Discussion
In the context of developing novel future strategies for SCIT management during the COVID-19 pandemic, our research confirmed that long-term efficacy of SCIT is not negatively affected by COVID-19 related treatment delay, in patients with AR (some also with asthma). In addition, we also demonstrated the presence of psychological symptoms, especially depressive symptoms, in patients undergoing SCIT during the COVID-19 outbreak.
During this study, we found that 25.35% of SCIT patients had withdrawn from treatment before V1, which is similar to findings from the recent EAACI survey in which 75% of patients underwent maintenance phase SCIT during the COVID-19 pandemic32. An objective reason for this would be that social quarantine was called for in response to the COVID-19 outbreak; and a subjective reason may be that patients avoided going to hospital during this time. Currently, the treatment for patients allergic to inhaled allergens who are not infected with COVID-19 is controversial. ARIA-EAACI33 recommends the continuation of SCIT, when infection prevention and control measures are strictly followed at the hospital according to the request of WHO34,35. On the contrary, American Academy of Allergy, Asthma & Immunology (AAAAI) 9 suggests that it is possible to delay SCIT injections to an interval of once every 2 weeks in the build-up phase, and once every 6 weeks in the maintenance phase (which matched our study design), or even to suspend treatment until social quarantine is cancelled. These diverse viewpoints inspired us to investigate whether there was a difference in clinical presentation between patients receiving SCIT on schedule, and those with a treatment delay. Our results showed that clinical symptoms, medication use, and quality of life were all within the normal range for SCIT patients. In addition, we found no significant difference between scheduled SCIT and delayed SCIT patients at the 1 year follow up period. The result demonstrated again the long-term efficacy of SCIT in patients with AR, even with a delay in therapy during the COVID-19 pandemic. This information may encourage patients who have had to delay SCIT to continue their treatment once the necessary social quarantine is over, to recover their allergen-specific immune tolerance and modify the progression of the disease.
Psychological disorder was also a notable element among patients undergoing SCIT during the COVID-19 pandemic. In a report from China, up to 35.1%, 20.1%, 18.2% of people showed depressive symptoms, the symptoms of anxiety disorders, and a change in sleep quality during the COVID-19 pandemic, respectively36. In our study, the depressive symptoms in both scheduled and delayed SCIT patients at V0 was significantly higher than at V1, and exceeded the normal range at both time points. Depressed patients reported an increase in symptoms, reduced quality of life, and poor control of symptoms during the SCIT, which was positively correlated with delayed treatment at V0. Our findings may serve to remind allergists/immunologists that the psychological burden on patients undergoing SCIT during the COVID-19 epidemic should be valued with the great attention, particularly with regard to depressive symptoms37. The introduction of patient education to relieve depression, should be included as part of the management of SCIT, has previously been suggested38.
Further developing the application of patient education and telemedicine is an important part of patient care during the unique circumstances brought by the COVID-19 pandemic39,40. Allergists/immunologists have been urged to respond to this need by extending the long-standing trust developed through years of face-to-face encounters into online resources41. To assist patients with scheduled SCIT, allergists/immunologists are recommended to post information on their web site and social media channels regarding frequently asked questions surrounding the COVID-19 outbreak, the changes to their SCIT practice setting, the differences between acute AR and asthma symptoms, as well as indications for COVID-19 testing. All of this can lower the psychological distress for patients before they seek help at hospitals or clinics42,43. The patients with delayed SCIT are recommended to continue with follow-up visits online, and when possible, home delivery and digital medicine services can be used to obtain scheduled questionnaires and monitor drug administration44,45. Local community organizations and health services can also be utilized to assist patients who are treated at home, and who may need support services to ensure optimal care46-49. This unique period during the COVID-19 pandemic brings not only challenges, but also the opportunities to update and improve the management of SCIT.
Our RWE study provides valuable information on physical and mental manifestations among patients undergoing delayed SCIT in a real-world setting, which is essential to the evidence base required for treatment practices50. Due to the limited design of the current study we are not able to make conclusions regarding the underlying mechanism of delayed SCIT immune responses. To investigate this further, immunopathological features such as allergen-specific immunoglobulin E (IgE) and immunoglobulin G4 antibodies, may be helpful.
In conclusion, we were able to confirm the long-term efficacy of SCIT in patients with AR, even in patients with delayed treatment due to the COVID-19 pandemic. In addition, comorbid mild depressive symptoms, which were more common in patients with not fully controlled SCIT, may require more attention.