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1.
LANCET DIGITAL HEALTH ; 4(4), 2022.
Article in English | Web of Science | ID: covidwho-1935260

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. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

2.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-335588

ABSTRACT

Background Remdesivir has been evaluated in clinical trial populations, but there is a sparsity of evidence evaluating effectiveness in general populations. Methods Adults eligible to be treated with remdesivir, requiring oxygen but not ventilated, were identified from UK patients hospitalised with COVID-19. Patients treated with remdesivir within 24h of hospitalisation were compared with propensity-score matched controls;estimates of effectiveness were calculated for short-term outcomes (14-day mortality, 28-day mortality, time-to-recovery among others) using multivariable modelling. Results 9,278 out of 39,330 patients satisfied eligibility criteria. 1,549 patients were identified as 'treated' and matched with 4,964 controls. Patients were 62% male, mean (SD) age 63.1 (15.6) years, 80% 'White' ethnicity, and symptomatic for a median of 6 days prior to baseline. There was no statistically significant benefit of remdesivir at 14 days in terms of mortality or clinical status;there were signals of effectiveness in time-to-recovery after day 9, and a reduction in 28-day mortality. Conclusion In a real-world setting, initiation of remdesivir within 24h of hospitalisation in conjunction with standard of care was not associated with a benefit at 14 days but supports clinical trial evidence of a potential reduction in 28-day mortality.

3.
Infectious Diseases: News, Opinions, Training ; 11(1):57-63, 2022.
Article in Russian | Scopus | ID: covidwho-1812111

ABSTRACT

The aim of the study is to validate the Russian version of the 4C Mortality Score scale and evaluate its accuracy in predicting the outcomes of severe COVID-19. Material and methods. The staff of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology received official permission from the authors to conduct a validation study of the 4C Mortality Score scale in Russia. In the course of the work, the linguistic and cultural ratification of the scale was carried out and its Russian-language version was prepared. Psychometric properties (reliability and validity) The Russian-language version was evaluated on a group of 78 patients (37 of whom were men, aged 34 to 88 years) with a confirmed diagnosis of COVID-19, hospitalized in the City Clinical Hospital No. 15 named after O.M. Filatov (Moscow) in the period from June to August 2021. Results. The linguocultural adaptation of the 4C Mortality Score scale was successfully carried out. High levels of reliability were obtained (Spearman correlation coefficient ρ=0.91, p<0.0001;Cronbach's alpha α=0.73, p=0.0002;Cohen's kappa κ=0.85, p<0.0001). It is shown that the 4C Mortality Score scores have a significant correlation with the COVID-GRAM scores (r=0.72, p=0.002) and NEWS2 (r=0.54, p=0.004). Conclusion. As a result of the validation study, the official Russian version of the 4C Mortality Score scale was developed. It is recommended for use by medical professionals of various specialties at all stages of providing medical care to patients with COVID-19. The scale is available for download on the website of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology (https://www.neurology.ru/reabilitaciya/centr-validacii-mezhdunarodnyh-shkal-i-oprosnikov). © 2022 by the authors.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330329

ABSTRACT

Introduction Shared characteristics between COVID-19 and pulmonary fibrosis, including symptoms, genetic architecture, and circulating biomarkers, suggests interstitial lung disease (ILD) development may be associated with SARS-CoV-2 infection. Methods The UKILD Post-COVID study planned interim analysis was designed to stratify risk groups and estimate the prevalence of Post-COVID Interstitial Lung Damage (ILDam) using the Post-HOSPitalisation COVID-19 (PHOSP-COVID) Study. Demographics, radiological patterns and missing data were assessed descriptively. Bayes binomial regression was used to estimate the risk ratio of persistent lung damage >10% involvement in linked, clinically indicated CT scans. Indexing thresholds of percent predicted DLco, chest X-ray findings and severity of admission were used to generate risk strata. Number of cases within strata were used to estimate the amount of suspected Post-COVID ILDam. Results A total 3702 people were included in the UKILD interim cohort, 2406 completed an early follow-up research visit within 240 days of discharge and 1296 had follow-up through routine clinical review. We linked the cohort to 87 clinically indicated CTs with visually scored radiological patterns (median 119 days;interquartile range 83 to 155, max 240), of which 74 people had ILDam. ILDam was associated with abnormal chest X-ray (RR 1.21 95%CrI 1.05;1.40), percent predicted DLco<80% (RR 1.25 95%CrI 1.00;1.56) and severe admission (RR 1.27 95%CrI 1.07;1.55). A risk index based on these features suggested 6.9% of the interim cohort had moderate to very-high risk of Post-COVID ILDam. Comparable radiological patterns were observed in repeat scans >90 days in a subset of participants. Conclusion These interim data highlight that ILDam was not uncommon in clinically indicated thoracic CT up to 8 months following SARS-CoV-2 hospitalisation. Whether the ILDam will progress to ILD is currently unknown, however health services should radiologically and physiologically monitor individuals who have Post-COVID ILDam risk factors.

