The DOI matches its Crossref record; 44 of the 46 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“This is typically referred to as a post-covid syndrome, characterized by several symptoms affecting quality of life (1–5).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., et al. (2020) · JAMA · doi:10.1001/jama.2020.1585 · Cited by 20,148
La certeza de lo impredecible: Cultura Educación y Sociedad en tiempos de COVID19
Martínez González, M. (2020) · DSPACE System - Metalibrary (University of the Coast) · Cited by 18,463
Vincent, J. L., Moreno, R., Takala, J., Willatts, S., De Mendonça, A., Bruining, H., Reinhart, C. K., Suter, P. M., & Thijs, L. G. (1996) · Intensive Care Medicine · doi:10.1007/bf01709751 · Cited by 11,674
Vincent, J.-L., de Mendonca, A., Cantraine, F., Moreno, R., Takala, J., Suter, P. M., Sprung, C. L., Colardyn, F., & Blecher, S. (1998) · Critical Care Medicine · doi:10.1097/00003246-199811000-00016 · Cited by 3,463
Making Neighborhood-Disadvantage Metrics Accessible — The Neighborhood Atlas
Kind, A. J. H., & Buckingham, W. R. (2018) · New England Journal of Medicine · doi:10.1056/nejmp1802313 · Cited by 3,310
Management of post-acute covid-19 in primary care
Greenhalgh, T., Knight, M., A’Court, C., Buxton, M., & Husain, L. (2020) · BMJ · doi:10.1136/bmj.m3026 · Cited by 1,771
Negative Controls: A Tool for Detecting Confounding and Bias in Observational Studies
Lipsitch, M., Tchetgen Tchetgen, E., & Cohen, T. (2010) · Epidemiology · doi:10.1097/ede.0b013e3181d61eeb · Cited by 1,583
A tutorial on propensity score estimation for multiple treatments using generalized boosted models
McCaffrey, D. F., Griffin, B. A., Almirall, D., Slaughter, M. E., Ramchand, R., & Burgette, L. F. (2013) · Statistics in Medicine · doi:10.1002/sim.5753 · Cited by 1,450
Balancing Covariates via Propensity Score Weighting
Li, F., Morgan, K. L., & Zaslavsky, A. M. (2016) · Journal of the American Statistical Association · doi:10.1080/01621459.2016.1260466 · Cited by 1,095
Thomas (2020) · doi:10.1001/jama.2020.7819 · Cited by 835
Cited by
Sorted by citations
Characterizing long COVID in an international cohort: 7 months of symptoms and their impact
Davis, H. E., Assaf, G. S., McCorkell, L., Wei, H., Low, R. J., Re'em, Y., Redfield, S., Austin, J. P., & Akrami, A. (2021) · eClinicalMedicine · doi:10.1016/j.eclinm.2021.101019 · Cited by 2,881
Long-term cardiovascular outcomes of COVID-19
Xie, Y., Xu, E., Bowe, B. C., & Al‐Aly, Z. (2022) · Nature Medicine · doi:10.1038/s41591-022-01689-3 · Cited by 2,125
Chen, C., Haupert, S. R., Zimmermann, L., Shi, X., Fritsche, L. G., & Mukherjee, B. (2022) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiac136 · Cited by 1,448
1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.
Huang, L., Yao, Q., Gu, X., Wang, Q., Ren, L., Wang, Y., Hu, P., Guo, L., Liu, M., Xu, J., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)01755-4 · Cited by 1,101
Symptoms and risk factors for long COVID in non-hospitalized adults
Subramanian, A., Nirantharakumar, K., Hughes, S., Myles, P. R., Williams, T., Gokhale, K. M., Taverner, T., Chandan, J. S., Brown, K. R., Simms-Williams, N., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01909-w · Cited by 1,108
Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection
Groff, D., Sun, A., Ssentongo, A. E., Ba, D. M., Parsons, N., Poudel, G. R., Lekoubou, A., Oh, J. S., Ericson, J. E., Ssentongo, P., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.28568 · Cited by 1,010
SARS-CoV-2 infection and persistence in the human body and brain at autopsy
Stein, S. R., Ramelli, S. C., Grazioli, A., Chung, J., Singh, M., Yinda, C. K., Winkler, C. W., Sun, J., Dickey, J. M., Ylaya, K., et al. (2022) · Nature · doi:10.1038/s41586-022-05542-y · Cited by 1,001
Collaborators, G. B. O. D. L. C., Hanson, S. W., Abbafati, C., Aerts, J. G. J. V., Al‐Aly, Z., Ashbaugh, C., Ballouz, T., Blyuss, O. B., Bobkova, P., Bonsel, G. J., et al. (2022) · JAMA · doi:10.1001/jama.2022.18931 · Cited by 1,015
Taquet, M., Dercon, Q., Luciano, S., Geddes, J. R., Husain, M., & Harrison, P. J. (2021) · PLoS Medicine · doi:10.1371/journal.pmed.1003773 · Cited by 948
“Another report, based on EHRs from American veterans (88% male) has also identified increased rates of sequelae in multiple body systems after COVID-19 compared to influenza [14].”
