Prevalence and risk factors for long COVID among adults in Scotland using electronic health records : a national, retrospective, observational cohort study

Acknowledgements This work was supported by the Chief Scientist Office, grant number COV/LTE/20/15. EAVE II is supported by a grant (MC_PC_19075) from the Medical Research Council; and a grant (MC_PC_19004) from BREATHE–The Health Data Research Hub for Respiratory Health, funded through the UK Research and Innovation Industrial Strategy Challenge Fund. LD was supported by a post-doctoral clinical fellowship from the Asthma UK Centre for Applied Research. SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). The authors would like to acknowledge the support of Dave Kelly and Lamorna Brown of Albasoft Ltd., and Sharon Kennedy, Mike Birnie, Safraj Shahul Hameed and Elliott Hall of Public Health Scotland for their involvement in obtaining approvals, provisioning, and linking data and the use of the secure analytical platform within the National Safe Haven. Funding Chief Scientist Office (Scotland), Medical Research Council, and BREATHE.Peer reviewe

Prevalence and risk factors for long COVID among adults in Scotland using electronic health records : a national, retrospective, observational cohort study

Background: Long COVID is a debilitating multisystem condition. The objective of this study was to estimate the prevalence of long COVID in the adult population of Scotland, and to identify risk factors associated with its development. Methods: In this national, retrospective, observational cohort study, we analysed electronic health records (EHRs) for all adults (≥18 years) registered with a general medical practice and resident in Scotland between March 1, 2020, and October 26, 2022 (98–99% of the population). We linked data from primary care, secondary care, laboratory testing and prescribing. Four outcome measures were used to identify long COVID: clinical codes, free text in primary care records, free text on sick notes, and a novel operational definition. The operational definition was developed using Poisson regression to identify clinical encounters indicative of long COVID from a sample of negative and positive COVID-19 cases matched on time-varying propensity to test positive for SARS-CoV-2. Possible risk factors for long COVID were identified by stratifying descriptive statistics by long COVID status. Findings: Of 4,676,390 participants, 81,219 (1.7%) were identified as having long COVID. Clinical codes identified the fewest cases (n = 1,092, 0.02%), followed by free text (n = 8,368, 0.2%), sick notes (n = 14,469, 0.3%), and the operational definition (n = 64,193, 1.4%). There was limited overlap in cases identified by the measures; however, temporal trends and patient characteristics were consistent across measures. Compared with the general population, a higher proportion of people with long COVID were female (65.1% versus 50.4%), aged 38–67 (63.7% versus 48.9%), overweight or obese (45.7% versus 29.4%), had one or more comorbidities (52.7% versus 36.0%), were immunosuppressed (6.9% versus 3.2%), shielding (7.9% versus 3.4%), or hospitalised within 28 days of testing positive (8.8% versus 3.3%%), and had tested positive before Omicron became the dominant variant (44.9% versus 35.9%). The operational definition identified long COVID cases with combinations of clinical encounters (from four symptoms, six investigation types, and seven management strategies) recorded in EHRs within 4–26 weeks of a positive SARS-CoV-2 test. These combinations were significantly (p < 0.0001) more prevalent in positive COVID-19 patients than in matched negative controls. In a case-crossover analysis, 16.4% of those identified by the operational definition had similar healthcare patterns recorded before testing positive. Interpretation:The prevalence of long COVID presenting in general practice was estimated to be 0.02–1.7%, depending on the measure used. Due to challenges in diagnosing long COVID and inconsistent recording of information in EHRs, the true prevalence of long COVID is likely to be higher. The operational definition provided a novel approach but relied on a restricted set of symptoms and may misclassify individuals with pre-existing health conditions. Further research is needed to refine and validate this approach

