of those with known SARS-CoV-2 vaccine status, 23%(181/773) CALWHIV and 22% (22/100) HIV negative participants received >=1 vaccine dose. 6%(43/762) of CALWHIV had a documented prior SARS-CoV-2 positive PCR (including 2 hospitalised for COVID, neither severe), and 16%(124/762) self-reported previous positive test and/or COVID-19 symptoms, giving a total of 17%(128/762) with any previous infection. Based on serum testing, 63%(562/898) of participants overall were seropositive on at least one sample (55% (269/488) Europe, 67% (205/307) SA CALWHIV, 85% (88/103) SA HIV negative group), and among the unvaccinated subgroup, 53%(408/765) were seropositive (41% (167/412) Europe, 64% (168/263) SA CALWHIV, 81% (73/90) SA HIV negative). Among samples taken prior to or in absence of vaccination, the proportion testing antibody positive increased over time (Figure). Of unvaccinated CALWHIV with >=1 positive result, 17%(52/299) reported any previous SARS-CoV-2 infection. Conclusion(s): Most CALWHIV were SARS-CoV-2 seropositive by mid-2022 despite low vaccine coverage. Fewer had documented or self-reported COVID-19 infection or disease, suggesting most infections were mild or asymptomatic. Seroprevalence of SARS-CoV-2 antibodies in Europe and South Africa, by HIV status and calendar quarter of sampling. Colours indicate dominant variant based on GISAID data for adults and children.
ABSTRACT
Serological responses to Covid-19 vaccines in adults post solid organ transplant are impaired [1]. We sought to measure antibodies to SARS-CoV-2 in adolescents post lung, heart, kidney-liver and kidney transplant following the vaccine rollout to 12-17 year-olds in the UK. We measured anti-spike, receptor binding domain and nucleocapsid IgG in adolescents attending our centre for routine drug monitoring after Pfizer/BioNTech BNT 162b2 was made available in autumn 2021, and collected information on prior infection from electronic records and via patient/parent recall. Samples were obtained from 42 participants, with paired samples pre and post vaccine in 14 patients. 52% had serological evidence of past exposure at baseline (fig 1). Receptor binding domain IgG was positive in all subjects at follow up, with spike IgG positive in 13/14 (p<0.001, fig 2). Individuals who had received vaccine and been infected had higher levels of spike IgG than those who had been infected and unvaccinated (p<0.05). All subjects demonstrated antibody responses to vaccine, and vaccine increases antibody levels in adolescents who have also had a SARS-CoV-2 infection in comparison to the unvaccinated. These data support an age-related relationship to antibody responses in post solid organ transplant recipients and support efforts to increase vaccine uptake in this at-risk group. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Background/Aims Effective symptom management may require the use of medications. Medication adherence may be hindered by formulation aspects, such as poor taste. Paediatric studies indicate, that despite concerns of swallowing solid dose forms, children prefer these to liquid forms. They find the solid dose forms more palatable. However, swallowing numerous solid dose forms, may present a significant 'pill' burden to patients and their care-givers. Filling empty gelatine capsules with requisite medications is seen and used as a way to address palatability, decrease pill burden and thereby increase compliance. Yet there is little evidence on the impact this practise may have on the effectiveness of over-encapsulated medicines. This study explored the effect of over-encapsulation on in vitro disintegration and dissolution, of some commonly used medicines in paediatric palliative care. Method Immediate release (Cyclizine Hydrochloride, Gabapentin, Paracetamol) and modified release preparations (Omeprazole, Diclofenac sodium) were over-encapsulated in size 00 gelatin and HPMC capsules (n=6). Dissolution and disintegration were tested according to Pharmacopeia standards. Statistical analyses, using Student's T-test and f1 and f2 tests (respectively) were applied to determine similarities or differences in disintegration or dissolution. Results Disintegration and dissolution was prolonged for all over-encapsulated immediate release preparations, especially when using HPMC capsules. However, percentage of drug dissolved met the acceptance criteria for immediate-release solid oral dosage. Over-encapsulation of modified release preparations did not lead to significant dissolution or disintegration changes. Conclusion Over-encapsulation, may delay medication release, especially for immediate release medicines however, medicine effectiveness may not be. Further studies are required before we can safely recommend use of over-encapsulation as an administration compliance aid.
