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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Arguinchona, L., Zagona‐Prizio, C., Joyce, M. E., Chan, E. D., & Maloney, J. P. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1054690 · Cited by 30
Changes in Electrical Brain Activity and Cognitive Functions Following Mild to Moderate COVID-19: A one-Year Prospective Study After Acute Infection
Appelt, P. A., Sisconetto, A. T., Sucupira, K. S. M. B., Neto, E. D. M., Chagas, T. D. J., Bazán, R., Cabral, A. M., Andrade, A. D. O., de Souza, L. A. P. S., & Luvizutto, G. J. (2022) · Clinical EEG and Neuroscience · doi:10.1177/15500594221103834 · Cited by 31
“However, some studies have found links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurological dysfunction both in the early stages(3) and the long term (long COVID).(4) According to recent studies, 36.”
Background
Effects of a randomized-controlled and online-supported physical activity intervention on exercise capacity, fatigue and health related quality of life in patients with post-COVID-19 syndrome
Kerling, A., Beyer, S. R., Dirks, M., Scharbau, M., Hennemann, A., Dopfer‐Jablonka, A., Lampe, V., Salzmann, J. H. W., Tegtbur, U., Drick, N., et al. (2024) · BMC Sports Science Medicine and Rehabilitation · doi:10.1186/s13102-024-00817-5 · Cited by 31
“The courses of PCS are varied but most of them lead to restrictions in everyday life caused by chronic fatigue, reduced exercise tolerance, dyspnea, neurocognitive problems, muscle pain, sleep disturbances and headache [8].”
Background
Olfactory immune response to SARS-CoV-2
Wellford, S. A., & Moseman, E. A. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01119-5 · Cited by 36
Non-coding RNAs expression in SARS-CoV-2 infection: Pathogenesis, clinical significance and therapeutic targets
Liu, X., Xiong, W., Ye, M., Lu, T., Yuan, K., Chang, S., Han, Y., Wang, Y., Lü, L., & Bao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01669-0 · Cited by 34
“122 Some hypotheses about the long COVID pathogenesis have been proposed, such as impaired autoimmunity, viral remnants, dysregulated dysbiosis, and tissue damage.”
Background
Consistency of inconsistency in long‐COVID‐19 pain symptoms persistency: A systematic review and meta‐analysis
Kerzhner, O., Berla, E., Har‐Even, M., Ratmansky, M., & Goor‐Aryeh, I. (2023) · Pain Practice · doi:10.1111/papr.13277 · Cited by 44
“114 119 Pathological innate immune system activation at viral uptake and replication areas, which leads to “site-specific” inflammation and vascular damage-induced hypoxia with subsequent tissue necrosis and organ-system damage, 18,115,120 probably account for long-COVID symptom development.”
Background
Divergent adaptive immune responses define two types of long COVID
Kervevan, J., Staropoli, I., Slama, D., Jeger‐Madiot, R., Donnadieu, F., Planas, D., Pietri, M. P., Loghmari-Bouchneb, W., Tanah, M. A., Robinot, R., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1221961 · Cited by 35
“Alternative etiologies proposed for long COVID include persistent tissue damage induced early during the acute stage of infection (4, 42).”
Background
Perceived Cognitive Deficits in Patients With Symptomatic SARS-CoV-2 and Their Association With Post–COVID-19 Condition
Liu, T. C., Yoo, S. M., Sim, M., Motwani, Y., Viswanathan, N., & Wenger, N. S. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.11974 · Cited by 30
“2–8 So-called brain fog in particular has been a common and debilitating symptom 9 affecting all age groups.”
