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‘Long-COVID’: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19
Open accessAbstract
Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.
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“whereas lower rates of depression (15 percent) also have been reported after hospitalization for COVID-19 (8).”
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Citations
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“Other symptoms such as general fatigue [9, 10], respiratory symptoms [11, 12], cognitive and mental health disorder [13, 14], and so forth [15, 16] have been reported as long-COVID.”
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Ali, A. M., & Kunugi, H. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18052772 · Cited by 60
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Esendagli, D. R., Yılmaz, A., Akçay, Ş., & Özlü, T. (2021) · TURKISH JOURNAL OF MEDICAL SCIENCES · doi:10.3906/sag-2106-238 · Cited by 66
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Hall, J., Myall, K. J., Lam, J. L., Mason, T. W., Mukherjee, B., West, A., & Dewar, A. (2021) · Thorax · doi:10.1136/thoraxjnl-2020-215861 · Cited by 57
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“Previous studies showed elevated CRP in COVID-19 patients following 2–3 months of full recovery [68,69].”
BackgroundA clinical review of long-COVID with a focus on the respiratory system
Daines, L., Zheng, B., Pfeffer, P., Hurst, J. R., & Sheikh, A. (2022) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0000000000000863 · Cited by 54
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Zhao, J., Schank, M., Wang, L., Dang, X., Cao, D., Khanal, S., Nguyen, L. N., Zhang, Y., Wu, X. Y., Adkins, J. L., et al. (2022) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.202200031 · Cited by 50
“KEYWORDS biomarkers, COVID-19, inflammation, long haulers, SARS-CoV-2 Abbreviations: COVID-19, coronavirus disease 2019; COV-LH, COVID-19 long haulers; COV-AS, COVID-19 asymptomatic survivors; HS, healthy subjects; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; PASC, post-acute sequelae of COVID-19; IL-6…”
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“Hospitalized and severely ill patients frequently report respiratory, gastrointestinal, pulmonary and neurological complaints months after recovery from acute infection [1].”
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“…reduction of CRP with a lower 1-year mortality after severe pneumonia and sepsis [15, 16], and there is evidence that persistently elevated CRP and need for ICU admission are independent risk factors for the development of post-COVID conditions, which were not followed-up in this trial [17, 18].”
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“The list comprised 27 symptoms selected in accordance with the current literature on PACS that were available at the time of the study [43,44] (see supplemental Table S1).”
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“Whilst multiple studies across global populations have established the primary symptoms characterising long COVID to include fatigue, shortness of breath, cough, cognitive impairment and anosmia, a plethora of persistent symptoms have been reported by patients (7, 8).”
BackgroundD-dimer testing: A narrative review
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“Furthermore, surviving patients may experience long-term symptoms (post-acute sequelae of COVID-19) that last for days to months after the acute symptoms have subsided, such as cough, shortness of breath (4), hypoxia, depression, sleeping disorders (5), cognitive disturbance, and cardiovascular insults (6), which inte…”
BackgroundCardiopulmonary Exercise Testing in Patients with Post-COVID-19 Syndrome
Barbagelata, L., Masson, W. M., Iglesias, D., Lillo, E., Migone, J. F., Orazi, M. L., & Furcada, J. M. (2021) · Medicina Clínica · doi:10.1016/j.medcli.2021.07.007 · Cited by 54
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“However even after resolution of the infection, some symptoms may persist for a significant period of time[5-7].”
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Espinoza‐Bravo, C., Arnal‐Gómez, A., Martínez‐Arnau, F. M., Núñez‐Cortés, R., Hernández‐Guillén, D., Flor-Rufino, C., & Cortés‐Amador, S. (2023) · Physical Therapy · doi:10.1093/ptj/pzad118 · Cited by 50
18F-FDG-PET Imaging for Post-COVID-19 Brain and Skeletal Muscle Alterations
Rudroff, T., Workman, C. D., & Ponto, L. L. B. (2021) · Viruses · doi:10.3390/v13112283 · Cited by 44
“Studies have also shown that PASC can impact children, young adults, and those who only had mild COVID-19 symptoms and did not require respiratory support or hospitalization [15,28].”
BackgroundRapid detection of SARS-CoV-2: The gradual boom of lateral flow immunoassay
He, J., Zhu, S., Zhou, J., Jiang, W., Yin, L., Su, L., Zhang, X., Chen, Q., & Li, X. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.1090281 · Cited by 44
“Infection with SARS-CoV-2 affects multiple organs, as ACE2 is present in large numbers in human lung and small intestine epithelial cells, making the respiratory (Mandal et al., 2021; Stavem et al., 2021) and digestive (Aiyegbusi et al.”
