Cited by 1,655Long-Term Effects of COVID-19COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 Research

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Long covid—mechanisms, risk factors, and management

Crook, Harry, Raza, Sanara, Nowell, Joseph, Young, Megan, Edison, Paul·2021·BMJ

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Abstract

Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.

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“27 We found the most significant point of difference between PASC and COVID-19 positive children was at the R00–R99 cluster of diagnostic codes ( Symptoms, signs, and abnormal clinical and laboratory findings, not otherwise classified ).”
Background
Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management
Yan, Z., Yang, M., & Lai, C. (2023) · Viruses · doi:10.3390/v15020533 · Cited by 28
Income differences in COVID-19 incidence and severity in Finland among people with foreign and native background: A population-based cohort study of individuals nested within households
Saarinen, S., Moustgaard, H., Remes, H., Sallinen, R. H., & Martikainen, P. (2022) · PLoS Medicine · doi:10.1371/journal.pmed.1004038 · Cited by 22
“Moreover, the clustering of severe illness could have long-lasting effects in the households as the severe illness increases the risk for long COVID symptoms [38].”
Background
Experiences, Emotions, and Health Consequences among COVID-19 Survivors after Intensive Care Unit Hospitalization
Piras, I., Piazza, M. F., Piccolo, C., Azara, A., Piana, A. F., Finco, G., & Galletta, M. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19106263 · Cited by 18
“) for not returning to “usual health” [46].”
Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication
Thiele, I., & Fleming, R. M. T. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.07.019 · Cited by 22
“, cognitive impairment [12] and long covid [13], which is characterised by a range of symptoms, such as fatigue, cognitive impairment, and shortness of breath [64].”
Risk factors and severity of functional impairment in long COVID: a single-center experience in Croatia
Banić, M., Makek, M. J., Samaržija, M., Muršić, D., Boras, Z., Trkeš, V., Baričević, D., Koršić, M., Basara, L., Glunčić, T. J., et al. (2022) · Croatian Medical Journal · doi:10.3325/cmj.2022.27 · Cited by 27
Autoantibodies in COVID-19: implications for disease severity and clinical outcomes
Galipeau, Y., Cooper, C., & Langlois, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1509289 · Cited by 20
Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study
Weigel, B., Eaton-Fitch, N., Thapaliya, K., & Marshall‐Gradisnik, S. (2024) · Quality of Life Research · doi:10.1007/s11136-024-03710-3 · Cited by 21
“…combined with the high prevalence of post-exertional malaise, also have implications for clinical practice, reinforcing the importance of pacing strategies and engagement of allied health professionals, such as occupational therapists, in the management of ME/CFS, as well as PCC [3, 8, 13, 31, 32].”
Background
Long COVID in a highly vaccinated but largely unexposed Australian population following the 2022 SARS‐CoV ‐2 Omicron wave: a cross‐sectional survey
Woldegiorgis, M. A., Cadby, G., Ngeh, S., Korda, R., Armstrong, P., Maticevic, J., Knight, P. R., Jardine, A., Bloomfield, L., & Effler, P. V. (2024) · The Medical Journal of Australia · doi:10.5694/mja2.52256 · Cited by 28
Risk factors for long COVID in children and adolescents: a systematic review and meta-analysis
Rayner, D. G., Wang, E., Su, C.-W., Patel, O. D., Aleluya, S., Giglia, A., Zhu, E., & Siddique, M. (2023) · World Journal of Pediatrics · doi:10.1007/s12519-023-00765-z · Cited by 22
High proportions of post-exertional malaise and orthostatic intolerance in people living with post-COVID-19 condition: the PRIME post-COVID study
Pagen, D., van Herck, M., van Bilsen, C. J. V., Brinkhues, S., Konings, K., den Heijer, C. D., Spruit, M., Hoebe, C., & Dukers-Muijrers, N. (2023) · medRxiv · doi:10.3389/fmed.2023.1292446 · Cited by 21
“Experienced symptoms are very heterogenous, including fatigue, dyspnea and cognitive disfunctions, among others (2, 3).”