Ambient air pollution exposure linked to long COVID among young adults: a nested survey in a population-based cohort in Sweden
Yu, Z., Ekström, S., Bellander, T., Ljungman, P. L. S., Pershagen, G., Eneroth, K., Kull, I., Bergström, A., Georgelis, A., Stafoggia, M., et al. (2023) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2023.100608 · Cited by 32
Determinants of long COVID among adults hospitalized for SARS-CoV-2 infection: A prospective cohort study
Bellan, M., Apostolo, D., Albè, A., Crevola, M., Errica, N., Ratano, G., Tonello, S., Minisini, R., D’Onghia, D., Baricich, A., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1038227 · Cited by 41
Use of the Postacute Sequelae of COVID-19 Diagnosis Code in Routine Clinical Practice in the US
McGrath, L. J., Scott, A., Surinach, A., Chambers, R. B., Benigno, M., & Malhotra, D. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.35089 · Cited by 42
“7) [1-743] Median (IQR) 56 (21-200) 40 (14-101) 59 (22-214) 51 (21-228) Abbreviation: ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification.”
Exercise Intolerance in Post-Acute Sequelae of COVID-19 and the Value of Cardiopulmonary Exercise Testing- a Mini-Review
Aparisi, Á., Ladrón, R., Ybarra-Falcón, C., Tobar, J., & Román, J. A. S. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.924819 · Cited by 36
“Although it is intuitive to think that patients with PASCwould be limited primarily by the cardiopulmonary system, studies indicate that most of these patients have (2) cardiac and pulmonary testing within normal values (3, 4).”
Background
SingStrong—A singing and breathing retraining intervention for respiratory and other common symptoms of long COVID: A pilot study
Cahalan, R., Meade, C., & Mockler, S. (2022) · Canadian Journal of Respiratory Therapy · doi:10.29390/cjrt-2021-074 · Cited by 42
“Evidence for the treatment of other common LC symptoms including fatigue and cognitive impairments (so-called “brain-fog”) is still emerging, but holistic management in a supportive setting is advocated [25].”
Background
The pathological maelstrom of COVID-19 and cardiovascular disease
Giacca, M., & Shah, A. M. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00029-5 · Cited by 37
Factors Associated with Severe COVID-19 and Post-Acute COVID-19 Syndrome in a Cohort of People Living with HIV on Antiretroviral Treatment and with Undetectable HIV RNA
Mazzitelli, M., Trunfio, M., Sasset, L., Leoni, D., Castelli, E., Menzo, S. L., Gardin, S., Putaggio, C., Brundu, M., Garzotto, P., et al. (2022) · Viruses · doi:10.3390/v14030493 · Cited by 38
“6% in the general population, but data about its real prevalence and whether PLWH are more likely to develop PACS is still unknown [21,48].”
BackgroundMethod
Treatments for COVID-19: Lessons from 2020 and new therapeutic options
Salasc, F., Lahlali, T., Laurent, E., Rosa‐Calatrava, M., & Pizzorno, A. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.11.002 · Cited by 39
Post-acute COVID-19 syndrome: a new tsunami requiring a universal case definition
Lledó, G. M., Sellarés, J., Brotons, C., Sans-Corrales, M., Antón, J. D., Blanco, J., Bassat, Q., Sarukhan, A., Miró, J. M., de Sanjosé, S., et al. (2021) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2021.11.015 · Cited by 42
“Infectious diseases, internal medicine, primary care medicine, infectious diseases specialists, cardiology, neurology, psychiatry, and rehabilitation, should be part of the multidisciplinary team and holistic approach [28,29].”
Dysfunctional breathing symptoms, functional impact and quality of life in patients with long COVID-19: a prospective case series
Genecand, L., Altarelli, M., Binkova, A., Loew, S., Vaudan, S., Gex, G., Bridevaux, P.-O., & Frésard, I. (2023) · BMJ Open Respiratory Research · doi:10.1136/bmjresp-2023-001770 · Cited by 37
Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study
Bruno, R. M., Badhwar, S., Abid, L., Agharazii, M., Anastasio, F., Bellien, J., Burghuber, O., Faconti, L., Filipovský, J., Ghiadoni, L., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf430 · Cited by 34
“42,43 Persistent inflammation and viral persistence after acute infection 44 may be involved in both long COVID symptoms and accelerated vascular ageing.”
