scholarly journals Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis

2020 ◽  
Author(s):  
Elizabeth R. Mann ◽  
Madhvi Menon ◽  
Sean Blandin Knight ◽  
Joanne E. Konkel ◽  
Christopher Jagger ◽  
...  
Keyword(s):  
Immune Response ◽  
Longitudinal Analysis ◽  
Disease Process ◽  
Added Value ◽  
Cross Sectional ◽  
Level Data ◽  
Hospitalised Patients ◽  
Immune Alterations ◽  
The Uk ◽  
Immune Profiling

AbstractBackgroundThe pathogenesis of COVID-19, caused by a novel strain of coronavirus (SARS-CoV-2), involves a complex host-virus interaction and is characterised by an exaggerated immune response, the specific components of which are poorly understood. Here we report the outcome of a longitudinal immune profiling study in hospitalised patients during the peak of the COVID-19 pandemic in the UK and show the relationship between immune responses and severity of the clinical presentation.MethodsThe Coronavirus Immune Response and Clinical Outcomes (CIRCO) study was conducted at four hospitals in Greater Manchester. Patients with SARS-CoV-2 infection, recruited as close to admission as possible, provided peripheral blood samples at enrolment and sequentially thereafter. Fresh samples were assessed for immune cells and proteins in whole blood and serum. Some samples were also stimulated for 3 hours with LPS and analysed for intracellular proteins. Results were stratified based on patient-level data including severity of symptoms and date of reported symptom onset.FindingsLongitudinal analysis showed a very high neutrophil to T cell ratio and abnormal activation of monocytes in the blood, which displayed high levels of the cell cycle marker, Ki67 and low COX-2. These properties all reverted in patient with good outcome. Unexpectedly, multiple aspects of inflammation were diminished as patients progressed in severity and time, even in ITU patients not recovering.InterpretationThis is the first detailed longitudinal analysis of COVID-19 patients of varying severity and outcome, revealing common features and aspects that track with severity. Patients destined for a severe outcome can be identified at admission when still displaying mild-moderate symptoms. We provide clues concerning pathogenesis that should influence clinical trials and therapeutics. Targeting pathways involved in neutrophil and monocyte release from the bone marrow should be tested in patients with COVID-19.FundingThe Kennedy Trust for Rheumatology Research, The Wellcome Trust, The Royal Society, The BBSRC, National Institute for Health Research (NIHR) Biomedical Research Centres (BRC).Research in contextEvidence before this studyAnalysis of the literature before the study via pubmed and bioRxiv searches using the terms COVID-19, SARS-CoV2, immune and inflammation (with the last search performed on 27th April 2020) showed evidence of an overactive immune response in a handful of studies in cross-sectional analyses all done at a single time point.Added value of this studyTo determine the role of the immune response in a disease process, it is necessary to correlate immune activity with clinical parameters dynamically. In this study patients presented to hospital at different stages of disease so we took samples at different time-points to provide an accurate picture of the relevant pathobiology. In order to avoid loss of large components of the immune system due to the processes of storage, longitudinal samples were interrogated in real time to reveal the full immune alterations in COVID-19.Implications of all the available evidenceRespiratory viruses continue to cause devastating global disease. The finding of altered myelopoiesis, with excess neutrophils and altered monocyte function, as dominant features in our study provides an incentive for clinical testing of therapeutics that specifically target this pathobiology. Given that inflammation is greatest prior to admission to intensive care, trials of specific immune-modulating therapies should be considered earlier in admission. Future studies of COVID-19 mechanisms should place more emphasis on longitudinal analyses since disease changes dramatically over time.

scholarly journals The Association of Serum Lipid and Lipoprotein Levels with Total and Differential Leukocyte Counts: Results of a Cross-sectional and Longitudinal Analysis of the UK Biobank

2020 ◽  
Author(s):  
Bradley Tucker ◽  
Sonia Sawant ◽  
Hannah McDonald ◽  
Kerry-Anne Rye ◽  
Sanjay Patel ◽  
...  
Keyword(s):  
Longitudinal Analysis ◽  
Positive Association ◽  
Hdl Cholesterol ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Lipoprotein A ◽  
Valid Data ◽  
Leukocyte Counts ◽  
The Uk ◽  
Relationship Of

Background and aims: There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort. Methods: The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9,058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression. Results: Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors a higher eosinophil count was associated with lower HDL cholesterol and apolipoproteinA-I concentration (p<0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p<0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p<0.001). In the longitudinal analysis lipoprotein(a) was inversely associated with basophil count in men but not women (p<0.001). Conclusion: Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leuokogenesis. However, unlike in murine models, the remainder of these relationships are modest which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans.

scholarly journals Outpatient antibiotic use in the four administrations of the UK: cross-sectional and longitudinal analysis

