Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study
Tak-Kyu Oh, In-Ae Song, Joon Lee, Woosik Eom, Young-Tae Jeon
International Journal of Environmental Research and Public Health, doi:10.3390/ijerph18136804
We aimed to investigate whether comorbid musculoskeletal disorders (MSD)s and pain medication use was associated with in-hospital mortality among patients with coronavirus disease 2019 . Adult patients (≥20 years old) with a positive COVID-19 diagnosis until 5 June 2020 were included in this study, based on the National Health Insurance COVID-19 database in South Korea. MSDs included osteoarthritis, neck pain, lower back pain, rheumatoid arthritis, and others, while pain medication included paracetamol, gabapentin, pregabalin, glucocorticoid, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids (strong and weak opioids), and benzodiazepine. Primary endpoint was in-hospital mortality. A total of 7713 patients with COVID-19 were included, and in-hospital mortality was observed in 248 (3.2%) patients. In multivariate logistic regression analysis, no MSDs (p > 0.05) were significantly associated with in-hospital mortality. However, in-hospital mortality was 12.73 times higher in users of strong opioids (odds ratio: 12.73, 95% confidence interval: 2.44-16.64; p = 0.002), while use of paracetamol (p = 0.973), gabapentin or pregabalin (p = 0.424), glucocorticoid (p = 0.673), NSAIDs (p = 0.979), weak opioids (p = 0.876), and benzodiazepine (p = 0.324) was not associated with in-hospital mortality. In South Korea, underlying MSDs were not associated with increased in-hospital mortality among patients with COVID-19. However, use of strong opioids was significantly associated with increased in-hospital mortality among the patients.
Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/ijerph18136804/s1, Table S1 : ICD-10 codes and Table S2 : The ICD-10 codes used by comorbidity to compute the Charlson comorbidity index. Informed Consent Statement: Informed consent was waived by the IRB, as the analyses were performed retrospectively using anonymized data derived from the South Korean NHIS database.
Conflicts of Interest: The authors declare no conflict of interest.
References
Briggs, Woolf, Dreinhöfer, Homb, Hoy et al., Reducing the global burden of musculoskeletal conditions, Bull. World Heal. Organ,
doi:10.2471/BLT.17.204891
Dagan, Barda, Kepten, Miron, Perchik et al., BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting, N. Engl. J. Med,
doi:10.1056/NEJMoa2101765
Diasso, Birke, Nielsen, Main, Højsted et al., The effects of long-term opioid treatment on the immune system in chronic non-cancer pain patients: A systematic review, Eur. J. Pain,
doi:10.1002/ejp.1506
Elm, Altman, Egger, Pocock, Gøtzsche et al., The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies, Ann. Intern. Med,
doi:10.7326/0003-4819-147-8-200710160-00010
Flint, Janowitz, Connell, Roberts, Denton et al., Tumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity, Cell Metab,
doi:10.1016/j.cmet.2016.10.010
Fredi, Cavazzana, Moschetti, Andreoli, Franceschini et al., COVID-19 in patients with rheumatic diseases in northern Italy: A single-centre observational and case-control study, Lancet Rheumatol,
doi:10.1016/S2665-9913(20)30169-7
Generaal, Vogelzangs, Macfarlane, Geenen, Smit et al., Basal inflammation and innate immune response in chronic multisite musculoskeletal pain, Pain,
doi:10.1016/j.pain.2014.05.007
Greenland, Mansournia, Altman, Sparse data bias: A problem hiding in plain sight, BMJ,
doi:10.1136/bmj.i1981
Haberman, Axelrad, Chen, Castillo, Yan et al., Covid-19 in Immune-Mediated Inflammatory Diseases-Case Series from New York, N. Engl. J. Med,
doi:10.1056/NEJMc2009567
Haberman, Castillo, Chen, Yan, Ramirez et al., COVID-19 in Patients with Inflammatory Arthritis: A Prospective Study on the Effects of Comorbidities and Disease-Modifying Antirheumatic Drugs on Clinical Outcomes, Arthritis Rheumatol,
doi:10.1002/art.41456
Kim, Fine, Li, Kimmel, Ngo et al., Disparities in United States hospitalizations for serious infections in patients with and without opioid use disorder: A nationwide observational study, PLoS Med,
doi:10.1371/journal.pmed.1003247
Mackinnon, Socías, Bardwell, COVID-19 and overdose prevention: Challenges and opportunities for clinical practice in housing settings, J. Subst. Abus Treat,
doi:10.1016/j.jsat.2020.108153
Manuel, Estabrook, The American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice, Clin. Transplant,
doi:10.1111/ctr.13511
Oh, Jeon, Choi, Trends in chronic opioid use and association with five-year survival in South Korea: A populationbased cohort study, Br. J. Anaesth,
doi:10.1016/j.bja.2019.08.012
Oh, Song, Trends in long-term glucocorticoid use and risk of 5-year mortality: A historical cohort study in South Korea, Endocrine,
doi:10.1007/s12020-020-02382-6
Pereira, Lawlor, Vigano, Dorgan, Bruera, Equianalgesic Dose Ratios for Opioids: A Critical Review and Proposals for Long-Term Dosing, J. Pain Symptom Manag,
doi:10.1016/S0885-3924(01)00294-9
Pierce, Bird, Hickman, Millar, National record linkage study of mortality for a large cohort of opioid users ascertained by drug treatment or criminal justice sources in England, 2005-2009, Drug Alcohol Depend,
doi:10.1016/j.drugalcdep.2014.09.782
Ray, Chung, Murray, Hall, Stein, Prescription of Long-Acting Opioids and Mortality in Patients with Chronic Noncancer Pain, JAMA,
doi:10.1001/jama.2016.7789
Schwetz, Calder, Rosenthal, Kattakuzhy, Fauci, Opioids and Infectious Diseases: A Converging Public Health Crisis, J. Infect. Dis,
doi:10.1093/infdis/jiz133
Shah, Kuo, Baillargeon, Raji, The impact of long-term opioid use on the risk and severity of COVID-19, J. Opioid Manag,
doi:10.5055/jom.2020.0597
Waghmare, Englund, Boeckh, How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation, Blood,
doi:10.1182/blood-2016-01-634873
Wang, Kaelber, Xu, Volkow, COVID-19 risk and outcomes in patients with substance use disorders: Analyses from electronic health records in the United States, Mol. Psychiatry,
doi:10.1038/s41380-020-00880-7
Weisberg, Gordon, Barry, Becker, Crystal et al., Long-term Prescription of Opioids and/or Benzodiazepines and Mortality Among HIV-Infected and Uninfected Patients, J. Acquir. Immune Defic. Syndr,
doi:10.1097/QAI.0000000000000591
Wilson, Ramage, Fagan, A Primary Care Response to COVID-19 for Patients with an Opioid Use Disorder, J. Rural. Heal,
doi:10.1111/jrh.12438
Wolfe, Caplan, Michaud, Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy, Arthritis Rheum,
doi:10.1002/art.21568