Long-term risk of psychiatric disorder and psychotropic prescription after SARS-CoV-2 infection among UK general population
Wang, Y., Su, B., Xie, J., García‐Rizo, C., & Prieto‐Alhambra, D. (2024) · Nature Human Behaviour · doi:10.1038/s41562-024-01853-4 · Cited by 36
“In addition, possible changes in behaviours such as decreased physical activity, having a poor diet, and increased avoidance of health care and social contact in some individuals following recovery from acute COVID-19 may also contribute to the increased risk of long-term psychiatric sequelae 2,20 .”
Treatment of COVID-19 during the Acute Phase in Hospitalized Patients Decreases Post-Acute Sequelae of COVID-19
Bonet, D. B., Caguana-Vélez, O. A., Durán, X., Comas, M., Posso, M., Admetlló, M., Blasco, A. H., Cuadrado‐Godia, E., Marco, E., Martín‐Ezquerra, G., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12124158 · Cited by 35
A cross-sectional study on the mental health of patients with COVID-19 1 year after discharge in Huanggang, China
Li, Z., He, J., Wang, Y., Bai, M., Zhang, Y., Chen, H., Li, W., Cai, Y., Chen, S., Qu, M., et al. (2022) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-022-01484-8 · Cited by 34
A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms
Badran, B., Huffman, S., Dancy, M., Austelle, C. W., Bikson, M., Kautz, S., & George, M. (2022) · Research Square · doi:10.21203/rs.3.rs-1716096/v1 · Cited by 29
Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic
Lin, S., Lau, L. H. S., Chanchlani, N., Kennedy, N. A., & Ng, S. C. (2022) · Gut · doi:10.1136/gutjnl-2021-326784 · Cited by 35
Detection of Male Hypogonadism in Patients with Post COVID-19 Condition
Yamamoto, Y., Otsuka, Y., Sunada, N., Tokumasu, K., Nakano, Y., Honda, H., Sakurada, Y., Hagiya, H., Hanayama, Y., & Otsuka, F. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11071955 · Cited by 35
“It is well known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets angiotensin-converting enzyme 2 (ACE2) receptors [29], and the testis and its Leydig cells are known to express ACE2 receptors abundantly [30].”
Background
Assessment of Microbiota in the Gut and Upper Respiratory Tract Associated with SARS-CoV-2 Infection
Li, J., Jing, Q., Li, J., Hua, M., Di, L., Song, C., Huang, Y., Wang, J., Chen, C., & Wu, A. R. (2020) · Microbiome · doi:10.1186/s40168-022-01447-0 · Cited by 36
“Moreover, SARS-CoV-2 infection can cause long-term effects on human health, with mechanisms largely unknown so far [3].”
Background
Unraveling Links between Chronic Inflammation and Long COVID: Workshop Report
Tandon, P., Abrams, N., Avula, L. R., Carrick, D. M., Chander, P., Divi, R. L., Dwyer, J. T., Gannot, G., Gordiyenko, N. V., Liu, Q., et al. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2300804 · Cited by 31
Trajectories of mental health outcomes following COVID-19 infection: a prospective longitudinal study
Badinlou, F., Rahimian, F., Hedman‐Lagerlöf, M., Lundgren, T., Abzhandadze, T., & Jansson‐Fröjmark, M. (2024) · BMC Public Health · doi:10.1186/s12889-024-17997-x · Cited by 35
“Additionally, several studies have highlighted the presence of fluctuations and relapses in post-COVID-19 fatigue over time [48, 71].”
Background
Depression and anxiety before and at the beginning of the COVID-19 pandemic and incident persistent symptoms: a prospective population-based cohort study
Matta, J., Robineau, O., Wiernik, E., Carrat, F., Severi, G., Touvier, M., Gouraud, C., Vedrines, C. O., Pitron, V., Ranque, B., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02179-9 · Cited by 41
“Further details regarding covariates are given in Supplemental Methods 1.”
Clinical characterization and factors associated with quality of life in Long COVID patients: Secondary data analysis from a randomized clinical trial
Samper-Pardo, M., León-Herrera, S., Oliván‐Blázquez, B., Gascón, S., & Sánchez‐Recio, R. (2023) · PLoS ONE · doi:10.1371/journal.pone.0278728 · Cited by 33
“(2021) has come to count 203 symptoms of this disease [18], coming to involve at least 10 organ systems, as verified by other studies [19].”
