Real‐World Impact of COVID‐19 on Subcutaneous Immunotherapy Persistence and Efficacy in Allergic Rhinitis

Allergic rhinitis (AR) is a chronic inflammatory condition driven by IgE-mediated hypersensitivity, which significantly impairs patients' quality of life [1]. Subcutaneous immunotherapy (SCIT) is a critical intervention for AR, offering clinical improvements, enhanced quality of life, and long-term cost-effectiveness [2]. However, its effectiveness depends on consistent treatment adherence, which external factors can disrupt [3]. The COVID-19 pandemic, characterized by widespread lockdowns, social distancing, and vaccination efforts, greatly disrupted routine healthcare services, including SCIT [3]. Understanding the pandemic's impact on SCIT persistence and efficacy in patients with AR is essential for optimizing SCIT management during global health crises [4]. Which previous studies have examined the short-term effects of the COVID-19 pandemic on SCIT adherence and efficacy [3], no research to date has explored its impact over a complete 3-year course. This study addresses this gap by evaluating these effects in real-world conditions, providing actionable data to guide future healthcare strategies. In this large, open observational cohort study with historical control, 1092 patients with AR sensitized to dust mites were included (Appendix S1). Compared with pre-pandemic patients with SCIT, those undergoing SCIT during the pandemic exhibited distinct clinical characteristics, including older age, longer AR duration, and more severe disease (p < 0.05) (Table 1). Notably, the proportion and average frequency of dose modifications and nonadherence during the 3-year SCIT period were significantly higher in the during-pandemic group, along with a more pronounced dropout rate (p < 0.001) (Table 1). Consistent with the previous study [5], significant differences in clinical characteristics, such as age, smoking status, BMI, AR duration disease severity, and SCIT persistence, were observed between dropout patients in the pre-pandemic and during-pandemic groups (p < 0.05) (Table S1). A further analysis of the pandemic phases revealed distinct reasons for SCIT dropout (Appendix S1). In the pre-pandemic phase, time constraints, self-perceived ineffectiveness, and injection frequency were the main reasons for dropout. In contrast, during the early pandemic, healthcare access challenges, COVID-19 transmission concerns, and COVID-19 infection were the primary reasons for dropout, Meanwhile, in the mid-pandemic phase, dropout was mainly driven by self-perceived ineffectiveness, healthcare access challenges, and economic burden (Figure S1). Additionally, unadjusted and adjusted logistic regression analyses identified the COVID-19 pandemic as a significant risk factor for SCIT dropout, independent of various potential confounding factors related to baseline characteristics (p < 0.05) (Table S2). Furthermore, the number of dose modification emerged as an independent risk factor for SCIT dropout both before and during the pandemic (p < 0.05). Interestingly, secondary immunotherapy appeared to be protective before the pandemic (p < 0.001). Under the influence of the pandemic, smoking and longer AR duration emerged as significant risk factors for SCIT dropout (p < 0.05) (Table S3). To comprehensively assess the changes in symptom severity and SCIT efficacy over the 3-year treatment course, we utilized validated scales that are widely applied in clinical practice and research to evaluate patients with AR. Further investigation revealed that compared with the pre-pandemic, patients with AR undergoing SCIT during the pandemic experienced significantly worsened symptoms and a more pronounced decline in quality of life at various time points throughout the 3-year SCIT course, despite following the same SCIT protocol (p < 0.05) (Figure 1A). Improvement scores on various scales at 1 and 3 years of SCIT, calculated as the difference between baseline and 1- and 3-year values, were significantly lower in the during-pandemic group compared with the pre-pandemic group (p < 0.05) (Figure 1B). This indicates that pandemic-related factors appear to have delayed early perceived efficacy during the first year of SCIT and reduced benefits observed at the 3-year mark. According to the primary SCIT efficacy criteria, 369 (89.3%) of pre-pandemic patients with AR and 104 (51.2%) of during-pandemic patients with AR achieved effective SCIT (Figure S2). The efficacy rate was significantly lower during the pandemic compared with the pre-pandemic period (p < 0.0001) (Figure S2B). To further explore these trends, unadjusted and adjusted logistic regression analysis revealed that the COVID-19 pandemic was a significant risk factor for SCIT efficacy, even after adjusting for various confounding factors (p < 0.001) (Table S4). This suggests that the pandemic itself directly contributed to compromised SCIT outcomes, independent of baseline severity or other confounding factors. One contributing factor may have been the increased dose modifications and nonadherence observed during the pandemic, which reflected treatment interruptions and logistical challenges. These disruptions likely interrupted the consistent allergen exposure essential for maintaining immunological tolerance, leading to delayed or diminished treatment efficacy. Additionally, factors, such as reduced healthcare access, increased indoor allergen exposure, decreased outdoor activity, and heightened psychological stress, likely exacerbated these effects, contributing to more severe AR symptoms, poorer quality of life, and an overall decline in SCIT efficacy. Building on these findings, further regression analyses were conducted to explore the multifactorial influences on SCIT efficacy. Given the differing clinical contexts and external challenges before and during the pandemic, we separately analyzed patient-specific and SCIT-specific factors in the two cohorts to better understand how these variables contributed to SCIT outcomes under distinct conditions. In the pre-pandemic cohort, a higher number of dose modifications was a significant risk factor for SCIT efficacy (p < 0.05) (Table S5), highlighting the importance of treatment continuity for achieving optimal outcomes. In contrast, in the during-pandemic cohort, older age, longer AR duration, and a higher number of dose modifications emerged as significant risk factors (p < 0.05) (Table S5). These findings suggest that SCIT efficacy during the pandemic faced more complex challenges, combining patient-specific characteristics with treatment-specific disruptions. Despite the challenges posed by the pandemic, the overall benefits of SCIT should not be overlooked [6]. There was still a significant downward trend in AR severity scores during SCIT, demonstrating that the overall benefits of SCIT remained substantial (Figure 1). Additionally, positive outcomes were observed, with more than half of the patients achieving effective results after 3 years of SCIT, reaffirming the effectiveness of SCIT even amid the COVID-19 pandemic (Figure 1 and Figure S2). The present study has several limitations. First, the subjects were recruited from a single medical center, which may increase the risk of selection bias. Second, statistical analysis did not perform an in-depth stratification on the basis of baseline characteristics, including age groups, which may limit the comprehensive interpretation of results. Third, patients with comorbid asthma were included without a comprehensive symptom evaluation, such as the Asthma Control Test or quality of life assessments. Additionally, no objective indicators were used to assess SCIT efficacy, making the results reliant on patients' subjective scale scores, which could be influenced by various factors. In conclusion, our findings underscore the significant impact of the COVID-19 pandemic on SCIT persistence and efficacy in patients with AR, consistently affecting the entire 3-year SCIT course. Notably, this study is the first to provide real-world data on the pandemic's effects on the persistence and efficacy of a complete 3-year SCIT regimen. These results highlight the need for resilient healthcare strategies to maintain continuity in SCIT management during global health crises. Furthermore, these insights could inform future public health preparedness and optimize treatment strategies for AR in similar circumstances. Xuan Yuan: data collection, statistical analysis, drafting of the manuscript. Liyuan Liu: analysis or interpretation of data. Benjian Zhang: acquisition, analysis, or interpretation of data. Shaobing Xie: study concept and design, and statistical analysis. Lai Meng: final statistical review, acquisition, analysis, or interpretation of data. Wei Zhong: acquisition, analysis, or interpretation of data. Jiaxin Jia: data collection and statistical analysis. Hua Zhang: data collection, acquisition, analysis, or interpretation of data. Weihong Jiang: administrative support and final statistical review. Zhihai Xie: study concept and design, final review of manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.