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Immuno-Thrombotic Complications of COVID-19: Implications for Timing of Surgery and Anticoagulation
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Mental health symptoms one year after acute COVID-19 infection: Prevalence and risk factors
Colizzi, M., Peghin, M., Martino, M. D., Bontempo, G., Gerussi, V., Palese, A., Isola, M., Tascini, C., & Balestrieri, M. (2022) · Revista de Psiquiatría y Salud Mental · doi:10.1016/j.rpsm.2022.05.008 · Cited by 50
Leitlinie S1: Long COVID: Differenzialdiagnostik und Behandlungsstrategien
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Kerzhner, O., Berla, E., Har‐Even, M., Ratmansky, M., & Goor‐Aryeh, I. (2023) · Pain Practice · doi:10.1111/papr.13277 · Cited by 44
Haunhorst, S., Bloch, W., Wagner, H., Ellert, C., Krüger, K., Vilser, D., Finke, K., Reuken, P. A., Pletz, M. W., Stallmach, A., et al. (2022) · Oxford Open Immunology · doi:10.1093/oxfimm/iqac006 · Cited by 46
“Furthermore, the increase of peak thrombin, shorter thrombin lag times, elevated D-dimer levels and the finding of fibrinolysis-resistant microclots suggest a persistent pro-thrombotic state and increased risk of thromboembolic events in long COVID patients [112, 134, 139, 140].”
BackgroundNiu, Y., Lv, Z.-H., Sun, C., Wen, Y.-Y., Tao, T.-Y., Qian, D., Tao, F.-P., & Yu, J.-H. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1112383 · Cited by 43
“(32) stated that CT lung abnormalities were found among 38% of COVID-19 survivors after discharge from the hospital at a median follow-up time of 54 days.”
BackgroundAlenazy, M. F., Aljohar, H. I., Alruwaili, A. R., Daghestani, M. H., Alonazi, M. A., Labban, R. S. M., El‐Ansary, A. K., & Balto, H. A. G. (2022) · Metabolites · doi:10.3390/metabo12100912 · Cited by 39
“Systematic follow-ups in published studies have identified that post-COVID-19 patients after hospitalization suffer from physical and psychological symptom burdens [83].”
BackgroundAnderson, R. M., Vegvari, C., Hollingsworth, T. D., Pi, L., Maddren, R., Ng, C. W., & Baggaley, R. F. (2021) · Interface Focus · doi:10.1098/rsfs.2021.0008 · Cited by 38
Severin, R. S., Franz, C. K., Farr, E. M., Meirelles, C., Arena, R. A., Phillips, S. A., Bond, S., Ferraro, F., & Faghy, M. A. (2022) · European Respiratory Review · doi:10.1183/16000617.0006-2022 · Cited by 37
Lung Function sequelae in COVID-19 Patients 3 Months After Hospital Discharge
Sibila, O., Albacar, N., Perea, L., Faner, R., Torralba, Y., Hernández‐González, F., Moisés, J., Sánchez-Ruano, N., Aymar, E. S., Badia, J. R., et al. (2021) · Archivos de Bronconeumología · doi:10.1016/j.arbres.2021.01.036 · Cited by 37
Napolitano, F., Xu, X., & Gao, X. (2021) · Briefings in Bioinformatics · doi:10.1093/bib/bbab456 · Cited by 37
Post-COVID-19 Syndrome Mechanisms, Prevention and Management
Najafi, M. B., & Javanmard, S. (2023) · International Journal of Preventive Medicine · doi:10.4103/ijpvm.ijpvm_508_21 · Cited by 38
“[164] Increased D‐dimer and CRP levels and decreased lymphocytes were found more common in long COVID patients than their fully recovered counterparts.[166] On the other hand, some studies showed no correlation between pro‐inflammatory biomarkers (e.”
BackgroundFineberg, N. A., Pellegrini, L., Wellsted, D. M., Hall, N., Corazza, O., Giorgetti, V., Cicconcelli, D., Theofanous, E., Sireau, N., Adam, D., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.07.001 · Cited by 36
“Therefore, we might infer that our results are not related to a physiological post-viral inflammatory syndrome sometimes described as “long-COVID” (Mandal et al., 2020), but to the psychological effects of living through the pandemic.”