BackgroundLong COVID after breakthrough SARS-CoV-2 infection
Al-Aly, Z., Bowe, B., & Xie, Y. (2022) · Nature Medicine · doi:10.1038/s41591-022-01840-0 · Cited by 866
Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
Thaweethai, T., Jolley, S. E., Karlson, E. W., Levitan, E. B., Levy, B. D., McComsey, G. A., McCorkell, L., Nadkarni, G. N., Parthasarathy, S., Singh, U., et al. (2023) · JAMA · doi:10.1001/jama.2023.8823 · Cited by 841
Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study
Ballering, A., van Zon, S. K. R., Hartman, T. O., & Rosmalen, J. G. M. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01214-4 · Cited by 833
Distinguishing features of long COVID identified through immune profiling
Klein, J., Wood, J., Jaycox, J. R., Dhodapkar, R. M., Lu, P., Gehlhausen, J. R., Tabachnikova, A., Greene, K., TABACOF, L. R., Malik, A. A., et al. (2023) · Nature · doi:10.1038/s41586-023-06651-y · Cited by 852
Taquet, M., Sillett, R., Zhu, L., Mendel, J., Camplisson, I., Dercon, Q., & Harrison, P. J. (2022) · The Lancet Psychiatry · doi:10.1016/s2215-0366(22)00260-7 · Cited by 737
Pathological sequelae of long-haul COVID
Mehandru, S., & Mérad, M. (2022) · Nature Immunology · doi:10.1038/s41590-021-01104-y · Cited by 675
Long COVID: post-acute sequelae of COVID-19 with a cardiovascular focus
Raman, B., Bluemke, D. A., Lüscher, T. F., & Neubauer, S. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac031 · Cited by 717
“In a study of 73 435 (median age 61 years, 88% men) non-hospitalized patients using the US Department of Veterans Affairs health services, Al-Aly et al.7 demonstrated a high risk of death and incident CV and metabolic diseases associated with COVID-19 beyond 30 days of infection.”
Acute and postacute sequelae associated with SARS-CoV-2 reinfection
Bowe, B. C., Xie, Y., & Al‐Aly, Z. (2022) · Nature Medicine · doi:10.1038/s41591-022-02051-3 · Cited by 656
Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records
Thompson, E. J., Williams, D. M., Walker, A. J., Mitchell, R. E., Niedzwiedz, C. L., Yang, T., Huggins, C. F., Kwong, A. S. F., Silverwood, R. J., Gessa, G. D., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30836-0 · Cited by 605
Swank, Z., Senussi, Y., Manickas-Hill, Z., Yu, X. G., Li, J. Z., Alter, G., & Walt, D. R. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac722 · Cited by 580
Long COVID science, research and policy
Al-Aly, Z., Davis, H., McCorkell, L., Soares, L., Wulf-Hanson, S., Iwasaki, A., & Topol, E. J. (2024) · Nature Medicine · doi:10.1038/s41591-024-03173-6 · Cited by 538
Alkodaymi, M. S., Omrani, O. A., Fawzy, N. A., Shaar, B. A., Almamlouk, R., Riaz, M. A., Obeidat, M. A., Obeidat, Y., Gerberi, D., Taha, R. M., et al. (2022) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2022.01.014 · Cited by 561
“An increasing risk gradient of new sequalae was observed with increasing COVID-19 severity [86,87].”
