People with gout, especially women, appear to be at higher risk for poor COVID-19 outcomes, including hospitalization and death, regardless of COVID-19 vaccination status, researchers suggest.
“We found that the risks of SARS-CoV-2 infection, 30-day hospitalization, and 30-day death among individuals with gout were higher than the general population irrespective of the vaccination status,” lead study author Dongxing Xie, MD, PhD, Xiangya Hospital, Central South University, Changsha, China, and his colleagues write in their large population study. “This finding informs individuals with gout, especially women, that additional measures, even after vaccination, should be considered in order to mitigate the risk of SARS-CoV-2 infection and its severe sequelae.”
People with gout, the most common inflammatory arthritis, often have other conditions that are linked to higher risk for SARS-CoV-2 infection and poor outcomes as well, including obesity, cardiovascular disease, and chronic kidney disease, the authors write. And elevated serum urate may contribute to inflammation and possible COVID-19 complications. But unlike diseases such as lupus and rheumatoid arthritis, little is known about SARS-CoV-2 infection risk among patients with gout.
As reported in Arthritis & Rheumatology, Xie and his research team used The Health Improvement Network ([THIN], now called IQVIA Medical Research Database) repository of medical conditions, demographics, and other details of around 17 million people in the United Kingdom to estimate the risk for SARS-CoV-2 infection, hospitalization, and death in people with gout. They compared those outcomes with outcomes of people without gout and compared outcomes of vaccinated vs nonvaccinated participants.
From December 2020 through October 2021, the researchers investigated the risk for SARS-CoV-2 breakthrough infection in vaccinated people between age 18 and 90 years who had gout and were hospitalized within 30 days after the infection diagnosis or who died within 30 days after the diagnosis. They compared these outcomes with the outcomes of people in the general population without gout after COVID-19 vaccination. They also compared the risk for SARS-CoV-2 infection and its severe outcomes between individuals with gout and the general population among unvaccinated people.
They weighted these comparisons on the basis of age, sex, body mass index, socioeconomic deprivation index score, region, and number of previous COVID-19 tests in one model. A more fully adjusted model also weighted the comparisons for lifestyle factors, comorbidities, medications, and healthcare utilization.
The vaccinated cohort consisted of 54,576 people with gout and 1,336,377 without gout from the general population. The unvaccinated cohort included 61,111 individuals with gout and 1,697,168 individuals without gout from the general population.
Women More Likely to Be Hospitalized and Die
The risk for breakthrough infection in the vaccinated cohort was significantly higher among people with gout than among those without gout in the general population, particularly for men, who had hazard ratios (HRs) ranging from 1.22 with a fully adjusted exposure score to 1.30 with a partially adjusted score, but this was not seen in women. The overall incidence of breakthrough infection per 1000 person-months for these groups was 4.68 with gout vs 3.76 without gout.
The researchers showed a similar pattern of a higher rate of hospitalizations for people with gout vs without (0.42/1000 person-months vs. 0.28); in this case, women had higher risks than did men, with HRs for women ranging from 1.55 with a fully adjusted exposure score to 1.91 with a partially adjusted score compared with 1.22 and 1.43 for men, respectively.
People with gout had significantly higher mortality than did those without (0.06/1000 person-months vs 0.04), but the risk for death was only higher for women, with HRs calculated to be 2.23 in fully adjusted exposure scores and 3.01 in partially adjusted scores.
These same comparisons in the unvaccinated cohort all went in the same direction as did those in the vaccinated cohort but showed higher rates for infection (8.69/1000 person-months vs 6.89), hospitalization (2.57/1000 person-months vs 1.71), and death (0.65/1000 person-months vs 0.53). Similar sex-specific links between gout and risks for SARS-CoV-2 infection, hospitalization, and death were seen in the unvaccinated cohort.
Patients With Gout and COVID-19 Need Close Monitoring
Four experts who were not involved in the study encourage greater attention to the needs of patients with gout.
Pamela B. Davis, MD, PhD, research professor at Case Western Reserve University, Cleveland, Ohio, told Medscape Medical News, “This study brings to attention yet another potentially vulnerable group for physicians to monitor closely if they are infected with SARS-CoV-2.
“It is not clear why women with gout are more vulnerable, but fewer women than men were in the cohort with gout, and the confidence intervals for the results in women were, in general, larger,” she said.
“The authors suggest that women with gout tend to be older and have more comorbidities than men with gout,” Davis added. “The excess risk diminishes when the model is fully adjusted for comorbidities, such as obesity, hypertension, or heart disease, suggesting that already-known antecedents of infection severity account for a great deal of the excess risk.”
Kevin D. Deane, MD, PhD, associate professor of medicine and chair in rheumatology research at the University of Colorado Anschutz Medical Campus in Aurora, advises physicians to keep in mind other conditions linked with increased risk for severe COVID-19, including advanced age, heart, lung, or kidney problems, and autoimmune diseases.
