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Critical Care Medicine

Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection

Educational Objective
To understand the association of red blood cell distribution width with mortality risk in hospitalized adults with COVID-19

1 Credit CME

JAMA Network Open

Published Online: September 23, 2020

Original Investigation

Article Information and Disclosures

Brody H. Foy, DPhil^1,2,3;

Jonathan C. T. Carlson, MD, PhD^1,4;

Erik Reinertsen, MD, PhD^1,5,6;

et al

Raimon Padros I. Valls, BA^1,6;

Roger Pallares Lopez, BA^1,6;

Eric Palanques-Tost, BA^1,6;

Christopher Mow, MS^1,7;

M. Brandon Westover, MD, PhD^8,9,10;

Aaron D. Aguirre, MD, PhD^1,6,11;

John M. Higgins, MD^1,2,3

Author Affiliations

¹Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston
²Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston
³Department of Systems Biology, Harvard Medical School, Boston, Massachusetts
⁴Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston
⁵Research Laboratory for Electronics, Massachusetts Institute of Technology, Cambridge
⁶Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston
⁷Partners Healthcare Enterprise Research Information Systems, Boston, Massachusetts
⁸Clinical Data AI Center and Neurology Department, Massachusetts General Hospital, Boston
⁹Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston
¹⁰Neurology Department, Harvard Medical School, Boston Massachusetts
¹¹Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston

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Key Points

Question In patients with SARS-CoV-2 infection, is there an association between mortality risk and red blood cell distribution width (RDW), a routine complete blood count component, at the time of admission and during hospitalization?

Findings In this cohort study of 1641 adult patients with SARS-CoV-2 infection who were hospitalized, elevated RDW at admission and increasing RDW during hospitalization were associated with statistically significant increases in mortality risk. The association between the RDW at admission and mortality risk was independent of D-dimer (dimerized plasmin fragment D) level, absolute lymphocyte count, demographic factors, and common comorbidities.

Meaning The findings suggest that an elevated RDW measured at admission and increasing RDW during hospitalization were associated with significantly higher mortality risk for patients with SARS-CoV-2 infection; RDW may be helpful for patient risk stratification.

Abstract

Importance Coronavirus disease 2019 (COVID-19) is an acute respiratory illness with a high rate of hospitalization and mortality. Biomarkers are urgently needed for patient risk stratification. Red blood cell distribution width (RDW), a component of complete blood counts that reflects cellular volume variation, has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases.

Objective To investigate whether an association between mortality risk and elevated RDW at hospital admission and during hospitalization exists in patients with COVID-19.

Design, Setting, and Participants This cohort study included adults diagnosed with SARS-CoV-2 infection and admitted to 1 of 4 hospitals in the Boston, Massachusetts area (Massachusetts General Hospital, Brigham and Women’s Hospital, North Shore Medical Center, and Newton-Wellesley Hospital) between March 4, 2020, and April 28, 2020.

Main Outcomes and Measures The main outcome was patient survival during hospitalization. Measures included RDW at admission and during hospitalization, with an elevated RDW defined as greater than 14.5%. Relative risk (RR) of mortality was estimated by dividing the mortality of those with an elevated RDW by the mortality of those without an elevated RDW. Mortality hazard ratios (HRs) and 95% CIs were estimated using a Cox proportional hazards model.

Results A total of 1641 patients were included in the study (mean [SD] age, 62[18] years; 886 men [54%]; 740 White individuals [45%] and 497 Hispanic individuals [30%]; 276 nonsurvivors [17%]). Elevated RDW (>14.5%) was associated with an increased mortality risk in patients of all ages. The RR for the entire cohort was 2.73, with a mortality rate of 11% in patients with normal RDW (1173) and 31% in those with an elevated RDW (468). The RR in patients younger than 50 years was 5.25 (normal RDW, 1% [n = 341]; elevated RDW, 8% [n = 65]); 2.90 in the 50- to 59-year age group (normal RDW, 8% [n = 256]; elevated RDW, 24% [n = 63]); 3.96 in the 60- to 69-year age group (normal RDW, 8% [n = 226]; elevated RDW, 30% [104]); 1.45 in the 70- to 79-year age group (normal RDW, 23% [n = 182]; elevated RDW, 33% [n = 113]); and 1.59 in those ≥80 years (normal RDW, 29% [n = 168]; elevated RDW, 46% [n = 123]). RDW was associated with mortality risk in Cox proportional hazards models adjusted for age, D-dimer (dimerized plasmin fragment D) level, absolute lymphocyte count, and common comorbidities such as diabetes and hypertension (hazard ratio of 1.09 per 0.5% RDW increase and 2.01 for an RDW >14.5% vs ≤14.5%; P < .001). Patients whose RDW increased during hospitalization had higher mortality compared with those whose RDW did not change; for those with normal RDW, mortality increased from 6% to 24%, and for those with an elevated RDW at admission, mortality increased from 22% to 40%.

Conclusions and Relevance Elevated RDW at the time of hospital admission and an increase in RDW during hospitalization were associated with increased mortality risk for patients with COVID-19 who received treatment at 4 hospitals in a large academic medical center network.

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Article Information

Accepted for Publication: August 17, 2020.

Published: September 23, 2020. doi:10.1001/jamanetworkopen.2020.22058

Corresponding Authors: John M. Higgins, MD (john_higgins@hms.harvard.edu), and Jonathan C. T. Carlson, MD, PhD (carlson.jonathan@mgh.harvard.edu), Simches Research Center, 185 Cambridge St, Boston, MA 02114.

Author Contributions: Dr Higgins had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Foy, Carlson, Westover, Aguirre, Higgins.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Foy, Reinertsen, Mow, Higgins.

Critical revision of the manuscript for important intellectual content: Foy, Carlson, Reinertsen, Padros I Valls, Pallares Lopez, Palanques-Tost, Westover, Aguirre, Higgins.

Statistical analysis: Foy, Higgins.

Obtained funding: Higgins.

Administrative, technical, or material support: Reinertsen, Mow, Aguirre, Higgins.

Supervision: Carlson, Westover, Aguirre, Higgins.

Conflict of Interest Disclosures: Dr Westover reported grants from the National Institutes of Health during the conduct of the study. Dr Aguirre reported grants from the CRICO Risk Management Foundation during the conduct of the study. Dr Higgins reported grants from the One Brave Idea Initiative and grants from Fast Grants at the Mercatus Center, George Mason University during the conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported by grants from the One Brave Idea Initiative and from Fast Grants at the Mercatus Center, George Mason University (Dr Higgins); grants from the CRICO Risk Management Foundation (Drs Westover and Aguirre); the Glenn Foundation for Medical Research and American Federation for Aging Research Breakthroughs in Gerontology Grant (Dr Westover); the American Academy of Sleep Medicine Foundation Strategic Research Award (Dr Westover), the Football Players Health Study grant at Harvard University (Dr Westover); a subcontract from Moberg ICU Solutions, Inc through the US Department of Defense (Dr Westover); and the following NIH grants: 1R01NS102190, 1R01NS102574, 1R01NS107291, and 1RF1AG064312 (Dr Westover).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection

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