6.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326972

ABSTRACT

The mutational landscape of SARS-CoV-2 varies at both the dominant viral genome sequence and minor genomic variant population. An early change associated with transmissibility was the D614G substitution in the spike protein. This appeared to be accompanied by a P323L substitution in the viral polymerase (NSP12), but this latter change was not under strong selective pressure. Investigation of P323L/D614G changes in the human population showed rapid emergence during the containment phase and early surge phase of wave 1 in the UK. This rapid substitution was from minor genomic variants to become part of the dominant viral genome sequence. A rapid emergence of 323L but not 614G was observed in a non-human primate model of COVID-19 using a starting virus with P323 and D614 in the dominant genome sequence and 323L and 614G in the minor variant population. In cell culture, a recombinant virus with 323L in NSP12 had a larger plaque size than the same recombinant virus with P323. These data suggest that it may be possible to predict the emergence of a new variant based on tracking the distribution and frequency of minor variant genomes at a population level, rather than just focusing on providing information on the dominant viral genome sequence e.g., consensus level reporting. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.

7.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326575

ABSTRACT

COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFNgamma based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4 + and/or CD8 + epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8 + T cells than spike-specific CD8 + T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8 + to CD4 + T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.

8.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):476-477, 2021.
Article in English | EMBASE | ID: covidwho-1570375

ABSTRACT

Background: The symptoms of the COVID-19 acute phase are well studied, but the long-term sequelae (post-COVID condition) are still poorly characterised. The aim of this study was to evaluate the prevalence of persistent symptoms in previously hospitalised adult patients with COVID-19 and assess risk factors for the post-COVID condition Method: Ambidirectional cohort study of patients over 18 years hospitalised to Sechenov University Hospital Network, Moscow, Russia with clinically diagnosed or laboratory-confirmed COVID-19 between April 8 and July 10, 2020. Study participants were interviewed 6-8 months after discharge via telephone using a follow-up case report form (CRF) developed by ISARIC in collaboration with WHO. Identified symptoms were categorised according to organ systems. Risk factors were assessed by multivariate logistic regression. Results: Among 4,755 patients discharged from the hospitals, 2,649 were subsequently interviewed. The median age of patients was 56 years (46-66), and 1,353 patients (51.1%) were female. The follow-up median time was 217.5 days (200.4-235.5). 1,247 (47.1%) participants reported persistent symptoms (since discharge). The most frequent symptoms were fatigue (21.2%, 551/2599), shortness of breath (14.5%, 378/2614) and forgetfulness (9.1%, 237/2597). Female gender was associated with chronic fatigue with an odds ratio of 1.67 (95% confidence interval 1.39-2.02), neurological 2.03 (1.60-2.58), mental 1.83 (1.41-2.40), respiratory 1.31 (1.06-1.62) and dermatological symptoms 3.26 (2.36-4.57), GI disturbances 2.50 (1.64-3.89) and sensory problems 1.73 (2.06-2.89). Pre-existing asthma was associated with a higher risk of neurological 1.95 (1.25-2.98) and mood and behavioural changes 2.02 (1.24-3.18). Conclusion: Six to eight months after COVID-19 nearly half of patients have symptoms lasting since discharge. The main risk factor for the majority of the development of long-term symptoms was female sex. Asthma may also serve as a risk factor for the post-COVID condition. Further follow-up of patients reporting the persistence of COVID-19 symptoms and the development of interventional approaches for the prevention of post-COVID manifestations are needed.

9.
Annals of Oncology ; 31:S992, 2020.
Article in English | EMBASE | ID: covidwho-805759

ABSTRACT

Background: The SARS-CoV-2 pandemic in the UK triggered a national characterisation protocol and information on co-morbidities including malignant neoplasm is recorded. A lack of prospective data regarding cancer patients with COVID-19 hampers the development of an evidence based approach in this population. The Clinical Characterisation Protocol-CANCER-UK is a UK multi-disciplinary project aimed at characterising the presentation and course of COVID-19 in cancer patients with the aim of informing practice. Methods: The international Severe Acute Respiratory and emerging Infections Consortium (ISARIC)-4C COVID-19 Clinical Information Network (CO-CIN) collects data on hospital inpatients with proven/high likelihood of COVID-19. Data was collected in 166 UK sites using a questionnaire adopted by the WHO. Data on patients with malignant neoplasm was extracted from the main dataset. We chose a priori to restrict any analysis of outcome to patients who were admitted more than 14 days before data extraction (13th May 2020). Results: As of 13th May 2020 1797 of 16160 participants had malignant neoplasm (8.6% of all cases). Age<50 62 (3.5%), 50-60 378 (21%), 70-79 558 (31%), 80+ 1002 (42%). Male 1147 (64%);Female 645 (36%). Commonest comorbidities chromic pulmonary disease (22%), chronic kidney disease (21%), uncomplicated diabetes (19%) and dementia (14%). Outcomes 35% discharged alive, 30% care ongoing & 35% died. Admiited to ICU: 150 cases (25% discharged alive,31% care ongoing & 45% died). Receiving invasive ventiation: 67 cases (18% discharged alive, 25% care ongoing:25% & 57% died). HR mortality for malignancy (adjusted for age, sex, other comorbidity): 1.13 (1.02-1.24, p=0.017). Data on presentation will be presented. Conclusions: Europe’s largest prospective COVID-19 dataset demonstrates that cancer is independently associated with mortality in patients admitted with COVID-19. Data collection is on-going and updated data will be presented including a comparison of cancer vs. non-cancer cohort with regard to presentation, comorbidity and otucomes. Clinical trial identification: ISRCTN66726260. Legal entity responsible for the study: and international Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Coronavirus Clinical Characterisation Consortium (ISARIC4C). Funding: UK Research and Innovation, Medical Research Council and Department for Health and Social Care. Disclosure: All authors have declared no conflicts of interest.

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