Key points

Background

The burden of the coronavirus disease 2019 (COVID-19) pandemic has been staggering globally with over 775 million reported cases and over 7 million deaths. Individuals with rheumatic diseases, who may be immunocompromised, have an increased risk of developing life-threatening complications. While most studies indicated no significant differences in the prevalence of COVID-19 infection compared to the general population, a study based in England found that individuals who had rheumatic conditions had an increased risk of COVID-19 related mortality (hazard ratio [HR] 1.2 [95% confidence interval (CI) 1.1–1.3]). Individuals with additional comorbidities like hypertension, cardiovascular disease or diabetes had even higher odds of developing a poor outcome, including the need for hospitalization or ventilatory support.

Inequities in adverse COVID-19 outcomes by race, ethnicity, socioeconomic status, and neighborhood exposures have been observed both in the overall population and in those with a rheumatic condition. Black and Hispanic populations had disproportionately higher rates of COVID-19 infection, intensive care unit admission, and related mortality. ^, In the COVID-19 Global Rheumatology Alliance physician registry, Black (odds ratio [OR] 2.7 [95% CI 1.9–4.0]), Latinx (OR 1.1 [95% CI 1.9–2.5]), and Asian (OR 2.7 [95% CI 1.2–6.2]) patients had significantly higher odds of hospitalization compared to White patients. Additionally, Latinx patients had 3-fold higher odds of requiring ventilatory support (OR 3.3 [95% CI 1.8–6.1]). Similar findings were observed among individuals with systemic lupus erythematosus (SLE); Black (OR 2.7 [95% CI 1.4–5.5]) and Hispanic (OR 2.76 [95% CI 1.34–5.69]) patients had higher odds of severe outcomes like hospitalization, oxygen/ventilatory requirement, and death, compared to White patients, adjusted for age, sex, region, time period, number of comorbidities, presence of renal or cardiovascular comorbidities, disease activity, exposure to glucocorticoids, and immunosuppressive medication category.

Vaccination remains a critical prevention tool against morbidity and mortality related to infectious diseases. For patients with autoimmune rheumatic diseases, a 2023 meta-analysis of 8 studies comprising 1348 patients found a pooled COVID-19 vaccine uptake rate estimated at 67% (I ² = 98%), indicating a persistent need for education and interventions to improve vaccination uptake. There is a paucity of studies investigating sociodemographic disparities in COVID-19 vaccine uptake in patients with rheumatic diseases. In a 1:1 age-, sex-, race-, and county-matched study of 342 patients with SLE and 350 patients without SLE, about 17% of patients with SLE remained unvaccinated 7 months after vaccines became available in 2021. This study found no differences in uptake between patients with and without SLE after adjusting for race, ethnicity, or area deprivation index. This rate was consistent with the overall United States (US) vaccination rate. However, the cohort was nearly 87% White and based in the upper Midwest and may not be sufficiently powered to draw conclusions regarding potential sociodemographic inequities.

Vaccine-preventable diseases have often shared an inverse relationship with vaccine uptake in historically marginalized communities. Racial and ethnic disparities in vaccination rates can stem from inequitable care access and delivery, driven by structural racism. Structural racism reflects the ways in which “societies foster racial discrimination through mutually reinforcing macro-level systems” (eg, housing, education, healthcare, and criminal justice). Thus, utilizing an equity lens allows for the consideration that different groups of individuals experience different sets of risk, needs, and opportunities due to legacies of inequity, injustice, and discrimination. ^, Therefore, interventions to improve overall vaccination uptake should specifically focus on the needs of populations that have been historically marginalized or made vulnerable to prevent the widening of already existing inequities. In this review, through an equity lens, we explore reasons for vaccine hesitancy and describe interventions to reduce hesitancy and improve COVID-19 vaccine uptake among individuals with rheumatic conditions. We describe 2 scalable interventions that are underway that utilize community-engaged strategies to increase COVID-19 vaccine uptake among historically marginalized individuals with rheumatic conditions in Alabama, Illinois, and Massachusetts.

Coronavirus disease 2019 vaccine hesistancy among individuals with rheumatic conditions

During the COVID-19 pandemic, vaccination became highly politicized, controversial, and a source of doubt. Despite its benefits and protection against viral infection, levels of skepticism and misinformation were high, leading to COVID-19 vaccine hesitancy. In 2019, vaccine hesitancy was identified by the World Health Organization as a top 10 threat to public health. Vaccine hesitancy is of particular concern among people with rheumatic conditions given their increased risk for adverse outcomes from serious infections like COVID-19. ^,

While acknowledging their increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients in an Italy-based study with rheumatic and musculoskeletal disease (54.9%, n = 344/626) were less likely to receive the COVID-19 vaccine compared to healthy controls (82.3%, n = 284/345). Further, differences exist in vaccine hesitancy when stratifying this population by race. A New York City-based study found that Black rheumatology outpatients were 4 times more likely than White rheumatology outpatients to express hesitancy toward COVID-19 vaccination (OR 4.29, [95% CI, 1.96–9.36]). Several studies have investigated reasons for this hesitancy to inform the design of interventions to increase COVID-19 vaccine uptake in patients with rheumatic conditions. Recurrent themes in the peer-reviewed literature highlight fear of disease flares, adverse events, vaccine efficacy, and lack of physician recommendation as important sources of hesitancy among individuals with rheumatic conditions.

