Combined bictegravir, emtricitabine and tenofovir alafenamide for treating people with HIV: a plain language summary of the BICSTaR study up to 1 year.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article about an ongoing study called the BICSTaR study.The BICSTaR study includes people with HIV (human immunodeficiency virus) who are taking a medicine called bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single tablet that contains 3 different drugs for the treatment of HIV. The drugs work together to reduce the levels of HIV so that the virus can no longer be detected by a blood test.People taking part in the study are adults with HIV living in Europe, Canada, Israel, Japan, South Korea, Singapore and Taiwan. People take 1 tablet of B/F/TAF once a day. They are either taking B/F/TAF as their first treatment for HIV, or they have switched to B/F/TAF from another HIV treatment.Researchers looked at how well B/F/TAF worked and how safe it was in people who took B/F/TAF for a year. WHAT ARE THE KEY TAKEAWAYS?: Researchers found that B/F/TAF worked well in almost all people in the study by reducing levels of HIV in the blood. The virus could not be found in the blood of more than 9 out of 10 (94%) people who were taking B/F/TAF as their first HIV medicine and more than 9 out of 10 people (97%) who had taken another HIV medicine before starting B/F/TAF. This is known as having an 'undetectable viral load' and is a major goal for HIV treatment success. Researchers did not find any evidence of HIV developing resistance to B/F/TAF, which might stop B/F/TAF from working properly.Around 1 out of 10 people (13%) had side effects (any unwanted sign or symptom that people have when taking a medicine that researchers think might be caused by the medicine) that might have been caused by B/F/TAF. Most of these side effects were not classified as serious. Less than 1 out of 100 (0.1%) people had serious side effects that might have been caused by B/F/TAF. Only 6 out of 100 people stopped taking B/F/TAF due to side effects caused by B/F/TAF. As a result, more than 9 out of 10 people (95%) took B/F/TAF for at least 1 year. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: B/F/TAF worked well in people with HIV in this study. Most people (around 9 out of 10) did not have any side effects.

Biomarker-Based Analysis of Pain in Patients with Tick-Borne Infections before and after Antibiotic Treatment.

Tick-borne illnesses (TBIs), especially those caused by Borrelia, are increasingly prevalent worldwide. These diseases progress through stages of initial localization, early spread, and late dissemination. The final stage often leads to post-treatment Lyme disease syndrome (PTLDS) or chronic Lyme disease (CLD), characterized by persistent and non-specific multisystem symptoms affecting multiple systems, lasting over six months after antibiotic therapy. PTLDS significantly reduces functional ability, with 82-96% of patients experiencing pain, including arthritis, arthralgia, and myalgia. Inflammatory markers like CRP and TNF-alpha indicate ongoing inflammation, but the link between chronic pain and other biomarkers is underexplored. This study examined the relationship between pain and biomarkers in TBI patients from an Irish hospital and their response to antibiotic treatment. Pain ratings significantly decreased after antibiotic treatment, with median pain scores dropping from 7 to 5 (U = 27215.50, p < 0.001). This suggests a persistent infection responsive to antibiotics. Age and gender did not influence pain ratings before and after treatment. The study found correlations between pain ratings and biomarkers such as transferrin, CD4%, platelets, and neutrophils. However, variations in these biomarkers did not significantly predict pain changes when considering biomarkers outside the study. These findings imply that included biomarkers do not directly predict pain changes, possibly indicating allostatic load in symptom variability among long-term TBI patients. The study emphasizes the need for appropriate antibiotic treatment for TBIs, highlighting human rights issues related to withholding pain relief.

Enhancing long COVID care in general practice: A qualitative study.

