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Extrapulmonary manifestations of COVID-19
Open accessAbstract
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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“Furthermore, the virus facilitates the release of coagulation factors, the secretion of inflammatory cytokines, and the formation of leukocyte-platelet aggregates, which might be important mechanisms leading to thromboembolic complications observed in severe COVID-19 (Ackermann et al., 2020; Gupta et al., 2020; Zhang et al., 2020b).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Gupta et al., 2020
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“Disease courses range from mainly asymptomatic and mild courses to more severe and critical courses in 10%–20% of symptomatic patients who are at considerable risk of fatality with many different organ systems involved in differing combinations and with variable symptoms (Gupta et al., 2020)”
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Metadata
- Authors
- Gupta, A., Madhavan, M. V., Sehgal, K., Nair, N., Mahajan, S., Sehrawat, T. S., Bikdeli, B., Ahluwalia, N., Ausiello, J. C., Wan, E. Y., Freedberg, D. E., Kirtane, A. J., Parikh, S. A., Maurer, M. S., Nordvig, A. S., Accili, D., Bathon, J. M., Mohan, S., Bauer, K. A., Leon, M. B., Krumholz, H. M., Uriel, N., Mehra, M. R., Elkind, M. S. V., Stone, G. W., Schwartz, A., Ho, D. D., Bilezikian, J. P., & Landry, D. W.
- Affiliations
- Yale New Haven Hospital (US)
- Columbia University Irving Medical Center (US)
- Beth Israel Deaconess Medical Center (US)
- Mayo Clinic (US)
- Icahn School of Medicine at Mount Sinai (US)
- Cardiovascular Research Foundation (US)
- NewYork–Presbyterian Hospital (US)
- Brigham and Women's Hospital (US)
- Aaron Diamond AIDS Research Center (US)
- Corresponding author
- Landry, Donald W.
- ORCID
- Gupta, Aakriti
- Madhavan, Mahesh V.
- Sehgal, Kartik
- Mahajan, Shiwani
- Sehrawat, Tejasav S.
- Bikdeli, Behnood
- Ahluwalia, Neha
- Ausiello, John C.
- Wan, Elaine Y.
- Freedberg, Daniel E.
- Kirtane, Ajay J.
- Parikh, Sahil A.
- Maurer, Mathew S.
- Nordvig, Anna S.
- Accili, Domenico
- Bathon, Joan M.
- Mohan, Sumit
- Bauer, Kenneth A.
- Leon, Martin B.
- Krumholz, Harlan M.
- Uriel, Nir
- Mehra, Mandeep R.
- Elkind, Mitchell S. V.
- Stone, Gregg W.
- Schwartz, Allan
- Ho, David D.
- Bilezikian, John P.
- Landry, Donald W.
- Venue
- Nature Medicine
- Published
- 2020-07
- Volume
- 26
- Issue
- 7
- Pages
- 1017-1032
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC11972613
- OpenAlex
- W3040801404
- Cited by
- 3,185
- References
- 261
- Citations by year
- 2026: 125 · 2025: 182 · 2024: 333 · 2023: 558 · 2022: 751 · 2021: 965 · 2020: 261
- FWCI
- 29.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (T32 - HL007854, K23- DK111847)
- U.S. Department of Defense (PR-181960)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (5T32 - NS007153)
- U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 - AR050026, U01- AR068043)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01 - MD014161, U01- DK116066)
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (K08-HL122526, R01 - HL152236, R03 - HL146881)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Dermatology › Dermatological and COVID-19 studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2, extrapulmonary manifestations, thrombotic complications, cardiac dysfunction, cardiac arrhythmias, acute coronary syndrome, acute kidney injury, gastrointestinal symptoms, hepatocyte injury, hyperglycemia, ketosis, neurological complications, ocular symptoms, skin complications, ACE2 receptor, thromboinflammation, endothelial injury, immune dysregulation
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Endothelium, Vascular, Humans, Inflammation, Organ Specificity, Pneumonia, Viral, Renin-Angiotensin System, Thrombosis, Coronavirus Infections, Disease Progression, Virus Internalization, Adaptive Immunity, Pandemics
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