Background
Mental health and cognitive function among medical students after the COVID-19 pandemic in China
Cheng, J., Liao, M., He, Z., Xiong, R., Ju, Y., Jin, L., Liu, B., Wu, B., & Zhang, Y. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1233975 · Cited by 21
“org experiencing seven symptoms during the previous 2 weeks as: (0) not at all, (1) on several days, (2) on more than half of the days, and (3) nearly every day.”
BackgroundInfluential
Long COVID and possible preventive options
Sebők, S., & Gyires, K. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01204-1 · Cited by 24
“Most of the trials on Long COVID-19 analyzed the effect of either dietary supplements, e.g., mitoquinone (synthetic analogue of coenzyme Q10 with antioxidant property), vitamin K 2 , Vitamin D 3 , and N-acetyl-cysteine, or drugs, with different mechanism of action, for example, lithium, which has multiple mechanisms i…”
BackgroundInfluential
Facile In-Tube-Center Packaging of Flexible Airflow Rate Microsensor for Simultaneous Respiration and Heartbeat Measurement
Farisi, M. A. A., Wang, Y., Hasegawa, Y., Matsushima, M., Kawabe, T., & Shikida, M. (2023) · IEEE Sensors Journal · doi:10.1109/jsen.2023.3272310 · Cited by 21
Multidimensional Sleep Health Prior to SARS-CoV-2 Infection and Risk of Post–COVID-19 Condition
Wang, S., Huang, T., Weisskopf, M. G., Kang, J. H., Chavarro, J. E., & Roberts, A. L. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.15885 · Cited by 23
Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients
Leonhardt, S., Jürgensen, C., Frohme, J., Grajecki, D., Adler, A., Sigal, M. J., Leonhardt, J., Voll, J. M., Kruse, J. M., Körner, R., et al. (2023) · Hepatology International · doi:10.1007/s12072-023-10521-0 · Cited by 23
The effects of obesity and metabolic abnormalities on severe COVID-19-related outcomes after vaccination: A population-based study
Fan, X., Han, J., Zhao, E., Fang, J., Wang, D., Cheng, Y., Shi, Y., Wang, Z., Yao, Z., Lü, P., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.02.016 · Cited by 23
“It is now well established that the risk of breakthrough SARSCoV-2 infections among the previously vaccinated, aswell as the risk of severe COVID-19, is increased in patients with advanced age and chronic medical conditions.(13,14,16) However, an older age is an unchangeable risk factor, and patients with severe chron…”
Background
Poor sleep quality, insomnia, and short sleep duration before infection predict long-term symptoms after COVID-19
Salfi, F., Amicucci, G., Corigliano, D., Viselli, L., D’Atri, A., Tempesta, D., & Ferrara, M. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.06.010 · Cited by 26
“manifestations after acute illness (Crook et al., 2021; Mazza et al., 2021, 2020; Phetsouphanh et al., 2022).”
Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection
Barnes, H. W., Demirdjian, S., Haddock, N. L., Kaber, G., Martinez, H. A., Nagy, N., Karmouty‐Quintana, H., & Bollyky, P. L. (2023) · Matrix Biology · doi:10.1016/j.matbio.2023.02.001 · Cited by 26
After the virus has cleared—Can preclinical models be employed for Long COVID research?
Jansen, E. B., Orvold, S. N., Swan, C. L., Yourkowski, A., Thivierge, B. M., Francis, M. E., Ge, A., Rioux, M. L., Darbellay, J., Howland, J. G., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010741 · Cited by 29
“PASC is a multiorgan disease that can cause complications in the lungs, heart, brain, spleen, liver, blood vessels, gastrointestinal tract, kidney, and pancreas as well as other organs [33].”