INTRODUCTION: Research suggests that general practice can play an important role in managing long COVID. However, studies investigating the perspectives of general practitioners (GPs) and patients are lacking and knowledge regarding optimal long COVID care in general practice is therefore limited. AIM: To investigate GPs' and patients' perspectives on the topic of long COVID and its management in general practice. METHODS: Brief questionnaires (GP n = 11, Patient n = 7) and in-depth semi-structured interviews (GP n = 10, Patient n = 7) were conducted with GPs and patients from Irish general practices during July 2022-January 2023. Interviews were conducted via telephone and audio recordings were transcribed. A phenomenological analysis involving reflexive thematic analysis and constant comparison techniques was adopted. RESULTS: Analysis of interviews with GPs (male = 7, female = 3; median age = 50yrs (IQR = 39.5-56)) and patients (males = 2, female = 5; median age = 58yrs (IQR = 45-62yrs) generated four themes. These were (1) Complex presentations (2) the value of standardising care, (3) choosing the right path, and (4) supportive and collaborative doctor-patient relationships. Strong agreement was observed among GPs and patients regarding the need for holistic and integrated multidisciplinary care. Supportive and collaborative doctor-patient relationships were largely well received by GPs and patients also. GPs strongly endorsed standardising long COVID care operations. CONCLUSION: GPs and patients indicated that structured, integrated, and collaborative care can help optimise long COVID management in general practice. GPs are advised to incorporate these elements into their long COVID care practices going forward. Future research examining stakeholder's perspectives using larger and longitudinal samples is advised to enhance the generalisability of evidence in this area.

Scrutinizing Clinical Biomarkers in a Large Cohort of Patients with Lyme Disease and Other Tick-Borne Infections.

Standard clinical markers can improve tick-borne infection (TBI) diagnoses. We investigated immune and other clinical biomarkers in 110 patients clinically diagnosed with TBIs before (T0) and after antibiotic treatment (T2). At T0, both the initial observation group and patients without seroconversion for tick-borne pathogens exhibited notably low percentages and counts of CD3 percentage (CD3%), CD3+ cells, CD8+ suppressors, CD4 percentage (CD4%), and CD4+ helper cells, with the latter group showing reductions in CD3%, CD3+, and CD8+ counts in approximately 15-22% of cases. Following treatment at the T2 follow-up, patients typically experienced enhancements in their previously low CD3%, CD3+ counts, CD4%, and CD4+ counts; however, there was no notable progress in their low CD8+ counts, and a higher number of patients presented with insufficient transferrin levels. Moreover, among those with negative serology for tick-borne infections, there was an improvement in low CD3% and CD3+ counts, which was more pronounced in patients with deficient transferrin amounts. Among those with CD57+ (n = 37) and CD19+ (n = 101) lymphocyte analysis, 59.46% of patients had a low CD57+ count, 14.85% had a low CD19 count, and 36.63% had a low CD19 percentage (CD19%). Similar findings were observed concerning low CD57+, CD19+, and CD19% markers for negative TBI serology patients. Overall, this study demonstrates that routine standard clinical markers could assist in a TBI diagnosis.

Distinct Inflammatory Phenotypes Are Associated With Subclinical and Clinical Cardiovascular Disease in People With Human Immunodeficiency Virus.

Despite inflammation being implicated in cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in 2 independent cohorts of PWH. We identified 3 distinct inflammatory clusters present in both cohorts that were associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.

Hepatitis C community prevalence is over-estimated: a prospective, birth cohort study.