Long-term neurologic outcomes of COVID-19
Xu, E., Xie, Y., & Al-Aly, Z. (2022) · Nature Medicine · doi:10.1038/s41591-022-02001-z · Cited by 530
Self-citationRisks and burdens of incident diabetes in long COVID: a cohort study
Xie, Y., & Al-Aly, Z. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00044-4 · Cited by 564
Natarajan, A., Zlitni, S., Brooks, E. F., Vance, S. E., Dahlen, A., Hedlin, H., Park, R. M., Han, A., Schmidtke, D. T., Verma, R., et al. (2022) · Med · doi:10.1016/j.medj.2022.04.001 · Cited by 420
Psychiatric and neuropsychiatric sequelae of COVID-19 – A systematic review
Schou, T. M., Joca, S. R. L., Wegener, G., & Bay-Richter, C. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.07.018 · Cited by 424
Gluckman, T. J., Bhave, N. M., Allen, L. A., Chung, E. H., Spatz, E. S., Ammirati, E., Baggish, A. L., Bozkurt, B., Cornwell, W. K., Harmon, K. G., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.02.003 · Cited by 431
Prevalence and Correlates of Long COVID Symptoms Among US Adults
Perlis, R. H., Santillana, M., Ognyanova, K., Safarpour, A., Trujillo, K. L., Simonson, M. D., Green, J., Quintana, A., Druckman, J. N., Baum, M., et al. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.38804 · Cited by 391
Changes in cognitive functioning after COVID-19: a systematic review and meta-analysis
Crivelli, L., Palmer, K., Calandri, I., Guekht, A., Beghi, E., Carroll, W., Frontera, J., García‐Azorín, D., Westenberg, E., Winkler, A. S., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12644 · Cited by 374
Comorbidities, multimorbidity and COVID-19
Russell, C. D., Lone, N., & Baillie, J. K. (2023) · Nature Medicine · doi:10.1038/s41591-022-02156-9 · Cited by 373
Serotonin reduction in post-acute sequelae of viral infection
Wong, A. C., Devason, A. S., Umana, I. C., Cox, T. O., Dohnalová, L., Litichevskiy, L., Perla, J., Lundgren, P., Etwebi, Z., Izzo, L., et al. (2023) · Cell · doi:10.1016/j.cell.2023.09.013 · Cited by 379
“The accompanying symptoms are diverse and often include fatigue, postexertional malaise, memory loss, and other neurocognitive impairments.(2) A major post-viral syndrome is ‘‘Long COVID,’’ manifesting as post-acute sequelae of COVID-19 (PASC), which are experienced by a subset of individuals after SARS-CoV-2 infectio…”
Bowe, B. C., Xie, Y., Xu, E., & Al-Aly, Z. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2021060734 · Cited by 352
“Covariates Covariates included a set of 29 predefined potential confounders of the association between COVID-19 and adverse kidney outcomes.(1,2,15) Demographic, behavioral, and contextual characteristics included age, Area Deprivation Index, race, sex, and smoking status.”
BackgroundMethodInfluentialMechanisms of long COVID and the path toward therapeutics
Peluso, M. J., & Deeks, S. G. (2024) · Cell · doi:10.1016/j.cell.2024.07.054 · Cited by 399
“1,2,18,291,292 Studies have begun to suggest several sex-based biological differences inimmuneresponses (higher anti-EBVresponses,higher frequencies of cytolytic, tissue homing T cell subsets), 135,293 which can be broadly summarized as a general exaggeration of both innate and adaptive immune…”
BackgroundPostacute sequelae of COVID-19 at 2 years
Bowe, B. C., Xie, Y., & Al‐Aly, Z. (2023) · Nature Medicine · doi:10.1038/s41591-023-02521-2 · Cited by 354
Menges, D., Ballouz, T., Anagnostopoulos, A., Aschmann, H. E., Domenghino, A., Fehr, J. S., & Puhan, M. A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254523 · Cited by 359
“Results of two recent studies comparing outcomes in individuals with COVID-19 to individuals with influenza are suggestive of a higher burden of a wide range of longer-term sequalae associated with COVID-19 [8, 41].”
