Racial and ethnic differences in COVID-19 outcomes: a call to action

The COVID-19 pandemic has demanded a huge effort to identify the risks associated with poor outcomes. The focus has been particularly relevant in patients with immune-mediated inflammatory diseases and those on therapies that suppress the immune system. Small early observational studies looked worrisome, but as data from larger studies became available a consistent picture became evident. Demographic risk factors such as age and comorbidity are really the salient factors, with some risk from underlying disease and a few specific therapeutic agents, such as rituximab.

Now that we are 2 years into the pandemic, the initial frenzy to generate data has receded, and we need to make sure that we are asking the right questions and designing studies appropriately to answer those questions. It is against this backdrop that the OPENSafely initiative has examined the question of the risk of poor outcomes in patients with immune-mediated inflammatory disease and those on immune-modifying therapy.¹ In The Lancet Rheumatology, Brian MacKenna and colleagues linked primary care data from the UK National Health Service with hospital prescription data for patients with immune-mediated inflammatory diseases.¹ They compared patients with immune-mediated inflammatory diseases with the general population and patients with immune-mediated inflammatory diseases on targeted or biological therapy with those on conventional therapies, such as methotrexate. Two-thirds of the cohort had inflammatory skin diseases, such as psoriasis, and some immune-mediated inflammatory diseases, such as multiple sclerosis, were excluded as well as some drugs, including abatacept, upadacitinib, and integrin inhibitors. The sample sizes of 1·1 million patients with immune-mediated inflammatory diseases and 200 000 patients on immune-modifying drugs are impressive. The authors reassuringly found that patients with immune-mediated inflammatory diseases have a small increased risk of poor outcomes after adjusting for comorbidities (hazard ratio 1·15 [95% CI 1·11–1·18] for COVID-19-related death, 1·16 [1·12–1·19] for COVID-19-related critical care admission or death, and 1·20 [1·17–1·23] for COVID-19-related hospital admission). This finding is in line with data from the US Veterans Affairs administration in patients with rheumatoid arthritis and the COVID-19 Global Rheumatology Alliance registry.² However, other groups have shown that the risk for poor outcomes largely disappears after adjusting for comorbidities.³ MacKenna and colleagues also showed that some agents, notably rituximab, are associated with poor outcomes; this finding has been shown previously by several groups across multiple diseases and further increases our confidence that rituximab has a negative effect on COVID-19 outcomes.4, 5, 6, 7 We can conclude from this and other studies that patients with immune-mediated inflammatory diseases are at an increased risk of poor outcomes definitely attributed to their comorbidities and also potentially to a degree their underlying disease and specific immunosuppressive drugs.

What does this latest study contribute beyond adding robustly collected confirmatory evidence? The authors examined the influence of race and ethnicity on outcomes in patients with rheumatic diseases who had COVID-19. In the general population, non-White individuals, such as those of South Asian and African race, had poorer outcomes than White people. The same is seen when outcomes by race and ethnicity are examined in the immune-mediated inflammatory disease groups. The increased hazard of death and hospital admission was not trivial, with hazard ratios above 1·50 and often above 2·00 depending on the specific analysis. These UK data follow a similar pattern to data published in the USA from the Global Rheumatology Alliance.⁸

Can we unravel these striking health disparities? The US National Institute of Minority Health and Health Disparities provides a useful framework for conceptualising factors relevant to understanding health disparities. Different domains (ie, biological, behavioural, physical or built environment, sociocultural environment, and health-care system) and levels of influence (ie, individual, interpersonal, community, and societal) within these domains are included in this framework.⁹ The pandemic has brought to light the many factors across these domains and levels of influence that underlie health disparities in COVID-19 outcomes. For example, individuals with rheumatic disease and low socioeconomic status might have greater disease severity and a higher comorbidity burden, both factors that drive more severe COVID-19 outcomes. Similarly, individuals from vulnerable groups might distrust the health-care system or have poor access to care, leading to treatment delays for COVID-19. Front-line jobs and crowded housing conditions increase the risk of SARS-CoV-2 transmission. Limited health literacy and misinformation among social networks might lead to lower vaccination rates and also inability to advocate for pre-exposure prophylaxis or outpatient COVID-19 therapies such as antivirals or monoclonal antibodies. Implicit or even overt bias among health-care professionals could lead to inadequate counselling on these and other important topics.

Given the complexity of the factors underlying these health disparities for people with rheumatic disease during the pandemic, what can we do to activate health equity? In the panel , we outline actions that individual rheumatologists and their clinics and communities can take to address COVID-19 health disparities. Rheumatologists can proactively counsel patients regarding prevention and treatment for COVID-19, filling educational gaps about vaccines, testing, pre-exposure prophylaxis, and treatment for patients who might not otherwise have access to this information. Clinics and health systems should build processes for population health management, including targeting culturally and linguistically appropriate evidence-based materials to patients at high risk. There are also actions that our communities and policy makers should take to protect vulnerable populations, particularly around addressing the many social determinants of health that conspire to put vulnerable populations at risk for poor health outcomes. The root causes of racial and ethnic disparities in COVID-19 outcomes for people with rheumatic diseases are complex, and solutions will need to be multifaceted. We have the skills and knowledge to start to address COVID-19 health disparities, and data from this study and others serve as a call to action to implement strategies to improve health equity for patients with rheumatic disease.

Panel. Activating health equity for patients with rheumatic diseases during the COVID-19 pandemic.

Individual clinicians

• •Counsel patients to have home COVID-19 tests available for prompt diagnosis, if financially feasible. Ensure that patients know where to get tested
• •Counsel patients about prevention (personal protective equipment, vaccinations)
• •Offer and arrange for pre-exposure prophylaxis for patients at high risk of poor outcomes from COVID-19, such as rituximab
• •Counsel patients about available antiviral and monoclonal antibody therapies, time windows for eligibility, and who to call to request these therapies

Clinic or health system

• •Collect high-quality data on patient race and ethnicity to identify and monitor health disparities
• •Counsel patients about adjusting immunosuppression for vaccination or infection
• •Use population health management, including tracking of vaccination rates among vulnerable groups
• •Target culturally and linguistically appropriate, evidence-based outreach and education to groups with low vaccination rates

Community organisations

• •Conduct outreach activities, including culturally and linguistically tailored COVID-19 prevention campaigns for immunocompromised patients
• •Provide educational, social, and other support to people with rheumatic diseases during the pandemic and ensure that this support reaches the most vulnerable populations

Policy makers

• •Ensure equitable access to COVID-19 testing and treatment
• •Provide free access to effective vaccines
• •Fund high-quality research investigating how best to protect immunocompromised patients, including those from vulnerable communities, from severe COVID-19
• •Address social determinants of health, including housing and food security

PCR reports personal fees from AbbVie, Atom Biosciences, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche, and Pfizer; meeting attendance support from Bristol Myers Squibb, Roche, Pfizer, and UCB; and grant funding from Janssen, Novartis, Pfizer, and UCB Pharma. JY is supported by US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases grants K24 AR074534 and P30 AR070155. She has received research grants from AstraZeneca, Gilead, and BMS Foundation, and has had consultancy roles with Pfizer, AstraZeneca, and Aurinia.