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Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank

Kolin et al., PLOS ONE, doi:10.1371/journal.pone.0241264
Nov 2020  
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Case -30% Improvement Relative Risk Metformin for COVID-19  Kolin et al.  Prophylaxis Does metformin reduce COVID-19 infections? Retrospective 397,064 patients in the United Kingdom More cases with metformin (not stat. sig., p=0.075) c19early.org Kolin et al., PLOS ONE, November 2020 Favorsmetformin Favorscontrol 0 0.5 1 1.5 2+
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 98 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 110 treatments. c19early.org
397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with metformin use, without statistical significance. Metformin is typically prescribed for diabetes, diabetes patients have significantly higher COVID-19 risk, and results are not adjusted for diabetes.
Study covers metformin and acetaminophen.
risk of case, 30.0% higher, RR 1.30, p = 0.08.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Kolin et al., 17 Nov 2020, retrospective, United Kingdom, peer-reviewed, 4 authors. Contact: dak4001@med.cornell.edu.
This PaperMetforminAll
Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank
David A Kolin, Scott Kulm, Paul J Christos, Olivier Elemento
PLOS ONE, doi:10.1371/journal.pone.0241264
Background Coronavirus disease 2019 has rapidly infected millions of people worldwide. Recent studies suggest that racial minorities and patients with comorbidities are at higher risk of Covid-19. In this study, we analyzed the effects of clinical, regional, and genetic factors on Covid-19 positive status. Methods The UK Biobank is a longitudinal cohort study that recruited participants from 2006 to 2010 from throughout the United Kingdom. Covid-19 test results were provided to UK Biobank starting on March 16, 2020. The main outcome measure in this study was Covid-19 positive status, determined by the presence of any positive test for a single individual. Clinical risk factors were derived from UK Biobank at baseline, and regional risk factors were imputed using census features local to each participant's home zone. We used robust adjusted Poisson regression with clustering by testing laboratory to estimate relative risk. Blood types were derived using genetic variants rs8176719 and rs8176746, and genomewide tests of association were conducted using logistic-Firth hybrid regression. Results This prospective cohort study included 397,064 UK Biobank participants, of whom 968 tested positive for Covid-19. The unadjusted relative risk of Covid-19 for Black participants was 3.66 (95% CI 2.83-4.74), compared to White participants. Adjusting for Townsend deprivation index alone reduced the relative risk to 2.44 (95% CI 1.86-3.20). Comorbidities that significantly increased Covid-19 risk included chronic obstructive pulmonary disease (adjusted relative risk [ARR] 1.64, 95% CI 1.18-2.27), ischemic heart disease (ARR 1.48, 95% CI 1.16-1.89), and depression (ARR 1.32, 95% CI 1.03-1.70). There was some evidence that angiotensin converting enzyme inhibitors (ARR 1.48, 95% CI 1.13-1.93) were associated with increased risk of Covid-19. Each standard deviation increase in the number of total individuals living in a participant's locality was associated with increased risk of ). Analyses of genetically inferred blood types
Supporting information S1 Appendix. (DOCX) Author Contributions Conceptualization: David A. Kolin, Scott Kulm, Olivier Elemento. Data curation
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{ 'indexed': {'date-parts': [[2022, 8, 23]], 'date-time': '2022-08-23T13:12:02Z', 'timestamp': 1661260322135}, 'reference-count': 48, 'publisher': 'Public Library of Science (PLoS)', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2020, 11, 17]], 'date-time': '2020-11-17T00:00:00Z', 'timestamp': 1605571200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': '<jats:sec id="sec001">\n' '<jats:title>Background</jats:title>\n' '<jats:p>Coronavirus disease 2019 (Covid-19) has rapidly infected millions of people ' 'worldwide. Recent studies suggest that racial minorities and patients with comorbidities are ' 'at higher risk of Covid-19. In this study, we analyzed the effects of clinical, regional, and ' 'genetic factors on Covid-19 positive status.