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1.
Anal Chem ; 94(19): 6919-6923, 2022 May 17.
Article in English | MEDLINE | ID: covidwho-1829921

ABSTRACT

Normalization to account for variation in urinary dilution is crucial for interpretation of urine metabolic profiles. Probabilistic quotient normalization (PQN) is used routinely in metabolomics but is sensitive to systematic variation shared across a large proportion of the spectral profile (>50%). Where 1H nuclear magnetic resonance (NMR) spectroscopy is employed, the presence of urinary protein can elevate the spectral baseline and substantially impact the resulting profile. Using 1H NMR profile measurements of spot urine samples collected from hospitalized COVID-19 patients in the ISARIC 4C study, we determined that PQN coefficients are significantly correlated with observed protein levels (r2 = 0.423, p < 2.2 × 10-16). This correlation was significantly reduced (r2 = 0.163, p < 2.2 × 10-16) when using a computational method for suppression of macromolecular signals known as small molecule enhancement spectroscopy (SMolESY) for proteinic baseline removal prior to PQN. These results highlight proteinuria as a common yet overlooked source of bias in 1H NMR metabolic profiling studies which can be effectively mitigated using SMolESY or other macromolecular signal suppression methods before estimation of normalization coefficients.


Subject(s)
COVID-19 , Humans , Magnetic Resonance Spectroscopy/methods , Metabolome , Metabolomics/methods , Proton Magnetic Resonance Spectroscopy
2.
Open Forum Infect Dis ; 9(5): ofac179, 2022 May.
Article in English | MEDLINE | ID: covidwho-1821760

ABSTRACT

Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11-1.70] ng/mL vs 0.24 [0.10-0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51-.60]).

3.
Euro Surveill ; 27(15)2022 Apr.
Article in English | MEDLINE | ID: covidwho-1793104

ABSTRACT

On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.


Subject(s)
COVID-19 , Hepatitis A , Child , Child, Preschool , Humans , Retrospective Studies , SARS-CoV-2 , Scotland/epidemiology
4.
The Lancet. Digital health ; 4(4):e220-e234, 2022.
Article in English | EuropePMC | ID: covidwho-1755949

ABSTRACT

Background Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. Methods We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Findings Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years;0·52 [0·46–0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. Interpretation Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. Funding UK National Institute for Health Research and UK Medical Research Council.

5.
ERJ Open Res ; 8(1)2022 Jan.
Article in English | MEDLINE | ID: covidwho-1690978

ABSTRACT

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320392

ABSTRACT

Background: Microbiological characterisation of co-infections and secondary infections in COVID-19 is lacking, while antimicrobial usage is high. We aimed to describe microbiologically-confirmed co-/secondary infections, and antimicrobial usage, in hospitalised patients with COVID-19.Methods: Hospitalised patients in England, Scotland, and Wales with confirmed/high likelihood SARS-CoV-2 infection were recruited to the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) prospective cohort study. Patients admitted between 6th February–8th June 2020 with a recorded outcome 28 days after admission were included. Organisms considered clinically insignificant were excluded.Findings: Microbiological investigations were recorded for 8649/48 902 patients, with significant respiratory or bloodstream bacterial/fungal infections recorded for 1107 patients. These were mostly secondary infections diagnosed >2 days after admission (70·6%, 762/1080 with known sample timing). Staphylococcus aureus then Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S. aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli then S. aureus. Among patients with available data, 37·0% (13 390/36 145) received antimicrobials prior to admission and 85·2% (39 258/46 061) in hospital, highest in critical care. We identified frequent use of broad-spectrum agents and use of carbapenems over carbapenem-sparing alternatives.Interpretation: In hospitalised patients with COVID-19, microbiologically-confirmed bacterial/fungal infections are rare, and more likely to be secondary infections. Gram-negative organisms and S. aureus are the predominant pathogens. The frequency and nature of antimicrobial usage is concerning, but tractable targets for stewardship interventions exist.Funding: This work is supported by grants from: the National Institute for Health Research (NIHR) [award CO-CIN-01], the Medical Research Council [grant MC_PC_19059] and by the NIHR Health Protection Research Unit (HPRU)in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907], NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation[OPP1209135], and Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform foR European Preparedness Against (Re-) emerging Epidemics (PREPARE) [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. LT is supported by a Wellcome Trust fellowship [205228/Z/16/Z]. PJMO is supported by a NIHR Senior Investigator Award [award 201385]. This research was funded in whole, or in part, by the Wellcome Trust. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The views expressed are those of the authors and not necessarily those of the DHSC, DID, NIHR, MRC, Wellcome Trust or PHE.Conflict of Interest: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the National Institute for Health Research (NIHR), the Medical Research Council (MRC), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London, NIHR Biomedical Research Centre at ImperialCollege Lo don, and NIHR Clinical Research Network for the submitted work;ABD reports grants fromDepartment of Health and Social Care (DHSC), during the conduct of the study, grants from Wellcome Trust, outside the submitted work;PJMO reports personal fees from consultancies and from European RespiratorySociety, grants from MRC, MRC Global Challenge Research Fund, EU, NIHR BRC, MRC/GSK, WellcomeTrust, NIHR (Health Protection Research Unit (HPRU) in Respiratory Infection), and is NIHR senior investigator outside the submitted work;his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the Society;JKB reports grants from MRC UK;MGS reportsgrants from DHSC NIHR UK, grants from MRC UK, grants from HPRU in Emerging and Zoonotic Infections,University of Liverpool, during the conduct of the study, other from Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work.Ethical Approval: Ethical approval was given by the South Central-Oxford C Research Ethics Committee in England (13/SC/0149), the Scotland A Research Ethics Committee (20/SS/0028), and the WHO Ethics Review Committee (RPC571 and RPC572, April 2013).