BackgroundInfluential
What are the long‐term holistic health consequences of COVID‐19 among survivors? An umbrella systematic review
Paterson, C. C., Davis, D. L., Roche, M. A., Bissett, B., Roberts, C., Turner, M. R., Baldock, E., & Mitchell, I. (2022) · Journal of Medical Virology · doi:10.1002/jmv.28086 · Cited by 24
“treatments, requirement for supplemental oxygen, ventilation, and so forth, (3) lack of healthy age‐matched controls, (4) absent control for change over time, (5) racial differences, (6) gender, (7) pregnancy, (8) frequency, severity, and burden of symptoms at the time of disease onset, (9) influence of biological fac…”
BackgroundMethod
Cognitive Difficulties, Psychological Symptoms, and Long Lasting Somatic Complaints in Adolescents with Previous SARS-CoV-2 Infection: A Telehealth Cross-Sectional Pilot Study
Tarantino, S., Graziano, S., Carducci, C., Giampaolo, R., & Capitello, T. G. (2022) · Brain Sciences · doi:10.3390/brainsci12080969 · Cited by 20
Factors associated with development and persistence of post-COVID conditions: A cross-sectional study
Miyazato, Y., Tsuzuki, S., Morioka, S., Terada, M., Kutsuna, S., Saito, S., Shimanishi, Y., Takahashi, K., Sanada, M., Akashi, M., et al. (2021) · Journal of Infection and Chemotherapy · doi:10.1016/j.jiac.2022.04.025 · Cited by 32
Long-COVID severe refractory cough: discussion of a case with 6-week longitudinal cough characterization
Kang, Y.-R., Oh, J.-Y., Lee, J.-H., Small, P., Chung, K., & Song, W.-J. (2022) · Asia Pacific Allergy · doi:10.5415/apallergy.2022.12.e19 · Cited by 21
“Long COVID (post-COVID syndrome) refers to an array of variable and fluctuating symptoms experienced after acute illness, with signs and symptoms that persist for 8–12 weeks and are not otherwise explicable [2].”
Background
Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence
Holford, P., Carr, A. C., Zawari, M., & Vizcaychipi, M. P. (2021) · Life · doi:10.3390/life11111166 · Cited by 23
“This is relevant to the long-term complications of COVID-19, or what is being referred to as ‘long COVID’ [61,62].”
Background
Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID
Yamamoto, Y., Otsuka, Y., Tokumasu, K., Sunada, N., Nakano, Y., Honda, H., Sakurada, Y., Hasegawa, T., Hagiya, H., & Otsuka, F. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12144737 · Cited by 26
“When long COVID is recognized, it has been hypothesized that the pathophysiology of this notorious condition is similar to that of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), post-traumatic stress disorder, or post-viral fatigue syndrome [11,12].”
Result
The prolonged impact of COVID-19 on symptoms, health-related quality of life, fatigue and mental well-being: a cross-sectional study
Brus, I. M., Spronk, I., Haagsma, J. A., de Groot, A., Tieleman, P., Biere‐Rafi, S., & Polinder, S. (2023) · Frontiers in Epidemiology · doi:10.3389/fepid.2023.1144707 · Cited by 17
“Therefore, the broadly applied approach to improve these symptoms is rehabilitation, with no treatments having proven to be effective for patients with this disabling condition (6, 7).”
Background
Sex and age affect acute and persisting COVID-19 illness
Vasilevskaya, A., Mushtaque, A., Tsang, M. Y., Alwazan, B., Herridge, M. S., Cheung, A. M., & Tartaglia, M. C. (2023) · Scientific Reports · doi:10.1038/s41598-023-33150-x · Cited by 20
Matching Assistive Technology, Telerehabilitation, and Virtual Reality to Promote Cognitive Rehabilitation and Communication Skills in Neurological Populations: A Perspective Proposal
Stasolla, F., Lopez, A., Akbar, K., Vinci, L. A., & Cusano, M. (2023) · Technologies · doi:10.3390/technologies11020043 · Cited by 20
COVID-19 and Cardiovascular Diseases: From Cellular Mechanisms to Clinical Manifestations
Shu, H., Zheng, W., Li, N., Zhang, Z., Ceesay, B. M., Peng, Y., Zhou, N., & Wang, D. W. (2023) · Aging and Disease · doi:10.14336/ad.2023.0314 · Cited by 25
“The long-term elevation of cardiac troponin in patients with LC is significantly related to the increase in mortality [144].”
