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Background The internet is now the first line source of health information for many people worldwide. In the current Coronavirus Disease 2019 (COVID-19) global pandemic, health information is being produced, revised, updated and disseminated at an increasingly rapid rate. The general public are faced with a plethora of misinformation regarding COVID-19 and the readability of online information has an impact on their understanding of the disease. The accessibility of online healthcare information relating to COVID-19 is unknown. We sought to evaluate the readability of online information relating to COVID-19 in four English speaking regions: Ireland, the United Kingdom, Canada and the United States, and compare readability of website source provenance and regional origin. Methods The Google® search engine was used to collate the first 20 webpage URLs for three individual searches for ‘COVID’, ‘COVID-19’, and ‘coronavirus’ from Ireland, the United Kingdom, Canada and the United States. The Gunning Fog Index (GFI), Flesch-Kincaid Grade (FKG) Score, Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG) score were calculated to assess the readability. Results There were poor levels of readability webpages reviewed, with only 17.2% of webpages at a universally readable level. There was a significant difference in readability between the different webpages based on their information source ( p  < 0.01). Public Health organisations and Government organisations provided the most readable COVID-19 material, while digital media sources were significantly less readable. There were no significant differences in readability between regions. Conclusion Much of the general public have relied on online information during the pandemic. Information on COVID-19 should be made more readable, and those writing webpages and information tools should ensure universal accessibility is considered in their production. Governments and healthcare practitioners should have an awareness of the online sources of information available, and ensure that readability of our own productions is at a universally readable level which will increase understanding and adherence to health guidelines.

The healthcare needs of refugees and people seeking asylum are often broad and complex, with a higher burden of communicable diseases. There are limited data describing migrants’ experiences of accessing healthcare in Ireland. This cross-sectional study describes the experiences of migrants accessing healthcare services through an Irish Infectious Diseases clinic. Individuals attending the infectious diseases services in our hospital who had migrated to Ireland were included. Data were collected via a questionnaire, focusing on factors that may limit access to care, including communication, accessibility, cost, and stigmatisation. Seventy-six patients participated in this study. N = 20 (26%) of patients reported a commuting time of more than two hours to attend our clinic. N = 11 (15%) had experienced being unable to access healthcare in Ireland due to cost. Trust in healthcare providers was high (88%), and patient-reported satisfaction with communication was high (>90%). Persons living in direct provision services were more likely to report issues around privacy and less likely to have registered with a general practitioner. Accessibility and privacy were among the biggest challenges faced by migrants attending infectious diseases services at our centre, while communication and trust in healthcare providers were identified as areas of strength. Considering the burden of infectious diseases in migrant populations, and the challenges that certain migrant populations face in accessing healthcare, it is important to identify potential barriers to accessing care in order to ensure equitable, effective care. This study seeks to identify and describe the challenges that migrants face when accessing care through an Irish infectious diseases clinic. The results can help inform service provision and allocation of resources at a local level, while also identifying an area for further research regarding the barriers to accessing care faced by migrant communities in Ireland.

The Republic of Ireland (ROI) has a low incidence of TB. A reform of TB services in 2003 recommended that the delivery of care to patients with TB should primarily be in the outpatient setting, with limited indications for hospitalization. Three hospitals were designated as TB centres. Our aim was to describe the utilization of hospital inpatient care by patients with TB in the ROI. We searched public hospital coding data to identify discharges between 01/01/2015-31/12/18 where TB was the principal diagnosis. The cost of TB episodes of care was calculated using payment rules for public hospitals in the ROI. We identified 1185 discharges with TB as the principal diagnosis. Of these, 68% (801/1185) were emergency episodes of care and 32% (384/1185) were elective. We estimate that 65.1% (818/1257) patients with TB notified in the ROI from 2015 to 2018 who had an episode of care in a public hospital was 65.1% (818/1257) and that 50.8% (639/1257) of those notified had an emergency episode of care. The estimated mean annual cost of TB inpatient care per year in the ROI from 2015 to 2018 was €2,638,828-2,955,047, with emergency episodes of care having a mean annual cost of €2,250,926-2,557,397 per year. The burden of TB on hospital inpatient care in the Republic of Ireland is significant.

Abstract Background We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID. Methods This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters. Results Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36–54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2–3] symptoms per individual in cluster 3 vs 6 [IQR, 5–7] and 4 [IQR, 3–5] in clusters 1 and 2, respectively; P < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning. Conclusions Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.

SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67–89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77–94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies. Evidence from trials suggests SARS-CoV-2 binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether this is accurate in the context of variants of concerns, or in the event of prior infection or vaccination remains unclear. Authors explore the performance of receptor binding domain IgG thresholds in predicting a level of neutralising capacity that has demonstrated protection against infection in vaccine trials

Objectives An estimated 1% of endovascular aneurysm repair (EVAR) devices become infected, carrying a high mortality rate. Surgical explantation is recommended and prognosis is guarded. This retrospective cohort analysis focuses on the role of outpatient parenteral antimicrobial therapy (OPAT) in the management of aortic vascular graft infections following EVAR. Methods Patients who received OPAT for aortic graft infections (AGI) following EVAR from 2014 to 2018 inclusive were identified using the OPAT database. Clinical, microbiological and radiological data were collected. Survivors were followed up for a median of 36 months (range 25–60) after first presentation with infection. Outcomes were assessed. Results Eleven cases with 20 OPAT episodes were identified: 10/11 male, median age 76 (IQR 71–81). Median time to presentation was 7 months (range 0–81 months) after EVAR. OPAT lead to a 55% reduction in length of hospital stay. One patient had graft explantation; four others had temporising measures. Eight of 11 were alive a median of 36 months after presentation with infection, having had a median of 2 re-treatments on OPAT (range 1–3). Seven of the eight survivors were on continuous suppressive oral antimicrobials; three were also intermittently on intravenous antibiotics for flares of infection. Patient/ infection outcomes were cure (1/11), improved (7/11), failure (3/11). Conclusion AGI following EVAR usually presents in the first year after graft deployment. OPAT has an important peri-operative role in patients suitable for curative surgery. OPAT followed by oral suppressive antimicrobial therapy can be a feasible long-term treatment for non-curative management of AGI. Survival in our cohort was longer than expected, and OPAT was feasible despite the complexity of these infections. OPAT can avoid multiple and lengthy hospital admissions and maximise time at home and quality of life in this cohort with life-limiting infection.

Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination. Here we describe a novel medium-throughput flow cytometry-based micro-neutralisation test to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type and Variants of Concern (VOC) in convalescent/vaccinated populations. Flow Cytometry-Based Micro-Neutralisation Test (Micro-NT) was performed in 96-well plates using clinical isolates WT-B, WT-B.1.177.18 and/or VOCs Beta and Omicron. Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, half-log) from 1:20 and pre-incubated with SARS-CoV-2 (1h, 37°C). Virus-plasma mixture were added onto Vero E6 or Vero E6/TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation, fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) were determined using non-linear regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Both Micro-NT and PRNT achieved comparable NT50 values. Further validation showed adequate correlation with PRNT using a panel of secondary standards of clinical convalescent and vaccinated plasma samples. We found the assay to be reproducible through measuring both repeatability and intermediate precision. Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we demonstrated that Micro-NT has broad dynamic range differentiating NT50s <1/20 to >1/5000. We could also characterise immune-escape VOC Beta and Omicron BA.5, achieving fold-reductions in neutralising capacity similar to those published. Our flow cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, and has been selected as an endpoint in clinical trials.

Background. Circumsporozoite protein (CS) is the antigenic target for RTS, S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy. Methods. We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP. Results. One of 15 vaccinées (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA METRAP achieved sterile protection after CHMI. Three of 15 vaccinées (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%-79%, compared with 79%-84% for ChAd63-MVA ME-TRAP. Conclusions. ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development. Clinical Trials Registration. NCT01623557.

Background Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. Methods In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. Results A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p  = 0.008) and an increase in cough (63% vs 17% p  < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p  = 0.004) and palpitations (12% vs 32% p  < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms. Conclusion This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination.

Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are thought to underlie the progression of coronavirus disease 2019 (COVID-19) to severe disease. We sought to determine whether early host immune-related gene expression could predict clinical progression to severe disease. We analysed the expression of 579 immunological genes in peripheral blood mononuclear cells taken early after symptom onset using the NanoString nCounter and compared SARS-CoV-2 negative controls with SARS-CoV-2 positive subjects with mild (SARS+ Mild) and Moderate/Severe disease to evaluate disease outcomes. Biobanked plasma samples were also assessed for type I (IFN-α2a and IFN-β), type II (IFN-γ) and type III (IFN-λ1) interferons (IFNs) as well as 10 additional cytokines using multiplex immunoassays. We identified 19 significantly deregulated genes in 62 SARS-CoV-2 positive subject samples within 5 days of symptom onset and 58 SARS-CoV-2 negative controls and found that type I interferon (IFN) signalling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1) and genes encoding proinflammatory cytokines (TNF, TNFSF4, PTGS2 and IL1B) were upregulated in both SARS+ groups. Moreover, we found that FCER1, involved in mast cell activation, was upregulated in the SARS+ Mild group but significantly downregulated in the SARS+ Moderate/Severe group. In both SARS+ groups we discovered elevated interferon type I IFN-α2a, type II IFN and type III IFN λ1 plasma levels together with higher IL-10 and IL-6. These results indicate that those with moderate or severe disease are characterised by deficiencies in a mast cell response together with IFN hyper-responsiveness, suggesting that early host antiviral immune responses could be a cause and not a consequence of severe COVID-19. This study suggests that early host immune responses linking defects in mast cell activation with host interferon responses correlates with more severe outcomes in COVID-19. Further characterisation of this pathway could help inform better treatment for vulnerable individuals.