Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

CTEPH is an uncommon complication of COVID-19: UK national surveillance and observational screening cohort studies.

INTRODUCTION: Pulmonary embolism (PE) is a well-recognised complication of COVID-19 infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established. METHODS: We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post hospital discharge according to existing risk scores using symptoms, ECG and NT pro-BNP. RESULTS: By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month, p=0.252). Of 334 confirmed CTEPD/CTEPH cases, 4 (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further 3 (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT. CONCLUSION: A-priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation.

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

OBJECTIVE: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies. DESIGN/PATIENTS: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study). MEASUREMENTS: Plasma steroids were quantified by liquid chromatography-mass spectrometry. Steroid concentrations were compared against disease severity (WHO ordinal scale) and validated symptom scores. Data are presented as geometric mean (SD). RESULTS: In the acute cohort (n = 239, 66.5% male), plasma cortisol concentration increased with disease severity (cortisol 753.3 [1.6] vs. 429.2 [1.7] nmol/L in fatal vs. least severe, p < .001). In males, testosterone concentrations decreased with severity (testosterone 1.2 [2.2] vs. 6.9 [1.9] nmol/L in fatal vs. least severe, p < .001). In the follow-up cohort (n = 198, 62.1% male, 68.9% ongoing symptoms, 165 [121-192] days postdischarge), plasma cortisol concentrations (275.6 [1.5] nmol/L) did not differ with in-hospital severity, perception of recovery, or patient-reported symptoms. Male testosterone concentrations (12.6 [1.5] nmol/L) were not related to in-hospital severity, perception of recovery or symptom scores. CONCLUSIONS: Circulating glucocorticoids in patients hospitalised with COVID-19 reflect acute illness, with a marked rise in cortisol and fall in male testosterone. These findings are not observed 5 months from discharge. The lack of association between hormone concentrations and common post-COVID symptoms suggests steroid insufficiency does not play a causal role in this condition.

The variation of anticoagulation prescribed in foot and ankle surgery in the UK - UK foot and ankle thrombo-embolism audit (UK-FATE).

INTRODUCTION: Venous thrombo-embolism (VTE) is a recognised complication of foot and ankle surgery. There are multiple possible anticoagulation treatments available in the UK to mitigate the risk of developing VTE. Our primary objective was to assess the variability of chemical anticoagulation prescribed in patients undergoing foot and ankle procedures. METHODS: This was a UK-based national, multicenter, prospective audit spanning a collection duration of 9 months on all foot and ankle procedures, carried out in 68 UK centers between 1st June 2022 and 30th November 2022, with a further 3-month follow up period. All patients who underwent a foot and ankle surgical procedure (including Achilles tendon rupture treatment) were included in this study. RESULTS: Data on a total of 13,569 patients was submitted. Following data cleansing, 11,363 patients were available for further analysis, with anticoagulation data available for 11,099 patients. There were eleven different chemical anticoagulation treatments recorded across the cohort. A total of 3630 (31.95 %) patients received no chemical anticoagulation. The patients receiving chemical anticoagulation medication could be split into 4 main groups. The most common chemical anticoagulation received was low molecular weight heparin (LMWH) (6303, 84.4 % of patients receiving chemical anticoagulation). Aspirin was given in 4.1 % (308 patients), a Factor Xa inhibitor in 10 % (744 patients) and other anticoagulants (e.g. Warfarin) in 1.5 % (114 patients). The overall VTE rate in this sub analysis of patients receiving chemical anticoagulation, was 1.1 % (83 cases out of 7469). There was no significant difference seen in incidence of VTE between types of anticoagulants, when confounding factors were considered. The duration of post-operative chemical prophylaxis used by participants for most chemical anticoagulants was 6 weeks (64.50 %). CONCLUSION: There was significant variability of chemical anticoagulants reported in the study, with five different categories of anticoagulants used (including no chemical anticoagulation), and none clearly superior/inferior. The duration of anticoagulation was consistent across types of thromboprophylaxis.

Characteristics of Patients Not Receiving Chemical Thromboprophylaxis Following Foot and Ankle Surgery: Data From the Multicenter, Prospective UK Foot and Ankle Thrombo-Embolism Audit (UK-FATE).