Background
Characteristics of Long COVID: Cases from the First to the Fifth Wave in Greater Tokyo, Japan
Hirahata, K., Nawa, N., & Fujiwara, T. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11216457 · Cited by 21
High Prevalence of Long-COVID Among Kidney Transplant Recipients: A Longitudinal Cohort Study
Amorim, C. E. N., Lafico, V., Cristelli, M. P., Viana, L. A., Corrêa, H. D. L., Lima, G. B. B., Silva, F. S. D. S., Lima, G. S. D. C. E., Rosa, T. D. S., Nakamura, M. R., et al. (2022) · Transplantation · doi:10.1097/tp.0000000000004359 · Cited by 23
Assessment of respiratory function and exercise tolerance at 4–6 months after COVID‐19 infection in patients with pneumonia of different severity
Pini, L., Montori, R., Giordani, J., Guerini, M., Orzes, N., Ciarfaglia, M., Arici, M., Cappelli, C., Piva, S., Latronico, N., et al. (2022) · Internal medicine journal (Print) · doi:10.1111/imj.15935 · Cited by 20
Respinos: A Portable Device for Remote Vital Signs Monitoring of COVID-19 Patients
Adiono, T., Ahmadi, N., Saraswati, C., Aditya, Y., Yudhanto, Y. P., Aziz, A., Wulandari, L., Maranatha, D., Khusnurrokhman, G., Riadi, A. R. W., et al. (2022) · IEEE Transactions on Biomedical Circuits and Systems · doi:10.1109/tbcas.2022.3204632 · Cited by 26
“COVID-19 can affect multiple systems in the body including (not limited to) the respiratory and cardiovascular systems [9].”
Background
Understanding and addressing long-COVID among migrants and ethnic minorities in Europe
Norredam, M., Hayward, S., Deal, A., Agyemang, C., & Hargreaves, S. (2022) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2022.100427 · Cited by 20
Versorgungsbedarfe zu Long-COVID aus Sicht von Betroffenen und Hausärzt*innen – eine Mixed-Methods-Studie aus Baden-Württemberg
Stengel, S., Hoffmann, M., Koetsenruijter, J., Peters-Klimm, F., Wensing, M., Merle, U., & Szécsényi, J. (2022) · Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen · doi:10.1016/j.zefq.2022.02.005 · Cited by 31
“Zur Genese werden verschiedene Hypothesen diskutiert, u.a. Inflammation, mikrovaskuläre Schädigungen, Hyperkoagulabilität, Fibrosierungen, (Auto-)Immunprozesse, Störungen der Blut-Hirn-Schranke sowie negative, mit der COVID-19-Pandemie assoziierte psychologische Faktoren [3,6].”
Influential
Einheitliche Basisversorgung von Kindern und Jugendlichen mit Long COVID
Töpfner, N., (DGPI), D. G. F. P. I. E. V., Alberer, M., Ankermann, T., (GPP), G. F. P. P. E. V., Bender, S., Deutsche Gesellschaft für Kinder- und Jugendpsychiatrie, P. U. P. E. V. (., Berner, R., de Laffolie, J., (GPGE), G. F. P. G. U. E. E. V., et al. (2022) · Monatsschrift Kinderheilkunde · doi:10.1007/s00112-021-01408-1 · Cited by 24
Lung Ultrasound as a First-Line Test in the Evaluation of Post-COVID-19 Pulmonary Sequelae
Clofent, D., Polverino, E., Felipe, A., Granados, G., Arjona-Peris, M., Andreu, J., Sánchez-Martínez, A., Varona, D., Cabanzo, L., Escudero, J. M., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.815732 · Cited by 20
“In addition, long COVID is another clinical entity that adds complexity to these uncertainties, as affected patients can manifest persistent respiratory symptoms without evidence of radiological or functional abnormalities on usual explorations (45, 46).”
Background
Counter-regulatory renin-angiotensin system in hypertension: review and update in the era of COVID-19 pandemic
Chen, H., Peng, J., Wang, T., Wen, J., Chen, S., Huang, Y., & Zhang, Y. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115370 · Cited by 19
Oligosaccharides as Potential Regulators of Gut Microbiota and Intestinal Health in Post-COVID-19 Management
Cheong, K., Chen, S., Teng, B., Veeraperumal, S., Zhong, S., & Tan, K. (2023) · Pharmaceuticals · doi:10.3390/ph16060860 · Cited by 32
“These symptoms can persist for weeks or even months, and they are collectively known as post-COVID-19 syndromes [6].”
