Evidence map›Paper›PMID 33548839›Full record

ArticleEBioMedicine2021

Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to severe SARS-CoV-2.

Tom G Richardson, Si Fang, Ruth E Mitchell, Michael V Holmes, George Davey Smith

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Tom G RichardsonMedical Research Council Integrative Epidemiology Unit (MRC IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom. Electronic address: tom.g.richardson@bristol.ac.uk.
Si FangMedical Research Council Integrative Epidemiology Unit (MRC IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
Ruth E MitchellMedical Research Council Integrative Epidemiology Unit (MRC IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
Michael V HolmesMedical Research Council Integrative Epidemiology Unit (MRC IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom; Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom.
George Davey SmithMedical Research Council Integrative Epidemiology Unit (MRC IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
University of Bristol · GB

Funding

British Heart Foundation FS/18/23/33512Medical Research Council MC_UU_00011/1Medical Research Council MR/S003886/1
6 · The paper itself

Abstract

backgroundDeveloping insight into the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to overcome the global pandemic caused by coronavirus disease 2019 (covid-19). In this study, we have applied Mendelian randomization (MR) to systematically evaluate the effect of 10 cardiometabolic risk factors and genetic liability to lifetime smoking on 97 circulating host proteins postulated to either interact or contribute to the maladaptive host response of SARS-CoV-2.

methodsWe applied the inverse variance weighted (IVW) approach and several robust MR methods in a two-sample setting to systemically estimate the genetically predicted effect of each risk factor in turn on levels of each circulating protein. Multivariable MR was conducted to simultaneously evaluate the effects of multiple risk factors on the same protein. We also applied MR using cis-regulatory variants at the genomic location responsible for encoding these proteins to estimate whether their circulating levels may influence severe SARS-CoV-2.

findingsIn total, we identified evidence supporting 105 effects between risk factors and circulating proteins which were robust to multiple testing corrections and sensitivity analyzes. For example, body mass index provided evidence of an effect on 23 circulating proteins with a variety of functions, such as inflammatory markers c-reactive protein (IVW Beta=0.34 per standard deviation change, 95% CI=0.26 to 0.41, P = 2.19 × 10

interpretationOur findings highlight several key proteins which are influenced by established exposures for disease. Future research to determine whether these circulating proteins mediate environmental effects onto risk of SARS-CoV-2 infection or covid-19 progression are warranted to help elucidate therapeutic strategies for severe covid-19 disease.

fundingThe Medical Research Council, the Wellcome Trust, the British Heart Foundation and UK Research and Innovation.

Indexed as

BiomarkersBody Mass IndexCardiovascular DiseasesCOVID-19C-Reactive ProteinFemaleGenome-Wide Association StudyHumansInterleukin-1Interleukin-6MaleSARS-CoV-2Severity of Illness IndexBiomarkersC-Reactive ProteinIL6 protein, humanInterleukin-1Interleukin-6Cardiometabolic risk factorsCirculating proteinsCovid19Mendelian randomizationSARS-CoV-2

Identifiers

PMID33548839
PMCPMC7857697
OpenAlexW3119646678

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.