ABSTRACT
Introduction The clinical manifestations of COVID-19 infection in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in multiple retrospective cohorts of patients, but there have been no prospective studies to date. Previous studies report that HSCT recipients are at higher risk, with cumulative incidence of death between 17-35%. Although an excessive pro-inflammatory viral response has been documented in the general population, its role in the immune incompetent HSCT setting has not been documented. We present a combined prospective and retrospective national study run through the UK IMPACT trial network to characterize the clinical and immunological features of COVID-19 infection in 96 adult and pediatric recipients of HSCT in the United Kingdom. Methods HSCT recipients of any age and transplanted for any indication, with an RT-PCR-proven COVID-19 infection, were eligible for this study. Patients within 72 hours of COVID-19 diagnosis, who had not received cytokine-targeted treatment, were recruited to a prospective cohort. All other patients were eligible for a retrospective cohort. Prospective patients provided blood samples within 72 hours of COVID-19 diagnosis, and again within 72 hours of clinical deterioration (defined as requirement for oxygen administration) if applicable. Follow-up data were collected on patients 30 and 100 days after COVID-19 diagnosis. Results 100 patients were recruited from 16 sites across the UK between May 2020-June 2021, comprising 12 in a prospective cohort and 88 recruited retrospectively. 96 patients were evaluable, as 4 proved ineligible post-registration. Patients were diagnosed with COVID-19 at a median of 11 months after HSCT. Patient/HSCT characteristics are shown Table 1. The most common symptoms associated with the onset of COVID-19 were fever in 8 prospective (73%) and 35 (41%) retrospective patients, followed by cough in 5 (45%) prospective and 35 (41%) retrospective patients and dyspnea in 4 (36%) prospective and 16 (19%) retrospective patients. 8 (73%) prospective and 40 (47%) retrospective patients were actively immunosuppressed at the time of COVID-19 infection. 16% of the patients had moderate/severe disease at baseline. At day 30 (±2 days) after COVID-19 diagnosis, 2 prospective and 8 retrospective patients continued to demonstrate SARS-CoV-2 positivity on respiratory PCR testing. The median time to viral clearance was 40 (IQR 17-78) days for the prospective and 34 (IQR 15-70) days for the retrospective cohort. Prolonged (more than 14 days) neutropenia was reported in 4 (5%) patients in the retrospective cohort, prolonged thrombocytopenia in 2 (18%) prospective and 11 (13%) retrospective patients. 1 retrospective patient developed secondary hemophagocytic lymphohistiocytosis, and graft rejection was reported in 1 (1%) retrospective patient, within 30 days of COVID-19 diagnosis. In the prospective cohort, 3 (27%) patients died, all by day 30, and all due to COVID-19. In the retrospective cohort, 13 (17%) patients died by day 30, rising to 18 (21%) by day 100, 61% of deaths were attributed to COVID-19. Lower baseline platelets (p=0.013, Mann-Whitney U test), lymphocytes (p=0.012), albumin (p=0.028), and higher baseline CRP (p=0.007), were seen in patients who died following COVID-19 diagnosis. Additionally, exploratory univariate logistic regression of the retrospective cohort found mortality at day 100 to be associated with increased age at diagnosis (OR 1.04, 95% CI 1.01-1.08, p=0.04), and no requirement compared with requirement for invasive ventilation (OR 0.02, 95% CI 0.00-0.16, p=0.001). The 11 prospective patients showed normal levels of interleukin (IL)-2, -4, -10, interferon gamma and tumor necrosis factor alpha at COVID-19 presentation. IL-6 was minimally raised (up to 127 pg/ml, nv<50) in 3/11 pts at presentation. Respiratory deterioration was not associated with detectable cytokine storm. Conclusion Our study confirms a significant mortality rate in patients affected by COVID-19 post HSCT and confirms age as well s requirement for invasive ventilation to be independent risk factors associated with death at day 100. Baseline laboratory data at disease presentation can identify patients at higher risk of COVID-19 related death. In the prospective cohort of our study, pathophysiology of the viral disease did not seem related to cytokine storm-mediated inflammation. [Formula presented] Disclosures: Protheroe: Jazz Pharmaceuticals: Honoraria;Astellas: Honoraria;Kite Gilead: Honoraria. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company. Craddock: Novartis Pharmaceuticals: Other: Advisory Board;Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nicholson: BMS/Celgene: Consultancy;Kite, a Gilead Company: Other: Conference fees, Speakers Bureau;Novartis: Consultancy, Other: Conference fees;Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.;Autolus: Patents & Royalties.