COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.4/5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history.

BACKGROUND: SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC). METHODS: In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests. RESULTS: 563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (ß = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or BA.4/5 infections. CONCLUSION: Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults. TRIAL REGISTRATION: NCT04750356.

Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants.

The emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics-such as varying levels of immunity-can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform Coronavirus Disease 2019 (COVID-19) planning and response and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both interindividual variation in Ct values and complex host characteristics-such as vaccination status, exposure history, and age-we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least 5 prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs. Trial Registration: The Legacy study is a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening for SARS-CoV-2 at University College London Hospitals or at the Francis Crick Institute (NCT04750356) (22,23). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469) and is sponsored by University College London Hospitals. Written consent was given by all participants.

Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants.

The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics - such as varying levels of immunity - can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics - such as vaccination status, exposure history and age - we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.

Cannabis in Palliative Care: A Systematic Review of Current Evidence.

CONTEXT: Palliative care aims to improve the quality of life in patients with incurable illness. Medicinal cannabis (MC) has been used in the palliative care setting to address multiple symptoms in patients. OBJECTIVES: To evaluate the full scope of available literature investigating the effects and potential harms of MC on symptom management and quality of life in palliative care. METHODS: PubMed, Embase, The Cochrane Library and clinicaltrials.gov were searched for eligible articles, published between 1960 and September 9, 2021. Quality of the evidence was assessed in accordance with Grading of Recommendations, Assessment, Development and Evaluations. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials. RESULTS: Fifty-two studies (20 randomised; 32 non-randomised) with 4786 participants diagnosed with cancer (n = 4491), dementia (n = 43), AIDS (n = 235), spasticity (n = 16), NORSE syndrome (n = 1) were included. The quality of evidence was 'very low' or 'low' for all studies, and low for only two randomised controlled trials. Positive treatment effects (statistical significance with P < 0.05) were seen for some MC products in pain, nausea and vomiting, appetite, sleep, fatigue, chemosensory perception and paraneoplastic night sweats in patients with cancer, appetite and agitation in patients with dementia and appetite, nausea and vomiting in patients with AIDS. Meta-analysis was unable to be performed due to the wide range of cannabis products used and the heterogeneity of the study outcomes. CONCLUSION: While positive treatment effects have been reported for some MC products in the palliative care setting, further high quality evidence is needed to support recommendations for its use in clinical practice.

Codevelopment of Patient Self-Examination Methods and Joint Count Reporting for Rheumatoid Arthritis.

OBJECTIVE: To determine whether training increases accuracy of self-reported joint counts in people with rheumatoid arthritis (RA) and describe the knowledge and techniques for self-examination of joints for reporting of RA disease activity. METHODS: This mixed-methods study included 10 patients with RA and four rheumatologists. A rheumatologist presented about joint inflammation and disease monitoring in RA. Patients then self-examined and reported 28-tender joint count (28-TJC) and 28-swollen joint count (28-SJC). Next, two paired rheumatologists examined patients and reported 28-TJC and 28-SJC. After watching a joint examination video for training physicians, patients discussed their training needs for self-examination, with discussion analyzed using thematic analysis. Self-examination techniques were determined by consensus. Finally, patients self-examined and reported 28-TJC and 28-SJC. Reliability between the first and second patient-reported 28-TJCs and 28-SJCs and rheumatologist pair-reported 28-TJC and 28-SJC was determined with the intraclass coefficient. RESULTS: The reliability for patient self-reported joint counts was higher for the 28-TJC than for the 28-SJC. Reliability improved following rheumatologist examination and training. Patients identified a preference for practical information rather than detailed information on joint anatomy and pathophysiology. Clear definitions of "swollen" and "tender" were important; patients found the concept of "tenderness" difficult. Techniques for self-examination and reporting of joint counts were agreed on and demonstrated in an instructional video. CONCLUSION: Training increased reliability of patient-reported joint counts. Patients with RA identified important aspects of training for self-examination and reporting of joint counts. An 8-minute instructional video was codeveloped; the next step is the evaluation of the video's impact on patient-reported joint counts.

