Overall, the results of this study showed that 74.4% of patients with SLE contracted COVID-19 during the first wave of the COVID-19 pandemic in China. Unfortunately, there is currently no epidemiologic data on the number of COVID-19 cases among the general population during the same period. Thus, it remains unclear whether patients with SLE are more susceptible to COVID-19 than those without SLE. Previous foreign studies have reported that the incidence rate of confirmed COVID-19 among patients with SLE is similar to that among the general population [6]. Nevertheless, some studies have also indicated that the prevalence rate of COVID-19 in patients with SLE is slightly higher than that in the general population [7], and this may be related to race, coverage of the COVID-19 test, and SLE severity. Owing to the shortage of antigens and the application of home quarantine during the COVID-19 pandemic, patients with mild symptoms or those who were asymptomatic did not undergo antigen or nucleic acid testing for COVID-19, resulting in a lower COVID-19 detection rate than the actual rate. In this study, patients with COVID-19 had mild conditions and were not admitted to the intensive care unit; also, their hospitalization rate was 4.2%. In contrast, the Global Rheumatology Alliance reported that the hospitalization rate of 1,606 patients with SLE was 30% [8], which was much higher than the hospitalization rate of the patients in this study. This may be because the majority of the patients with SLE included in this study had stable conditions. In addition, at the point our study was conducted, China had already gained sufficient experience in dealing with COVID-19 for nearly three years, i.e., people had a better understanding of the disease progression and the health care system was more robust than those of other countries. Furthermore, the variant leading to this COVID-19 pandemic was the Omicron variant. The Omicron variant is characterized by wide prevalence, high transmission intensity, mild clinical manifestations, short incubation period, and good prognosis in most patients, and all these may have contributed to the low hospitalization rate among our patients.
Hydroxychloroquine was widely used for COVID-19 prophylaxis in the early stage of the COVID-19 pandemic due to its weak base-like chemical structure and immunomodulatory properties. However, a growing number of subsequent studies have revealed insufficient evidence for the effectiveness of hydroxychloroquine in preventing COVID-19 [9, 10]. One study has even reported very low-quality evidence that the combination of hydroxychloroquine and azithromycin increases the risks of mortality and adverse events [11]. In our study, the use of hydroxychloroquine was similar in patients with and without COVID-19 (82.8% vs. 86.7%, respectively, P = 0.507), which is also consistent with the findings of previous studies [9, 10, 12].
The use of glucocorticoid in clinical practice has long been considered a double-edged sword. As an irreplaceable agent in the treatment of SLE, the use of glucocorticoid during the COVID-19 pandemic raised concerns among patients with SLE due to the pan-immunosuppressive effect of glucocorticoid and the subsequent increased risk of infection. Most studies have revealed a dose-dependent positive correlation between the use of glucocorticoid with COVID-19 infection, hospitalization rate, and adverse outcomes in patients with SLE [7, 13–16]. In contrast, some studies have found that glucocorticoid has no effect on the risk for COVID-19 [17]. Conversely, Ugarte-Gil MF et al. [8] reported that adverse outcomes increased in patients with COVID-19 when the glucocorticoid dose was < 5 mg/day. Our study further identified a negative correlation between the dose of glucocorticoid and COVID-19. This negative correlation may be promoted by the potent anti-inflammatory effect of glucocorticoid itself, which can inhibit the inflammatory storm and reduce the incidence rate of COVID-19 during the pandemic. From another perspective, patients with SLE taking higher doses of glucocorticoid may be more cautious regarding disease management during the COVID-19 pandemic, including the strengthening of self-protection measures and isolation from the public, resulting in a lower rate of COVID-19 among them. In addition, the survey only recorded the dosage of glucocorticoid during the COVID-19 pandemic instead of the cumulative dose of glucocorticoid. Individuals who were on low doses of glucocorticoid may have higher cumulative doses, thus contributing to the results obtained in our study.
Overall, our study showed that the use of immunosuppressants, such as methotrexate, mycophenolate mofetil, and azathioprine, does not increase the risk of COVID-19, which is also consistent with the findings of previous studies [13, 18]. A total of 26 patients in our study took biological agents, predominantly belimumab and telitacicept. Belimumab inhibits the survival of autoimmune B cells primarily by binding to the receptors of the soluble B lymphocyte stimulator (BLyS). Telitacicept inhibits a proliferation inducing ligand (APRIL) in both BLyS and B lymphocytes, further affecting the differentiation and maturation of B lymphocytes. From a mechanistic perspective, both drugs ultimately effectively reduce the body's immune response, which should theoretically result in increased susceptibility to COVID-19 and risk for poor prognosis. Nevertheless, our findings have suggested that the use of biological agents in patients with SLE does not increase the risk for COVID-19 and adverse outcomes. At present, there is still a lack of research data on the effects of biological agents on COVID-19, with only a single-digit number of reports being available. One Belgian study suggested an increased hospitalization rate among patients with SLE who were taking belimumab after having COVID-19 [13]; however, this study had a small sample size of only two patients. Our study also had a small sample size, with only 7.4% of patients with SLE using biological agents. Further studies with larger sample sizes investigating the effects of biological agents on COVID-19 and poor prognosis are required to provide us with more reliable evidence. In addition, at the early stage of COVID-19 or onset of suspicious clinical manifestations of COVID-19, such as fever, runny nose, and nasal congestion, patients with SLE can rapidly contact their physicians by phone or WeChat to discontinue the use of biological agents in a timely manner, which may contribute to the absence of any adverse outcomes.
Our study also discovered that the patients with SLE who discontinued hormone, immunosuppressants, or biological agents after developing COVID-19 (17.6%) did not experience elevated disease activity or even an episode of SLE, which is not consistent with the findings of a previous study [7]. This discrepancy in the findings may be because most of our patients with SLE had stable disease conditions (90.3% with SLEDAI scores of 0–4 and 8.3% with SLEDAI scores of 5–9) and underwent regular follow-up. In addition, the discontinuation of medications was mostly performed under the guidance of their physicians and the monitoring of relevant indicators. Moreover, most of the discontinued medications were biological agents (9.3%), whereas only 5.3% of the patients with SLE discontinued hormone and immunosuppressants. Zucchi D et al. [7] found that 75% of patients who discontinued some of their medications by themselves experienced elevated SLE disease activity. The discontinuation of therapy thus appears to be an important factor leading to elevated disease activity. Overall, during the COVID-19 pandemic, it is not recommended for patients with SLE to discontinue their medications of their own volition; however, adjustment of medication regimens according to their conditions may be performed under the guidance of their physicians.
This study has a few limitations. The study had a retrospective design, where documentation was primarily conducted through a combination of survey and medical record review. Therefore, heterogeneity exists due to the differences in age, literacy level, and disease awareness of the patients. Moreover, not all the patients underwent nucleic acid or antigen testing. As such, some asymptomatic patients or patients with mild symptoms may have been missed, resulting in a lower prevalence rate than the actual rate.
In conclusion, our study showed that most patients with SLE who developed COVID-19 have a favorable prognosis, while the long-term use of low-dose hormone and immunosuppressants does not increase the adverse outcomes in patients with SLE. A review of previous studies suggested that abrupt dose reduction or discontinuation of medications by the patients themselves may be an important factor contributing to elevated SLE disease activity or even episodes of SLE. As such, it is not recommended for patients to discontinue their medications by themselves, and their treatment should be individualized according to the assessment of the condition of COVID-19 and SLE disease activity.