COVID‐19 outcomes among rheumatic disease patients in Kuwait: Data from the COVID‐19 Global Rheumatology Alliance (C19‐GRA) physician registry

Abstract Purpose We aimed to assess the characteristics of inflammatory rheumatic disease (IRD) patients in Kuwait diagnosed with COVID‐19 and the factors linked with hospitalization, complications, and mortality. Methods Data of IRD patients from Kuwait diagnosed with COVID‐19 between March 2020 and March 2021, submitted to the COVID‐19 Global Rheumatology Alliance physician‐reported registry, were included in our analysis. Data on patients' age, gender, smoking, diagnosis, IRD activity, and other comorbidities were collected. Statistical Package for the Social Sciences (SPSS), version 25, was used for statistical analysis. Results A total of 52 patients were included, with a mean age of 55 years (±14). The majority of patients were ≤65 years (77%), female (77%), non‐smokers (80.8%), and diagnosed with rheumatoid arthritis (67.0%). Of the included patients, 19.2%, 9.6%, and 7.7% reported having methotrexate monotherapy, antimalarials monotherapy, and interleukin‐6 inhibitors monotherapy immediately before COVID‐19, respectively. Most of the included patients (92.3%) were either in remission or had minimal/low disease activity, while others (7.7%) had moderate disease activity. Forty‐three patients (82.7%) were hospitalized, while 11 patients (25.6%) required ventilation (invasive or non‐invasive). Ten of the ventilated patients (90.9%) received glucocorticoids as part of the local protocol to treat severe COVID symptoms, and 4 patients (7.69%) died. The duration till symptom‐free ranged between 0 to 30 days, with a mean value of 10 days (±6.5). Conclusion The current study provides timely real‐world evidence regarding characteristics and potential risk factors linked to poor COVID‐19‐related outcomes in the IRD population in Kuwait.


| INTRODUC TI ON
There is insufficient reliable data to guide our knowledge of outcomes in patients with inflammatory rheumatic diseases (IRD) or those who are immunosuppressed after SARS-CoV-2 infection, leading to uncertainty about chronic disease treatment in such patients. [1][2][3] Previous literature has highlighted the uncertainty if individuals with IRD fall into a susceptible, higher-risk group for being infected with SARS-CoV-2 and have poor outcomes. 4-6 Compared to people without IRD, IRD patients appear to have similar or slightly worse results. 5,7 However, crucial illness-related confounding variables (eg, disease activity or therapies) have not been previously discussed.
COVID-19 and its subsequent complications have been treated with medications typically used to treat IRD, raising issues regarding the influence of these therapies on SARS-CoV-2 infection outcomes. [8][9][10] Previous literature had even suggested continuing immunomodulatory or immunosuppressive medication in order to control IRD activity, avoid the progression of the disease, and avoid joint/organ damage caused by chronic inflammation. 11 Even during a pandemic, the withdrawal of effective medicines should be supported by scientific data.
In March 2020, a worldwide network of rheumatologists, data scientists, as well as patients, created a COVID-19 physicianreported case registry to collect more comprehensive data related to IRD patients infected with SARS-CoV-2. 12,13 Analyzing the collected data showed that older age, as well as comorbidities, were linked to hospitalization and severe COVID-19 outcome compared to the findings in the general population. 4, 14,15 The current study aimed to assess the clinical characteristics of IRD patients in Kuwait diagnosed with COVID-19 from the data submitted to the COVID-19 Global Rheumatology Alliance (C19-GRA) physician-reported registry. Moreover, we investigated the factors linked with hospitalization, complications, and mortality among these patients.

| Study population and data source
In the current study, we included patients from Kuwait who entered the registry as of March 2020. The detailed C19-GRA physicianreported registry has been previously described. 12,16,17 The data collected was multicenter, with Jaber Alahmed Alsabah Hospital being the source of most cases as the major COVID-19 center in Kuwait.
The included patients were IRD patients with a COVID-19 diagnosis. The diagnosis of COVID-19 was reported by the physicians, whether it was diagnosed by polymerase chain reaction (PCR) test, metagenomic analysis, computed tomography imaging, laboratory investigations, or preliminary clinical diagnosis based on the clinical manifestations. Data on patients' age, gender, the status of smoking, medications prior to COVID-19 diagnosis, IRD activity, and other comorbidities were captured. Moreover, we collected laboratory findings and COVID-19-related data in terms of the time of diagnosis, clinical manifestations, treatment, admission to the hospital, and the maximum level of care received.

| Medications prior to COVID-19
The medications before COVID-19 diagnosis were categorized as follows: 1. conventional synthetic disease-modifying anti-rheumatic drugs The physicians reported the duration from the onset of symptoms either until the resolution of the symptoms or death.

| Statistical analysis
For statistical analysis, Statistical Package for the Social Sciences (SPSS) for Windows, version 25, was used. Continuous variables are reported as mean and standard deviation (SD) for normally distributed data or median and interquartile range (IQR) for non-normally distributed data. While dichotomous data are reported as frequency and percentage (%).

| IRD patients with COVID-19 stratified by COVID-19 complications
The demographic characteristics and the immune-modulating medications stratified by COVID-19 complications are shown in Table 4.

| Days of hospitalization
The duration till symptom-free ranged between 0 to 30 days, with a mean value of 10 days (SD = 6.5). The detailed descriptive analysis of the days of hospitalization of the included patients is shown in Table S3.

| DISCUSS ION
The COVID-19 pandemic undoubtedly influences the therapeutic approach to rheumatic diseases, whose infectious risk is considerably higher than the general population due to an overall im-

AUTH O R CO NTR I B UTI O N S
Fatemah Abutiban wrote the manuscript with input from all authors.
All authors reviewed the results and approved the final version of the manuscript.

ACK N OWLED G EM ENTS
The COVID-19 Global Rheumatology Alliance Registry, Professor Khalid Aljarallah, Head of the Rheumatology Unit at Jaber Alahmed Hospital, State of Kuwait.

CO N FLI C T O F I NTE R E S T
All authors declare no conflict of interests.