Patient and clinician views on an app for rheumatoid arthritis disease monitoring: Function, implementation and implications.

AIM: Best practice management for rheumatoid arthritis (RA) involves regular clinical assessment of RA disease activity. This is not achievable with current rheumatology systems of care. We aimed to use opinions from people with RA and their specialist rheumatology healthcare professionals to inform development of a mobile app for people with RA for recording their disease activity data for potential integration into clinical service, and assess usability of the app. METHOD: In phase 1 we interviewed nine people with RA and seven healthcare professionals. In phase 2 we developed an app with professional software developers. In phase 3 we evaluated app usability for people with RA using the System Usability Scale (SUS). RESULTS: Interview data showed four themes regarding functionality and implementation of a patient-held app in RA care: (a) variable app acceptance and readiness; (b) app use to reduce barriers; (c) pros and cons of patient-reported outcomes; and (d) allocation of clinics by need. The app developed has high usability in people with RA using the app on their own device for a month (SUS 79.5, n = 16) or using the app on a study device for 10 minutes (SUS 83, n = 100). CONCLUSION: People with RA and healthcare professionals have clearly identified features, benefits and risks of an app for self-assessment of RA and incorporation into clinical care. An app developed informed by these opinions has high usability. Next steps are development and validation of a method of patient-performed joint counts, and implementation, with evaluation, in the clinical setting.

Apps for People With Rheumatoid Arthritis to Monitor Their Disease Activity: A Review of Apps for Best Practice and Quality.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis requiring long-term treatment with regular monitoring by a rheumatologist to achieve good health outcomes. Since people with RA may wish to monitor their own disease activity with a smartphone app, it is important to understand the functions and quality of apps for this purpose. OBJECTIVE: The aim of our study was to assess the features and quality of apps to assist people to monitor their RA disease activity by (1) summarizing the available apps, particularly the instruments used for measurement of RA disease activity; (2) comparing the app features with American College of Rheumatology and European League against Rheumatism (ACR and EULAR) guidelines for monitoring of RA disease activity; and (3) rating app quality with the Mobile App Rating Scale (MARS). METHODS: Systematic searches of the New Zealand iTunes and Google Play app stores were used to identify all apps for monitoring of RA disease activity that could be used by people with RA. The apps were described by both key metadata and app functionality. App adherence with recommendations for monitoring of RA disease activity in clinical practice was evaluated by identifying whether apps included calculation of a validated composite disease activity measure and recorded results for future retrieval. App quality was assessed by 2 independent reviewers using the MARS. RESULTS: The search identified 721 apps in the Google Play store and 216 in the iTunes store, of which 19 unique apps met criteria for inclusion (8 from both app stores, 8 iTunes, and 3 Google Play). In total, 14 apps included at least one validated instrument measuring RA disease activity; 7 of 11 apps that allowed users to enter a joint count used the standard 28 swollen and tender joint count; 8 apps included at least one ACR and EULAR-recommended RA composite disease activity (CDA) measure; and 10 apps included data storage and retrieval. Only 1 app, Arthritis Power, included both an RA CDA measure and tracked data, but this app did not include the standard 28 tender and swollen joint count. The median overall MARS score for apps was 3.41/5. Of the 6 apps that scored ≥4/5 on the overall MARS rating, only 1 included a CDA score endorsed by ACR and EULAR; however, this app did not have a data tracking function. CONCLUSIONS: This review found a lack of high-quality apps for longitudinal assessment of RA disease activity. Current apps fall into two categories: simple calculators primarily for rheumatologists and data tracking tools for people with RA. The latter do not uniformly collect data using validated instruments or composite disease activity measures. There is a need for appropriate, high-quality apps for use by rheumatologists and patients together in co-management of RA.

Patient-Clinician Co-Design Co-Participation in Design of an App for Rheumatoid Arthritis Management via Telehealth Yields an App with High Usability and Acceptance.

People with chronic conditions like rheumatoid arthritis (RA) self-manage on a day to day basis. They may be able to assess disease activity and communicate this via an app to their healthcare team to enable clinical review for medical management at the most appropriate times. This work describes the succesful co-design of a patient-held app for monitoring and communication of RA disease activity.