Cited by 3,185COVID-19 Clinical Research StudiesLong-Term Effects of COVID-19Dermatological and COVID-19 studies

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Extrapulmonary manifestations of COVID-19

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Gupta, Aakriti, Madhavan, Mahesh V., Sehgal, Kartik, Nair, Nandini, 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.·2020·Nature Medicine

DOI 10.1038/s41591-020-0968-3PMC PMC11972613

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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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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
Publisher: Springer Science and Business Media LLC
Published: 2020-07
Volume: 26
Issue: 7
Pages: 1017-1032
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/s41591-020-0968-3
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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