Extrapulmonary manifestations of COVID-19

doi:10.1038/s41591-020-0968-3

Review

. 2020 Jul;26(7):1017-1032.

doi: 10.1038/s41591-020-0968-3. Epub 2020 Jul 10.

Extrapulmonary manifestations of COVID-19

Aakriti Gupta^#^{1

2

3}, Mahesh V Madhavan^#^{1

2}, Kartik Sehgal^#^{4

5

6}, Nandini Nair⁷, Shiwani Mahajan^{3

8}, Tejasav S Sehrawat⁹, Behnood Bikdeli^{1

2

3}, Neha Ahluwalia¹⁰, John C Ausiello⁷, Elaine Y Wan¹, Daniel E Freedberg¹¹, Ajay J Kirtane², Sahil A Parikh^{1

2}, Mathew S Maurer¹, Anna S Nordvig¹², Domenico Accili⁷, Joan M Bathon¹³, Sumit Mohan^{14

15}, Kenneth A Bauer^{4

6}, Martin B Leon^{1

2}, Harlan M Krumholz^{3

8

16}, Nir Uriel¹, Mandeep R Mehra¹⁷, Mitchell S V Elkind^{12

15}, Gregg W Stone^{2

18}, Allan Schwartz¹, David D Ho¹⁹, John P Bilezikian⁷, Donald W Landry²⁰

Affiliations

¹ Division of Cardiology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
² Clinical Trials Center, Cardiovascular Research Foundation, New York, NY, USA.
³ Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA.
⁴ Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶ Harvard Medical School, Boston, MA, USA.
⁷ Division of Endocrinology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, New York, NY, USA.
⁸ Division of Cardiology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁰ Division of Cardiology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Division of Digestive and Liver Diseases, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
¹² Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University and the NewYork-Presbyterian Hospital, New York, NY, USA.
¹³ Division of Rheumatology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
¹⁴ Division of Nephrology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
¹⁵ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹⁶ Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA.
¹⁷ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
¹⁸ Division of Cardiology, Department of Medicine, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁹ Aaron Diamond AIDS Research Center, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
²⁰ Division of Nephrology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA. dwl1@cumc.columbia.edu.

^# Contributed equally.

PMID: 32651579
DOI: 10.1038/s41591-020-0968-3

Review

Extrapulmonary manifestations of COVID-19

Aakriti Gupta et al. Nat Med. 2020 Jul.

. 2020 Jul;26(7):1017-1032.

doi: 10.1038/s41591-020-0968-3. Epub 2020 Jul 10.

Authors

Affiliations

¹ Division of Cardiology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
² Clinical Trials Center, Cardiovascular Research Foundation, New York, NY, USA.
³ Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA.
⁴ Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶ Harvard Medical School, Boston, MA, USA.
⁷ Division of Endocrinology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, New York, NY, USA.
⁸ Division of Cardiology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁰ Division of Cardiology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Division of Digestive and Liver Diseases, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
¹² Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University and the NewYork-Presbyterian Hospital, New York, NY, USA.
¹³ Division of Rheumatology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
¹⁴ Division of Nephrology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
¹⁵ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹⁶ Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, USA.
¹⁷ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
¹⁸ Division of Cardiology, Department of Medicine, the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁹ Aaron Diamond AIDS Research Center, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.
²⁰ Division of Nephrology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY, USA. dwl1@cumc.columbia.edu.

^# Contributed equally.

PMID: 32651579
DOI: 10.1038/s41591-020-0968-3

Abstract

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

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References

1. Dong, E., Du, H. & Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. 20, 533–534 (2020). - PubMed - PMC
1. Guan, W. J. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020). - PubMed
1. Shi, S. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2020.0950 (2020).
1. Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054–1062 (2020). - PubMed - PMC
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[1] Dong, E., Du, H. & Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. 20, 533–534 (2020). - PubMed - PMC

[2] Dong, E., Du, H. & Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. 20, 533–534 (2020). - PubMed - PMC

[3] Guan, W. J. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020). - PubMed

[4] Guan, W. J. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020). - PubMed

[5] Shi, S. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2020.0950 (2020).

[6] Shi, S. et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2020.0950 (2020).

[7] Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054–1062 (2020). - PubMed - PMC

[8] Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054–1062 (2020). - PubMed - PMC

[9] Wu, C. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. https://doi.org/10.1001/jamainternmed.2020.0994 (2020).

[10] Wu, C. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. https://doi.org/10.1001/jamainternmed.2020.0994 (2020).

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Extrapulmonary manifestations of COVID-19

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Extrapulmonary manifestations of COVID-19

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