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Objectives: The aim of this study was to assess the cause-specific mortality rate related to COVID-19 (CMR) in patients with rheumatic and musculoskeletal diseases (RMDs) and COVID-19 and to analyze the role of the different RMDs in their mortality risk. Methods: An observational longitudinal study was conducted during the first pandemic wave in our center. Patients with the diagnosis of RMDs and COVID-19 were included. Main outcome is the death related to COVID-19. Independent variable – type of RMDs: autoimmune rheumatic diseases (ARD), such as chronic inflammatory arthritis (CIA) and connective tissue diseases (CTD) and non-autoimmune Rheumatic Diseases (non-ARD). Survival techniques were used to estimate the CMR per 1000 patients-month with a 95% confidence interval (CI), and Cox multivariate regression analysis was run to examine the effect of ARD compared to non-ARD on mortality risk adjusted by confounders. Results were expressed by Hazard Ratio (HR) and CI. Results: Overall, 405 patients were included (642.5 patients-month). During the study period, 44 (10.86%) deaths were recorded. CMR was 68.48 (50.96–92.01). After adjusting for confounders, HR of mortality in ARD compared to non-ARD did not achieve statistical significance [HR: 1.15 (0.64–2.07)], neither CTD versus CIA nor CTD versus non-ARD. Age and certain comorbidities which are being diagnosed in March compared to April or May [HR: 2.43 (1.1–5.55)] increased the mortality risk. Glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) dropped from the final model. Conclusion: In patients with RMDs and COVID-19, CMR was 6.8% patients-month. This study shows that mortality risk is higher in males, older patients, and similar between CTD, CIA, and non-ARD. COVID-19 management improved after the first month of pandemic. Plain Language Summaries Mortality related to the outbreak of COVID-19 in patients with rheumatic and musculoskeletal diseases Why was this study done? - To report the COVID-19-specific mortality rate in patients with a variety of RMDs during the first pandemic peak in a tertiary hospital in Madrid and to analyze the role of specific types of ARD and other possible factors in the risk of death related to COVID-19. What did the researchers do? - We performed a retrospective observational study during the first wave of the COVID-19 pandemic in Madrid, Spain. What did the researchers find? - In this study, neither the different diagnoses of RMDs, including CIA, CTD, or non-ARD disease or its treatment were not implicated as a potential risk of death related to COVID-19 - In consonance with other studies, RMDs patients and COVID-19, older age, male sex, and certain comorbidities implied more mortality risk - Our data reflect COVID-19 severity in a particular context, time, and population. In times of the absence of COVID-19 vaccine, healthcare, social, and political measures taken to contain the coronavirus outbreak have worked properly. What do the findings mean? - The presence of comorbidities in RMDs patients represents a greater risk than the different types of RMDs themselves, in the development of COVID-19 fatal outcome. It is important to integrate the control of comorbidities in the daily management.