ResultWang, W., Wang, C.-Y., Wang, S., & Wei, J. C. (2022) · EClinicalMedicine · doi:10.1016/j.eclinm.2022.101619 · Cited by 343
COVID-19, Hyperglycemia, and New-Onset Diabetes
Khunti, K., Prato, S. D., Mathieu, C., Kahn, S. E., Gabbay, R. A., & Buse, J. B. (2021) · Diabetes Care · doi:10.2337/dc21-1318 · Cited by 342
“Department of Veterans Affairs reported a higher burden of new-onset diabetes 6 months following COVID-19 (61).”
BackgroundRisks of mental health outcomes in people with covid-19: cohort study
Xie, Y., Xu, E., & Al-Aly, Z. (2022) · BMJ · doi:10.1136/bmj-2021-068993 · Cited by 384
Komaroff, A. L., & Lipkin, W. I. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1187163 · Cited by 366
“New onset of major diseases including diabetes mellitus, cardiovascular diseases (including myocardial infarction), stroke and pulmonary failure (incidence increased by 150–400%), and a greatly increased risk of death (160%) in the first year following acute COVID-19, compared to matched populations that did not devel…”
BackgroundPeluso, M. J., Lu, S., Tang, A. F., Durstenfeld, M. S., Ho, H.-E., Goldberg, S. A., Forman, C. A., Munter, S. E., Hoh, R., Tai, V., et al. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiab490 · Cited by 332
Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases
Zollner, A., Koch, R., Jukic, A., Pfister, A., Meyer, M., Rössler, A., Kimpel, J., Adolph, T. E., & Tilg, H. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.04.037 · Cited by 320
“Postacute COVID-19 typically involves symptoms including severe fatigue, cognitive dysfunction, or pain.(11) Poor baseline health status and severe acute COVID-19 convey risk for the development of postacute COVID-19, however, also mild COVID-19 (eg, in nonhospitalized patients) may culminate in postacute sequelae.”
Association of Treatment With Nirmatrelvir and the Risk of Post–COVID-19 Condition
Xie, Y., Choi, T., & Al‐Aly, Z. (2023) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2023.0743 · Cited by 352
Xie, Y., Bowe, B. C., & Al‐Aly, Z. (2021) · Nature Communications · doi:10.1038/s41467-021-26513-3 · Cited by 301
“Table 1 Characteristics of (1) users of Veterans Health Administration (VHA), (2) non-hospitalized people with COVID-19, (3) hospitalized COVID-19 but not admitted to intensive care, and (4) hospitalized COVID-19 admitted to intensive care.”
BackgroundInfluentialEpigenetic memory of coronavirus infection in innate immune cells and their progenitors
Cheong, J.-G., Ravishankar, A., Sharma, S., Parkhurst, C. N., Grassmann, S. A., Wingert, C. K., Laurent, P., Ma, S., Paddock, L., Miranda, I. C., et al. (2023) · Cell · doi:10.1016/j.cell.2023.07.019 · Cited by 309
Mapping the effectiveness and risks of GLP-1 receptor agonists
Xie, Y., Choi, T., & Al-Aly, Z. (2025) · Nature Medicine · doi:10.1038/s41591-024-03412-w · Cited by 300
Self-citationBarrett, C. E., Koyama, A. K., Alvarez, P., Chow, W., Lundeen, E. A., Perrine, C. G., Pavkov, M. E., Rolka, D. B., Wiltz, J. L., Bull–Otterson, L., et al. (2022) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm7102e2 · Cited by 293
Koc, H. C., Xiao, J., Liu, W., Li, Y., & Chen, G. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.75056 · Cited by 310
“Such health conditions post a significant burden on the quality of life among COVID survivors (Figure 1) [27-29].”
BackgroundLong-term perturbation of the peripheral immune system months after SARS-CoV-2 infection
Ryan, F. J., Hope, C. M., Masavuli, M. G., Lynn, M. A., Mekonnen, Z. A., Yeow, A. E. L., García-Valtanen, P., Al-Delfi, Z., Gummow, J., Ferguson, C. C., et al. (2022) · BMC Medicine · doi:10.1186/s12916-021-02228-6 · Cited by 288
Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome
Paul, B. D., Lemle, M. D., Komaroff, A. L., & Snyder, S. H. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2024358118 · Cited by 276
Postacute Sequelae of SARS-CoV-2 Infection in the Pre-Delta, Delta, and Omicron Eras
Xie, Y., Choi, T., & Al‐Aly, Z. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403211 · Cited by 290
Matta, J., Wiernik, E., Robineau, O., Carrat, F., Touvier, M., Severi, G., de Lamballerie, X., Blanché, H., Deleuze, J.-F., Gouraud, C., et al. (2022) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.6454 · Cited by 266
Komaroff, A. L., & Lipkin, W. I. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.06.002 · Cited by 276
“The samewas true when hospitalized COVID-19 patients were compared with hospitalized influenza patients [41].”