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec002">\n' '<jats:title>Methods</jats:title>\n' '<jats:p>The UK Biobank is a longitudinal cohort study that recruited participants from 2006 ' 'to 2010 from throughout the United Kingdom. Covid-19 test results were provided to UK Biobank ' 'starting on March 16, 2020. The main outcome measure in this study was Covid-19 positive ' 'status, determined by the presence of any positive test for a single individual. Clinical ' 'risk factors were derived from UK Biobank at baseline, and regional risk factors were imputed ' 'using census features local to each participant’s home zone. We used robust adjusted Poisson ' 'regression with clustering by testing laboratory to estimate relative risk. Blood types were ' 'derived using genetic variants rs8176719 and rs8176746, and genomewide tests of association ' 'were conducted using logistic-Firth hybrid regression.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec003">\n' '<jats:title>Results</jats:title>\n' '<jats:p>This prospective cohort study included 397,064 UK Biobank participants, of whom 968 ' 'tested positive for Covid-19. The unadjusted relative risk of Covid-19 for Black participants ' 'was 3.66 (95% CI 2.83–4.74), compared to White participants. Adjusting for Townsend ' 'deprivation index alone reduced the relative risk to 2.44 (95% CI 1.86–3.20). Comorbidities ' 'that significantly increased Covid-19 risk included chronic obstructive pulmonary disease ' '(adjusted relative risk [ARR] 1.64, 95% CI 1.18–2.27), ischemic heart disease (ARR 1.48, 95% ' 'CI 1.16–1.89), and depression (ARR 1.32, 95% CI 1.03–1.70). There was some evidence that ' 'angiotensin converting enzyme inhibitors (ARR 1.48, 95% CI 1.13–1.93) were associated with ' 'increased risk of Covid-19. Each standard deviation increase in the number of total ' 'individuals living in a participant’s locality was associated with increased risk of Covid-19 ' '(ARR 1.14, 95% CI 1.08–1.20). Analyses of genetically inferred blood types confirmed that ' 'participants with type A blood had increased odds of Covid-19 compared to participants with ' 'type O blood (odds ratio [OR] 1.16, 95% CI 1.01–1.33). A meta-analysis of genomewide ' 'association studies across ancestry groups did not reveal any significant loci. Study ' 'limitations include confounding by indication, bias due to limited information on early ' 'Covid-19 test results, and inability to accurately gauge disease severity.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec004">\n' '<jats:title>Conclusions</jats:title>\n' '<jats:p>When assessing the association of Black race with Covid-19, adjusting for deprivation ' 'reduced the relative risk of Covid-19 by 33%. In the context of sociological research, these ' 'findings suggest that discrimination in the labor market may play a role in the high relative ' 'risk of Covid-19 for Black individuals. In this study, we also confirmed the association of ' 'blood type A with Covid-19, among other clinical and regional factors.</jats:p>\n' '</jats:sec>', 'DOI': '10.1371/journal.pone.0241264', 'type': 'journal-article', 'created': { 'date-parts': [[2020, 11, 17]], 'date-time': '2020-11-17T13:33:35Z', 'timestamp': 1605620015000}, 'page': 'e0241264', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 20, 'title': 'Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank', 'prefix': '10.1371', 'volume': '15', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-5306-023X', 'authenticated-orcid': True, 'given': 'David A.', 'family': 'Kolin', 'sequence': 'first', 'affiliation': []}, {'given': 'Scott', 'family': 'Kulm', 'sequence': 'additional', 'affiliation': []}, {'given': 'Paul J.', 'family': 'Christos', 'sequence': 'additional', 'affiliation': []}, {'given': 'Olivier', 'family': 'Elemento', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2020, 11, 17]]}, 'reference': [ { 'key': 'pone.0241264.ref001', 'author': 'COVID-19 in Racial and Ethnic Minority Groups', 'journal-title': 'Centers for Disease Control and Prevention'}, { 'key': 'pone.0241264.ref002', 'article-title': 'COVID-19 and Racial/Ethnic Disparities', 'author': 'M Webb