BACKGROUND: Hepatitis C virus infection is often asymptomatic, and many patients may be unaware they are infected. Community-based, birth cohort screening has been advocated to identify these patients. It has been estimated that 0.7-1% of individuals born between 1965 and 1985 in Ireland are infected. The cost-effectiveness of screening is critically dependent on the population prevalence. AIMS: The aim is to determine the community prevalence of hepatitis C virus infection in the birth cohort 1965-1985. METHODS: Residual serum samples from blood tests ordered by community general practitioners were anonymised and analysed for the presence of hepatitis C antibody ± antigen. Twelve large general hospitals throughout the country participated. RESULTS: A total of 14,320 samples were tested, 9347 of which were from the birth cohort 1965-1985. Seventy-two samples were positive for hepatitis C antibody of which 12 were positive for hepatitis C antigen (17%). The overall prevalence of hepatitis C antigen in the birth cohort was 0.09%. A higher prevalence (0.39%) was identified in males in two urban areas of Dublin. CONCLUSIONS: Hepatitis C virus seroprevalence was much lower than previously estimated. The proportion of antibody positive patients with hepatitis C antigen was also lower than expected suggesting the effects of treatment and/or high spontaneous viral clearance. Universal birth cohort screening is unlikely to be cost-effective. Targeted birth cohort screening in high prevalence areas could be considered.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

Impact of vaccination and variants of concern on long COVID clinical phenotypes.

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.

A Longitudinal Study of a Large Clinical Cohort of Patients with Lyme Disease and Tick-Borne Co-Infections Treated with Combination Antibiotics.

The rising prevalence of tick-borne infections (TBIs) necessitates further attention. This study retrospectively investigated the types of TBIs, symptoms, and if combination antibiotics were helpful within a patient cohort at an infectious disease clinic in Ireland. In this chart audit of 301 individuals (184 female, 117 male) tested for TBIs, 140 (46.51%) had positive antibody responses for TBIs from an ELISA (enzyme-linked immunoassay) that was based on a modified two-tiered testing protocol. A total of 93 (66.43%) patients had positive antibody responses to one TBI: 83 (59.29%) for Borrelia, 7 (5.00%) for Rickettsia, and 1 (0.71%) each for either Babesia, Bartonella, or Ehrlichia. The remaining 47 (33.57%) patients were infected with multiple TBIs. These patients were treated with combination antibiotics and monitored at two subsequent follow-ups. Only 2 of 101 patients (1.98%) had discontinued treatment by the second follow-up. In the first follow-up with 118 patients, 70 (59.32%) reported pain and 48 (40.68%) had neurological symptoms. In the next follow-up of 101 patients, 41 (40.59%) had pain while 30 (29.70%) had neurological symptoms. There were statistically significant reductions in the incidence of pain (41.43%) and neurological (37.50%) symptoms between follow-ups. Thus, our study demonstrates that combination antibiotics effectively relieve TBI symptoms with good patient tolerance.

Post-COVID care delivery: The experience from an Irish tertiary centre's post-COVID clinic.

BACKGROUND: The long-term effects of SARS-CoV-2 infection and optimal follow-up approach are not well-recognised. Here we describe the implementation of a post-COVID clinic in an Irish tertiary centre after the first wave of the pandemic. This study describes the characteristics of our patient cohort and the operations and outcomes of the clinic, exploring some of the risk factors for developing post-COVID syndrome and the appropriateness of the triage system employed. METHODS: All SARS-CoV-2 positive patients from March 10th to June 14th 2020 were telephone-triaged as red, amber or green based on ongoing symptoms with clinic appointments scheduled accordingly. All clinic visits were face-to-face with the infectious diseases medical team and a proforma for each patient was completed. Data were collected retrospectively by reviewing the proformas and the electronic medical record (EMR). RESULTS: 311 patients attended the clinic. Median time from illness to clinic appointment was 95 days (IQR 77-105.5). 204 patients (66%) were female, 192 (62%) were hospital staff, and the median age was 43 years (IQR 31-53). 138 patients (44%) had required hospital admission. At their first clinic visit 219 patients (70%) had ongoing symptoms. A further appointment was made for 62 patients (20%). 34 patients (11%) were discussed at an MDT meeting, and 55 (18%) were referred onward to a specialist service. 85% of those triaged green, 73% of those triaged amber, and 39% of those triaged red did not receive further follow up after one clinic visit. Patients were more likely to require follow up with reported dyspnoea (OR 5.6; 95% CI 2.8-11.3; p <0.001), cough (OR 3.0; 95% CI 1.1-8.4, p = 0.04), and palpitations (OR 3.6; 95% CI 1.0-12.3; p = 0.04). Female sex was associated with increased odds of a higher triage category (OR 1.8; 95% CI 1.08 to 3.20; p = 0.02), as was requiring admission to hospital (OR 4.0; 95% CI 2.34 to 6.90; p < 0.001). CONCLUSION: The long-term effects of COVID-19 are significant with 70% of our cohort experiencing persistent symptoms. Persistent dyspnoea, cough and palpitations were associated with increased need for follow up. This study also suggests that a traffic light telephone-triage service followed by a face-to-face medical-led clinic could be an effective way of identifying patients who require further management.

