Background The outbreak of COVID-2019 is becoming a global public health emergency MESHD. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia HP, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia HP, and discuss the relationship between hypoxemia HP severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient. Methods This is a retrospective study from 3 patients with 2019-nCoV infection MESHD admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia MESHD Pneumonia HP (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs MESHD, treatment and clinical outcome in detail. Blood SERO samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis. Results Apart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia HP during the hospitalization, and the severity of hypoxemia HP was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died. Conclusions We discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia HP severity was closely related with host immune cell levels, and the vicious circle between immune disorder and gut microbiota imbalance may be a high risk of fatal pneumonia MESHD pneumonia HP. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia HP is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder and gut dysbiosis MESHD may be a high risk of fatal pneumonia MESHD pneumonia HP.