One source of hesitancy has been concern for rheumatic disease flares following COVID-19 vaccination, with discrepancies between degree of hesitancy and actual burden of documented flares. One study (N = 5619) demonstrated that risk of disease flares following COVID-19 vaccination was less than 5%. ^, However, 25% (n = 763/2921) of individuals with autoimmune or inflammatory rheumatic diseases in a China-based study believed that the vaccine would aggravate their disease. An earlier study based in the Netherlands found that 32% (n = 164/515) of patients with systemic autoimmune disease feared the vaccine would aggravate their disease. These results are further corroborated by a 2022 study from Greece, which found that 2% (n = 9/441) of vaccinated patients experienced disease flares, yet 24.2% (n = 29/120) of unvaccinated patients refused vaccination out of fear of disease flares. Additionally, nearly 30% (n = 53/184) of individuals with RA believed that they would need to discontinue their medications to get vaccinated, further contributing to this fear. The consistency among these international studies reflects perceived risk of disease flare as a key barrier to COVID-19 vaccination for people with rheumatic conditions, and also as a potential target for an educational intervention.

Studies among individuals with rheumatic conditions have also reported varying levels of concern about side effects and adverse events related to COVID-19 vaccines. ^{, , ,} A study based in India showed that 35% (n = 29/82) of vaccinated individuals with autoimmune rheumatic diseases self-reported symptoms of redness or swelling at the inoculation site, weakness, and muscle soreness. ^, In a study based in China among 3104 individuals with autoimmune inflammatory rheumatic diseases, 20.2% (n = 591) believed that their disease would increase the incidence of adverse events following vaccination. Due to this risk, 19.9% (n = 347) were unwilling to be vaccinated. A study from the Netherlands reported that 52% (n = 154/296) of patients with rheumatoid arthritis (RA) refused the vaccine due to concerns about adverse events, and in a small subset of patients with SLE, this figure rose to 83% (n = 15/18).

COVID-19 vaccine development occurred quickly in response to its dire need during the beginning of the pandemic. This pace created concerns regarding vaccine efficacy with 61% (n = 384/633) of patients in doubt or unwilling to be vaccinated in the Netherlands believing that no long-term research was performed in its development and rollout. In fact, nearly 35% (n = 108/324) of patients in a study based in China reported that the vaccine could cause COVID-19 infection, with other studies affirming strong associations between fear of infection and willingness to receive the vaccine. ^, Social media, community perceptions, and fears about vaccine development have resulted in misinformation regarding vaccination among individuals with rheumatic conditions. When asked where they obtained information about vaccines, nearly 70% (n = 716/1026) of patients with rheumatic conditions said the internet was their primary source; less than 30% (n = 304/1026) cited guidance from their doctors.

Misinformation and a general lack of information, as highlighted in the literature, have contributed to COVID-19 vaccine hesitancy among individuals with rheumatic conditions. Structural racism and experiences of everyday discrimination may relate to heightened vaccine hesitancy among minoritized groups; a scoping review found that two-thirds (n = 41/60) of articles cited structural or systemic racism as a source of medical mistrust regarding vaccinations. A 2023 qualitative study aimed to understand barriers and facilitators to vaccine uptake in Black communities in greater Chicago and Boston and included physicians, community leaders and individuals living with rheumatic conditions (n = 20). The investigators found that mistrust was a significant barrier to vaccination; conspiracy theories, racism, and historic injustices, and factors related to vaccine development and to the healthcare system were specific subthemes mentioned. Conspiracy theories, referred to as the “belief that the vaccine and pandemic is a result of a secret plot,” was the most common subtheme mentioned by 60% (n = 12/20) of participants. Participants in this study recognized the role that general mistrust in the medical system plays in vaccine hesitancy, noting the impact that prior incidents have on current attitudes toward vaccination. Mistrust in the healthcare system can be tied to racism and historic injustices; 7 participants mentioned the role of medical racism on hesitancy. Half of the participants acknowledged concerns about vaccine development, specifically the speed of development and the vaccine’s function, as a reason for hesitancy, with 1 participant describing the vaccine as “experimental.”

Among respondents with autoimmune rheumatic conditions who expressed hesitancy toward receiving the vaccine in a 2021 international study, a small percent (5%, n = 158/3109) reported that their physicians advised against vaccination. Fragoulis and colleagues reported similar results in their 2021 phone interview survey study, where 5.8% (n = 7/120) of respondents declined vaccination because it was not recommended by their rheumatologist. These results raise concern, as those who did not receive recommendations to be vaccinated had “the highest comorbidity burden,” according to a study conducted by Sen and colleagues. ^, A significant proportion of individuals with autoimmune and rheumatic conditions were at risk for severe COVID-19, yet did not perceive themselves as such, or did and were still hesitant to be vaccinated. ^, Further, 23% (n = 4926/21,164) of patients reported lack of physician recommendation as the “primary factor for booster hesitancy.” Physicians could increase vaccination rates in this population by over 20%, highlighting the “importance of patient education in this context.” ^,