Background
Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database
Shah, A., Subramanian, A., Lewis, J., Dhalla, S., Ford, E., Haroon, S., Kuan, V., & Nirantharakumar, K. (2023) · medRxiv · doi:10.1101/2023.01.06.23284202 · Cited by 19
Trend and Co-occurrence Network of COVID-19 Symptoms From Large-Scale Social Media Data: Infoveillance Study
Wu, J., Wang, L., Hua, Y., Li, M., Zhou, L., Bates, D. W., & Yang, J. (2023) · Journal of Medical Internet Research · doi:10.2196/45419 · Cited by 20
“Concurrently, clinicians have endeavored to analyze clinical symptoms to guide therapeutic strategies [7].”
Corticosteroids induced avascular necrosis of hip, a “long COVID-19” complication: Case report
Annam, P., Manda, A., Myneni, U. K., Sahar, A. N., Prasad, N., Sam, K. K., Sahu, S., & Reddy, K. K. (2022) · Annals of Medicine and Surgery · doi:10.1016/j.amsu.2022.104753 · Cited by 19
“Long COVID also damages multiple organs including, but not limited to, the respiratory, musculo-skeletal, neurological, cardiovascular, and gastrointestinal systems [3].”
Global slowness and increased intra-individual variability are key features of attentional deficits and cognitive fluctuations in post COVID-19 patients
Ortelli, P., Benso, F., Ferrazzoli, D., Scarano, I., Saltuari, L. L., Sebastianelli, L., Versace, V., & Maestri, R. (2022) · Scientific Reports · doi:10.1038/s41598-022-17463-x · Cited by 24
Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome
Piazza, M., Cicco, M. D., Pecoraro, L., Ghezzi, M., Peroni, D. G., & Comberiati, P. (2022) · Biomolecules · doi:10.3390/biom12040556 · Cited by 28
“Long COVID-19 may be due to long-term damage to different organs—such as lung, brain, kidney, and heart—caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis [15].”
Background
Post-COVID syndrome. The never ending challenge
Boix, V., & Merino, E. (2022) · Medicina clínica (Ed. impresa) · doi:10.1016/j.medcle.2021.10.005 · Cited by 19
Person-Centered Healthcare Practice in a Pandemic Context: An Exploration of People's Experience of Seeking Healthcare Support
Curnow, E., Tyagi, V., Salisbury, L., Stuart, K., Melville-Jóhannesson, B., Nicol, K., McCormack, B. G., Dewing, J., Magowan, R., Sagan, O., et al. (2021) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2021.726210 · Cited by 29
“Findings from this study support previous research which identified negative mental health impacts from the pandemic (41).”
Result
Defining and measuring long COVID fatigue: a scoping review
Thomas, B., Pattinson, R., Edwards, D. J., Dale, C., Jenkins, B., Lande, H., Bundy, C., & Davies, J. L. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-088530 · Cited by 20
Precision phenotyping for curating research cohorts of patients with unexplained post-acute sequelae of COVID-19
Azhir, A., Hügel, J., Tian, J., Cheng, J., Bassett, I. V., Bell, D. S., Bernstam, E. V., Farhat, M. R., Henderson, D. W., Lau, E. S., et al. (2024) · Med · doi:10.1016/j.medj.2024.10.009 · Cited by 18
Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024
Untersmayr, E., Venter, C., Smith, P. K., Rohrhofer, J., Ndwandwe, C., Schwarze, J., Shannon, E., Sokolowska, M., Sadlier, C., & O'Mahony, L. (2024) · International Archives of Allergy and Immunology · doi:10.1159/000535736 · Cited by 18
“In addition, system-speci ﬁ c manifestations such as cardiopulmonary, neurocognitive, or gastrointestinal symptoms, as well as neuropsychiatric symptoms including anxiety and depression can occur [3].”
Background
Increased risk of chronic fatigue syndrome following infection: a 17-year population-based cohort study
Chang, H., Kuo, C.-F., Yu, T.-S., Ke, L.-Y., Hung, C.-L., & Tsai, S.-Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04636-z · Cited by 18
“Studies involving multiple cohorts and cross-sectional studies have reported similarities between the symptoms of long COVID and CFS, such as cognitive impairment and fatigue over a follow-up duration ranging from 12 weeks to 6 months [43, 44].”
Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review
Chen, T., Chang, C., Yang, C., Tsai, I., Wei, C., Yang, H.-W., & Yang, C. (2023) · Nutrients · doi:10.3390/nu15173802 · Cited by 17
Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19
Zhang, J., Zhang, Y., Xia, Y., & Sun, J. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.03.034 · Cited by 19
Imaging and neuropathological findings in patients with Post COVID-19 Neurological Syndrome—A review
Okrzeja, J., Garkowski, A., Kubas, B., & Moniuszko-Malinowska, A. M. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1136348 · Cited by 23
“The hospitalization and intensive care unit (ICU) stay, as well as the duration of critical disease, are likely to impact the occurrence of neuropsychiatric disorders after infection too (18).”
Background
Systematic Review and Meta-Analysis of Clinically Relevant Executive Functions Tests Performance after COVID-19
Velichkovsky, B. B., Razvaliaeva, A. Y., Khlebnikova, A. A., Manukyan, P. A., Kasatkin, V. N., & Barmin, A. V. (2023) · Behavioural Neurology · doi:10.1155/2023/1094267 · Cited by 24
“These symptoms have a negative impact on the quality of life, mental health, and employment, can last for months after recovery and emerge even in non-hospitalized or asymptomatic patients [1, 3].”
Background
SARS-CoV-2 elicits non-sterilizing immunity and evades vaccine-induced immunity: implications for future vaccination strategies
Beukenhorst, A. L., Koch, C. M., Hadjichrysanthou, C., Alter, G., de Wolf, F., Anderson, R. M., & Goudsmit, J. (2023) · European Journal of Epidemiology · doi:10.1007/s10654-023-00965-x · Cited by 18
“Further data on progressing to long COVID is needed, especially in the younger age groups that otherwise have lower risks of severe disease [55, 56].”
Background
Differential patterns of cross-reactive antibody response against SARS-CoV-2 spike protein detected for chronically ill and healthy COVID-19 naïve individuals
Jaago, M., Rähni, A., Pupina, N., Pihlak, A., Sadam, H., Tuvikene, J., Avarlaid, A., Planken, A., Planken, M., Haring, L., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-20849-6 · Cited by 23
Enhanced Zif-8-Enabled Colorimetric Co2 Sensing Through Dye-Precursor Synthesis
Davey, A. K., Li, Z., Lefton, N., Leonhardt, B. E., Dods, M. N., Dai, C., Kahn, S., Zettl, A., Carraro, C., & Roya, M. (2022) · Social Science Research Network · doi:10.2139/ssrn.4167518 · Cited by 18
Twelve Months and Counting: Following Clinical Outcomes in Critical COVID-19 Survivors
Taniguchi, L., Aliberti, M. J., Dias, M. B., Jacob-Filho, W., & Avelino-Silva, T. (2022) · Annals of the American Thoracic Society · doi:10.1513/annalsats.202207-630oc · Cited by 18
Musculoskeletal symptoms in patients with long COVID: A cross-sectional study on Iranian patients
Azadvari, M., Haghparast, A., Nakhostin-Ansari, A., Razavi, S. Z. E., & Hosseini, M. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e10148 · Cited by 18
“Incidence of long COVID is higher in patients with comorbidities such as cardiovascular and respiratory diseases or severe COVID-19 infection [4, 9].”
Background
Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study
Leong, K.-H., Yip, H., Kuo, C.-F., & Tsai, S. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03461-0 · Cited by 24
“The treatments of CFS were believed to have a potential effect of relieving fatigue in long COVID cases [22, 25].”
What Do We Need to Know About Musculoskeletal Manifestations of COVID-19?