The role and uses of antibodies in COVID-19 infections: a living review

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity

T cell phenotypes in COVID-19 - a living review

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation

Overview of approved and upcoming vaccines for SARS-CoV-2: a living review

The rapid design and implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is testament to a successfully coordinated global research effort. While employing a variety of different technologies, some of which have been used for the first time, all approved vaccines demonstrate high levels of efficacy with excellent safety profiles. Despite this, there remains an urgent global demand for coronavirus disease 2019 vaccines that require further candidates to pass phase 3 clinical trials. In the expectation of SARS-CoV-2 becoming endemic, researchers are looking to adjust the vaccine constructs to tackle emerging variants. In this review, we outline different platforms used for approved vaccines and summarize latest research data with regards to immunogenicity, dosing regimens and efficiency against emerging variants

Overview of approved and upcoming vaccines for SARS-CoV-2: a living review

The rapid design and implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is testament to a successfully coordinated global research effort. While employing a variety of different technologies, some of which have been used for the first time, all approved vaccines demonstrate high levels of efficacy with excellent safety profiles. Despite this, there remains an urgent global demand for coronavirus disease 2019 vaccines that require further candidates to pass phase 3 clinical trials. In the expectation of SARS-CoV-2 becoming endemic, researchers are looking to adjust the vaccine constructs to tackle emerging variants. In this review, we outline different platforms used for approved vaccines and summarize latest research data with regards to immunogenicity, dosing regimens and efficiency against emerging variants

Role of ciliary protein intraflagellar transport protein 88 in the regulation of cartilage thickness and osteoarthritis development in mice

Objective: mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO).Methods: Ift88fl/fl and aggrecanCreERT2 mice were crossed to create a strain of cartilage-specific Ift88-KO mice (aggrecanCreERT2;Ift88fl/fl). In these Ift88-KO mice and Ift88fl/fl control mice, tibial articular cartilage thickness was assessed by histomorphometry, and the integrity of the cartilage was assessed using Osteoarthritis Research Society International (OARSI) damage scores, from adolescence through adulthood. In situ mechanisms of cartilage damage were investigated in the microdissected cartilage sections using immunohistochemistry, RNAScope analysis, and quantitative polymerase chain reaction. Osteoarthritis (OA) was induced in aggrecanCreERT2;Ift88fl/fl mice and Ift88fl/fl control mice using surgical destabilization of the medial meniscus (DMM). Following tamoxifen injection and DMM surgery, the mice were given free access to exercise on a wheel.Results: deletion of Ift88 resulted in progressive reduction in the thickness of the medial tibial cartilage in adolescent mice, as well as marked atrophy of the cartilage in mice during adulthood. In aggrecanCreERT2;Ift88fl/fl mice at age 34 weeks, the median thickness of the medial tibial cartilage was 89.42 μm (95% confidence interval [95% CI] 84.00–93.49), whereas in Ift88fl/fl controls at the same age, the median cartilage thickness was 104.00 μm (95% CI 100.30–110.50; P &lt; 0.0001). At all time points, the median thickness of the calcified cartilage was reduced. In some mice, atrophy of the medial tibial cartilage was associated with complete, spontaneous degradation of the cartilage. Following DMM, aggrecanCreERT2;Ift88fl/fl mice were found to have increased OARSI scores of cartilage damage. In articular cartilage from maturing mice, atrophy was not associated with obvious increases in aggrecanase-mediated destruction or chondrocyte hypertrophy. Of the 44 candidate genes analyzed, only Tcf7l2 expression levels correlated with Ift88 expression levels in the microdissected cartilage. However, RNAScope analysis revealed that increased hedgehog (Hh) signaling (as indicated by increased expression of Gli1) was associated with the reductions in Ift88 expression in the tibial cartilage from Ift88-deficient mice. Wheel exercise restored both the articular cartilage thickness and levels of Hh signaling in these mice.Conclusion: our results in a mouse model of OA demonstrate that IFT88 performs a chondroprotective role in articular cartilage by controlling the calcification of cartilage via maintenance of a threshold of Hh signaling during physiologic loading