Hesitancy to receive other vaccines among individuals with rheumatic conditions

Similar to COVID-19 infection, compared to the general population, individuals with systemic rheumatic conditions have an increased risk of infectious diseases such as influenza, pneumonia, and shingles with poorer outcomes. Despite this, vaccine uptake is suboptimal with estimates as low as 33% for influenza, 13% for pneumococcus, and 24.3% for diphtheria–tetanus–poliomyelitis vaccines. ^, Similar factors including lack of information and awareness, lack of physician recommendations, perception of good health, lack of time, concerns about efficacy, and fear of adverse effects have been associated with low uptake of these vaccines. Younger age, lower educational attainment, and belonging to a minoritized group were negatively associated with influenza vaccine uptake. ^, While some studies found that type of immunosuppression influenced vaccine uptake, others did not. ^,

While there are nuanced differences between reasons for uptake of different vaccinations, according to a 2021 multinational study, willingness to get the COVID-19 vaccine was higher among individuals who had been vaccinated against influenza in the last 3 years, or pneumococcal vaccination in the last 5 years. Further, studies have shown that, similar to COVID-19, the most common reasons for non-COVID-19 vaccine hesitancy were fear of side effects, lack of awareness of infection risk, concerns about effectiveness, and lack of recommendation by a physician. A 2019 study of vaccine coverage in patients with primary Sjögren’s syndrome found that 40.3% (n = 23/57) of unvaccinated respondents attributed influenza vaccine hesitancy to fear of side effects; 79.1% (n = 77/111) of respondents attributed pneumococcal vaccine hesitancy to lack of vaccine recommendation by a physician. There are also differences in patient awareness of adverse effects based on disease treatment class. As shown by Jaques and colleagues, patients who were treated with disease-modifying antirheumatic drugs alone were “were less aware of increased risk of infectious complications compared to patients treated with biologics.” Despite consensus surrounding the benefit of vaccinations, vaccine uptake for patients with chronic inflammatory rheumatic disease remains lower than desired, with one study reporting only 33.4% (n = 180/540) of patients vaccinated against influenza and 49.1% (n = 265/540) vaccinated against pneumococcal infection.

Interventions to improve uptake of vaccination among individuals with rheumatic conditions

While fears surrounding vaccination do exist, targeted interventions have the potential to increase vaccine uptake. 54.7% (n = 954/1745) of patients in China with autoimmune inflammatory rheumatic disease who were uncertain or unwilling to get vaccinated said that they would if advised to by a physician. Moreover, 66% of patients in one study reported that they were vaccinated because their physician recommended it. By increasing educational tools and materials available to providers to share with their patients, vaccine hesitancy may be addressed among those unsure about vaccination. When one considers inequities by race and ethnicity, both in infection burden and vaccine uptake, special consideration and focused efforts are needed to address reasons for vaccine hesitancy, including those that stem from experiences of racism.

Several strategies to increase overall vaccination rates in people at risk for vaccine-preventable infections have been recommended. These include increasing patients’ awareness about the need for vaccination using reminders and letters, improving access to vaccines in patient homes, and reminding clinicians to recommend the appropriate vaccines. ^, While there are no randomized clinical trials comparing the effect of interventions to improve uptake of appropriate vaccinations among people with rheumatic conditions, results of several studies using quasi-experimental or non-randomized trial designs have been reported.

Discussion

Despite the known risks of serious infections to individuals with systemic rheumatic conditions, and the reassuring data regarding vaccine safety, uptake is suboptimal for all vaccinations, and specifically for COVID-19 vaccination. The reasons are multifaceted and are more pronounced among minoritized populations. Interventions to increase uptake of influenza and pneumococcal vaccinations based in clinical settings have yielded mixed results suggesting the need for heightened patient involvement and community engagement, as well as attention to the nuanced reasons driving hesitancy particularly around COVID-19 vaccination. Two interventions are currently underway that focus on Black and Latinx individuals who were disproportionately affected by COVID-19 and who have persistently lower rates of COVID-19 vaccination compared to White individuals. One intervention showcases diverse patient voices describing their motivations for COVID-19 vaccination and the other leverages community leaders to disseminate vaccination information through their social networks. If successful, these low-cost readily implementable interventions may be scalable to other medical centers and regions. Further interventions are also needed for physicians and other providers to promote vaccination uptake for patients with systemic rheumatic conditions while also paying attention to the unique reasons driving hesitancy among individual patients. Leveraging both patient-physician partnerships and community-academic partnerships may increase both vaccine uptake and overall trust in healthcare that could spill over to other domains where significant inequities exist.

Summary

COVID-19 vaccine uptake remains low among individuals with rheumatic conditions with significant inequities by race and ethnicity. While there are hospital-based interventions to improve uptake of influenza and pneumococcal vaccine, there are no published results of interventions to improve COVID-19 vaccine uptake among individuals with rheumatic conditions. Interventions that are both hospital-based and community-based, and that address mistrust and experiences of racism are underway leveraging educational and trust-building strategies to improve uptake.