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Journal articleHurst EA, Mellanby RJ, Handel I, et al., 2021,
Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study
, BMJ Open, Vol: 11, Pages: 1-11, ISSN: 2044-6055Objectives The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.Design Cross-sectional study.Setting and participants Plasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measures Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality.Results Vitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (<25 nmol/L) were prevalent in COVID-19 (29.3% and 44.4%, respectively), influenza A (47.3% and 37.6%) and critical illness survivors (30.2% and 56.8%). In COVID-19 and influenza A, total 25(OH)D measured early in illness was lower in patients who received IMV (19.6 vs 31.9 nmol/L (p<0.0001) and 22.9 vs 31.1 nmol/L (p=0.0009), respectively). In COVID-19, biologically active free 25(OH)D correlated with total 25(OH)D and was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators.Conclusions Vitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at
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Journal articleBrown JC, Moshe M, Blackwell A, et al., 2021,
Inactivation of SARS-CoV-2 in chlorinated swimming pool water
, Water Research, Vol: 205, Pages: 1-4, ISSN: 0043-1354SARS-CoV-2 transmission remains a global problem which exerts a significant direct cost to public health. Additionally, other aspects of physical and mental health can be affected by limited access to social and exercise venues as a result of lockdowns in the community or personal reluctance due to safety concerns. Swimming pools reopened in the UK on April 12th 2021, but the effect of swimming pool water on inactivation of SARS-CoV-2 has not yet been directly demonstrated. Here we demonstrate that chlorinated water which adheres to UK swimming pool guidelines is sufficient to reduce SARS-CoV-2 infectious titre by at least 3 orders of magnitude.
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Journal articleSgalla G, Iovene B, Bruni T, et al., 2021,
Telemedicine-enabled, Hotel-based Management of Patients with COVID-19: A Single-Center Feasibility Study
, ANNALS OF THE AMERICAN THORACIC SOCIETY, Vol: 18, Pages: 1743-1746, ISSN: 1546-3222 -
Journal articleShaw RJ, Abrams ST, Austin J, et al., 2021,
Circulating histones play a central role in COVID-19-associated coagulopathy and mortality
, Haematologica: the hematology journal, Vol: 106, Pages: 2493-2498, ISSN: 0390-6078 -
Journal articleMarciniak SJ, Farrell J, Rostron A, et al., 2021,
COVID-19 pneumothorax in the UK: a prospective observational study using the ISARIC WHO clinical characterisation protocol
, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936- Author Web Link
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Journal articleRussell CD, Fairfield CJ, Drake TM, et al., 2021,
Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study
, The Lancet Microbe, Vol: 2, Pages: E354-E365, ISSN: 2666-5247BackgroundMicrobiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19.MethodsThe International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded.FindingsWe analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and 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 a
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Journal articleYates T, Zaccardi F, Islam N, et al., 2021,
Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort
, BMC Infectious Diseases, Vol: 21, Pages: 1-9, ISSN: 1471-2334BackgroundAlthough age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched.MethodsWe used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories.ResultsThe analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50–69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and
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Journal articleWard H, Atchison C, Whitaker M, et al., 2021,
Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The second wave of infection in England is apparen
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Journal articleDrake TM, Riad AM, Fairfield CJ, et al., 2021,
Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study
, The Lancet, Vol: 398, Pages: 223-237, ISSN: 0140-6736BACKGROUND: 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
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Journal articleCOVID-19 Host Genetics Initiative, 2021,
Mapping the human genetic architecture of COVID-19
, Nature, Vol: 600, Pages: 472-477, ISSN: 0028-0836The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
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