All I Need is the Air that I Breathe

‘In its incredible diversity, drawing has been a primary and primal medium for conveying an artist’s vision; it is also the starting point for its development and elaboration. No matter what an artist’s individual treatment of a specific surface for drawing is, what is self-evident, ultimately, is the immediacy of the gesture out of which any kind of drawing emerges. This immediacy of gesture in drawing, and its pronounced utility during a period of crisis, are the focal points of All I Need Is the Air that I Breathe, an exhibition inspired by the song The Air that I Breathe (1972) by the British band The Hollies. In these pandemic times, drawing takes on a new urgency: It goes beyond a mere practice of producing and capturing linear forms on different mediums to serve as a valuable tool in navigating the straits in which the majority of artists have found themselves in recent months. Drawing could be the answer to the existential questions raised in the current social landscape. Through drawing anxiety can be both communicated and alleviated.

Yesterday, Today and Forever - 5 Year Anniversary

Art Seen is delighted to announce the group exhibition titled Yesterday, Today and Forever curated by Maria Stathi. This exhibition is to mark the five years celebration of the gallery and highlights sixteen of the collaborative artists as well as 4 guest artists. Participating artists: Spyros Anastasiou (CY), Irini Bachlitzanaki (GR), David J Batchelor (UK), Raymonde Beraud (CY), Angus Braithwaite (UK), Savvas Christodoulides (CY), Gary Colclough (UK), Theodoulos Gregoriou (CY), Panayiotis Doukanaris (CY), Ramon Kalisperas (CY), Eva Marathaki (GR), Jost Münster (DE), Vicky Pericleous (CY), Mary Plant (CY), Amy Stephens (UK), Lefteris Tapas (CY), Diana Taylor (UK), Maria Theodoraki (GR), Amikam Toren (IL) and Alison Turnbull (UK). For the past five years, the curatorial line of the owner Maria Stathi, aims at the promotion and projection of the art scene in Nicosia by presenting important solo and group exhibitions. Art Seen focuses and expands on curatorial and art practices that investigate modes of contemporary making and exhibiting. Art Seen curates, displays and promotes work of both local and international artists, in a wide range of approaches and mediums. Nonetheless these works contribute to an imaginative critical language of art making and thinking today. Now more than ever, Art Seen remains committed to its founding ideals for supporting and promoting contemporary creation and providing an open space for contemporary art while pushing the boundaries. The artist Diana Taylor responds to the curatorial idea of the exhibition and develops the following reasoning: "What is it about this time that we live in that so compels us to reflect inwards upon our present and how it is defined? We live in a time of the ‘re’: of re-assembling, re-contextualising and re-appropriating images repeatedly, reinterpreting their meanings- one picture reposted over the last. In considering our contemporary condition, we can understand that what prevails is the paradoxical sense of not being fully in the now, or with time as the word directly translates, rather there exist multiple and constantly shifting temporalities, layered one upon another. Contemporaneity sees the end of a linear understanding of art history; rather it is punctuated by a sense of anachronism, poly-temporality and contradiction: of being here, now, then and there at the same time. It is not surprising then, that in an age of rapidly advancing technologies and mass consumption, our gaze also remains in the rear view mirror, looking back to sensibilities of the past and to material traditions. Simultaneously then we are deconstructing the past, negotiating a push/pull of things and times both coming together and falling apart- yesterday, today and forever. Yesterday, Today and Forever surveys this notion of contemporaneity whilst celebrating the five year history of Art Seen contemporary and artists who have exhibited at the gallery since it opened." Art Seen organisation was founded in 2015 by curator Maria Stathi, as an opportunity to expand on cultural exchanges and synergies within the cultural scene of Cyprus and beyond. Previously she was the director of Anthony Reynolds Gallery, in the West End in London, for over five years and of Omikron Gallery, Nicosia. In the last decade she has curated more than 19 solo and 16 group exhibitions of both leading and emerging artists

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally