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.

PubMed Disclaimer

Cited by

Dynamic changes in coagulation parameters and correlation with disease severity and mortality in patients with COVID-19.
Xu W, Fei L, Huang CL, Li WX, Xie XD, Li Q, Chen L. Xu W, et al. Aging (Albany NY). 2021 May 24;13(10):13393-13404. doi: 10.18632/aging.203052. Epub 2021 May 24. Aging (Albany NY). 2021. PMID: 34031269 Free PMC article.
COVID-19 in trauma: a propensity-matched analysis of COVID and non-COVID trauma patients.
Yeates EO, Grigorian A, Schellenberg M, Owattanapanich N, Barmparas G, Margulies D, Juillard C, Garber K, Cryer H, Tillou A, Burruss S, Figueras RA, Mladenov G, Brenner M, Firek C, Costantini T, Santorelli J, Curry T, Wintz D, Biffl WL, Schaffer KB, Duncan TK, Barbaro C, Diaz G, Johnson A, Chinn J, Naaseh A, Leung A, Grabar C, Nahmias J. Yeates EO, et al. Eur J Trauma Emerg Surg. 2021 Oct;47(5):1335-1342. doi: 10.1007/s00068-021-01699-9. Epub 2021 May 25. Eur J Trauma Emerg Surg. 2021. PMID: 34031703 Free PMC article.
Immunological Interfaces: The COVID-19 Pandemic and Depression.
Perlmutter A. Perlmutter A. Front Neurol. 2021 Apr 23;12:657004. doi: 10.3389/fneur.2021.657004. eCollection 2021. Front Neurol. 2021. PMID: 33967944 Free PMC article. Review.
GB-2 inhibits ACE2 and TMPRSS2 expression: In vivo and in vitro studies.
Wu CY, Lin YS, Yang YH, Shu LH, Cheng YC, Liu HT. Wu CY, et al. Biomed Pharmacother. 2020 Dec;132:110816. doi: 10.1016/j.biopha.2020.110816. Epub 2020 Oct 10. Biomed Pharmacother. 2020. PMID: 33049583 Free PMC article.
De novo pancytopaenia in an older adult with severe COVID-19 infection.
Lee H, Thein OS, Muneer T. Lee H, et al. BMJ Case Rep. 2022 Nov 15;15(11):e252609. doi: 10.1136/bcr-2022-252609. BMJ Case Rep. 2022. PMID: 36379633 Free PMC article.

See all "Cited by" articles

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
1. 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).

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

K08 HL122526/HL/NHLBI NIH HHS/United States

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Other Literature Sources
- H1 Connect
- The Lens - Patent Citations Database
Miscellaneous
- NCI CPTAC Assay Portal

[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).

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Extrapulmonary manifestations of COVID-19

Affiliations

Extrapulmonary manifestations of COVID-19

Authors

Affiliations

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Miscellaneous