ResultQingjin Yiqi granules for post‐COVID‐19 condition: A randomized clinical trial
Pang, W., Yang, F., Zhao, Y., Dai, E., Feng, J., Huang, Y., Guo, Y., Zhou, S., Huang, M. X., Zheng, W., et al. (2022) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.12465 · Cited by 35
Pathophysiology, diagnosis, and management of neuroinflammation in covid-19
Brown, R. L., Benjamin, L. A., Lunn, M. P., Bharucha, T., Zandi, M. S., Hoskote, C., McNamara, P., & Manji, H. (2023) · BMJ · doi:10.1136/bmj-2022-073923 · Cited by 37
Mental health outcomes of adults hospitalized for COVID-19: A systematic review
Veazie, S., Lafavor, B., Vela, K., Young, S., Sayer, N. A., Carlson, K. F., & O'Neil, M. E. (2022) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2022.100312 · Cited by 35
Raw, R. K., Kelly, C. A., Rees, J. C., Wroe, C., & Chadwick, D. (2021) · Journal of Infection · doi:10.1016/j.jinf.2021.05.035 · Cited by 35
Post‐COVID‐19 complications: Multisystemic approach
Suvvari, T. K., Kutikuppala, L. V. S., Tsagkaris, C., Corriero, A. C., & Kandi, V. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27222 · Cited by 34
Cheng, D., Calderwood, C., Skyllberg, E., & Ainley, A. (2021) · BMJ Open Respiratory Research · doi:10.1136/bmjresp-2020-000813 · Cited by 37
Good Cholesterol Gone Bad? HDL and COVID-19
Kluck, G. E. G., Yoo, J., Sakarya, E. H., & Trigatti, B. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910182 · Cited by 37
Tan, H. Q. M., Pendolino, A. L., Andrews, P. J., & Choi, D. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-054598 · Cited by 37
Ladlow, P., O’Sullivan, O., Bennett, A. N., Barker-Davies, R. M., Houston, A. D., Chamley, R. R., May, S., Mills, D. S., Dewson, D., Rogers-Smith, K., et al. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00138.2022 · Cited by 35
Michelutti, M., Furlanis, G., Stella, A. B., Bellavita, G., Frezza, N., Torresin, G., Ajčević, M., & Manganotti, P. (2022) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2022.120355 · Cited by 37
Rahman, T., Chowdhury, M. E. H., Khandakar, A. A., Mahbub, Z. B., Hossain, M. S. A., Alhatou, A., Abdalla, E. O. I., Muthiyal, S., Islam, K. F., Kashem, S. B. A., et al. (2023) · Neural Computing and Applications · doi:10.1007/s00521-023-08606-w · Cited by 34
“Despite the benefits of radiological imaging being non-invasive and the application of machine learning speeding up the diagnosis, several studies have favored accurate blood biomarkers since variations in them can also help determine the severity, and progression of an abnormality [40, 41].”
BackgroundKooner, H. K., McIntosh, M. J., Matheson, A. M., Venegas, C., Radadia, N., Ho, T. N., Haider, E. A., Konyer, N. B., Santyr, G. E., Albert, M. S., et al. (2022) · BMJ Open Respiratory Research · doi:10.1136/bmjresp-2022-001235 · Cited by 33
Persistence of Symptoms After Discharge of Patients Hospitalized Due to COVID-19
Wu, L., Wu, Y., Xiong, H., Mei, B., & You, T. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.761314 · Cited by 34
“The term “long COVID” is used to describe people who recovered from acute disease but still report long-term effects from the infection or common clinical symptoms that last much longer than expected (14).”
BackgroundPost-acute sequelae of SARS-CoV-2 infection (Long COVID) in older adults
Russell, S. J., Parker, K., Lehoczki, A., Lieberman, D. B., Partha, I. S., Scott, S. J., Phillips, L. R., Fain, M. J., & Nikolich‐Žugich, J. (2024) · GeroScience · doi:10.1007/s11357-024-01227-8 · Cited by 33
Interplay between Comorbidities and Long COVID: Challenges and Multidisciplinary Approaches
Ashmawy, R., Hammouda, E. A., El‐Maradny, Y. A., Aboelsaad, I., Hussein, M., Uversky, V. N., & Redwan, E. M. M. M. (2024) · Biomolecules · doi:10.3390/biom14070835 · Cited by 35
“Studies have observed decreased lung diffusion capacity, restrictive lung patterns, and small airway abnormalities in long COVID patients, suggesting potential long-term pulmonary damage [83].”
BackgroundLong Haulers—What Is the Evidence for Post-COVID Fatigue?