Analysis of Line and Tube Detection Performance of a Chest X-ray Deep Learning Model to Evaluate Hidden Stratification.

This retrospective case-control study evaluated the diagnostic performance of a commercially available chest radiography deep convolutional neural network (DCNN) in identifying the presence and position of central venous catheters, enteric tubes, and endotracheal tubes, in addition to a subgroup analysis of different types of lines/tubes. A held-out test dataset of 2568 studies was sourced from community radiology clinics and hospitals in Australia and the USA, and was then ground-truth labelled for the presence, position, and type of line or tube from the consensus of a thoracic specialist radiologist and an intensive care clinician. DCNN model performance for identifying and assessing the positioning of central venous catheters, enteric tubes, and endotracheal tubes over the entire dataset, as well as within each subgroup, was evaluated. The area under the receiver operating characteristic curve (AUC) was assessed. The DCNN algorithm displayed high performance in detecting the presence of lines and tubes in the test dataset with AUCs > 0.99, and good position classification performance over a subpopulation of ground truth positive cases with AUCs of 0.86-0.91. The subgroup analysis showed that model performance was robust across the various subtypes of lines or tubes, although position classification performance of peripherally inserted central catheters was relatively lower. Our findings indicated that the DCNN algorithm performed well in the detection and position classification of lines and tubes, supporting its use as an assistant for clinicians. Further work is required to evaluate performance in rarer scenarios, as well as in less common subgroups.

Antibody-drug conjugates come of age in oncology.

Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of highly cytotoxic agents, potentially reducing the severity of side effects by preferentially targeting their payload to the tumour site. ADCs are being increasingly used in combination with other agents, including as first-line cancer therapies. As the technology to produce these complex therapeutics has matured, many more ADCs have been approved or are in late-phase clinical trials. The diversification of antigenic targets as well as bioactive payloads is rapidly broadening the scope of tumour indications for ADCs. Moreover, novel vector protein formats as well as warheads targeting the tumour microenvironment are expected to improve the intratumour distribution or activation of ADCs, and consequently their anticancer activity for difficult-to-treat tumour types. However, toxicity remains a key issue in the development of these agents, and better understanding and management of ADC-related toxicities will be essential for further optimization. This Review provides a broad overview of the recent advances and challenges in ADC development for cancer treatment.

MSeg: A Composite Dataset for Multi-Domain Semantic Segmentation.

We present MSeg, a composite dataset that unifies semantic segmentation datasets from different domains. A naive merge of the constituent datasets yields poor performance due to inconsistent taxonomies and annotation practices. We reconcile the taxonomies and bring the pixel-level annotations into alignment by relabeling more than 220,000 object masks in more than 80,000 images, requiring more than 1.34 years of collective annotator effort. The resulting composite dataset enables training a single semantic segmentation model that functions effectively across domains and generalizes to datasets that were not seen during training. We adopt zero-shot cross-dataset transfer as a benchmark to systematically evaluate a model's robustness and show that MSeg training yields substantially more robust models in comparison to training on individual datasets or naive mixing of datasets without the presented contributions. A model trained on MSeg ranks first on the WildDash-v1 leaderboard for robust semantic segmentation, with no exposure to WildDash data during training. We evaluate our models in the 2020 Robust Vision Challenge (RVC) as an extreme generalization experiment. MSeg training sets include only three of the seven datasets in the RVC; more importantly, the evaluation taxonomy of RVC is different and more detailed. Surprisingly, our model shows competitive performance and ranks second. To evaluate how close we are to the grand aim of robust, efficient, and complete scene understanding, we go beyond semantic segmentation by training instance segmentation and panoptic segmentation models using our dataset. Moreover, we also evaluate various engineering design decisions and metrics, including resolution and computational efficiency. Although our models are far from this grand aim, our comprehensive evaluation is crucial for progress. We share all the models and code with the community.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