BACKGROUND: Although the rate of venous thromboembolism (VTE) after foot and ankle surgery is low, multiple factors influence risk for individual patients. Furthermore, there are no clear guidelines on which patients may benefit from chemical thromboprophylaxis. Our aim was to assess patients not treated with chemical thromboprophylaxis after foot and ankle surgery, and to report on their specific patient and surgical risk factors for VTE. METHODS: This was a multicenter, prospective, national audit of patients undergoing foot and ankle surgery (including Achilles tendon ruptures) from 68 participating UK centers. The study was conducted between June 1, 2022, and November 30, 2022, with a further 3-month follow-up. Following data cleansing, 3309 patients were included who did not receive postoperative thromboprophylaxis. RESULTS: Most patients were elective cases (2589 patients, 78.24%) with ASA grade I or II (2679 patients, 80.96%), fully weightbearing postoperatively (2752 patients, 83.17%), and either without ankle splintage, or splinted in a plantigrade boot (2797 patients, 84.53%). The VTE rate was 0.30% overall (11 cases), with no VTE-related mortality. No single demographic, surgical, or postoperative factor was associated with reduced risk of VTE. However, patients who had elective or trauma surgery not involving the ankle, who were ASA grade I or II and who were weightbearing immediately postoperatively (without splinting or in a plantigrade boot) had a VTE rate of 0.05% (1 of 1819 patients), compared with 0.67% (10 of 1490 patients, P = .002). CONCLUSION: Patients not receiving chemical thromboprophylaxis had a low incidence of symptomatic VTE, although they do represent a curated group considered lower risk. Within this group we describe characteristics associated with a substantially lower risk of VTE. All patients should be assessed on an individual basis, and further work is required to substantiate our findings.

The Training to Improve Dyspnoea Study- Patient Experiences of Using a High Frequency Airway Oscillating Device.

Introduction: The High Frequency Airway Oscillating device (HFAO) was developed to help patients with COPD feel less breathless through flow resistive respiratory muscle training and fixed rate oscillations. Previous work has demonstrated that this device can improve inspiratory muscle strength over and above a sham device. Both groups improved their breathlessness and preserved clinical benefits though there were no statistically significant differences seen over and above the sham device. It is important to understand patient perceptions of using a device and how this may influence their treatment and therefore a qualitative analysis was conducted to understand participant experiences of a HFAO device. Methods: This was an exploratory qualitative analysis involving participants recruited to the Training to Improve Dyspnoea (TIDe) study. Participants completed a satisfaction survey and were invited to take part in a focus group. Focus groups were conducted by a researcher independent to the randomised controlled trial. Data was analysed independently by two researchers using inductive thematic analysis, and themes/sub-themes were agreed jointly. Data is presented in themes and sub themes and triangulated with survey response data. Results: Fourteen participants were recruited to two focus groups (71% male, mean [SD] age 64[9] years). The key themes were patient selection, device use, and investment. Patient selection explores the disease characteristics, emotional impact and management of care. Device use explores the device prescription and usage, routine and lifestyle and effectiveness. Investment covers accessibility, understanding, benefits vs participation and overall perceptions of the device. Conclusion: This research demonstrates the complexity of device interventions and that key considerations should be given to patient selection, the device use itself and, the time and cost investment required for participants to successfully implement the device into daily life.

A shared decision-making intervention between health care professionals and individuals undergoing Pulmonary Rehabilitation: An iterative development process with qualitative methods.

BACKGROUND: Pulmonary Rehabilitation (PR) services typically offer programmes to support individuals living with COPD make rehabilitation choices that best meet their needs, however, uptake remains low. Shared Decision-Making (SDM; e.g., Patient Decision Aids (PtDA)) interventions increase informed and values-based decision-making between individuals and healthcare professionals (HCPs). We aimed to develop an intervention to facilitate PR SDM which was acceptable to individuals living with COPD and PR HCPs. METHODS: An iterative development process involving qualitative methods was adopted. Broad overarching frameworks included: complex intervention development framework, the multiple stakeholder decision making support model, and the Ottawa Decision Support Framework. Development included: assembling a steering group, outlining the scope for the PtDA, collating data to inform the PtDA design, prototype development, alpha testing with individuals with COPD (n = 4) and PR HCPs (n = 8), PtDA finalisation, and design and development of supporting components. This took nine months. RESULTS: The PtDA was revised six times before providing an acceptable, comprehensible, and usable format for all stakeholders. Supporting components (decision coaching training and a consultation prompt) were necessary to upskill PR HCPs in SDM and implement the intervention into the PR pathway. CONCLUSIONS: We have developed a three-component SDM intervention (a PtDA, decision coaching training for PR healthcare professionals, and a consultation prompt) to support individuals living with COPD make informed and values-based decision about PR together with their PR healthcare professional. Clear implementation strategies are outlined which should support its integration into the PR pathway.