2008 ◽  
Vol 62 (6) ◽  
pp. 1441-1447 ◽  
Author(s):  
Peter Davey ◽  
Matus Ferech ◽  
Faranak Ansari ◽  
Arno Muller ◽  
Herman Goossens
Keyword(s):  
Longitudinal Analysis ◽  
Antibiotic Use ◽  
Cross Sectional ◽  
The Uk

scholarly journals Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

2020 ◽  
Vol 5 (51) ◽  
pp. eabd6197 ◽  
Author(s):  
Elizabeth R. Mann ◽  
Madhvi Menon ◽  
Sean Blandin Knight ◽  
Joanne E. Konkel ◽  
Christopher Jagger ◽  
...  
Keyword(s):  
Immune Response ◽  
Hospital Admission ◽  
Mononuclear Cells ◽  
Elevated Serum ◽  
Peripheral Blood Mononuclear ◽  
Immune Signatures ◽  
Enhanced Expression ◽  
The Uk ◽  
And Function ◽  
Immune Profiling

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.

scholarly journals Regional variation in COVID-19 positive hospitalisation across Scotland during the first wave of the pandemic and its relation to population density: A cross-sectional observation study

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253636
Author(s):  
Andrew Rideout ◽  
Calum Murray ◽  
Chris Isles
Keyword(s):  
Population Density ◽  
Regional Variation ◽  
Social Deprivation ◽  
Health Board ◽  
Observation Study ◽  
Cross Sectional ◽  
Hospitalised Patients ◽  
The Uk ◽  
Restrictive Measures ◽  
Health Boards

Background There have been large regional differences in COVID-19 virus activity across the UK with many commentators suggesting that these are related to age, ethnicity and social class. There has also been a focus on cases, hospitalisations and deaths rather than on hospitalisation rates expressed per 100,000 population. The purpose of our study was to examine regional variation in COVID-19 positive hospitalisation rates in Scotland during the first wave of the pandemic and the possibility that these might be related to population density. Methods and findings This was a repeated point prevalence study. The number of COVID-19 positive patients hospitalised in the eleven Scottish mainland health boards peaked at 1517 on 19th April, then fell to a low of 243 on 16th August before rising slightly to 262 on 15th September. In July, August and September only four boards had more than 5 hospitalised patients. There was a statistically significant relationship between hospitalisation rates and population density on 97.7% of individual days during the first wave of the pandemic (Pearson’s r 0.62–0.93, with 123 of a possible 174 days having p values <0.001). Multiple linear regression analyses performed on data from the 11 mainland boards across six time points suggest that population density accounted for 70.2% of the variation in hospitalisation rate in April, 72.3% in May, 81.2% in June, 91.0% in July, 91.0% in August, and 88.1% in September. Neither population median age nor median social deprivation score at health board level were statistically significant in the final model for hospitalisation. Conclusion There were large differences in crude COVID-19 hospitalisation rates across the 11 mainland Scottish health boards, that were significantly related to population density. Given that lockdown was originally introduced to prevent the NHS from being overwhelmed, we believe our results support a regional rather than a national approach to lifting or reimposing more restrictive measures, and that hospitalisation rates should be part of the decision making process.

scholarly journals Survey of young people in one region of the UK on accessing COVID-19 information (SOCIAL)

2021 ◽  
Vol 5 (1) ◽  
pp. e000942
Author(s):  
Oliver G P Lawton ◽  
Sarah A Lawton ◽  
Lisa Dikomitis ◽  
Joanne Protheroe ◽  
Joanne Smith ◽  
...  
Keyword(s):  
Social Media ◽  
Young People ◽  
Significant Role ◽  
Online Survey ◽  
Descriptive Statistics ◽  
Sources Of Information ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Education Gaps ◽  
The Uk

COVID-19 has significantly impacted young people’s lives yet little is known about the COVID-19 related sources of information they access. We performed a cross-sectional survey of pupils (11–16 years) in North Staffordshire, UK. 408 (23%) pupils responded to an online survey emailed to them by their school. Descriptive statistics were used to summarise the data. Social media, accessed by 68%, played a significant role in the provision of information, despite it not being considered trustworthy. 89% felt that COVID-19 had negatively affected their education. Gaps in the provision of information on COVID-19 have been identified.

scholarly journals Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044384
Author(s):  
Guduru Gopal Rao ◽  
Alexander Allen ◽  
Padmasayee Papineni ◽  
Liyang Wang ◽  
Charlotte Anderson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Severe Infection ◽  
Older Age ◽  
Cross Sectional ◽  
North West ◽  
Icu Admission ◽  
Risk Of Death ◽  
Hospitalised Patients ◽  
Increased Risk

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

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