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

There has been an important change in the clinical characteristics and immune profile of COVID-19 patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4 and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) has been identified as an important cause of death of children with COVID-19. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. Atopic diseases, such as allergic asthma and rhinitis, have been shown to be associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, EAACI developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging SARS-CoV-2 variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID.

Reply to: “COVID-19 pandemic and environment: not only air pollution”. M.Carminati et al.

Background: The impact of physical activity (PA) on immune response is a hot topic in exercise immunology, but studies involving asthmatic children are scarce. We examine the level of PA and TV attendance (TVA) in asthmatic children to assess the role on asthma control and immune response to various stimulants. Methods: Weekly PA and daily TVA were obtained from questionnaires at inclusion of the PreDicta study. PBMC cultures were stimulated with phytohemagglutinin (PHA), R848, poly I:C and zymosan. Cytokines were measured and quantified in cell culture supernatants using luminometric multiplex immunofluorescence beads-based assay. Results: Asthmatic preschoolers showed significantly more TVA than their healthy peers (58.6% vs. 41.5% 1-3h daily and only 25.7% vs. 47.2% ≤ 1h daily). Poor asthma control was associated with less frequent PA (75% no or occasional activity in uncontrolled vs. 20% in controlled asthma; 25% ≥ 3x weekly vs. 62%). Asthmatics with increased PA exhibited elevated cytokine levels in response to stimulants, suggesting a readiness of circulating immune cells for type-1, -2 and -17 cytokine release compared to low-PA and high-TVA subjects. Low PA and high TVA were associated with increased proinflammatory cytokines. Proinflammatory cytokines were correlating with each other in in-vitro immune responses of asthmatic children, but not healthy controls. Conclusion: Asthmatic children show more sedentary behavior than healthy subjects, while poor asthma control leads to a decrease in PA. Asthmatic children profit from exercise, as elevated cytokine levels in stimulated conditions indicate an immune system prepared for a strong response in case of infection.

The coronavirus disease 2019 pandemic (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented global social and economic impact, and numerous deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung disease, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type-I interferon secretion capacity, and pregnancy. Possible complications include acute respiratory distress syndrome, shock, disseminated coagulopathy, acute kidney injury, pulmonary embolism, and secondary bacterial pneumonia. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1, Krebs von den Lungen-6 (KL-6) and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of COVID-19.

In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2 and Covid-19.

Background Currently, the coronavirus disease 2019 (COVID-19) has become pandemic globally. 10-20% of the cases are severe and more than 397,000 deaths have occurred. The risk factors for the mortality of critically ill COVID-19 patients remain to be elucidated. Conclusions Survived severe and non-survived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Logistic regression revealed several risk factors such as elder age, greater affected lobe numbers and higher level of serum CRP for the mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings indicate the advancement of the disease and may be helpful in predicting the progression of severe patients.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date it has resulted in ~5.6 million confirmed cases and caused 353,334 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socio-economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo-embolic complications and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non-allergic COVID-19 children in aspects of incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.