Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis


  • Jhonny K. Fajar Brawijaya Internal Medicine Research Center, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
  • Muhammad Ilmawan Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
  • Sukamto Mamada Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar, Indonesia
  • Endang Mutiawati Department of Neurology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Neurology, Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia
  • Milda Husnah Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Hanifah Yusuf Department of Pharmacology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Firzan Nainu Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar, Indonesia
  • Salin Sirinam Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
  • Synat Keam School of Medicine, University of Western Australia, Perth, Western Australia, Australia
  • Youdiil Ophinni Ragon Institute of MGH, MIT and Harvard, Harvard Medical School, Harvard University, Cambridge, MA, USA; Immunology Frontier Research Center, Osaka University, Osaka, Japan
  • Francesco Rosiello Department of Public Health and Infectious Disease, Sapienza-University of Rome, Rome, Italy
  • Marhami Fahriani Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Sandro GV. Rosa Diretoria de Patentes, Divisão De Farmácia - Instituto Nacional Da Propriedade Industrial, Rio de Janeiro, Brasil; Programa De Pós-Graduação Em Ciências Aplicadas a Produtos Para Saúde, Faculdade De Farmácia, Universidade Federal Fluminense, Brasil



COVID-19, prolonged symptoms, long-term effect, neuromuscular, systematic review


This study was conducted to determine the prevalence of prolonged neuromuscular symptoms, including fatigue, anosmia, headache, myalgia, and joint pain in COVID-19 survivors hospitalized with mild, moderate, or severe infections worldwide. The search was conducted up to January 30th, 2021 using three databases (PubMed, Scopus, and Web of Science) to identify potentially eligible studies. Data on study characteristics, follow-up characteristics, and severity of COVID-19 during hospitalization were collected in accordance with PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of relevant articles. The estimated prevalence of specific prolonged neuromuscular symptoms and the association between COVID-19 severity and occurrence of prolonged neuromuscular symptoms was analyzed wherever appropriate. Database search yielded 4,050 articles and 22 articles were included for meta-analysis. The estimated prevalence of prolonged fatigue was recorded in 21.2% (95%CI: 11.9%–34.8%) of 3,730 COVID-19 survivors. Persistent anosmia was recorded in 239 of 2,600 COVID-19 survivors (9.7%, 95%CI: 6.1%–15.2%). In 84 out of 2,412 COVID-19 survivors (8.9%, 95%CI: 3.2%–22.6%), prolonged headache was observed. A total of 53 out of 1,125 COVID-19 patients (5.6%, 95%CI: 2.1%–14.2%) complained of persistent myalgia even after being discharged from the hospital. The prevalence of prolonged joint pain was in 15.4% (95%CI: 8.2%–27.2%) of subjects. Due to data scarcity on COVID-19 severity and prolonged neuromuscular symptoms, association analysis could not be conducted. Widespread concern regarding long-term impacts of COVID-19 was raised after several studies reported prolonged symptoms in COVID-19 survivors. Numerous theories have been proposed to address this concern; however, as the research on this pandemic is still ongoing, no explanation is definitive yet. Therefore, follow-up studies in COVID-19 survivors after recovery from COVID-19 are warranted to determine the pathogenesis of prolonged symptoms. PROSPERO registration: CRD42021242332.




Original Article