Three-year outcomes of post-acute sequelae of COVID-19
Cai, M., Xie, Y., Topol, E. J., & Al‐Aly, Z. (2024) · Nature Medicine · doi:10.1038/s41591-024-02987-8 · Cited by 276
COVID-19 and metabolic disease: mechanisms and clinical management
Steenblock, C., Schwarz, P. E. H., Ludwig, B., Linkermann, A., Zimmet, P., Kulebyakin, K. Y., Va, T., Markov, A. G., Lehnert, H., de Angelis, M. H., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00244-8 · Cited by 256
Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review
Sylvester, S. V., Rusu, R., Chan, B., Bellows, M., O’Keefe, C., & Nicholson, S. (2022) · Current Medical Research and Opinion · doi:10.1080/03007995.2022.2081454 · Cited by 290
Taquet, M., Dercon, Q., & Harrison, P. J. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.04.013 · Cited by 246
“We investigated the 6-month incidence of all acute and post-acute outcomes which have been shown to be significantly associated with COVID-19 in four large-scale studies based on electronic health records (Al-Aly et al., 2021; Daugherty et al., 2021; Taquet et al., 2021b, 2021a), namely:”
Verlohren, S., Brennecke, S. P., Galindo, A., Karumanchi, S. A., Mirković, L., Schlembach, D., Stepan, H., Vatish, M., Zeisler, H., & Rana, S. (2021) · Pregnancy Hypertension · doi:10.1016/j.preghy.2021.12.003 · Cited by 253
Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19
Ramakrishnan, R. K., Kashour, T., Hamid, Q. A., Halwani, R., & Tleyjeh, I. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.686029 · Cited by 246
“Multiple clinical studies have identified the prevalence of lingering damage in COVID-19 survivors post hospitalization across the United States (US) (8, 9), Asia (10) and Europe (3, 11– 13).”
BackgroundLong COVID and Post-infective Fatigue Syndrome: A Review
Sandler, C. X., Wyller, V. B., Moss-Morris, R. E., Buchwald, D., Crawley, E. M., Hautvast, J. L. A., Katz, B. Z., Knoop, H., Little, P. S., Taylor, R. R., et al. (2021) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofab440 · Cited by 243
“Multiple studies have identified significant long-term complications of severe acute COVID-19 infection and the associated hospitalization, including pulmonary, cardiac, neurological, and psychiatric conditions—many of which may manifest with the complaint of persistent fatigue [32, 33].”
Cohen, K., Ren, S., Heath, K., Dasmariñas, M. C., Jubilo, K. G., Guo, Y., Lipsitch, M., & Daugherty, S. E. (2022) · BMJ · doi:10.1136/bmj-2021-068414 · Cited by 223
Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID‐19
Munblit, D., Bobkova, P., Spiridonova, E., Shikhaleva, A., Gamirova, A., Blyuss, O. B., Nekliudov, N. A., Bugaeva, P., Andreeva, M., DunnGalvin, A., et al. (2021) · Clinical & Experimental Allergy · doi:10.1111/cea.13997 · Cited by 244
DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia
Lam, L., Murphy, S., Kokkinaki, D., Venosa, A., Sherrill-Mix, S. A., Casu, C., Rivella, S., Weiner, A. I., Park, J., Shin, S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abj1008 · Cited by 221
“12 of 14 of RBC-DNA binding and clearance on sustained anemia and immune recovery (49, 50).”
BackgroundData-driven identification of post-acute SARS-CoV-2 infection subphenotypes
Zhang, H., Zang, C., Xu, Z., Zhang, Y., Xu, J., Bian, J., Morozyuk, D., Khullar, D., Zhang, Y., Nordvig, A. S., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02116-3 · Cited by 187
“Several studies have found that PASC could include a diverse set of symptoms and signs involving many organ systems 10–12 .”