7.
Nephrol Dial Transplant ; 37(2): 271-284, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1648225

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS: A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS: Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS: AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Cohort Studies , Hospital Mortality , Humans , Male , Prospective Studies , Retrospective Studies , Risk Factors , SARS-CoV-2 , United Kingdom , World Health Organization
8.
ERJ open research ; 2021.
Article in English | EuropePMC | ID: covidwho-1610380

ABSTRACT

Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.

9.
Thorax ; 2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1528562

ABSTRACT

PURPOSE: To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19. METHODS: Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. RESULTS: 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, -0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions. CONCLUSION: Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making. TRIAL REGISTRATION NUMBER: ISRCTN66726260.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292404

ABSTRACT

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: : A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis. Results: : 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17;10%), unlikely (n=56;35%), probable (n=67;42%) or very likely (n=21;13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84);p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87);p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (p<0.001), illness perception (p<0.001), anxiety and depression (p<0.001), physical activity (p<0.001) and predicted maximal oxygen utilization (ml/kg/min) (p<0.001). These measures were associated with adjudicated myocarditis. Conclusions: : The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration : ClinicalTrials.gov identifier is NCT04403607.

11.
PLoS One ; 16(11): e0259213, 2021.
Article in English | MEDLINE | ID: covidwho-1496532

ABSTRACT

Healthcare workers have had the longest and most direct exposure to COVID-19 and consequently may suffer from poor mental health. We conducted one of the first repeated multi-country analysis of the mental wellbeing of medical doctors (n = 5,275) at two timepoints during the COVID-19 pandemic (June 2020 and November/December 2020) to understand the prevalence of anxiety and depression, as well as associated risk factors. Rates of anxiety and depression were highest in Italy (24.6% and 20.1%, June 2020), second highest in Catalonia (15.9% and 17.4%, June 2020), and lowest in the UK (11.7% and 13.7%, June 2020). Across all countries, higher risk of anxiety and depression symptoms were found among women, individuals below 60 years old, those feeling vulnerable/exposed at work, and those reporting normal/below-normal health. We did not find systematic differences in mental health measures between the two rounds of data collection, hence we cannot discard that the mental health repercussions of the pandemic are persistent.


Subject(s)
Anxiety/etiology , COVID-19/psychology , Depression/etiology , Occupational Diseases/psychology , Physicians/psychology , Adult , Female , Health Personnel/psychology , Humans , Italy , Male , Middle Aged , Pandemics
12.
Nephrol Dial Transplant ; 37(2): 271-284, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1475823

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS: A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS: Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS: AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Cohort Studies , Hospital Mortality , Humans , Male , Prospective Studies , Retrospective Studies , Risk Factors , SARS-CoV-2 , United Kingdom , World Health Organization
13.
Science ; 374(6567): eabj3624, 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1440797

ABSTRACT

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.


Subject(s)
2',5'-Oligoadenylate Synthetase/genetics , 2',5'-Oligoadenylate Synthetase/metabolism , COVID-19/genetics , COVID-19/physiopathology , RNA, Double-Stranded/metabolism , RNA, Viral/metabolism , SARS-CoV-2/physiology , 5' Untranslated Regions , A549 Cells , Animals , COVID-19/enzymology , COVID-19/immunology , Chiroptera/genetics , Chiroptera/virology , Coronaviridae/enzymology , Coronaviridae/genetics , Coronaviridae/physiology , Endoribonucleases/metabolism , Humans , Interferons/immunology , Isoenzymes/genetics , Isoenzymes/metabolism , Phosphoric Diester Hydrolases/genetics , Phosphoric Diester Hydrolases/metabolism , Polymorphism, Single Nucleotide , Protein Prenylation , RNA, Double-Stranded/chemistry , RNA, Double-Stranded/genetics , RNA, Viral/chemistry , RNA, Viral/genetics , Retroelements , SARS-CoV-2/genetics , Severity of Illness Index , Virus Replication
14.
Lancet Reg Health Eur ; 8: 100186, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1397545

ABSTRACT

BACKGROUND: This study sought to establish the long-term effects of Covid-19 following hospitalisation. METHODS: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). FINDINGS: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. INTERPRETATION: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. FUNDING: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.