Result
COVID ‐19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain
Roczkowsky, A., Limonta, D., Fernandes, J. P., Branton, W. G., Clarke, M., Hlavay, B. A., Noyce, R. S., Joseph, J. T., Ogando, N. S., Das, S., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26679 · Cited by 29
“Among COVID-19 survivors, 10 to 30% develop persistent multi-system symptoms, termed postacute sequelae of COVID-19 (PASC), resulting in >15% of patients with PASC displaying neurocognitive impairments.(1,3) The mechanisms underlying COVID-19associated neurological disabilities remain unknown.”
Background
Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms
Percze, A. R., Nagy, A., Polivka, L., Bárczi, E., Czaller, I., Kovats, Z., Varga, J., Ballai, J. H., Muller, V., & Horvath, G. (2023) · InflammoPharmacology · doi:10.1007/s10787-023-01190-4 · Cited by 28
“Several studies have documented the fact that fatigue is a major manifestation of long COVID (Crook et al. 2021).”
Background
Cardiovascular and autonomic dysfunction in long-COVID syndrome and the potential role of non-invasive therapeutic strategies on cardiovascular outcomes
Allendes, F., Díaz, H. S., Ortíz, F. C., Marcus, N. J., Quintanilla, R. A., Inestrosa, N. C., & Río, R. D. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2022.1095249 · Cited by 33
“Healthcare organizations have stated that research priorities should aim to identify characteristics of long-COVID however given the diffuse and varied presentation of this condition this will undoubtedly be a challenging task (44).”
BackgroundInfluential
Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective
Guzmán-Esquivel, J., Mendoza-Hernandez, M. A., Guzman-Solorzano, H. P., Sarmiento-Hernandez, K. A., Rodriguez-Sanchez, I. P., Martínez‐Fierro, M. L., Paz-Michel, B. A., Murillo‐Zamora, E., Rojas‐Larios, F., Lugo‐Trampe, Á., et al. (2023) · Healthcare · doi:10.3390/healthcare11020197 · Cited by 28
A comprehensive characterization of patients diagnosed with post-COVID-19 condition in Sweden 16 months after the introduction of the International Classification of Diseases Tenth Revision diagnosis code (U09.9): a population-based cohort study
Bygdell, M., Leach, S., Lundberg, L., Gyll, D., Martikainen, J., Santosa, A., Li, H., Gisslén, M., & Nyberg, F. (2022) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2022.11.021 · Cited by 28
Long-term COVID symptoms, work ability and fitness to work in healthcare workers hospitalized for sars-CoV-2 infection
Mendola, M., Leoni, M., Cozzi, Y., Manzari, A., Tonelli, F., Metruccio, F., Tosti, L., Battini, V., Cucchi, I., Costa, M. C., et al. (2022) · La Medicina del lavoro · doi:10.23749/mdl.v113i5.13377 · Cited by 28
Social Life of Females with Persistent COVID-19 Symptoms: A Qualitative Study
Aghaei, A., Zhang, R., Taylor, S., Tam, C.-C., Yang, C., Li, X., & Qiao, S. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19159076 · Cited by 27
SARS-CoV-2 and Multiple Sclerosis: Potential for Disease Exacerbation
MacDougall, M., Sleiman, J. E.-H., Beauchemin, P., & Rangachari, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.871276 · Cited by 30
“Symptoms of these affections range from persistent chest pain and dyspnea to coagulopathy, fatigue, and cognitive changes (26).”
Background
Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: a longitudinal analysis of 1581 UK adults
Paul, E., & Fancourt, D. E. (2022) · BMC Public Health · doi:10.1186/s12889-022-14123-7 · Cited by 36
6 and 12 month outcomes in patients following COVID-19-related hospitalization: a prospective monocentric study
Martino, G. P., Benfaremo, D., Bitti, G., Valeri, G., Postacchini, L., Marchetti, A., Angelici, S., & Moroncini, G. (2022) · Internal and Emergency Medicine · doi:10.1007/s11739-022-02979-x · Cited by 32
“Long COVID or post-acute CoronaVirus Disease 19 (COVID-19) syndrome is a recently described condition characterized by persisting symptoms after acute Severe Acute Respiratory Syndrome—CoronaVirus 2 (SARS-CoV-2) infection that cannot be explained by an alternative diagnosis [1].”