Stengel, A., Malek, N. P., Zipfel, S., & Goepel, S. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.677934 · Cited by 32
Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome
Milić, J., Barbieri, S., Gozzi, L., Brigo, A., Beghé, B., Verduri, A., Bacca, E., Iadisernia, V., Cuomo, G., Dolci, G., et al. (2022) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofac003 · Cited by 33
Skilbeck, L., Spanton, C., & Paton, M. (2023) · Journal of Patient-Reported Outcomes · doi:10.1186/s41687-023-00570-2 · Cited by 37
Guaraldi, G., Milić, J., Cesari, M., Leibovici, L., Mandreoli, F., Missier, P., Rozzini, R., Cattelan, A. M., Motta, F., Mussini, C., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101686 · Cited by 33
Taylor, R. R., Trivedi, B., Patel, N., Singh, R., Ricketts, W. M., Elliott, K., Yarwood, M. J., White, V., Hylton, H., Allen, R., et al. (2021) · Clinical Medicine · doi:10.7861/clinmed.2021-0037 · Cited by 32
Acanfora, D., Acanfora, C., Ciccone, M. M., Scicchitano, P., Bortone, A. S., Uguccioni, M., & Casucci, G. (2021) · Viruses · doi:10.3390/v13101904 · Cited by 30
“In addition to the persistence of symptoms, it is also possible to detect abnormalities of chest radiographs and biomarkers [46].”
BackgroundClinical picture and long-term symptoms of SARS-CoV-2 infection in an Italian pediatric population
Bloise, S., Isoldi, S., Marcellino, A., Luca, E. D., Dilillo, A., Mallardo, S., Martucci, V., Sanseviero, M., Giudice, E. D., Iorfida, D., et al. (2022) · The Italian Journal of Pediatrics/Italian journal of pediatrics · doi:10.1186/s13052-022-01270-1 · Cited by 31
“Furthermore, we found that children, like the adult population [15, 16, 28], may also experience persistent symptoms but with a lower prevalence.”
BackgroundQuality of life after COVID-19 without hospitalisation: Good overall, but reduced in some dimensions
Garratt, A., Ghanima, W., Einvik, G., & Stavem, K. (2021) · Journal of Infection · doi:10.1016/j.jinf.2021.01.002 · Cited by 31
Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysisPreprint
Badenoch, J., Rengasamy, E. R., Watson, C. J., Jansen, K., Chakraborty, S., Sundaram, R. D., Hafeez, D., Burchill, E., Saini, A., Thomas, L., et al. (2021) · medRxiv · doi:10.1101/2021.04.30.21256413 · Cited by 31
Characteristics and determinants of pulmonary long COVID
Patton, M. J., Benson, D. G., Robison, S. W., Raval, D., Locy, M. L., Patel, K., Grumley, S. A., Levitan, E. B., Morris, P. E., Might, M., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.177518 · Cited by 30
Acute and Chronic Effects of COVID-19 on the Cardiovascular System
Arévalos, V., Ortega‐Paz, L., Rodríguez-Arias, J. J., Calvo-López, M., Golvano, L. C. C., Salazar-Rodríguez, A., Sabaté-Tormos, M., Spione, F., Sabaté, M., & Brugaletta, S. (2021) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd8100128 · Cited by 29
“However, persistent symptoms (fatigue and breathlessness) were found in more than two-thirds of them despite laboratory and radiographic improvement [89].”
Background
Metadata
- Authors
- Mandal, S., Barnett, J., Brill, S. E., Brown, J. S., Denneny, E. K., Hare, S. S., Heightman, M., Hillman, T. E., Jacob, J., Jarvis, H. C., Lipman, M. C. I., Naidu, S. B., Nair, A., Porter, J. C., Tomlinson, G. S., & Hurst, J. R.
- Affiliations
- Royal Free London NHS Foundation Trust (GB)
- University College London Hospitals NHS Foundation Trust (GB)
- University College Hospital (GB)
- Corresponding author
- Hurst, John R
- ORCID
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2020-11-10
- Volume
- 76
- Issue
- 4
- Pages
- 396-398
- ISSN
- 0040-6376 (ISSN-L)
- 1468-3296
- PMC
- PMC7615158
- OpenAlex
- W3101401355
- Cited by
- 864
- References
- 7
- Citations by year
- 2026: 18 · 2025: 50 · 2024: 111 · 2023: 181 · 2022: 263 · 2021: 235 · 2020: 6
- FWCI
- 74.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thorax (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (Z/17/Z, 209553, 209553/Z/17/Z)
- National Institute for Health and Care Research
- University College London Hospitals NHS Foundation Trust
- Medical Research Council (MR/N007727/1)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Social Sciences › Psychology › Clinical Psychology › COVID-19 and Mental Health
- Keywords
- long COVID, persistent symptoms, dyspnea, cough, fatigue, depression, D-dimer, C-reactive protein, biomarkers, chest X-ray abnormalities, post-discharge follow-up, rehabilitation
- MeSH terms
- COVID-19, SARS-CoV-2, Cross-Sectional Studies, Diagnostic Imaging, Female, Hospitalization, Humans, Lung, Male, Middle Aged, Severity of Illness Index, Biomarkers, Pandemics
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