17.
PLoS One ; 16(8): e0256316, 2021.
Article in English | MEDLINE | ID: covidwho-1362092

ABSTRACT

Efficient and effective viral detection methodologies are a critical piece in the global response to COVID-19, with PCR-based nasopharyngeal and oropharyngeal swab testing serving as the current gold standard. With over 100 million confirmed cases globally, the supply chains supporting these PCR testing efforts are under a tremendous amount of stress, driving the need for innovative and accurate diagnostic solutions. Herein, the utility of a direct-to-PCR method of SARS-CoV-2 detection grounded in mechanical homogenization is examined for reducing resources needed for testing while maintaining a comparable sensitivity to the current gold standard workflow of nasopharyngeal and oropharyngeal swab testing. In a head-to-head comparison of 30 patient samples, this initial clinical validation study of the proposed homogenization-based workflow demonstrated significant agreeability with the current extraction-based method utilized while cutting the total resources needed in half.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Specimen Handling/instrumentation , COVID-19 Nucleic Acid Testing/instrumentation , Feasibility Studies , Humans , Nasopharynx/virology , Oropharynx/virology , Prospective Studies , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity , Workflow
18.
Lancet Respir Med ; 9(7): 773-785, 2021 07.
Article in English | MEDLINE | ID: covidwho-1337040

ABSTRACT

BACKGROUND: Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital. METHODS: In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260. FINDINGS: Between March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32·3% (95% CI 31·8-32·7) in March 9 to April 26, 2020, to 16·4% (15·0-17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65-0·71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10·2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22·2%, OR 0·95 (0·94-0·95) of the reduction in in-hospital mortality. INTERPRETATION: The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain. FUNDING: National Institute for Health Research and the Medical Research Council.


Subject(s)
COVID-19/mortality , Hospital Mortality , Aged , Aged, 80 and over , COVID-19/epidemiology , Clinical Protocols , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology , World Health Organization
19.
Lancet ; 398(10296): 223-237, 2021 07 17.
Article in English | MEDLINE | ID: covidwho-1313499

ABSTRACT

BACKGROUND: COVID-19 is a multisystem disease and patients who survive might have in-hospital complications. These complications are likely to have important short-term and long-term consequences for patients, health-care utilisation, health-care system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and effect of COVID-19 complications, particularly in those who survive, using the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK. METHODS: We did a prospective, multicentre cohort study in 302 UK health-care facilities. Adult patients aged 19 years or older, with confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 were included in the study. The primary outcome of this study was the incidence of in-hospital complications, defined as organ-specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities. FINDINGS: Between Jan 17 and Aug 4, 2020, 80 388 patients were included in the study. Of the patients admitted to hospital for management of COVID-19, 49·7% (36 367 of 73 197) had at least one complication. The mean age of our cohort was 71·1 years (SD 18·7), with 56·0% (41 025 of 73 197) being male and 81·0% (59 289 of 73 197) having at least one comorbidity. Males and those aged older than 60 years were most likely to have a complication (aged ≥60 years: 54·5% [16 579 of 30 416] in males and 48·2% [11 707 of 24 288] in females; aged <60 years: 48·8% [5179 of 10 609] in males and 36·6% [2814 of 7689] in females). Renal (24·3%, 17 752 of 73 197), complex respiratory (18·4%, 13 486 of 73 197), and systemic (16·3%, 11 895 of 73 197) complications were the most frequent. Cardiovascular (12·3%, 8973 of 73 197), neurological (4·3%, 3115 of 73 197), and gastrointestinal or liver (0·8%, 7901 of 73 197) complications were also reported. INTERPRETATION: Complications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause a substantial strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19. FUNDING: National Institute for Health Research and the UK Medical Research Council.


Subject(s)
COVID-19/complications , Clinical Protocols/standards , Comorbidity , Hospital Mortality , Hospitalization , Age Factors , Aged , COVID-19/epidemiology , Cardiovascular Diseases , Female , Hospitals , Humans , Male , Nervous System Diseases , Prospective Studies , Respiratory Tract Diseases , SARS-CoV-2 , United Kingdom/epidemiology , World Health Organization
20.
Philos Trans R Soc Lond B Biol Sci ; 376(1829): 20200265, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1309685

ABSTRACT

Since it was first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. Using a transmission model, we estimate a basic reproductive number of 3.11 (95% CI, 2.39-4.13), indicating that 58-76% of transmissions must be prevented to stop increasing. We also estimate a case ascertainment rate in Wuhan of 5.0% (95% CI, 3.6-7.4). The true size of the epidemic may be significantly greater than the published case counts suggest, with our model estimating 21 022 (prediction interval, 11 090-33 490) total infections in Wuhan between 1 and 22 January. We discuss our findings in the light of more recent information. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.


Subject(s)
COVID-19/epidemiology , Pandemics , SARS-CoV-2/pathogenicity , Basic Reproduction Number , COVID-19/transmission , COVID-19/virology , China/epidemiology , Humans , SARS-CoV-2/genetics
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