COVID-19 and the long-term cardio-respiratory and metabolic health complications
Ashton, R. E. M., Ansdell, P., Hume, E., Maden‐Wilkinson, T., Ryan, D. J., Tuttiett, E. R., & Faghy, M. A. (2022) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2302053 · Cited by 30
“COVID-19 binds to ACE-2 [44] and enters cells via ACE-2 receptors present on the cells of multiple organs [45].”
Background
What is quality in long covid care? Lessons from a national quality improvement collaborative and multi-site ethnography
Greenhalgh, T., Darbyshire, J. L., Lee, C., Ladds, E. C., & Ceolta‐Smith, J. (2024) · BMC Medicine · doi:10.1186/s12916-024-03371-6 · Cited by 40
Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID
Naidu, A. S., Wang, C., Rao, P., Mancini, F., Clemens, R., Wirakartakusumah, A., Chiu, H., Yen, C., Porretta, S., Mathai, I., et al. (2024) · npj Science of Food · doi:10.1038/s41538-024-00261-2 · Cited by 32
Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation
Salvucci, F., Codella, R., Coppola, A., Zacchei, I., Grassi, G., Anti, M., Nitisoara, N., Luzi, L., & Gazzaruso, C. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1202696 · Cited by 27
“A lot of therapies, including rehabilitation, nutritional counseling, psychological support, immunomodulator, acupuncture, antidepressants, steroids, beta-blockers, cough suppressants, non-steroidal anti-inflammatory drugs, analgesics, nutraceutical agents, vitamins, and anticoagulants, have been proposed and used to…”
BackgroundMethodInfluential
Long-COVID syndrome: physical–mental interplay in the spotlight
Thurner, C., & Stengel, A. (2023) · InflammoPharmacology · doi:10.1007/s10787-023-01174-4 · Cited by 29
Within and between-day variation and associations of symptoms in Long Covid: Intensive longitudinal study
Burton, C. D., Dawes, H., Goodwill, S. R., Thelwell, M., & Dalton, C. (2023) · PLoS ONE · doi:10.1371/journal.pone.0280343 · Cited by 32
“Evidence exists for multiple pathophysiologic mechanisms in Long Covid [3, 5].”
Background
Incidence of post-COVID syndrome and associated symptoms in outpatient care in Bavaria, Germany: a retrospective cohort study using routinely collected claims data
Donnachie, E., Hapfelmeier, A., Linde, K., Tauscher, M., Gerlach, R., Greissel, A., & Schneider, A. (2022) · BMJ Open · doi:10.1136/bmjopen-2022-064979 · Cited by 27
Fatigue in Post-COVID-19 Syndrome: Clinical Phenomenology, Comorbidities and Association With Initial Course of COVID-19
Diem, L., Fregolente, L. G., Warncke, J. D., Hammer, H. N., Friedli, C., Kamber, N., Jung, S., Bigi, S., Funke-Chambour, M., Chan, A., et al. (2022) · Journal of Central Nervous System Disease · doi:10.1177/11795735221102727 · Cited by 32
“Regarding the demographic characteristics of our study population, the majority of patients were women, between 40 - 50 years of age and not hospitalized due to the initial COVID-19 course, which is in line with the contemporary literature.(7,11) Sleep disturbances and depressive mood were two other common symptoms in…”
Result
Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study.
Al-hakeim, H., Al-Rubaye, H., Al-Hadrawi, D. S., Almulla, A., & Maes, M. (2022) · medRxiv · doi:10.1101/2022.04.25.22274251 · Cited by 27
Inflammaging at the Time of COVID-19
Zazzara, M. B., Bellieni, A., Calvani, R., Coelho‐Júnior, H. J., Picca, A., & Marzetti, E. (2022) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2022.03.003 · Cited by 32
“Evidence shows that cytokine levels are still increased in patients with long COVID and the maintenance of a lowgrade chronic inflammation could be one of the mechanisms that might explain symptom persistence.(30,34,35) From this perspective, long COVID bears resemblance with postintensive care syndrome (PICS).”
