{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:14:16Z","timestamp":1791562456474,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["23fk0108585h0001"],"award-info":[{"award-number":["23fk0108585h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japanese Society of Hospital General Medicine","award":["23fk0108585h0001"],"award-info":[{"award-number":["23fk0108585h0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences.<\/jats:p>","DOI":"10.3390\/jcm14144918","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T11:26:37Z","timestamp":1752233197000},"page":"4918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase"],"prefix":"10.3390","volume":"14","author":[{"given":"Hiroshi","family":"Akiyama","sequence":"first","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4588-5888","authenticated-orcid":false,"given":"Yasue","family":"Sakurada","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6015-6128","authenticated-orcid":false,"given":"Yuki","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-6864","authenticated-orcid":false,"given":"Kazuki","family":"Tokumasu","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Takase","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Omura","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-9095","authenticated-orcid":false,"given":"Fumio","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1056\/NEJMsb2408466","article-title":"National Academies of Sciences, Engineering; Medicine Committee on Examining the Working Definition for Long Covid. Long Covid Defined","volume":"391","author":"Ely","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s42399-022-01167-4","article-title":"Post-acute sequelae of COVID-19 (PASC): A meta-narrative review of pathophysiology, prevalence, and management","volume":"4","author":"Munipalli","year":"2022","journal-title":"SN Compr. Clin. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1016\/S1473-3099(21)00703-9","article-title":"A clinical case definition of post-COVID-19 condition by a Delphi consensus","volume":"22","author":"Soriano","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","article-title":"Long COVID: Major findings, mechanisms and recommendations","volume":"21","author":"Davis","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e294","DOI":"10.1016\/S1473-3099(24)00769-2","article-title":"Targeting the SARS-CoV-2 reservoir in long COVID","volume":"25","author":"Proal","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5500","DOI":"10.1016\/j.cell.2024.07.054","article-title":"Mechanisms of long COVID and the path toward therapeutics","volume":"187","author":"Peluso","year":"2024","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Matsuda, Y., Sakurada, Y., Otsuka, Y., Tokumasu, K., Nakano, Y., Sunada, N., Honda, H., Hasegawa, T., Takase, R., and Omura, D. (2024). Changes in Working Situations of Employed Long COVID Patients: Retrospective Study in Japanese Outpatient Clinic. J. Clin. Med., 13.","DOI":"10.3390\/jcm13133809"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e074425","DOI":"10.1136\/bmj-2022-074425","article-title":"Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: Population based, longitudinal cohort study","volume":"381","author":"Ballouz","year":"2023","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e421","DOI":"10.1016\/S2589-7500(23)00056-0","article-title":"Profiling post-COVID-19 condition across different variants of SARS-CoV-2: A prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations","volume":"5","author":"Canas","year":"2023","journal-title":"Lancet Digit. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1038\/s41467-022-29521-z","article-title":"Persistent COVID-19 symptoms in a community study of 606,434 people in England","volume":"13","author":"Whitaker","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2231790","DOI":"10.1001\/jamanetworkopen.2022.31790","article-title":"Two-Year Health Outcomes in Hospitalized COVID-19 Survivors in China","volume":"5","author":"Yang","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1001\/jama.2022.18931","article-title":"Estimated Global Proportions of Individuals with Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021","volume":"328","author":"Hanson","year":"2022","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Meierkord, A., Schulze, D., Gertler, M., Seybold, J., Mall, M.A., Kurth, T., Mockenhaupt, F.P., and Theuring, S. (2025). Post-infection symptoms up to 24 months after COVID-19: A matched cohort study in Berlin, Germany. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1513664"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1056\/NEJMe2400189","article-title":"Long Covid and Impaired Cognition\u2014More Evidence and More Work to Do","volume":"390","author":"Rosen","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1001\/jamainternmed.2023.0750","article-title":"Risk Factors Associated with Post-COVID-19 Condition: A Systematic Review and Meta-analysis","volume":"183","author":"Tsampasian","year":"2023","journal-title":"JAMA Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e42315","DOI":"10.2196\/42315","article-title":"Epidemiology, Symptomatology, and Risk Factors for Long COVID Symptoms: Population-Based, Multicenter Study","volume":"9","author":"Wong","year":"2023","journal-title":"JMIR Public Health Surveill."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.5694\/mja2.52458","article-title":"Factors associated with general practitioner-led diagnosis of long COVID: An observational study using electronic general practice data from Victoria and New South Wales, Australia","volume":"221","author":"Kamalakkannan","year":"2024","journal-title":"Med. J. Aust."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106297","DOI":"10.1016\/j.jinf.2024.106297","article-title":"The persistence of myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis","volume":"89","author":"Dehlia","year":"2024","journal-title":"J. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wood, M.S., Halmer, N., Bertolli, J., Amsden, L.B., Nugent, J.R., Lin, J.S., Rothrock, G., Nadle, J., Chai, S.J., and Cope, J.R. (2024). Impact of COVID-19 on myalgic encephalomyelitis\/chronic fatigue syndrome-like illness prevalence: A cross-sectional survey. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0309810"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s11606-024-09290-9","article-title":"Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study","volume":"40","author":"Vernon","year":"2025","journal-title":"J. Gen. