ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) is an emerging global medical challenge and glucocorticoids remain the most promising therapy. Osteonecrosis (ON) is a disease caused by reduced blood flow to bones in the joints, which will rapidly induce joint destroy. ON had been frequently identified among convalescent patients after Severe Acute Respiratory Syndrome (SARS). Considering the similarity of SARS and COVID-19 on their pathogen, clinical characteristics and therapeutic strategies, it is particularly worrying whether ON will be a common sequela among convalescent COVID-19 patient.Methods: This multi-strategy study integrating different research methods, such as meta-analysis, systematic review and cross-sectional investigation. At first, two meta-analyses were performed on the incidence of osteonecrosis among SARS patients and the clinical data of glucocorticoid exposure among COVID-19 patients. Then, a systematic review of low-dosage glucocorticoid associated osteonecrosis and a real-world cross-sectional investigation of glucocorticoid exposure of COVID-19 patients in China Wuhan were also provided. Moreover, the pathogenesis, diagnosis, prevention, and treatment options for osteonecrosis after COVID-19 infection were further described.Findings: Our meta-analysis showed that 32% of SARS patients had developed ON after receiving glucocorticoid treatment with high dose, and our system review also supported that low level glucocorticoid exposure may lead to the occurrence of ON. Similarly, 40% of COVID-19 patients had undergone glucocorticoid treatment according to our meta-analysis. The cross-sectional investigation in China Wuhan found that the average of cumulative glucocorticoid exposure level was 504 mg calculated by the dosage of methylprednisolone. Notably, a confirmed osteonecrosis case after COVID-19 was identified during our investigation. Preventive management of ON shall better start with regular clinical followup observation.Interpretation: Growing evidence of the glucocorticoid therapy for COVID-19 patients prompts us to put forward the risk-classification-based early screening and early prevention protocol of ON, which may be of clinical significance in favorable prognosis of this disease.Registration Details: PROSPERO, registration number CRD42020203536.Funding Information: This study was supported by the Special Project For COVID-19 Prevention and Management of Ministry of Education of China (2020-JYB-YJ-023), the National Key Research and Development Program of China (2019ZX09731-002) and the State Key Program of National Natural Science Foundation of China (82030122).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The protocol for the investigation study has been registered in the Chinese Clinical Trial Registry (ChiCTR), (URL: http://www.chictr.org.cn/showproj.aspx?proj=61769, No. ChiCTR2000038333). This study was approved by the Ethics Institutional Review Board of the Third Affiliated Hospital of Beijing University of Chinese Medicine (No. BZYSY-2020KYKTPJ-06), and informed consent was obtained from every participant patient.