Persistent physical symptoms after COVID-19 infection and the risk of Somatic Symptom Disorder
Horn, M., Wathelet, M., Amad, A., Martignène, N., Lathiere, T., Khelfaoui, K., Rousselle, M., El Qaoubii, O., Vuotto, F., Faure, K., et al. (2023) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2023.111172 · Cited by 27
Natural course of post-COVID symptoms in adults and children
Sugiyama, A., Takafuta, T., Sato, T., Kitahara, Y., Yoshinaga, Y., Abe, K., Chhoung, C., Akuffo, G. A., Phyo, Z., Kurisu, A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-54397-y · Cited by 27
Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: A nationwide register-linked cohort study in Denmark
Mkoma, G., Ndaago, A. I., Benfield, T., Rostila, M., Cederström, A., Petersen, J. H., & Norredam, M. (2024) · PLoS Medicine · doi:10.1371/journal.pmed.1004280 · Cited by 26
“…(dyspnoea, cough, and chest pain), and neurological symptoms (headache, depression, and memory loss) persisting beyond weeks or months after the acute phase of COVID-19 infection, the condition known as long COVID as per National Institute for Health and Care Excellence (NICE) guidelines [2–5].”
Background
Low-dose Naltrexone Improves post–COVID-19 condition Symptoms
Tamariz, L. J., Bast, E. S., Klimas, N. G., & Palacio, A. (2024) · Clinical Therapeutics · doi:10.1016/j.clinthera.2023.12.009 · Cited by 27
HEART Rate Variability Biofeedback for LOng COVID Dysautonomia (HEARTLOC): Results of a Feasibility Study
Corrado, J., Iftekhar, N., Halpin, S. J., Li, M., Tarrant, R., Grimaldi, J., Simms, A. D., O’Connor, R. J., Casson, A. J., & Sivan, M. (2024) · Advances in Rehabilitation Science and Practice · doi:10.1177/27536351241227261 · Cited by 25
Cardiorespiratory dysautonomia in post‐COVID‐19 condition: Manifestations, mechanisms and management
Fedorowski, A., Olsén, M. F., Nikesjö, F., Janson, C., Bruchfeld, J., Lerm, M., & Hedman, K. (2023) · Journal of Internal Medicine · doi:10.1111/joim.13652 · Cited by 32
Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study
Jackson, C., Stewart, I. D., Plekhanova, T., Cunningham, P. S., Hazel, A. L., Al-Sheklly, B., Aul, R., Bolton, C. E., Chalder, T., Chalmers, J. D., et al. (2023) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(23)00124-8 · Cited by 35
“Mediation analysis identified that reduced muscle function and anxiety, both recognised causes of dyspnoea, 3 could partially mediate the association between sleep disturbance and dyspnoea.”
Background
Orthostatic tachycardia after covid-19
Espinosa-González, A. B., Master, H., Gall, N. P., Halpin, S. J., Rogers, N., & Greenhalgh, T. (2023) · BMJ · doi:10.1136/bmj-2022-073488 · Cited by 30
Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study
Morioka, S., Tsuzuki, S., Maruki, T., Terada, M., Miyazato, Y., Kutsuna, S., Saito, S., Shimanishi, Y., Takahashi, K., Sanada, M., et al. (2023) · Public Health · doi:10.1016/j.puhe.2023.01.008 · Cited by 35
Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX
Putilina, M. V., Mutovina, Z. Y., Kurushina, O. V., Khalilova, D. M., Николаевна, С. Е., Степанова, С. Б., Хорева, М. А., & Стариков, А. С. (2022) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202212201184 · Cited by 28
Multidimensional phenotyping of the post‐COVID ‐19 syndrome: A Swiss survey study
Diem, L., Schwarzwald, A., Friedli, C. D., Hammer, H. N., Fregolente, L. G., Warncke, J. D., Weber, L., Kamber, N., Chan, A., Bassetti, C. L., et al. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13938 · Cited by 28
Neurocognitive and Psychosocial Characteristics of Pediatric Patients With Post-Acute/Long-COVID: A Retrospective Clinical Case Series
Ng, R., Vargas, G., Jashar, D. T., Morrow, A. K., & Malone, L. A. (2022) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acac056 · Cited by 31
The Role of Cellular Immunity in the Protective Efficacy of the SARS-CoV-2 Vaccines
Sun, Z., Wu, T., Xie, H., Li, Y., Zhang, J., Su, X., & Qi, H. (2022) · Vaccines · doi:10.3390/vaccines10071103 · Cited by 29
“Studies have shown that SARS-CoV-2 replication in endothelial cells causes serious damage to the lungs and respiratory tract in the respiratory system, which is similar to the cardiovascular system [108,109].”
