Cited by 1,518Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 Research

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High-dimensional characterization of post-acute sequelae of COVID-19

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Al-Aly, Ziyad, Xie, Yan, Bowe, Benjamin·2021·Nature

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Abstract

The acute clinical manifestations of COVID-19 have been well characterized 1,2, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30 days after diagnosis. We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were not hospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.

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“A range of sequelae remain after cure, including respiratory neurological disorders, neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, and more.(35) Moreover, there are no specific drugs available to control the virus, and the vaccine’s effect…”
Background
Molecular Mechanisms Responsible for Diabetogenic Effects of COVID-19 Infection—Induction of Autoimmune Dysregulation and Metabolic Disturbances
Grubišić, B., Švitek, L., Ormanac, K., Sabo, D., Mihaljević, I., Bilić-Čurčić, I., & Kolarić, T. O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411576 · Cited by 18
COVID Vaccination as a Strategy for Cardiovascular Disease Prevention
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Pulmonale Manifestationen bei Long-COVID
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“survived the disease were approximately 39% more likely to have a diabetes diagnosis in the 6 months after infection [15].”
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“102 following the infection, an excess risk of chronic respiratory failure, cardiac rhythm disorders, acute coronary syndromes, hypercoagulability, encephalopathy, dementia, memory difficulties, stroke, kidney injury, diabetes, and anemia have been reported (potentially increasing the burden on individuals and on the…”
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Síndrome pós-COVID-19 entre hospitalizados por COVID-19: estudo de coorte após 6 e 12 meses da alta hospitalar
Rocha, R. P. S., Andrade, A. C. D. S., Melanda, F. N., & Muraro, A. P. (2024) · Cadernos de Saúde Pública · doi:10.1590/0102-311xpt027423 · Cited by 12
Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner: Cohort Study
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“Postacute sequelae of COVID-19 (PASC), also known as long COVID, is a loosely categorized consequence of acute infection that is related to dysfunction across multiple biological systems [2].”
Influential
Circulating miRNAs in the Plasma of Post-COVID-19 Patients with Typical Recovery and Those with Long-COVID Symptoms: Regulation of Immune Response-Associated Pathways
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Infection-associated chronic conditions: Why Long Covid is our best chance to untangle Osler’s web
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Morbidity of SARS-CoV-2 in the evolution to endemicity and in comparison with influenza
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“However, there is full awareness of the multiorgan consequences of SARS-CoV-2 infection 1,26,27 .”
Living With Long COVID: Everyday Experiences, Health Information Barriers and Patients' Quality of Life
Ortega‐Martin, E., & Álvarez‐Gálvez, J. (2025) · Health Expectations · doi:10.1111/hex.70290 · Cited by 13
“Although many individuals fully recover, some manifest long ‐ lasting symptoms, even after mild cases [6 – 8].”
Clinical features of patients who visited the outpatient clinic for long COVID in Japan
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“The severity of acute COVID-19 was also reported to be related to long COVID in a large study in the United States [4], but some previous reports have not found this link [15,16].”
STIMULATE-ICP-CAREINEQUAL (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways) study protocol: Defining usual care and examining inequalities in Long Covid support
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Authors: Al-Aly, Z., Xie, Y., & Bowe, B.
Affiliations: VA St. Louis Health Care System (US)
ORCID: Al-Aly, Ziyad
Xie, Yan
Bowe, Benjamin
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2021-04-22
Volume: 594
Issue: 7862
Pages: 259-264
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-021-03553-9
OpenAlex: W3153493739
Cited by: 1,518
References: 46
Citations by year: 2026: 95 · 2025: 170 · 2024: 268 · 2023: 365 · 2022: 391 · 2021: 228
FWCI: 149.17
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
Research Square (acceptedVersion, cc-by)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: U.S. Department of Veterans Affairs
American Society of Nephrology
McDonnell Center for Systems Neuroscience
Topics: Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords: post-COVID-19 sequelae, long COVID, COVID-19 mortality, health resource utilization, pulmonary sequelae, neurocognitive disorders, mental illness, metabolic disorders, cardiovascular disease, gastrointestinal diseases, fatigue, musculoskeletal pain, anemia, medication use, laboratory abnormalities, disease severity, intensive care unit admission, veterans
MeSH terms: COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Post-Acute COVID-19 Syndrome, Female, Hospitalization, Humans, Influenza, Human, Male, Outpatients, Risk, Time Factors, United States, United States Department of Veterans Affairs, Cohort Studies, Databases, Factual, Electronic Health Records, Datasets as Topic

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High-dimensional characterization of post-acute sequelae of COVID-19

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