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1.
Clin Med (Lond) ; 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1912146

ABSTRACT

INTRODUCTION: Breathing pattern disorders (BPDs) are a common cause of chronic breathlessness, including after acute respiratory illnesses such as COVID pneumonia. BPD is however underdiagnosed, partly as a result of difficulty in clinically assessing breathing pattern. The Breathing Pattern Assessment Tool (BPAT) has been validated for use in diagnosing BPD in patients with asthma but to date has not been validated in other diseases. METHODS: Patients undergoing face-to-face review in a post-COVID clinic were assessed by a respiratory physician and specialist respiratory physiotherapist. Assessment included a Dyspnoea-12 (D12) questionnaire to assess breathlessness, physiotherapist assessment of breathing pattern including manual assessment of respiratory motion, and BPAT assessment. The sensitivity and specificity of BPAT for diagnosis of BPD in post-COVID patients was assessed. RESULTS: BPAT had a sensitivity of 89.5% and specificity of 78.3% for diagnosing BPD in post-COVID breathlessness. Patients with a BPAT score above the diagnostic cut-off had higher levels of breathlessness than those with lower BPAT scores (D12 score mean average 19.4 vs 13.2). CONCLUSION: BPAT has high sensitivity and moderate specificity for BPD in patients with long COVID. This would support its use as a screening test in clinic, and as a diagnostic tool for large cohort studies.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330891

ABSTRACT

BACKGROUND: Vitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Randomized controlled trials of vitamin D to prevent coronavirus disease 2019 (Covid-19) have not yet reported. METHODS: We randomly assigned 6200 U.K. adults to receive an offer of a postal finger-prick 25-hydroxyvitamin D (25[OH]D) test with provision of a 6-month supply of higher-dose vitamin D (3200 IU/d, n=1550) or lower-dose vitamin D (800 IU/d, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). The primary outcome was the proportion of participants experiencing at least one swab test- or doctor-confirmed acute respiratory infection (ARI) of any cause at six months. Secondary outcomes included incidence of swab test-confirmed Covid-19. RESULTS: Of 3100 participants offered testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no-offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no-offer 1.09, 95% CI 0.82-1.46;lower-dose vs. no-offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no-offer groups developed Covid-19 (OR for higher-dose vs. no-offer 1.13, 0.78-1.63;lower-dose vs. no-offer 1.39, 0.98-1.97). CONCLUSIONS: Among adults with a high baseline prevalence of vitamin D insufficiency, implementation of a test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or Covid-19.

3.
BMJ Open ; 12(2): e057408, 2022 02 07.
Article in English | MEDLINE | ID: covidwho-1673446

ABSTRACT

INTRODUCTION: Long COVID-19 is a distressing, disabling and heterogeneous syndrome often causing severe functional impairment. Predominant symptoms include fatigue, cognitive impairment ('brain fog'), breathlessness and anxiety or depression. These symptoms are amenable to rehabilitation delivered by skilled healthcare professionals, but COVID-19 has put severe strain on healthcare systems. This study aims to explore whether digitally enabled, remotely supported rehabilitation for people with long COVID-19 can enable healthcare systems to provide high quality care to large numbers of patients within the available resources. Specific objectives are to (1) develop and refine a digital health intervention (DHI) that supports patient assessment, monitoring and remote rehabilitation; (2) develop implementation models that support sustainable deployment at scale; (3) evaluate the impact of the DHI on recovery trajectories and (4) identify and mitigate health inequalities due to the digital divide. METHODS AND ANALYSIS: Mixed-methods, theoretically informed, single-arm prospective study, combining methods drawn from engineering/computer science with those from biomedicine. There are four work packages (WP), one for each objective. WP1 focuses on identifying user requirements and iteratively developing the intervention to meet them; WP2 combines qualitative data from users with learning from implementation science and normalisation process theory, to promote adoption, scale-up, spread and sustainability of the intervention; WP3 uses quantitative demographic, clinical and resource use data collected by the DHI to determine illness trajectories and how these are affected by use of the DHI; while WP4 focuses on identifying and mitigating health inequalities and overarches the other three WPs. ETHICS AND DISSEMINATION: Ethical approval obtained from East Midlands - Derby Research Ethics Committee (reference 288199). Our dissemination strategy targets three audiences: (1) Policy makers, Health service managers and clinicians responsible for delivering long COVID-19 services; (2) patients and the public; (3) academics. TRIAL REGISTRATION NUMBER: Research Registry number: researchregistry6173.


Subject(s)
COVID-19 , Anxiety , COVID-19/complications , Humans , Prospective Studies , SARS-CoV-2
4.
Curr Opin Pulm Med ; 28(3): 174-179, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1672376

ABSTRACT

PURPOSE OF REVIEW: Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system. RECENT FINDINGS: Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12 months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID. SUMMARY: Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.


