Comparative outcome of patients with systemic autoimmune rheumatic disease affected by COVID-19 infection—An Asian perspective

The coronavirus disease 2019 (COVID-19) is a pandemic posing a great challenge worldwide since December 2019. With the emergence of less virulent Omicron variant, the disease burden has been greatly reduced. Nevertheless, a proportion of COVID-19 patients developed persistent residual symptoms months after recovery from the acute infection, leading to the so-called “long COVID.” Previous studies reported a slightly higher COVID-19 infection rate in patients with systemic autoimmune rheumatic diseases (SARD).¹ Notably, such COVID-19 acute infection produced worse outcomes in SARD patients, mostly contributed by their comorbidities. In addition, our recent meta-analysis also suggested a slightly higher prevalence of long COVID in SARD patients when compared with the general population.² It is of great importance to study the adverse impact of COVID-19 in SARD patients.

Despite the poorer immunogenecity, vaccines and further booster doses are still effective in SARD patients against acute COVID-19 infection, preventing worse outcomes and even development of long COVID.^{3, 4} Outpatient treatments, including nirmatrelvir–ritonavir and monoclonal antibodies, have greatly improved patient outcomes,⁵ despite a possible higher risk for rebound after oral antiviral treatments, in SARD patients.⁶ Along with the emergence of Omicron variant, all these factors contributed to significantly improved outcomes in SARD patients with time. Nevertheless, pre-existing health disparity in SARD patients deepens, and this remains an issue even after the pandemic. Country-level societal factors, such as the levels of economic development and medical capacity, also influence COVID-19 outcomes, in addition to individual-level factors, in SARD patients.⁷ In line with this, despite differences between countries, the coverage of vaccination and antivirals was generally lower in Asia when compared with North America and Europe.⁸

Asian ethnicity is associated with an increased risk for COVID-19 infection. Nevertheless, researches on COVID-19 infection are relatively few in Asian SARD patients (Table 1). During the initial outbreak, a relative risk of as high as 10.77 (95% CI: 5.41, 21.44) in SARD patients when compared with the general population has been reported by Chen et al. in a tertiary center at Wuhan, China.⁹ Nevertheless, another population-based study in Hong Kong discovered no increased infection risk in SARD patients.¹⁰ Despite the different study design, SARD patients may be more vulnerable to the infection of the virus during the initial outbreak due to their immunosuppressive status, as in Wuhan, the first epicenter of COVID-19. After the SARD patients being aware of the disease, protection measures can be eagerly undertaken by these patients to lower the infection risk. In terms of the disease severity, Chen et al. indicated a mortality rate of 38% in eight SARD patients at Wuhan, China, with an odds ratio of 12.26 (95% CI: 2.93, 51.33).⁹ Conversely, in another early report on 17 SARD patients with COVID-19 at a tertiary hospital in Wuhan, China, the rate of ICU admission was not different when compared with the general population.¹¹ The increased prevalence (adjusted OR: 1.19, 95% CI: 1.03, 1.40) and worse outcomes (adjusted OR for severe outcomes: 1.26, 95% CI: 1.02, 1.59; adjusted OR for death: 1.69, 95% CI: 1.01, 2.84) in SARD patients were also reported in a Koran nationwide cohort study.¹² The strong influence of comorbidities on COVID-19 outcomes was observed in the Japanese nationwide registry and in an Indian tertiary center.^{13, 14} To be noted, Asian races are associated with poorer outcomes and even higher risks for developing long COVID after COVID-19 infection in the general population.^{15, 16} In addition, there are many low-income countries with high levels of income inequality in Asia, where SARD patient outcomes after COVID-19 infection could be even worse. There is an urgent need to formulate a strategy to deal with COVID-19 infection in Asian SARD patients. Interestingly, a cohort study based on the TriNetX U.S. database demonstrated a higher risk for developing autoimmune diseases in Caucasian individuals and a higher risk for developing systemic lupus erythematosus in Asian individuals after COVID-19 infection.¹⁷

There are a number of questions to be answered for these SARD patients. For example, their optimal vaccination schedule and late immunomodulatory treatment for COVID-19 infection should be determined. The effect of long COVID on the disease activity and life quality of SARD patients is still unknown. In particular, effects of prior use of disease-modifying antirheumatic drugs (DMARDs) and other disease-specific factors on long COVID in SARD patients await exploration.² Finally, the barrier to COVID-19 care for Asian SARD patients should be addressed. Digital health may be one means to promote public health measures and eliminate the gap of social inequity.¹⁸ Studies from India and Hong Kong suggested that SARD patients accept telemedicine, and telemedicine is a feasible option.^{19, 20} Nevertheless, the development of well-validated tools to evaluate disease activity in remote care is crucial for both SARD patients and physicians.²⁰

SARD patients are more vulnerable to COVID-19 with more disease complications than the general population (Figure 1). Among Asian SARD patients, racial and societal factors further deepen their health disparity and worsen their COVID-19 outcomes. Effective interventions to prevent the complications of COVID-19 in SARD patients, especially long COVID, should be contemplated by the whole society of Asian rheumatologists.

The work was supported by the Ministry of Science and Technology, R.O.C. (grant number: 105-2320-B-005-006). This work was supported by Taichung Veterans General Hospital (TCVGH-1123801C), Taichung, Taiwan, Republic of China.

The authors declare no conflicts of interests.