BackgroundMethodInfluentialWang, B., Zhang, L., Wang, Y., Dai, T., Qin, Z., Zhou, F., & Zhang, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00986-0 · Cited by 187
Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT
Bell, M. L., Catalfamo, C. J., Farland, L. V., Ernst, K. C., Jacobs, E. T., Klimentidis, Y. C., Jehn, M., & Pogreba-Brown, K. (2021) · PLoS ONE · doi:10.1371/journal.pone.0254347 · Cited by 181
“A large study using Veteran Administration electronic health records reported increased risk of death, morbidity, heath resource utilization, and medication use among individuals who survived at least 30 days following COVID-19 diagnosis [12].”
BackgroundAddressing the post-acute sequelae of SARS-CoV-2 infection: a multidisciplinary model of care
Parker, A. M., Brigham, E. P., Connolly, B. A., McPeake, J. M., Agranovich, A. V., Kenes, M. T., Casey, K. S., Reynolds, C., Schmidt, K. F. R., Kim, S. Y., et al. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(21)00385-4 · Cited by 178
Generalisable long COVID subtypes: findings from the NIH N3C and RECOVER programmes
Reese, J., Blau, H., Casiraghi, E., Bergquist, T., Loomba, J. J., Callahan, T. J., Laraway, B. J., Antonescu, C., Coleman, B., Gargano, M. A., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104413 · Cited by 190
“54 We suggest that analogous algorithms could be used to evaluate data gathered from prospective studies of long COVID patients to extend and deepen our characterization of phenotypic clusters by including data that are currently dif fi cult to ascertain reliably from EHR data, including symptoms…”
Reduction in life expectancy in Brazil after COVID-19
Castro, M. C., Gurzenda, S., Turra, C. M., Kim, S., Andrasfay, T., & Goldman, N. (2021) · Nature Medicine · doi:10.1038/s41591-021-01437-z · Cited by 164
Kikkenborg Berg, S., Dam Nielsen, S., Nygaard, U., Bundgaard, H., Palm, P., Rotvig, C., & Vinggaard Christensen, A. (2022) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(22)00004-9 · Cited by 168
Proposed subtypes of post‐COVID‐19 syndrome (or long‐COVID) and their respective potential therapies
Yong, S. J., & Liu, S. (2021) · Reviews in Medical Virology · doi:10.1002/rmv.2315 · Cited by 173
“), among 73,435 COVID‐19 survivors (non‐hospitalised) compared to matched controls and influenza patients at 4‐month.(57) Another controlled cohort study involving 236,379 COVID‐19 patients also found that the risks of neurological and psychiatric diseases were higher than matched controls with other respiratory tract…”
ResultMagnúsdóttir, I., Lovik, A., Unnarsdóttir, A. B., McCartney, D. L., Ask, H., Kõiv, K., Christoffersen, L. A. N., Johnson, S. U., Hauksdóttir, A., Fawns‐Ritchie, C., et al. (2022) · The Lancet Public Health · doi:10.1016/s2468-2667(22)00042-1 · Cited by 164
Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease
Balcom, E. F., Nath, A., & Power, C. (2021) · Brain · doi:10.1093/brain/awab302 · Cited by 163
“Many survivors of the acute infection experience persistent and incapacitating neurological symptoms, which can have socioeconomic and personal consequences.(1) It is thus imperative that there is a thorough understanding of the evolving clinical syndromes and the underlying pathophysiological mechanisms, enabling rat…”
BackgroundS1-Leitlinie Post-COVID/Long-COVID
Koczulla, A. R., Ankermann, T., Behrends, U., Berlit, P., Böing, S., Brinkmann, F., Franke, C., Glöckl, R., Gogoll, C., Hummel, T. R., et al. (2021) · Pneumologie · doi:10.1055/a-1551-9734 · Cited by 164
Zhou, Y., Xu, J., Hou, Y., Leverenz, J. B., Kallianpur, A. R., Mehra, R., Liu, Y., Yu, H., Pieper, A. A., Jehi, L. E., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00850-3 · Cited by 165
“Another study using 73,000 non-hospitalized COVID-19 survivors shows various incident sequalae, such as mental health disorders and neurocognitive disorders [15].”
