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High-dimensional characterization of post-acute sequelae of COVID-19
Open accessPublished version of a preprint
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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“This is typically referred to as a post-covid syndrome, characterized by several symptoms affecting quality of life (1–5).”
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MethodWong, R., Hall, M. A., Wiggen, T. D., Johnson, S., Huling, J. D., Turner, L. E., Wilkins, K. J., Yeh, H., Stürmer, T., Bramante, C. T., et al. (2024) · Diabetes Care · doi:10.2337/dc24-1003 · Cited by 6
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“…of PASC in US veterans showed that incident adverse cardiac outcomes, including arrhythmias, increased markedly at 6 months after infection, compared with uninfected individuals, with the excess burden highest among those previously hospitalized or in the ICU during their infection (13).”
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Can essential fatty acids (EFAs) prevent and ameliorate post-COVID-19 long haul manifestations?
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Structural basis of rosmarinic acid inhibitory mechanism on SARS-CoV-2 main protease
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Human umbilical cord‐derived mesenchymal stem cell transplantation improves the long COVID
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Endothelial cells as paracrine mediators of long COVID
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Long Covid, a great imitator of the 21th century
Goldman, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.1026425 · Cited by 6
“Pain medications including opioids, antidepressant drugs and anxiolytic drugs are frequently used (10), often without adequate surveillance.”
BackgroundLong-term outcomes in COVID-19 patients who recovered from the first wave of the pandemic
Cui, D., Chen, S., Feng, S., Jia, M., Wang, Y., Xiao, W., Sun, Y., Huang, Q., Ma, L., Leng, Z., et al. (2022) · National Science Review · doi:10.1093/nsr/nwac192 · Cited by 6
“However, PCC is incompletely understood.”
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Abdominal imaging associates body composition with COVID-19 severity
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“A complex array of sequelae associated with COVID-19 have been reported [2], the risks of which increase in tandem with disease severity [3].”
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„Coronasomnia“ – Resilienzförderung durch Insomniebehandlung
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COVID‐19‐specific metabolic imprint yields insights into multiorgan system perturbations
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A Multimodal Approach in the Treatment of Persistent Post-COVID
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“Linked to this is the therapy goal of avoiding increased intake of sedatives, opioids, and antidepressants, which is often described in post-COVID patients [28].”
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“Long-term persistent symptoms have been reported [5-7].”
Symptoms of Long-COVID 1-Year after a COVID-19 outbreak among sailors on a French aircraft carrier
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The ambulatory care of patients with post-acute sequelae of COVID-19
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“The preselected patients are referred from primary care to further special treatment, most of them to pulmonology [2].”
BackgroundManta, A., Michelakis, I., Dafni, M., Spanoudaki, A., Krontira, S., Tsoutsouras, T., Flessa, K., Papadopoulos, C., Mantzos, D. S., & Tzavara, V. (2023) · Journal of Investigative Medicine · doi:10.1177/10815589231212899 · Cited by 6
“2 The reported frequencies of persistent long-term symptoms vary significantly in different studies and appear to be even higher than the ones observed in our cohort.”
ResultDu, Y., Zhao, W., Lei, D., & Liu, J. (2021) · Psychoradiology · doi:10.1093/psyrad/kkab019 · Cited by 6
“However, several large cohort studies followed up for 6 months found that the neuropsychiatric sequelae of COVID-19 survivors were mainly sleep difficulties, anxiety, and depression (Al-Aly et al. , 2021; Huang et al. , 2021a; Taquet et al. , 2021a).”
BackgroundBrown, P. A., McGuinty, M., Argyropoulos, C., Clark, E. G., Colantonio, D., Giguère, P., & Hiremath, S. S. (2022) · medRxiv · doi:10.1101/2022.05.18.22275234 · Cited by 6
Metadata
- Authors
- Al-Aly, Z., Xie, Y., & Bowe, B.
- Affiliations
- VA St. Louis Health Care System (US)
- Venue
- Nature
- Published
- 2021-04-22
- Volume
- 594
- Issue
- 7862
- Pages
- 259-264
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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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