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Morita, S., Tokumasu, K., Otsuka, Y., Honda, H., Nakano, Y., Sunada, N., Sakurada, Y., Matsuda, Y., Soejima, Y., and Ueda, K. (2024). Phase-dependent trends in the prevalence of myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) related to long COVID: A criteria-based retrospective study in Japan. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0315385"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.31662\/jmaj.2021-0036","article-title":"Case Management of COVID-19 (Secondary Version)","volume":"4","author":"Kato","year":"2021","journal-title":"JMA J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1348\/1359107041557048","article-title":"Measuring fatigue in sarcoidosis: The Fatigue Assessment Scale (FAS)","volume":"9","author":"Michielsen","year":"2004","journal-title":"Br. J. Health Psychol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"658","DOI":"10.2169\/internalmedicine.4101-24","article-title":"Reliability and Validity of the Japanese Version of the Fatigue Assessment Scale","volume":"64","author":"Tokumasu","year":"2025","journal-title":"Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.jval.2016.03.1834","article-title":"Comparison of Value Set Based on DCE and\/or TTO Data: Scoring for EQ-5D-5L Health States in Japan","volume":"19","author":"Shiroiwa","year":"2016","journal-title":"Value Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/archpsyc.1965.01720310065008","article-title":"A Self-Rating Depression Scale","volume":"12","author":"Zung","year":"1965","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_27","unstructured":"(2016). Medical Laboratories (Standard No. ISO 15189)."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yamamoto, Y., Otsuka, Y., Tokumasu, K., Sunada, N., Nakano, Y., Honda, H., Sakurada, Y., Hasegawa, T., Hagiya, H., and Otsuka, F. (2023). Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome in Patients with Long COVID. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144737"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ofae027","DOI":"10.1093\/ofid\/ofae027","article-title":"Two-Year Longitudinal Study Reveals That Long COVID Symptoms Peak and Quality of Life Nadirs at 6\u201312 Months Postinfection","volume":"11","author":"Demko","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101019","DOI":"10.1016\/j.eclinm.2021.101019","article-title":"Characterizing long COVID in an international cohort: 7 months of symptoms and their impact","volume":"38","author":"Davis","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e2238804","DOI":"10.1001\/jamanetworkopen.2022.38804","article-title":"Prevalence and Correlates of Long COVID Symptoms Among US Adults","volume":"5","author":"Perlis","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fischer, A., Zhang, L., Elbeji, A., Wilmes, P., Snoeck, C.J., Larche, J., Oustric, P., Ollert, M., and Fagherazzi, G. (2025). Trajectories of persisting COVID-19 symptoms up to 24 months after acute infection: Findings from the Predi-Covid cohort study. BMC Infect. Dis., 25.","DOI":"10.1186\/s12879-025-11023-0"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41591-021-01292-y","article-title":"Attributes and predictors of long COVID","volume":"27","author":"Sudre","year":"2021","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2305899","DOI":"10.1080\/0167482X.2024.2305899","article-title":"Clinical characteristics of female long COVID patients with menstrual symptoms: A retrospective study from a Japanese outpatient clinic","volume":"45","author":"Sakurada","year":"2024","journal-title":"J. Psychosom. Obstet. Gynaecol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4851","DOI":"10.1016\/j.cell.2023.09.013","article-title":"Serotonin reduction in post-acute sequelae of viral infection","volume":"186","author":"Wong","year":"2023","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00737-024-01497-3","article-title":"Mental health during the COVID-19 pandemic: An international comparison of gender-related home and work-related responsibilities, and social support","volume":"28","author":"Eugene","year":"2025","journal-title":"Arch. Womens Ment. Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1016\/S0140-6736(22)00008-3","article-title":"Quantifying the effects of the COVID-19 pandemic on gender equality on health, social, and economic indicators: A comprehensive review of data from March, 2020, to September, 2021","volume":"399","author":"Flor","year":"2022","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lei, L., Li, H., Yan, F., and Xiao, Y. (2013). Hyperlipidemia impaired innate immune response to periodontal pathogen porphyromonas gingivalis in apolipoprotein E knockout mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071849"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.archoralbio.2014.06.004","article-title":"Hyperlipidemia causes changes in inflammatory responses to periodontal pathogen challenge: Implications in acute and chronic infections","volume":"59","author":"Chen","year":"2014","journal-title":"Arch. Oral. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"184","DOI":"10.12997\/jla.2021.10.2.184","article-title":"Immunologic Aspects of Dyslipidemia: A Critical Regulator of Adaptive Immunity and Immune Disorders","volume":"10","author":"Kim","year":"2021","journal-title":"J. Lipid Atheroscler."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S2213-8587(22)00355-2","article-title":"Risks and burdens of incident dyslipidaemia in long COVID: A cohort study","volume":"11","author":"Xu","year":"2023","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Fujita, K., Otsuka, Y., Sunada, N., Honda, H., Tokumasu, K., Nakano, Y., Sakurada, Y., Obika, M., Hagiya, H., and Otsuka, F. (2023). Manifestation of Headache Affecting Quality of Life in Long COVID Patients. J. Clin. Med., 12.","DOI":"10.3390\/jcm12103533"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/4918\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:08:25Z","timestamp":1760033305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/4918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":42,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14144918"],"URL":"https:\/\/doi.org\/10.3390\/jcm14144918","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,11]]}}}