BackgroundCOVID-19 therapeutics: Challenges and directions for the future
Robinson, P. C., Liew, D. F. L., Tanner, H. L., Grainger, J. R., Dwek, R. A., Reisler, R. B., Steinman, L., Feldmann, M., Ho, L., Hussell, T., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119893119 · Cited by 158
“Encouragingly, studies are shedding light on the pathogenesis of the most common complaints in long-COVID, namely pulmonary and neurologic symptoms (14, 16).”
BackgroundKompaniyets, L., Bull–Otterson, L., Boehmer, T. K., Baca, S., Alvarez, P., Hong, K., Hsu, J., Harris, A. M., Gundlapalli, A. V., & Saydah, S. (2022) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm7131a3 · Cited by 161
Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis
Zhang, T., Mei, Q., Zhang, Z., Walline, J. H., Liu, Y., Zhu, H., & Zhang, S. (2022) · BMC Medicine · doi:10.1186/s12916-022-02656-y · Cited by 173
Xie, Y., Choi, T., & Al‐Aly, Z. (2023) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(23)00684-9 · Cited by 154
Nalbandian, A., Desai, A. D., & Wan, E. Y. (2022) · Annual Review of Medicine · doi:10.1146/annurev-med-043021-030635 · Cited by 163
A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings
Sneller, M. C., Liang, C., Marques, A. R., Chung, J. Y., Shanbhag, S. M., Fontana, J. R., Raza, H., Okeke, O., Dewar, R. L., Higgins, B. P., et al. (2022) · Annals of Internal Medicine · doi:10.7326/m21-4905 · Cited by 160
“001 Chest pain/discomfort 0 (0) 16 (8) 1 (2.”
Pathogenesis of Respiratory Viral and Fungal Coinfections
Salazar, F., Bignell, E., Brown, G. D., Cook, P. C., & Warris, A. (2021) · Clinical Microbiology Reviews · doi:10.1128/cmr.00094-21 · Cited by 164
Rao, S., Lee, G. M., Razzaghi, H., Lorman, V., Mejías, A., Pajor, N. M., Thacker, D., Webb, R. D., Dickinson, K., Bailey, L. C., et al. (2022) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2022.2800 · Cited by 152
Long-term cardiac pathology in individuals with mild initial COVID-19 illness
Püntmann, V. O., Martin, S. S., Shchendrygina, A., Hoffmann, J., Ka, M. M., Giokoglu, E., Vanchin, B., Holm, N., Karyou, A., Laux, G. S., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02000-0 · Cited by 161
Evolving phenotypes of non-hospitalized patients that indicate long COVID
Estiri, H., Strasser, Z. H., Brat, G. A., Semenov, Y. R., Aaron, J. R., Agapito, G., Albayrak, A., ALESSIANI, M., Amendola, D. F., Anthony, L. L. L. J., et al. (2021) · BMC Medicine · doi:10.1186/s12916-021-02115-0 · Cited by 155
“Al-Aly specifically documents increased memory problems and strokes [40].”
BackgroundKhullar, D., Zhang, Y., Zang, C., Xu, Z., Wang, F., Weiner, M. G., Carton, T. W., Rothman, R. L., Block, J. P., & Kaushal, R. (2023) · Journal of General Internal Medicine · doi:10.1007/s11606-022-07997-1 · Cited by 149
Systematic Review of the Prevalence of Long COVID
Woodrow, M., Carey, C., Ziauddeen, N., Thomas, R., Akrami, A., Lutje, V., Greenwood, D. C., & Alwan, N. A. (2023) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofad233 · Cited by 162
“Studies such as Al-Aly et al [16] that investigated medical diagnoses in the period after COVID-19, report cardiovascular, neurological, and other system-specific clinical sequelae, providing a substantial excess burden in those who survived the acute phase of COVID-19 [13].”