Pires, R. E. S., Reis, I. G. N., Waldolato, G., Pires, D. D., Bidolegui, F., & Giordano, V. (2022) · JBJS Reviews · doi:10.2106/jbjs.rvw.22.00013 · Cited by 40
Impact of the post‐COVID‐19 condition on health care after the first disease wave in Lombardy
Mannucci, P., Nobili, A., Tettamanti, M., D'Avanzo, B., Galbussera, A., Remuzzi, G., Fortino, I., Leoni, O., & Harari, S. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13493 · Cited by 18
Pros and Cons of CAD/CAM Technology for Infection Prevention in Dental Settings during COVID-19 Outbreak
Barenghi, L., Barenghi, A., Garagiola, U. M., Blasio, A. D., Giannì, A. B., & Spadari, F. (2021) · Sensors · doi:10.3390/s22010049 · Cited by 17
Síndrome post-COVID. El desafío continúa
Boix, V., & Merino, E. (2021) · Medicina clínica (Ed. impresa) · doi:10.1016/j.medcli.2021.10.002 · Cited by 18
Post‐infection pulmonary sequelae after COVID‐19 among patients with lung transplantation
Mahan, L., Lill, I., Halverson, Q., Mohanka, M., Lawrence, A., Joerns, J., Bollineni, S., Kaza, V., Hoz, R. L. L., Zhang, S., et al. (2021) · Transplant Infectious Disease · doi:10.1111/tid.13739 · Cited by 18
Epidemiology of adult chronic cough: disease burden, regional issues, and recent findings
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“However, further studies on why this phenomenon occurs are warranted [40, 42].”
Background
Determinants of COVID-19 Related Length of Hospital Stays and Long Covid in Ghana: A Cross-Sectional Analysis
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Gao, D., Xiang, Q., Lu, G., Tong, J., Jiang, W., Yu, X., Wang, R., Lv, Z., & Li, D. (2022) · BMC Psychology · doi:10.1186/s40359-022-00934-1 · Cited by 17
“COVID-19 poses enormous risks, as it not only aggravates the condition of patients with underlying diseases and accelerates death in the elderly [8–10], but also has many long-term symptoms that cannot be ignored, such as fatigue, muscle, and joint pain, lung abnormalities, abnormal liver, and kidney function, loss of…”
Background
Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review
Lee, E., Ozigbo, A. A., Varón, J., Halma, M. T. J., Laezzo, M., Ang, S. P., & Iglesias, J. I. (2025) · Biomolecules · doi:10.3390/biom15091339 · Cited by 27
“The recent COVID-19 pandemic demonstrates that many patients have suffered long-lasting and continued post-viral sequelae such as fatigue, exercise intolerance, dizziness, brain fog, depression, myocarditis, and dysautonomia [18].”
Psychosocial Aspects of the Lived Experience of Long COVID: A Systematic Review and Thematic Synthesis of Qualitative Studies
Eberhardt, J., Gibson, B., Portman, R. M., Carthy, N., Rowlands, S., Batchelor, R., Kane, L., & Kılınç, S. (2024) · Health Expectations · doi:10.1111/hex.70071 · Cited by 25

Authors: Crook, H., Raza, S., Nowell, J., Young, M., & Edison, P.
Affiliations: Imperial College London (GB)
Corresponding author: Edison, Paul
ORCID: Edison, Paul
Venue: BMJ
Publisher: BMJ
Published: 2021-07-26
Volume: 374
Pages: n1648
ISSN: 1756-1833 (ISSN-L)
DOI: 10.1136/bmj.n1648
OpenAlex: W3186314395
Cited by: 1,655
References: 0
Citations by year: 2026: 85 · 2025: 205 · 2024: 329 · 2023: 508 · 2022: 466 · 2021: 60
FWCI: 43.57
Type: journal article
Language: en
Update notices: correction (2021-08-03)
Open access: closed
Licence: bmj.com/coronavirus/usage (tdm)
Locations: BMJ (publishedVersion)
PubMed (publishedVersion)
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: long COVID, SARS-CoV-2, persistent symptoms, fatigue, dyspnea, cardiac anomalies, cognitive impairment, sleep disorders, post-traumatic stress disorder, myalgia, risk factors, treatment options
MeSH terms: Global Burden of Disease, COVID-19, Post-Acute COVID-19 Syndrome, Clinical Trials as Topic, Combined Modality Therapy, Humans, Risk Factors, Severity of Illness Index, Incidence, Practice Guidelines as Topic, Drug Repositioning

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Long covid—mechanisms, risk factors, and management

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