Pre-existing traits associated with Covid-19 illness severity

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Abstract

Importance

Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.

Objective

To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection.

Design

Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.

Setting

A large, multihospital healthcare system in Southern California.

Participants

All patients with confirmed Covid-19 infection (N = 442).

Results

Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P = 0.001), African American (OR 2.1, P = 0.011), obese (OR 2.0, P = 0.021), with diabetes mellitus (OR 1.8, P = 0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (P _interaction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P = 0.003) irrespective of age, race, or morbidity profile.

Conclusions and relevance

In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.

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Most cited references 36

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Author and article information

Contributors

Joseph E. Ebinger: Role: Data curationRole: Formal analysisRole: InvestigationRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Natalie Achamallah: Role: Data curationRole: Writing – review & editing

Hongwei Ji: Role: Data curationRole: Formal analysisRole: InvestigationRole: ValidationRole: Writing – original draftRole: Writing – review & editing

Brian L. Claggett: Role: Formal analysisRole: InvestigationRole: Writing – review & editing

Nancy Sun: Role: InvestigationRole: Writing – review & editing

Patrick Botting: Role: InvestigationRole: Writing – review & editing

Trevor-Trung Nguyen: Role: InvestigationRole: Writing – review & editing

Eric Luong: Role: InvestigationRole: Writing – review & editing

Elizabeth H. Kim: Role: InvestigationRole: Writing – review & editing

Eunice Park: Role: InvestigationRole: Writing – review & editing

Yunxian Liu: Role: InvestigationRole: Writing – review & editing

Ryan Rosenberry: Role: InvestigationRole: Writing – review & editing

Yuri Matusov: Role: InvestigationRole: Writing – review & editing

Steven Zhao: Role: InvestigationRole: Writing – review & editing

Isabel Pedraza: Role: InvestigationRole: Writing – review & editing

Tanzira Zaman: Role: InvestigationRole: Writing – review & editing

Michael Thompson: Role: InvestigationRole: Writing – review & editing

Koen Raedschelders:

ORCID: http://orcid.org/0000-0003-0835-4762

Role: InvestigationRole: Writing – review & editing

Anders H. Berg: Role: InvestigationRole: Writing – review & editing

Jonathan D. Grein: Role: ConceptualizationRole: InvestigationRole: Writing – review & editing

Paul W. Noble: Role: Investigation

Sumeet S. Chugh: Role: InvestigationRole: Writing – review & editing

C. Noel Bairey Merz: Role: InvestigationRole: Writing – review & editing

Eduardo Marbán: Role: InvestigationRole: Writing – review & editing

Jennifer E. Van Eyk: Role: InvestigationRole: Writing – review & editing

Scott D. Solomon: Role: InvestigationRole: Writing – review & editing

Christine M. Albert: Role: InvestigationRole: Writing – review & editing

Peter Chen: Role: SupervisionRole: Writing – review & editing

Susan Cheng:

ORCID: http://orcid.org/0000-0002-4977-036X

Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing

Yu Ru Kou: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 23 July 2020

Publication date Collection: 2020

Publication date PMC-release: 23 July 2020

Volume: 15

Issue: 7

Electronic Location Identifier: e0236240

Affiliations

[1 ] Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[2 ] Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[3 ] Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[4 ] Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[5 ] Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China

[6 ] Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America

[7 ] Enterprise Information Systems Data Intelligence Team, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[8 ] Advanced Clinical Biosystems Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[9 ] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[10 ] Department of Epidemiology, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[11 ] Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

[12 ] Barbra Streisand Women’s Heart Center, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

National Yang-Ming University, TAIWAN

Author notes

Competing Interests: The authors have declared that no competing interests exist.

* E-mail: peter.chen@ 123456cshs.org (PC); susan.cheng@ 123456cshs.org (SC)

Author information

Koen Raedschelders http://orcid.org/0000-0003-0835-4762

Susan Cheng http://orcid.org/0000-0002-4977-036X

Article

Publisher ID: PONE-D-20-12746

DOI: 10.1371/journal.pone.0236240

PMC ID: 7377468

PubMed ID: 32702044

SO-VID: b3da5d54-64b0-4bd6-ad1e-2bddc39274ce

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 1 May 2020

Date accepted : 1 July 2020

Page count

Figures: 4, Tables: 3, Pages: 16

Funding

Funded by: Erika J. Glazer Family Foundation

Award Recipient :

ORCID: http://orcid.org/0000-0002-4977-036X

Susan Cheng

This work was supported in part by the Erika J. Glazer Family Foundation (JEE; JEVE; CNBM; SC). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.

Custom metadata

Data Availability The data that support the findings of this study are available from Cedars-Sinai Medical Center, upon reasonable request. The data are not publicly available due to the contents including information that could compromise research participant privacy/consent. Please direct inquiries to: biodatacore@ 123456cshs.org .

Outbreaks COVID-19

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Pre-existing traits associated with Covid-19 illness severity

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Abstract

Importance

Objective

Design

Setting

Participants

Results

Conclusions and relevance

Related collections

PLOS: COVID-19 pandemic

Most cited references 36

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical Characteristics of Coronavirus Disease 2019 in China

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

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Cited by 87

Most referenced authors 4,070