Effect of co-morbidities on outcomes of first metatarsophalangeal joint fusion: A systematic review.

Introduction: The pre-existing co-morbidities have a major impact on the outcomes of Orthopaedic procedures as shown by the several studied in various contexts. However, the specific influence of these co-morbidities on first metatarsophalangeal joint fusion remains relatively underexplored. This study aims to address this gap by examining the association between co-morbidities such as obesity, smoking, diabetes, advancing age, and rheumatoid arthritis, and the outcomes of first metatarsophalangeal joint fusion. Methods: A comprehensive search was conducted across multiple databases, including MEDLINE, EMBASE, and CINAHL. Relevant articles were identified and processed using Covidence, with independent assessment conducted to ensure inclusion criteria were met. The focus of the review was on analysing the effects of specific co-morbidities on fusion outcomes. Results: Seven qualifying studies were identified for full-text extraction, revealing significant heterogeneity across the literature, which hindered direct statistical comparisons. The findings presented inconclusive effects of obesity on fusion outcomes, with ambiguous impacts observed for diabetes mellitus and smoking. Additionally, no discernible variance was observed in functional outcomes across different age groups. Furthermore, steroid usage in rheumatoid arthritis cases demonstrated delayed fusion in revision procedures, while primary outcomes remained uncertain. Conclusion: This systematic review highlights the need for further research with standardised methodologies to better understand the correlation between pre-existing co-morbidities and outcomes in first metatarsophalangeal joint fusion. By elucidating these relationships, clinicians can better tailor treatment approaches and optimise patient care in this specific Orthopaedic context. Level of evidence: Level III.

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery.

BACKGROUND: Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss, improve visualization in the surgical field, and to potentially reduce surgical time. There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure, placement site, and duration of use. There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery. AIM: To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery. METHODS: Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken. Intraoperative tourniquet duration, tourniquet pressure and site, and postoperative pain scores using Visual Analogue Score were collected in immediate recovery, at six hours and at 24 h post-op. Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure, duration, site, and pain scores using Pearson correlation coefficient. RESULTS: All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh. There was no correlation between the site of the tourniquet and pain scores in recovery, at six hours and after 24 h. There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op (r = 0.14, P = 0.04) but not at six or 24 h post-operatively. CONCLUSION: This study shows that there was no statistically significant correlation between tourniquet pressure, site and post-op pain in patients undergoing foot and ankle surgery. The choice of using a tourniquet is based on the surgeon's preference, with the goal of minimizing the duration of its application at the operative site.

Incidence, demographics, characteristics and management of acute Achilles tendon rupture: An epidemiological study.

BACKGROUND: Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients' quality of life. The incidence, characteristics and management of ATR in the United Kingdom (UK) is poorly understood. This investigation aims to understand the incidence of ATR in the UK. METHODS: Prospective data collection of ATR incidence from a United Kingdom Emergency department. Retrospective review of management protocols and immobilisation duration from electronic medical records. RESULTS: ATR incidence is 8 per 100,000 people per annum. Participants were predominately male (79.2%) and primarily reported a sporting mechanism of injury (65.2%). Mean immobilisation duration was 63.1 days. 97.1% were non-surgically managed post ATR. 46.2% of participants had experienced a previous ATR or Achilles tendinopathy prior to their current ATR. CONCLUSION: The incidence of ATR found was 8. cases per 100,000 people per annum. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Almost one quarter (23.3%) of individuals report Achilles pain prior to ATR.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study - PHOSP-COVID.

Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group. Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.

Long COVID and cardiovascular disease: a prospective cohort study.

BACKGROUND: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. OBJECTIVES: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. METHODS: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. RESULTS: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). CONCLUSION: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need. TRAIL REGISTRATION NUMBER: ISRCTN10980107.

Cognitive and psychiatric symptom trajectories 2-3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK.

BACKGROUND: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study. FINDINGS: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20). INTERPRETATION: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.