Researchers in New Zealand and Australia have conducted a study showing that people with rheumatoid arthritis may be at an increased risk of death if they develop coronavirus disease 2019 (COVID-19) after becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The team used data from the UK Biobank to assess whether the two most common inflammatory arthropathies – gout and rheumatoid arthritis – are risk factors for being diagnosed with or dying from the disease.
In a population-based analysis of more than 470,000 people, neither condition was associated with an increased risk of being diagnosed with COVID-19.
However, rheumatoid arthritis, but not gout, was associated with an increased risk of death from the disease, after adjustment for comorbidities and other risk factors.
“We found an increased risk of death from RA [rheumatoid arthritis], and this needs to be further explored in large datasets where a range of other factors can be investigated (e.g., RA therapies),” say Tony Merriman from the University of Otago and colleagues from the University of Auckland and University of Queensland.
A preprint version of the paper is available on the server medRxiv*, while the article undergoes peer review.
Concerns about gout and COVID-19 risks
Gout is caused by an overreactive innate immune response to monosodium urate crystals in the joints; a response that is driven by auto-inflammatory interleukin-1β (IL-1β).
Theoretically, this could lead to an increased immune response to infection with SARS-CoV-2 – the agent that causes COVID-19.
Furthermore, high serum levels of the pro-inflammatory factors IL-6, IL-8 and tumor necrosis factor-α (TNF-α) have been associated with poor outcomes in COVID-19. Since individuals with gout have higher circulating levels of these cytokines, they may also be at risk of these poor outcomes, say the research team.
Gout is also strongly associated with cardiometabolic comorbidities such as heart disease, type 2 diabetes, and kidney disease, all of which are known risk factors for COVID-19-related death.
Rheumatoid arthritis is a T-cell and B-cell mediated autoimmune disease that, again, targets the joints.
The condition is characterized by high circulating levels of TNF-α and IL-6, and, like gout, could potentially lead to an increased immune response to SARS-CoV-2. Rheumatoid arthritis is also associated with a greater risk of cardiovascular disease.
However, there is a paucity of data available on COVID-19 outcomes among people with these common inflammatory arthropathies, say the researchers.
“Information on the risk of death from COVID-19 for people with gout and rheumatoid arthritis is scarce,” they write.
What did the researchers do?
The researchers set out to investigate whether gout and arthritis are associated with an increased risk of COVID-19 diagnosis or COVID-19-related death.
The team used UK Biobank data, including information on hospital diagnoses from 1991 up to June 30th, 2020; SARS-CoV-2 tests carried out between March 16th and August 24th, 2020, and death records up to August 14th, 2020.
All associations were analyzed using multivariate-adjusted logistic regression to control for age, sex, ethnicity, Townsend deprivation index, BMI, smoking status and 14 comorbidities.
Three analyses were conducted
Analysis A tested for associations between gout or rheumatoid arthritis and COVID-19 diagnosis in a population-based cohort of 473,139 individuals.
Analysis B tested for associations between each of the conditions and death among a case-control cohort of 2,073 individuals who had been diagnosed with COVID-19.
Analysis C also used the population-based cohort to test for associations between each of the conditions and death from COVID-19.
What did the study find?
No association was identified between gout or rheumatoid arthritis and COVID-19 diagnosis in the population-based cohort, and neither condition was associated with death among the diagnosed individuals.
However, rheumatoid arthritis was associated with a 1.8-fold increased risk of death in the population-based cohort. Gout, on the other hand, was not associated with any increased risk of death in this cohort.
The findings need to be checked using larger datasets
“In a population-based analysis there is an increased risk of death by COVID-19 for people with rheumatoid arthritis independent of comorbidities, but not gout,” write the researchers.
The researchers say it is important that the findings presented here are replicated in larger administrative datasets.
“These datasets would allow for more stratification and use of additional models to fully explore factors including medications that might influence the observed association with RA [rheumatoid arthritis],” they write.
“If our association were replicated, investigation of the reasons for the relationship between RA and death from COVID-19 would improve understanding and potentially improve clinical management of COVID-19,” concludes the team.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.