Does allergen immunotherapy impact the susceptibility and severity of COVID-19？To the editor,Allergic asthma (AA) and allergic rhinitis (AR) might be protective against SRAS-CoV-2 infection and progress to severe disease of coronavirus disease 2019 (COVID-19)1. COVID-19 vaccination was safe and well tolerated in patients receiving allergen immunotherapy (AIT)2,3, and the adherence to subcutaneous immunotherapy (SCIT) was not affected during COVID-19 pandemic4. Whether AIT impacts the susceptibility and severity of COVID-19 is still unknown. In December 2022, China ended its “Zero-COVID” policy and more than 70% of the population got infected with SARS-CoV-2 within one month. We conducted an online WeChat questionnaire between 3rd Jan and 10th Jan 2023 to investigate the infection and hospitalization rates and symptom duration of COVID-19 in AR and/or AA patients receiving SCIT with house-dust mite (HDM) extract in China. The relatives of these SCIT patients, who did not receive SCIT, were also surveyed and divided into two groups: allergy group and non-allergy group. The study was approved by the Medical Ethic Committee of Tongji Hospital of Huazhong University of Science and Technology (Approval Number: TJ-IRB20230204). The informed consent was waived since the voluntary nature of responding to the questionnaire.A total of 1246 SCIT patients and 1078 of their relatives (370 allergic and 708 non-allergic) responded to the questionnaire. SCIT patients were generally younger than allergy and non-allergy group. The proportion of male were higher in SCIT patients compared to allergy and nonallergy group. 82.4% of the SCIT patients were diagnosed with AR, only 5.3% were asthmatics, and the rest were AR with asthma (12.3%). The average duration of AIT was 1.4 ± 1.3 years. SCIT patients had a lower proportion of both at least one dose and completed three doses of COVID-19 vaccines when compared to allergy and non-allergy group (P = 0.000) (Table S1).Most respondents had been infected with SARS-CoV-2. SCIT was associated with a lower infection rate (78.6%) compared to allergy (81.4%) and non-allergy group (81.5%) (P < 0.0001) (Table S2). The duration of COVID-19 symptoms was shorter in SCIT group (5.7 ± 4.0 days) compared to allergy group (7.0 ± 4.5 days, P = 0.000) and non-allergy group (7.7 ± 4.4 days, P = 0.000) (Table S2). The hospitalization rate was 0.4% in SCIT group, which was significantly lower than that in non-allergy group (1.73%) (P = 0.008).We then performed a two-to-one matching of SCIT group with allergy and non-allergy group to adjust age and sex difference between the three groups. The infection rate was still slightly lower in SCIT group compared to allergy and non-allergy group (78.3% vs. 81.9%, 81.4%). The duration of symptoms and hospitalization rate did not show much difference among three groups after adjusting (Table 1).Moreover, we found that patients receiving 6-12 months SCIT had a shorter duration of symptoms caused by SARS-CoV-2 infection compared to those in SCIT course < 6 months and those receiving SCIT > 12 months, even though only one fourth of them completed three doses of COVID-19 vaccines (Table 2). shorter duration of symptoms. The duration of SCIT has no impacts on both infection and hospitalization rate (Table 2).A lower expression of angiotensin converting enzyme 2 (ACE2) in airway epithelia5 may contribute to the protecting effect of type 2 inflammation against SARS-CoV-2 infection and severe COVID-196. This study revealed an almost same infection rates in allergic and non-allergic individuals after adjusting age and sex, suggesting ACE2 expression level had no effect on Omicron infection. More importantly, SCIT patients has a slightly lower infection rate compared to allergy and non-allergy groups, suggesting that repeated allergen stimulation during SCIT in HDM-sensitized individuals may elicit a strong T cell response with ability to cross-react with SARS-CoV-2, as demonstrated in silico analysis7, which may protect SCIT individuals from infection. The proportion with three doses COVID-19 vaccines were significantly lower in SCIT patients, albeit SCIT was reported to dampen immune responses to SASR-CoV-2 vaccines8, the infection rate of SARS-CoV-2 was still lower in SCIT patients. We also observed a shorter duration of symptoms due to SARS-CoV-2 infection in those receiving 6-12 months HDM-SCIT compared to those receiving < 6 months and > 12 months HDM-SCIT, consistent with previous studies showing the immune responses to SCIT reach a peak during 6-12 months9. EAACI stated recently in a position paper that AIT and COVID-19 immune responses do not seem to interfere negatively, and AIT patients might even benefit from AIT10. Thus, our results for the first time demonstrated that SCIT may have a protective effect against SARS-CoV-2 infection, especially immediately after completing the dose-escalation phase.KEYWORDS: Allergic rhinitis; Allergen immunotherapy; SARS-CoV-2; Coronavirus disease 2019; InfectionCONFLICT OF INTEREST: The authors declare that they have no conflicts of interest.Author Contributions: YDG, RFZ and YDC conceived the study, YW and HuC designed the questionnaire and collected data. XD, HaC, YQY and HLL dispensed the questionnaire and monitored the survey. RFZ analyzed the data and YDG wrote the manuscript. All authors contributed to the final review.Acknowledgment : We thank all members of Hubei Provincial Doctors Association Allergic Physicians Branch for their help in the recruitment of patients and relatives into this study.Funding information: none.Yin Wang1Huan Chen2Xiang Dong3Hao Chen1Hui-ling Liang3Ya-qi Yang1Yan-dan Chen2Rong-fei Zhu1Ya-dong Gao3Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Otolaryngology-Head and Neck Surgery and Allergy, Central Hospital of Huangshi City, Huangshi, ChinaDepartment of Allergology, Zhongnan Hospital of Wuhan University, Wuhan China

Background: Laboratory abnormalities associated with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19) have been reported in many observational studies. However, there are significant heterogeneities in patient characteristics and research methodologies in these studies. Objectives: We aimed to provide an updated synthesis of the association between laboratory abnormalities and COVID-19 prognosis. Methods: We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, and the China National Knowledge Infrastructure (CNKI) for studies reporting hematological, coagulation, inflammatory, and immunological results during hospital admission of COVID-19 patients with different severities and outcomes. Results: A total of 64 studies were included in the current meta-analysis, with 8 hematological, 3 coagulation, 5 inflammatory, and 23 immunological variables reported. Of them, white blood cell (WBC) and neutrophil counts, D-dimer level, procalcitonin (PCT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferretin, serum amyloid A (SAA), interleukins (ILs)–2R, IL-6, and IL-10 were significantly increased in severely ill patients and non-survivors. Meanwhile, non-severely ill patients and survivors presented significantly higher counts of eosinophils, lymphocytes, and CD4+ and CD8+ T cells. Conclusions: The current meta-analysis provides a comprehensive and updated synthesis of the association between admission laboratory abnormalities with severity and mortality of COVID-19. Our results highlight that increases in the levels of PCT, ESR, CRP, ferretin, SAA, IL-2R, IL-6, and IL-10 were associated with disease deterioration, whereas elevated eosinophils, lymphocytes, and T-cell subsets might serve as indicators of favorable outcomes.

Abstract: Background: The diagnosis of COVID-19 relies mainly on viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis. SARS-CoV-2-specific antibody detection is convenient, safe, and highly sensitive. IgM and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA, and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. Methods: COVID-19 patients, divided into a severe & critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA, and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results, and other data were recorded for all patients. Results: Compared to the traditional IgM–IgG combined antibodies, IgA–IgG combined antibodies are better for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe & critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Conclusions: Detection of SARS-CoV-2-specific combined IgA–IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.