Subject(s)
COVID-19 , COVID-19/complications , COVID-19/epidemiology , Cough , Humans , Respiratory System , SARS-CoV-2
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296652

ABSTRACT

Background: There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year. Methods PHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five-months and one-year after hospital discharge. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five-months. Inflammatory protein profiling from plasma at the five-month visit was performed. Findings 2320 participants have been assessed at five months after discharge and 807 participants have completed both five-month and one-year visits. Of these, 35.6% were female, mean age 58.7 (SD 12.5) years, and 27.8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five months 501/165 (25.6%) and one year 232/804 (28.9%). Factors associated with being less likely to report full recovery at one year were: female sex OR 0.68 (95% CI 0.46-0.99), obesity OR 0.50 (95%CI 0.34-0.74) and IMV OR 0.42 (95%CI 0.23-0.76). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate/cognitive, mild relating to the severity of physical, mental health and cognitive impairments at five months in a larger sample. There was elevation of inflammatory mediators of tissue damage and repair in both the very severe and the moderate/cognitive clusters compared to the mild cluster including interleukin-6 which was elevated in both comparisons. Overall, there was a substantial deficit in median (IQR) EQ5D-5L utility index from pre-COVID (retrospective assessment) 0.88 (0.74-1.00), five months 0.74 (0.60-0.88) to one year: 0.74 (0.59-0.88), with minimal improvements across all outcome measures at one-year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 remain substantial one year after discharge across a range of health domains with the minority in our cohort feeling fully recovered. Patient perceived health-related quality of life remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

6.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294849

ABSTRACT

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood. Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function. Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity. Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services. Funding: UKRI and NIHR

7.
Lancet Respir Med ; 9(12): 1467-1478, 2021 12.
Article in English | MEDLINE | ID: covidwho-1545512

ABSTRACT

Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.


Subject(s)
COVID-19/complications , Respiration Disorders , Consensus , Humans , Research , SARS-CoV-2
8.
Thorax ; 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1541926

ABSTRACT

BACKGROUND: Risk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. METHODS: We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19. RESULTS: We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0-30.0 kg/m2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2 versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use. CONCLUSIONS: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04330599).

9.
Lancet Respir Med ; 9(11): 1275-1287, 2021 11.
Article in English | MEDLINE | ID: covidwho-1514340

ABSTRACT

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.


Subject(s)
COVID-19 , Health Status , Mental Health , Acute Disease , Adult , Aged , COVID-19/complications , Cognition , Comorbidity , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology
11.
Front Immunol ; 12: 678570, 2021.
Article in English | MEDLINE | ID: covidwho-1295637

ABSTRACT

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/prevention & control , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Cell Surface Display Techniques/methods , Data Mining/methods , Epitopes/immunology , Humans , Immunization, Passive/methods
12.
Clin Med (Lond) ; 21(4): e384-e391, 2021 07.
Article in English | MEDLINE | ID: covidwho-1262676

ABSTRACT

BACKGROUND: The COVID-19 pandemic has strained healthcare systems and how best to address post-COVID health needs is uncertain. Here we describe the post-COVID symptoms of 675 patients followed up using a virtual review pathway, stratified by severity of acute COVID infection. METHODS: COVID-19 survivors completed an online/telephone questionnaire of symptoms after 12+ weeks and a chest X-ray. Dependent on findings at virtual review, patients were provided information leaflets, attended for investigations and/or were reviewed face-to-face. Outcomes were compared between patients following high-risk and low-risk admissions for COVID pneumonia, and community referrals. RESULTS: Patients reviewed after hospitalisation for COVID pneumonia had a median of two ongoing physical health symptoms post-COVID. The most common was fatigue (50.3% of high-risk patients). Symptom burden did not vary significantly by severity of hospitalised COVID pneumonia but was highest in community referrals. Symptoms suggestive of depression, anxiety and post-traumatic stress disorder were common (depression occurred in 24.9% of high-risk patients). Asynchronous virtual review facilitated triage of patients at highest need of face-to-face review. CONCLUSION: Many patients continue to have a significant burden of post-COVID symptoms irrespective of severity of initial pneumonia. How best to assess and manage long COVID will be of major importance over the next few years.


Subject(s)
COVID-19 , COVID-19/complications , Follow-Up Studies , Humans , Pandemics , SARS-CoV-2
14.
ERJ Open Res ; 7(1)2021 Jan.
Article in English | MEDLINE | ID: covidwho-1076124

ABSTRACT

Asthma therapy, including monoclonal antibodies, was not associated with #COVID19 infection or hospitalisation in a UK severe asthma population. Shielding led to a reported worsening of mental health in nearly half of patients contacted (47%). https://bit.ly/3jImUsG.

15.
Front Immunol ; 11: 605170, 2020.
Article in English | MEDLINE | ID: covidwho-1004679

ABSTRACT

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/pathology , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/immunology , B-Lymphocytes/immunology , COVID-19/immunology , Female , High-Throughput Nucleotide Sequencing , Humans , Lymphopenia/immunology , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology
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