Solving the puzzle of Long Covid
Al‐Aly, Z., & Topol, E. J. (2024) · Science · doi:10.1126/science.adl0867 · Cited by 142
Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study
Tesch, F., Ehm, F., Vivirito, A., Wende, D., Batram, M., Loser, F., Menzer, S., Jacob, J., Roessler, M., Seifert, M., et al. (2023) · Clinical Rheumatology · doi:10.1007/s10067-023-06670-0 · Cited by 142
Long COVID: aiming for a consensus
Munblit, D., O’Hara, M. E., Akrami, A., Perego, E., Olliaro, P., & Needham, D. M. (2022) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(22)00135-7 · Cited by 138
Long-term gastrointestinal outcomes of COVID-19
Xu, E., Xie, Y., & Al‐Aly, Z. (2023) · Nature Communications · doi:10.1038/s41467-023-36223-7 · Cited by 141
“(1) we modified our covariate selection by increasing covariate inclusion to 300 high dimensional variables (instead of the 100 high dimensional variables used in the main analysis)when constructing the inverse probabilityweight; (2) we restricted covariate selection only to pre-defined variables when constructing the…”
MethodBajema, K. L., Berry, K., Streja, E., Rajeevan, N., Li, Y., Mutalik, P., Yan, L., Cunningham, F. E., Hynes, D. M., Rowneki, M., et al. (2023) · Annals of Internal Medicine · doi:10.7326/m22-3565 · Cited by 134
“We also assessed the incidence of 34 potential post-COVID conditions described in the literature (17-20) (Supplemental Table 8) from day 31-180 following the index date.”
MethodLi, J., Zhou, Y., Ma, J., Zhang, Q., Shao, J., Liang, S., Yu, Y., Li, W., & Wang, C. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01640-z · Cited by 150
Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK
Rezel‐Potts, E., Douiri, A., Sun, X., Chowienczyk, P., Shah, A. M., & Gulliford, M. C. (2022) · PLoS Medicine · doi:10.1371/journal.pmed.1004052 · Cited by 136
“New-onset hyperglycaemia has been reported in COVID-19 patients, sometimes representing “stress hyperglycaemia,” and is associated with worse prognosis [5,11].”
BackgroundMethodWarren, C. M., Snow, T. T., Lee, A., Shah, M. M., Heider, A., Blomkalns, A. L., Betts, B. A., Buzzanco, A. S., González, J. C., Chinthrajah, R. S., et al. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.25524 · Cited by 135
“millions ill—some for manymonths, with a subset whomay continue to experience long-term adverse health effects.(31,32)Moreover, allergic reactions are highly treatable, and even severe anaphylaxis usually can be promptly mitigated with appropriate preparation andmedication, as all patients in the present case series e…”
BackgroundPeluso, M. J., Kelly, J. D., Lu, S., Goldberg, S. A., Davidson, M. C., Mathur, S., Durstenfeld, M. S., Spinelli, M. A., Hoh, R., Tai, V., et al. (2021) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofab640 · Cited by 128
Angiotensin-converting enzyme 2—at the heart of the COVID-19 pandemic
Oudit, G. Y., Wang, K., Viveiros, A., Kellner, M. J., & Penninger, J. M. (2023) · Cell · doi:10.1016/j.cell.2023.01.039 · Cited by 136
Gut Microbiome Alterations in COVID-19
Zuo, T., Wu, X., Wen, W., & Lan, P. (2021) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2021.09.004 · Cited by 134
Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?
Bisaccia, G., Ricci, F., Recce, V., Serio, A., Iannetti, G., Chahal, A. A., Ståhlberg, M., Khanji, M. Y., Fedorowski, A., & Gallina, S. (2021) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd8110156 · Cited by 129
“disorders, and a spectrum of symptoms related to poor general wellbeing, even after the resolution of the acute illness [2].”
BackgroundPost-Acute COVID-19 Syndrome and the cardiovascular system: What is known?
Dixit, N. M., Churchill, A., Nsair, A., & Hsu, J. J. (2021) · American Heart Journal Plus Cardiology Research and Practice · doi:10.1016/j.ahjo.2021.100025 · Cited by 129
“7 times higher incidence of arrhythmia at 6-months post-COVID-19 in non-hospitalized patients compared to matched controls; however, whether this was due to truly higher arrhythmia burden or higher rate of detection in the COVID-19 cohort is unknown [47].”
Risks and burdens of incident dyslipidaemia in long COVID: a cohort study
Xu, E., Xie, Y., & Al‐Aly, Z. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00355-2 · Cited by 130
Hou, Y., Gu, T., Ni, Z., Shi, X., Ranney, M. L., & Mukherjee, B. (2025) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofaf533 · Cited by 165
“Different studies considered different comorbidities, listed in Supplementary Results 3.”
Influential
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
