AUTHOR=Wang Bowen , Peng Mengjia , Yang Li , Li Guokai , Yang Jie , Yundan Ciren , Zeng Xiaohua , Wei Qianqi , Han Qi , Liu Chang , Ding Ke , Peng Kaige , Kang Wen TITLE=Clinical and Immunological Characteristics of Patients With Adenovirus Infection at Different Altitude Areas in Tibet, China JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 11 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.739429 DOI=10.3389/fcimb.2021.739429 ISSN=2235-2988 ABSTRACT=Background: The severities of human Adenoviruses (HAdVs) infection are diverse in different areas of Tibet, China, where a large altitude span emerges. Serious consequences may be caused by medical staff if the clinical stages and immunological conditions of patients in high altitude areas are misjudged. However, the clinical symptoms, immunological characteristics and environmental factors of HAdVs infection patients at different altitude areas have not been well described. Methods: In this retrospective, multicenter cohort study, we analyzed the patients who were confirmed HAdVs infection by PCR tests in General Hospital of Tibet Military Command or CDC (the Center for Disease Control and Prevention) of Tibet Military Command from January 1st, 2019 to December 31st, 2020. Demographic, clinical, laboratory, radiological and epidemiological data were collected from medical records system and compared among different altitude areas. The inflammatory cytokines as well as the subsets of monocytes and regulatory T cells of patients were also obtained and analyzed during this study. Results: 686 patients had been identified by laboratory-confirmed HAdVs infection, including low-altitude group (n=62), medium-altitude group (n=206), high-altitude group (n=230) and ultra-high-altitude group (n=188). Referring to the environmental factors regression analysis, altitude and relative humidity were tightly associated with the number of infected patients (P<0.01). Higher incidence rate of general pneumonia (45.7%) or severe pneumonia (8.0%) occurred in ultra-high-altitude group (P<0.05). The incubation period, serial interval, course of disease and PCR positive duration were prolonged to various extent compared with low-altitude group (P<0.05). Different from those in low altitude areas, the levels of IL-1 β, IL-2, IL-4, IL-6, IL-8, IL-10, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, TNF-α, TNF-β and VEGF in plasma of ultra-high-altitude group were increased (P<0.05), while the proportion of non-classical monocytes and regulatory T cells was apparently decreased (P<0.05). Conclusions: Findings of this research indicated that patients with HAdVs infection in high-altitude areas had severe clinical symptoms and prolonged course of disease. During clinical works, much more attentions should be paid to observe the changes of their immunological conditions. Quarantine of patients in high-altitude areas should be appropriately extended to block the virus shedding.