Background
Persistent Symptoms After Acute COVID-19 Infection in Omicron Era
Jung, Y. H., Ha, E.-H., Choe, K. W., Lee, S., Jo, D. H., & Lee, W. J. (2022) · Journal of Korean Medical Science · doi:10.3346/jkms.2022.37.e213 · Cited by 28
Symptoms Compatible With Long Coronavirus Disease (COVID) in Healthcare Workers With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection—Results of a Prospective Multicenter Cohort
Strahm, C., Seneghini, M., Güsewell, S., Egger, T., Leal-Neto, O. B., Brucher, A., Lemmenmeier, E., Kleeb, D. M., Möller, J. C., Rieder, P., et al. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac054 · Cited by 52
“Fourth, the Delta variant, which was not yet the predominant strain when the study was conducted, might differently impact the occurrence of long-COVID symptoms [40].”
Determinants of COVID-19-Related Length of Hospital Stays and Long COVID in Ghana: A Cross-Sectional Analysis
Crankson, S., Pokhrel, S., & Anokye, N. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19010527 · Cited by 26
Paroxysmal Supraventricular Tachycardia and Cardiac Arrest: A presentation of Pulmonary Embolism With Infarction as a Sequela of Long COVID Syndrome
Talwar, D., Kumar, S., Acharya, S., Khanna, S., & Hulkoti, V. S. (2021) · Cureus · doi:10.7759/cureus.18572 · Cited by 27
“Pulmonary embolism was indeed reported to occur in COVID-19 patients who are critically ill despite the use of thromboprophylaxis which questions the possibility of a higher dose of thromboprophylaxis in severely ill patients [1].”
Background
Severe Fatigue and Memory Impairment Are Associated with Lower Serum Level of Anti-SARS-CoV-2 Antibodies in Patients with Post-COVID Symptoms
Molnár, T., Várnai, R., Schranz, D., Závori, L., Péterfi, Z., Sipos, D., Tökés‐Füzesi, M., Illés, Z., Büki, A., & Csécsei, P. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10194337 · Cited by 31
Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
Bradley, E. S., Zeamer, A. L., Bucci, V., Cincotta, L., Salive, M.-C., Dutta, P., Mutaawe, S., Anya, O., Tocci, C., Moormann, A. M., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1009440 · Cited by 21
Upstream lipid and metabolic systems are potential causes of Alzheimer's disease, Parkinson's disease and dementias
Cooper, O., Hallett, P. J., & Ole Isacson, A. (2022) · FEBS Journal · doi:10.1111/febs.16638 · Cited by 26
“Such inﬂam-matory stimuli can include viral infections [6,7,22,23].”
Background
Memory alterations after COVID-19 infection: a systematic review
Llana, T., Zorzo, C., Méndez-López, M., & Méndez, M. (2022) · Applied Neuropsychology Adult · doi:10.1080/23279095.2022.2123739 · Cited by 26
“However, irrespective of the severity of the neurological symptoms of COVID-19 in the acute phase, many patients who had mild or moderate COVID-19 present long-term neuropsychological alterations (Crook et al., 2021; Frontera et al., 2021).”
Background

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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