“It will be of interest to know if treating gout leads to improved COVID-19 outcomes,” he said.
“I would be very cautious about the finding that there was not a difference in outcomes in individuals with gout based on vaccination status,” he cautioned, urging clinicians to “still strongly recommend vaccines according to guidelines.”
Sarah E. Waldman, MD, associate clinical professor of infectious diseases at UC Davis Health in Sacramento, California, called the study interesting but not surprising.
“The reason for increased risk for COVID-19 infection among those with gout may have to do with their underlying inflammatory state. Additional research needs to be done on this topic.
“Retrospective population-based cohort studies can be difficult to interpret due to biases,” she added. Associations identified in this type of study do not determine causation.
“As the researchers noted, those with gout tend to have additional comorbidities as well as advanced age,” she said. “They may also seek medical care more often and be tested for SARS-CoV-2 more frequently.”
Waldman advises clinicians to counsel patients with gout about their potential increased infection risk and ways they can protect themselves, including COVID-19 vaccinations.
Thanda Aung, MD, MS, a rheumatologist and assistant clinical professor of medicine at in the University of California, Los Angeles, said that women with gout appearing to be at greater risk than are men for serious COVID-19 complications is interesting, but more research to explore the link is needed.
“The strong association between gout and COVID-19 infection could involve coexisting conditions such as diabetes, hypertension, cardiovascular disease, and chronic kidney disease,” Aung added.
Earlier Studies Show Links Between Gout and Severe COVID-19 Outcomes
Lead author Kanon Jatuworapruk, MD, PhD, of Thammasat University in Pathumthani, Thailand, and his colleagues investigated characteristics and outcomes of people with gout who were hospitalized for COVID-19 between March 2020 and October 2021, using data from the COVID-19 Global Rheumatology Alliance registry.
“This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death,” the authors write in ACR Open Rheumatology . “This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.”
In their study, the average age of the 163 patients was 63 years, and 85% were men. Most lived in the Western Pacific Region and North America, and 46% had two or more comorbidities, most commonly hypertension, cardiovascular disease, diabetes, chronic kidney disease, and obesity. The researchers found that:
Sixty-eight percent of the cohort required supplemental oxygen or ventilatory support during hospitalization.
Sixteen percent of deaths were related to COVID-19, with 73% of deaths occurring in people with two or more comorbidities.
Ruth K. Topless, assistant research fellow in the Department of Biochemistry at the University of Otago in Dunedin, New Zealand, is the lead author on a study she and her colleagues conducting using the UK Biobank database’s 459,837 participants in the United Kingdom, including 15,871 people with gout, through April 6, 2021, to investigate whether gout is a risk factor for diagnosis of COVID-19 and COVID-19–related death.
“Gout is a risk factor for COVID-19-related death in the UK Biobank cohort, with an increased risk in women with gout, which was driven by risk factors independent of the metabolic comorbidities of gout,” the researchers conclude in The Lancet Rheumatology .
In their study, gout was linked with COVID-19 diagnosis (odds ratio [OR], 1.20; 95% CI, 1.11-1.29) but not with risk for COVID-19–related death in the group of patients with COVID-19 (OR, 1.20; 95% CI, 0.96-1.51). In the entire cohort, gout was linked with COVID-19–related death (OR, 1.29; 95% CI, 1.06-1.56); women with gout were at increased risk for COVID-19–related death (OR, 1.98; 95% CI, 1.34-2.94), but men with gout were not (OR, 1.16; 95% CI, 0.93-1.45). The risk for COVID-19 diagnosis was significant in the nonvaccinated group (OR, 1.21; 95% CI, 1.11-1.30) but not in the vaccinated group (OR, 1.09; 95% CI, 0.65-1.85).
Editorial Authors Join in Recommending Further Related Research
In a commentary in The Lancet Rheumatology about the UK Biobank and other related research, Christoffer B. Nissen, MD, of University Hospital of Southern Denmark in Sonderborg, and his co-authors call the Topless and colleagues study “an elegantly conducted analysis of data from the UK Biobank supporting the hypothesis that gout needs attention in patients with COVID-19.”
Further studies are needed to investigate to what degree a diagnosis of gout is a risk factor for COVID-19 and whether treatment modifies the risk of a severe disease course,” they write. “However, in the interim, the results of this study could be considered when risk stratifying patients with gout in view of vaccination recommendations and early treatment interventions.”
Each of the three studies received grant funding. Several of the authors of the studies report financial involvements with pharmaceutical companies. All outside experts commented by email and report no relevant financial involvements.
Arthritis Rheumatol. Published online September 9, 2022. Full text
ACR Open Rheumatol. Published online August 24, 2022. Full text
Lancet Rheumatol. Published online January 28, 2022. Full text