key: cord-0990598-1adhh2kr authors: Conway, Richard; Nikiphorou, Elena; Demetriou, Christiana A; Low, Candice; Leamy, Kelly; Ryan, John G; Kavanagh, Ronan; Fraser, Alexander D; Carey, John J; O’Connell, Paul; Flood, Rachael M; Mullan, Ronan H; Kane, David J; Ambrose, Nicola; Stafford, Frances; Robinson, Philip C; Liew, Jean W; Grainger, Rebecca; McCarthy, Geraldine M title: Temporal Trends in COVID-19 outcomes in People with Rheumatic Diseases in Ireland: data from the COVID-19 Global Rheumatology Alliance registry date: 2022-03-08 journal: Rheumatology (Oxford) DOI: 10.1093/rheumatology/keac142 sha: ca0fa8e41f4643a262a02a23370371ad3dafeb67 doc_id: 990598 cord_uid: 1adhh2kr OBJECTIVES: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24th March 2020 and 9(th) July 2021 were analysed. Differences in the likelihood of hospitalisation and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher’s exact test, as appropriate. Trends in odds of hospitalisation and mortality over time were investigated using logistic regression with the time period as a categorical variable. RESULTS: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities, and specific comorbidities of cancer, cardiovascular, and pulmonary disease were more common in those hospitalised. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalised. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalisation or mortality did not change over time. CONCLUSION: No temporal trend was observed in either COVID-19 related hospitalisation or mortality outcomes for people with rheumatic disease in Ireland. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting Coronavirus disease 2019 continue to present a global health crisis. Significant improvements in COVID-19 outcomes have been demonstrated over time (1) (2) (3) (4) (5) . This may relate to accumulating clinical experience leading to an improvement in care (6) along with beneficial effects of several immunomodulating treatments in severe COVID-19 (7) (8) (9) (10) . It is unclear whether outcomes for people with rheumatic disease who develop COVID-19 are also improving, with some studies reporting improved outcomes (4, 11) . Since outcomes following SARS-CoV-2 infection may also vary depending on the geography and ethnicity of affected populations, it is important to explore outcomes in different locations and over time (12) (13) (14) (15) (16) . We have previously reported predictors of hospitalisation in people with rheumatic disease who developed COVID-19 in the first five months of the pandemic in Ireland (17) . In this study we examine temporal trends in COVID-19 outcomes in people with rheumatic disease in Ireland in the first 16 months of the pandemic. Data regarding individuals with rheumatic disease with COVID-19 are entered into one of two parallel international data portals hosted in the United States and United Kingdom. Details of the C19-GRA registries have been published previously (18, 19) . Cases in this study were entered into the C19-GRA provider registry from 24th March 2020 to 9th July 2021. Data were collected on baseline rheumatic disease status including demographic and clinical variables such as age, sex, smoking status, rheumatic disease diagnosis, disease activity (as Page 5 of 18 Rheumatology 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 per the physician's global assessment (remission, low, moderate, or high/severe)), and comorbidities. Medications were categorised as previously described (17 Appropriate confounders were identified as those demographic and clinical variables that were associated with both the outcome of interest as well as with timing/wave of diagnosis. These confounders were corrected for in each model. The significance of any suspected trend was tested using the "contrast" post-estimation command. This study was approved by the Irish National Research Ethics Committee for COVID-19 (20-NREC-COV-010). The committee waived the need for written informed consent as the data were fully anonymised. The 212 cases had a median age of 58.0 years (IQR:45.5-73.0) and the majority were female (59.4%). Most had IA (136/212 64.2%) with the balance having gout (35/212, 16.5%) and CTD or other diagnoses (50/212, 23.6%). The majority of patients (46.2%) were in remission, with 35.6% of cases having low disease activity. Seventy cases (33%) had no comorbidities; among those with comorbidities, cardiovascular and pulmonary diseases were the most prevalent (42% and 17.5%, respectively). Just under half of cases were hospitalized (92/212, 43%) and 22 (10.4%) died. Demographic and clinical details according to hospitalisation are shown in Table 1 . Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities, and specific comorbidities of cancer and cardiovascular and pulmonary disease were more common in those hospitalised. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Patients at either high or low disease activity were more likely to be hospitalised. A diagnosis of IA, csDMARD and/or b/tsDMARD use were less frequent in those hospitalised. Demographic and clinical details according to mortality are shown in Table 1 . Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Cases diagnosed during wave 2 displayed a decrease in the likelihood of hospitalisation compared to wave 1, whereas cases diagnosed during wave 3 had increased hospitalisation odds compared to wave 1 , but all changes were non-significant, as was the quadratic trend in the odds for hospitalisation between the three waves. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 In terms of mortality, cases diagnosed in each successive wave demonstrated again non-statistically significant increased likelihoods of mortality, and a non-statistically increasing linear trend in the odds of mortality across waves (Figure 1 ). The sensitivity analysis restricting our results to the two institutions with rigorous case-finding methodology, reporting 59% of cases, did not alter the overall results. This is the largest and most detailed report of people with rheumatic disease and COVID-19 from Ireland. We have previously reported associations of clinical features with hospitalisation (17). We did not identify any reduction in odds for hospitalisation or mortality over time. This lack of change in odds of hospitalisation and mortality over time was in contrast to other data where clear improvements in COVID-19 outcomes have been demonstrated for non-rheumatic disease patients over time (1, 2, 21) . Likely contributors are better general care measures as well as targeted treatments such as glucocorticoids and tocilizumab (7, 8) . One explanatory hypothesis may be that people with rheumatic diseases, who may be receiving long-term immunomodulating treatments, may be less likely to benefit from the use of these treatments in the setting of subsequent severe COVID-19. Alternatively, our small sample size may have limited ability to demonstrate a change. The roll out of the COVID-19 vaccine in Ireland occurred in conjunction with the third COVID-19 wave and may have impacted on our findings. Previous studies in rheumatic disease patients have suggested some improvement in outcomes over time (4, 5, 11) . A cohort study from Boston of 143 rheumatic disease patients demonstrated a reduction in rates of mechanical ventilation, but not of hospitalisation or mortality, over time (11) . An exposure scored matched analysis study of 8540 rheumatic disease patients using the US TriNetX 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 electronic health record database reported a reduction in the risks of hospitalisation, mechanical ventilation, and mortality when comparing a late cohort to an early cohort (4). The findings of these studies, and the current work, must be interpreted with cognisance of the limitations, including selection bias, unmeasured confounders, and possible artefact related to the identification of milder cases over time as testing capacity expanded (5). Our study has several limitations. While this is the largest study of people with rheumatic disease and COVID-19 from Ireland, the statistical power of our study is limited by the low number of cases; we did not undertake multivariable analyses due to this. The C19-GRA is a physician-entered registry and is limited by selection bias with a likely tendency to report more severe cases. There is also the possibility that the reporting of cases varied over time potentially influencing our results. However, restricting our data to the two institutions with rigorous case ascertainment did not alter the overall findings. The C19-GRA is also a case-based registry with no denominator population, therefore inferences cannot be made about the incidence of COVID-19 in people with rheumatic diseases. Additionally, the C19-GRA is by design restricted to people with rheumatic disease and COVID-19, therefore, comparisons cannot be made to people with non-rheumatic disease and COVID-19 nor to rheumatic disease in the absence of COVID-19. In conclusion our findings demonstrate no difference in hospitalisation or mortality in patients with rheumatic disease across the first three COVID-19 waves in Ireland. 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