HepCare Plus: Enhancing Primary Care Identification and Treatment of Hepatitis C Virus in High-Risk Individuals.

Hepatitis C Virus (HCV) disproportionately affects people who inject drugs, migrants, prisoners and the homeless. An integrated, peer-led model of care involving primary and secondary care is required to enhance the identification and treatment of HCV in these marginalised groups. HepCare Plus builds on the network and achievements of HepCare Europe (a co-funded Third Health Programme of the European Union/Health Service Executive project). It further identifies those not accessing care and facilitates prompt assessment and treatment of those diagnosed with HCV, with the aid of a peer support worker (PSW) and a community HCV nurse specialist. Of 109 individuals identified and assessed for HCV treatment, 100 commenced HCV treatment. Despite interruptions to treatment (COVID-19 pandemic and national health service cyberattack) there was a high-level of treatment completion with PSW engagement (98%, n = 98). Eighty (73%) individuals were previously aware of a positive HCV status, highlighting the ongoing need to address barriers preventing marginalised groups from engaging with care. HepCare Plus reiterates the defining role of peer-led community interventions in HCV treatment engagement and the need for continuous open-ended HCV care. It provides a sustainable framework to meaningfully combat HCV and achieve the United Nations Sustainable Development Goal of HCV elimination by 2030.

Integrating Hepatitis C Care for Opioid Substitution Treatment Patients Attending General Practice: Feasibility, Clinical, and Cost-Effectiveness Analysis.

BACKGROUND: Hepatitis C virus (HCV) infection is common among people who inject drugs, yet well-described barriers mean that only a minority have accessed HCV treatment. Recent developments in HCV diagnosis and treatment facilitate innovative approaches to HCV care that improve access to, and uptake of, care by people who inject drugs. OBJECTIVE: This study aims to examine feasibility, acceptability, likely clinical effectiveness, and cost-effectiveness of an integrated model of HCV care for patients receiving opioid substitution treatment in general practice. METHODS: A pre- and postintervention design with an embedded economic analysis was used to establish the feasibility, acceptability, and clinical and cost-effectiveness of a complex intervention to optimize HCV identification and linkage to HCV treatment among patients prescribed methadone in primary care. The "complex intervention" comprised general practitioner (GP)/practice staff education, nurse-led clinical support, and enhanced community-based HCV assessment of patients. General practices in North Dublin were recruited from the professional networks of the research team and from GPs who attended educational sessions. RESULTS: A total of 135 patients from 14 practices participated. Follow-up data were collected 6 months after intervention from 131 (97.0%) patients. With regard to likely clinical effectiveness, among patients with HCV antibody positivity, there was a significant increase in the proportions of patients who had a liver FibroScan (17/101, 16.8% vs 52/100, 52.0%; P<.001), had attended hepatology/infectious diseases services (51/101, 50.5% vs 61/100 61.0%; P=.002), and initiated treatment (20/101, 19.8% vs 30/100, 30.0%; P=.004). The mean incremental cost-effectiveness ratio of the intervention was €13,255 (US $13,965.14) per quality-adjusted life-year gained at current full drug list price (€39,729 [US $41,857.48] per course), which would be cost saving if these costs are reduced by 88%. CONCLUSIONS: The complex intervention involving clinical support, access to assessment, and practitioner education has the potential to enhance patient care, improving access to assessment and treatment in a cost-effective manner.

Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study.

Background: Up to 37.7% of patients experience symptoms beyond 12 weeks after infection with SARS-CoV-2. To date care for people with long covid has centred around multidisciplinary rehabilitation, self care and self pacing. No pharmacotherapy has been shown to be beneficial. Methods: In this single centre interventional pre post study, the safety of Low Dose Naltrexone (LDN) was explored in patients with Post COVID-19 Syndrome (PCS), defined by NICE as patients with ongoing symptoms 12 or more weeks after initial infections with SARS-CoV-2 where alternative explanation for symptoms cannot be found. Patients were recruited through a Post COVID clinic, had a baseline quality of life questionnaire in symmetrical Likert format, were prescribed 2 months (1 mg month one, 2 mg month two) of LDN and repeated the same questionnaire at the end of the second month. Patients were monitored to adverse events. Findings: In total 52 patients participated of whom 40(76.9%) were female. The median age was 43.5 years(IQR 33.2-49). Healthcare workers represented the largest occupational cohort n = 16(34.8%). The median time from diagnosis of COVID-19 until enrolment was 333 days (IQR 171-396.5). Thirty-eight participants (73.1%) were known to commence LDN, two of whom (5.3%) stopped taking LDN post commencement due to new onset diarrhoea and also described fatigue. In total 36(69.2%) participants completed the questionnaire at the end of the two-month period. Improvement was seen in 6 of 7 parameters measured; recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤ 0.001), improvement in mood approached but was not significant (p = 0.054). Conclusions: LDN is safe in patients with PCS and may improve well-being and reduce symptomatology in this cohort. Randomised control trials are needed to further explore this.

Assessing the impact of COVID-19 at 1-year using the SF-12 questionnaire: Data from the Anticipate longitudinal cohort study.

BACKGROUND: Few studies to date have explored the health-related quality of life (HRQoL) in patients with long COVID. METHODS: The Anticipate Study is a prospective single-centre observational cohort study. Hospitalised and nonhospitalised patients were seen at a dedicated post-COVID clinic at a 2-4 month (Timepoint 1) and 7-14 month follow-up (Timepoint 2). The main objectives of this study are to assess the longitudinal impact of COVID-19 in patients using the 12-item Short Form Survey (SF-12) score, a health-related quality of life tool, and to identify predictors of developing post-COVID-19 syndrome (PoCS). In addition, we aimed to describe symptomatology and identify predictors of PoCS at 1-year. RESULTS: A total of 155 patients were enrolled, 105 (68%) were female aged 43.3 (31-52) years. In total 149 (96%) and 94 (61%) patients completed follow-up at median 96 (76-118) days and 364 (303-398) days. The overall cohort had significantly reduced physical composite score (PCS) of the SF-12 (45.39 [10.58] vs 50 [10], p = 0.02). Participants with PoCS had significantly lower scores than those without symptoms at 1-year follow-up (37.2 [10.4] v 46.1 [10.9] p <0.001), and scores for these patients did not improve over the 2 Timepoints (PCS 34.95 [10.5] - 37.2 [10.4], p = 0.22). Fatigue was the most common symptom. Those with 5 or more symptoms at initial diagnosis had lower PCS and mental composite score (MCS) at 1-year. Predictors of PoCS at 1-year were lower PCS and higher baseline heart rate (HR) at clinic review median 3 months after COVID-19. CONCLUSION: Patients with PoCS have lower PCS scores during follow-up, which did not significantly improve up to a 1-year follow-up. Lower PCS scores and higher HR at rest can be used in the weeks after COVID-19 can help predict those at risk of PoCS at 1 year.

Identification of Distinct Long COVID Clinical Phenotypes Through Cluster Analysis of Self-Reported Symptoms.

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.