{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:20Z","timestamp":1787028620713,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T00:00:00Z","timestamp":1638057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Patients recovered from a COVID-19 infection often report vague symptoms of fatigue or dyspnoea, comparable to the manifestations in patients with central sensitisation. The hypothesis was that central sensitisation could be the underlying common aetiology in both patient populations. This study explored the presence of symptoms of central sensitisation, and the association with functional status and health-related quality of life, in patients post COVID-19 infection. Patients who were previously infected with COVID-19 filled out the Central Sensitisation Inventory (CSI), the Post-COVID-19 Functional Status (PCFS) Scale and the EuroQol with five dimensions, through an online survey. Eventually, 567 persons completed the survey. In total, 29.73% of the persons had a score of &lt;40\/100 on the CSI and 70.26% had a score of \u226540\/100. Regarding functional status, 7.34% had no functional limitations, 9.13% had negligible functional limitations, 37.30% reported slight functional limitations, 42.86% indicated moderate functional limitations and 3.37% reported severe functional limitations. Based on a one-way ANOVA test, there was a significant effect of PCFS Scale group level on the total CSI score (F(4,486) = 46.17, p &lt; 0.001). This survey indicated the presence of symptoms of central sensitisation in more than 70% of patients post COVID-19 infection, suggesting towards the need for patient education and multimodal rehabilitation, to target nociplastic pain.<\/jats:p>","DOI":"10.3390\/jcm10235594","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"5594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Is Central Sensitisation the Missing Link of Persisting Symptoms after COVID-19 Infection?"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2271-9855","authenticated-orcid":false,"given":"Lisa","family":"Goudman","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"},{"name":"STIMULUS Research Group (reSearch and TeachIng neuroModULation Uz bruSsel), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Pain in Motion (PAIN) Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Research Foundation\u2014Flanders (FWO), 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"De Smedt","sequence":"additional","affiliation":[{"name":"STIMULUS Research Group (reSearch and TeachIng neuroModULation Uz bruSsel), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Department of Physical Medicine and Rehabilitation, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Noppen","sequence":"additional","affiliation":[{"name":"Chief Executive Officer, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0577-5449","authenticated-orcid":false,"given":"Maarten","family":"Moens","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"},{"name":"STIMULUS Research Group (reSearch and TeachIng neuroModULation Uz bruSsel), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Pain in Motion (PAIN) Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Department of Radiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1001\/jamaoto.2020.1591","article-title":"Olfactory Loss of Function as a Possible Symptom of COVID-19\u2014Reply","volume":"146","author":"Eliezer","year":"2020","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s00296-020-04561-0","article-title":"Arthralgia as an initial presentation of COVID-19: Observation","volume":"40","author":"Joob","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1474-4422(20)30109-5","article-title":"Guillain-Barre syndrome associated with SARS-CoV-2 infection: Causality or coincidence?","volume":"19","author":"Zhao","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/jmv.25722","article-title":"Understanding of COVID-19 based on current evidence","volume":"92","author":"Sun","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"687","DOI":"10.3389\/fneur.2020.00687","article-title":"Neurological and Musculoskeletal Features of COVID-19: A Systematic Review and Meta-Analysis","volume":"11","author":"Abdullahi","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bpa.2020.12.011","article-title":"COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment\u2014A narrative review","volume":"35","author":"Pfortmueller","year":"2021","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"m1985","DOI":"10.1136\/bmj.m1985","article-title":"Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol: Prospective observational cohort study","volume":"369","author":"Docherty","year":"2020","journal-title":"BMJ"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.dsx.2020.03.013","article-title":"Cardiovascular disease and COVID-19","volume":"14","author":"Bansal","year":"2020","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1053\/j.gastro.2020.03.065","article-title":"Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from a Hong Kong Cohort: Systematic Review and Meta-analysis","volume":"159","author":"Cheung","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1136\/svn-2020-000398","article-title":"Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management","volume":"5","author":"Zhou","year":"2020","journal-title":"Stroke Vasc. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0140-6736(21)01900-0","article-title":"Understanding long COVID: A modern medical challenge","volume":"398","author":"The","year":"2021","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: Implications for the diagnosis and treatment of pain","volume":"152","author":"Woolf","year":"2011","journal-title":"Pain"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nijs, J., Lahousse, A., Kapreli, E., Bilika, P., Saracoglu, I., Malfliet, A., Coppieters, I., De Baets, L., Leysen, L., and Roose, E. (2021). Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future. J. Clin. Med., 10.","DOI":"10.3390\/jcm10153203"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jpain.2012.11.012","article-title":"The Central Sensitization Inventory (CSI): Establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample","volume":"14","author":"Neblett","year":"2013","journal-title":"J. Pain Off. J. Am. Pain Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1080\/09593985.2020.1766181","article-title":"Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19","volume":"36","author":"Candan","year":"2020","journal-title":"Physiother. Theory Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1001\/jama.2020.12603","article-title":"Persistent Symptoms in Patients after Acute COVID-19","volume":"324","author":"Carfi","year":"2020","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"868","DOI":"10.7326\/0003-4819-134-9_Part_2-200105011-00011","article-title":"A review of the evidence for overlap among unexplained clinical conditions","volume":"134","author":"Aaron","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/j.1533-2500.2011.00493.x","article-title":"The development and psychometric validation of the central sensitization inventory","volume":"12","author":"Mayer","year":"2012","journal-title":"Pain Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1097\/AJP.0000000000000306","article-title":"The Dutch Central Sensitization Inventory (CSI): Factor Analysis, Discriminative Power, and Test-Retest Reliability","volume":"32","author":"Kregel","year":"2016","journal-title":"Clin. J. Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1093\/pm\/pnaa210","article-title":"Establishing Central Sensitization-Related Symptom Severity Subgroups: A Multicountry Study Using the Central Sensitization Inventory","volume":"21","author":"Neblett","year":"2020","journal-title":"Pain Med."},{"key":"ref_22","first-page":"757","article-title":"A novel tool to monitor the individual functional status after COVID-19: The Post-COVID-19 Functional Status (PCFS) scale","volume":"21","author":"Corsi","year":"2020","journal-title":"G. Ital. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2001494","DOI":"10.1183\/13993003.01494-2020","article-title":"The Post-COVID-19 Functional Status scale: A tool to measure functional status over time after COVID-19","volume":"56","author":"Klok","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/07853890109002087","article-title":"EQ-5D: A measure of health status from the EuroQol Group","volume":"33","author":"Rabin","year":"2001","journal-title":"Ann. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"The EuroQol Group (1990). EuroQol\u2014A new facility for the measurement of health-related quality of life. Health Policy, 16, 199\u2013208.","DOI":"10.1016\/0168-8510(90)90421-9"},{"key":"ref_26","unstructured":"EuroQol Group (2014). Self-Reported Population Health: An International Perspective Based on EQ-5D, Springer."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1097\/j.pain.0000000000001184","article-title":"Recently introduced definition of \u201cnociplastic pain\u201d by the International Association for the Study of Pain needs better formulation","volume":"159","author":"Aydede","year":"2018","journal-title":"Pain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"T10","DOI":"10.1016\/j.jpain.2015.08.010","article-title":"Assessment of Chronic Pain: Domains, Methods, and Mechanisms","volume":"17","author":"Fillingim","year":"2016","journal-title":"J. Pain Off. J. Am. Pain Soc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1097\/j.pain.0000000000002324","article-title":"Chronic nociplastic pain affecting the musculoskeletal system: Clinical criteria and grading system","volume":"162","author":"Kosek","year":"2021","journal-title":"Pain"},{"key":"ref_30","first-page":"338","article-title":"Differences between Women with Traumatic and Idiopathic Chronic Neck Pain and Women without Neck Pain: Interrelationships among Disability, Cognitive Deficits, and Central Sensitization","volume":"97","author":"Coppieters","year":"2017","journal-title":"Phys. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1586\/ern.12.41","article-title":"Abnormal endogenous pain modulation is a shared characteristic of many chronic pain conditions","volume":"12","author":"Staud","year":"2012","journal-title":"Expert Rev. Neurother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1097\/j.pain.0000000000000689","article-title":"Reliability of conditioned pain modulation: A systematic review","volume":"157","author":"Kennedy","year":"2016","journal-title":"Pain"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Soon, B., Vicenzino, B., Schmid, A.B., and Coppieters, M.W. (2017). Facilitatory and inhibitory pain mechanisms are altered in patients with carpal tunnel syndrome. PLoS ONE, 12.","DOI":"10.14264\/uql.2017.268"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1097\/01.brs.0000435027.50317.d7","article-title":"Changes in pressure pain threshold in patients with chronic nonspecific low back pain","volume":"38","author":"Imamura","year":"2013","journal-title":"Spine"},{"key":"ref_35","first-page":"307","article-title":"Differences in Pain Processing between Patients with Chronic Low Back Pain, Recurrent Low Back Pain, and Fibromyalgia","volume":"20","author":"Goubert","year":"2017","journal-title":"Pain Physician"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s12967-018-1644-y","article-title":"Chronic viral infections in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS)","volume":"16","author":"Rasa","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.7326\/0003-4819-102-1-7","article-title":"Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection","volume":"102","author":"Straus","year":"1985","journal-title":"Ann. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1001\/jama.1987.03390170053027","article-title":"A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?","volume":"257","author":"Holmes","year":"1987","journal-title":"JAMA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000164104","article-title":"Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health care worker with chronic fatigue syndrome. Case report","volume":"65","author":"Martin","year":"1997","journal-title":"Pathobiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103","DOI":"10.7326\/0003-4819-116-2-103","article-title":"A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection","volume":"116","author":"Buchwald","year":"1992","journal-title":"Ann. Intern. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1348-0421.1994.tb01827.x","article-title":"Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome","volume":"38","author":"Yalcin","year":"1994","journal-title":"Microbiol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1386-6532(99)00079-7","article-title":"Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients","volume":"16","author":"Ablashi","year":"2000","journal-title":"J. Clin. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s100960050420","article-title":"Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and\/or fibromyalgia syndrome","volume":"18","author":"Nasralla","year":"1999","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15838","DOI":"10.1038\/s41598-020-72718-9","article-title":"Immune dysfunction following COVID-19, especially in severe patients","volume":"10","author":"Song","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e202000955","DOI":"10.26508\/lsa.202000955","article-title":"Profiling of immune dysfunction in COVID-19 patients allows early prediction of disease progression","volume":"4","author":"Rendeiro","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12974-019-1524-2","article-title":"An update on reactive astrocytes in chronic pain","volume":"16","author":"Li","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1097\/ALN.0000000000002130","article-title":"Neuroinflammation and Central Sensitization in Chronic and Widespread Pain","volume":"129","author":"Ji","year":"2018","journal-title":"Anesthesiology"},{"key":"ref_48","first-page":"1031824","article-title":"COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis","volume":"3","author":"Klein","year":"2021","journal-title":"Res. Sq."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1615\/JEnvironPatholToxicolOncol.2021038365","article-title":"Dialogue between Neuroinflammation and Neurodegenerative Diseases in COVID-19","volume":"40","author":"Chowdhury","year":"2021","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12955-021-01691-2","article-title":"Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19","volume":"19","author":"Machado","year":"2021","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1097\/BRS.0000000000000220","article-title":"Estimating EQ-5D values from the Oswestry Disability Index and numeric rating scales for back and leg pain","volume":"39","author":"Carreon","year":"2014","journal-title":"Spine"},{"key":"ref_52","first-page":"7","article-title":"Prevalence of Functional Limitation in COVID-19 Recovered Patients Using the Post COVID-19 Functional Status Scale","volume":"59","author":"Pant","year":"2021","journal-title":"JNMA J. Nepal Med. Assoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6317","DOI":"10.1038\/s41467-020-19741-6","article-title":"Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission","volume":"11","author":"Peckham","year":"2020","journal-title":"Nat. Commun."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/23\/5594\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:37:01Z","timestamp":1760168221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/23\/5594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,28]]},"references-count":53,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["jcm10235594"],"URL":"https:\/\/doi.org\/10.3390\/jcm10235594","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,28]]}}}