Hooper', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': 'pone.0241264.ref003', 'article-title': 'Hospitalization and Mortality among Black Patients and White Patients ' 'with Covid-19', 'author': 'EG Price-Haywood', 'year': '2020', 'journal-title': 'New England Journal of Medicine'}, { 'key': 'pone.0241264.ref004', 'doi-asserted-by': 'crossref', 'first-page': '398', 'DOI': '10.1007/s40615-020-00756-0', 'article-title': 'The COVID-19 Pandemic: a Call to Action to Identify and Address Racial ' 'and Ethnic Disparities', 'volume': '7', 'author': 'CT Laurencin', 'year': '2020', 'journal-title': 'Journal of Racial and Ethnic Health Disparities'}, { 'key': 'pone.0241264.ref005', 'unstructured': 'Coronavirus (COVID-19) related deaths by ethnic group, England and ' 'Wales: 2 March 2020 to 10 April 2020. Office for National Statistics. ' '2020. Available: ' 'https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/coronavirusrelateddeathsbyethnicgroupenglandandwales/2march2020to10april2020'}, { 'key': 'pone.0241264.ref006', 'article-title': 'Does comorbidity increase the risk of patients with COVID-19: evidence ' 'from meta-analysis.', 'author': 'B Wang', 'year': '2020', 'journal-title': 'Aging.'}, { 'key': 'pone.0241264.ref007', 'doi-asserted-by': 'crossref', 'first-page': 'm1329', 'DOI': '10.1136/bmj.m1329', 'article-title': 'Socioeconomic gradient in health and the covid-19 outbreak', 'author': 'RY-N Chung', 'year': '2020', 'journal-title': 'BMJ'}, { 'key': 'pone.0241264.ref008', 'doi-asserted-by': 'crossref', 'first-page': '303', 'DOI': '10.1016/j.dsx.2020.04.004', 'article-title': 'Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and ' 'practical considerations', 'volume': '14', 'author': 'AK Singh', 'year': '2020', 'journal-title': 'Diabetes & Metabolic Syndrome: Clinical Research & Reviews.'}, { 'key': 'pone.0241264.ref009', 'doi-asserted-by': 'crossref', 'first-page': 'm1185', 'DOI': '10.1136/bmj.m1185', 'article-title': 'Non-steroidal anti-inflammatory drugs and covid-19', 'author': 'P Little', 'year': '2020', 'journal-title': 'BMJ'}, { 'key': 'pone.0241264.ref010', 'article-title': 'Association of Use of Angiotensin-Converting Enzyme Inhibitors and ' 'Angiotensin II Receptor Blockers With Testing Positive for Coronavirus ' 'Disease 2019 (COVID-19).', 'author': 'N Mehta', 'year': '2020', 'journal-title': 'JAMA Cardiology'}, { 'key': 'pone.0241264.ref011', 'article-title': 'Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin ' 'Receptor Blocker Use With COVID-19 Diagnosis and Mortality', 'author': 'EL Fosbøl', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': 'pone.0241264.ref012', 'article-title': 'What Does and Does Not Correlate With COVID-19 Death Rates?', 'author': 'C Knittel', 'year': '2020', 'journal-title': 'MIT Center for Energy and Environmental Policy Research'}, { 'key': 'pone.0241264.ref013', 'article-title': 'Self-reported symptoms of covid-19 including symptoms most predictive ' 'of SARS-CoV-2 infection, are heritable', 'author': 'FM Williams', 'year': '2020', 'journal-title': 'Genetic and Genomic Medicine'}, { 'key': 'pone.0241264.ref014', 'article-title': 'Clinical and molecular characterization of COVID-19 hospitalized ' 'patients', 'author': 'E Benetti', 'year': '2020', 'journal-title': 'Genetic and Genomic Medicine'}, { 'key': 'pone.0241264.ref015', 'article-title': 'ACE2 polymorphisms as potential players in COVID-19 outcome', 'author': 'AS Khayat', 'year': '2020', 'journal-title': 'Genetic and Genomic Medicine'}, { 'key': 'pone.0241264.ref016', 'article-title': 'Genomewide Association Study of Severe Covid-19 with Respiratory ' 'Failure.', 'author': 'D Ellinghaus', 'year': '2020', 'journal-title': 'New England Journal of Medicine'}, { 'key': 'pone.0241264.ref017', 'article-title': 'Importance of collecting data on socioeconomic determinants from the ' 'early stage of the COVID-19 outbreak onwards', 'author': 'S Khalatbari-Soltani', 'year': '2020', 'journal-title': 'Journal of Epidemiology and Community Health'}, { 'key': 'pone.0241264.ref018', 'article-title': 'COVID-19 and African Americans.', 'author': 'CW Yancy', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': 'pone.0241264.ref019', 'unstructured': 'Nomis Official Labor Market Statistics. 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