Abbreviations ARDS acute respiratory distress syndrome IFN interferon IL interleukin MERS Middle East respiratory syndrome rRT‐PCR real‐time reverse‐transcriptase polymerase chain reaction COVID‐19 coronavirus disease 2019 SARS‐CoV‐2 severe acute respiratory syndrome coronavirus 2 An epidemic illness caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), now named Coronavirus Disease 2019 (COVID‐19), occurred in Wuhan, China. ~(1) The human‐to‐human contagious transmission of SARS‐CoV‐2 has been confirmed, leading to rapid spreading to tens of thousands of patients in China and other regions in the world. ~(2) , ~(3) , ~(4) , ~(5) Organ dysfunction, including acute respiratory distress syndrome (ARDS), shock, and death may occur. ~(6) Therefore, many COVID‐19 patients also suffered from anxiety, especially under treatment in intensive care units. However, due to currently very limited treatment options and no developed vaccines available for COVID‐19, new treatment approaches are urgently needed. There were quite a few critical cases suffering from immune imbalance, ~(7) for which the efficacy of antiviral drugs might remain unsatisfactory or insufficient, especially in the later stages of disease progression. Thalidomide, referred to phocomelia, has been introduced as an anti‐inflammatory therapy with remarkable efficacy in many autoimmune disorders, such as psoriasis, systemic lupus erythematosus, and inflammatory bowel disease, in which the suppressive effect of thalidomide on the pro‐inflammatory cytokines, including interleukin (IL)‐6, tumor necrosis factor (TNF)‐α, and interferon (IFN), was revealed. ~(8) , ~(9) , ~(10) In addition, thalidomide has been known for its co‐stimulatory effect on proliferation of T?cells following CD3 activation. ~(11) Based on the effect of reducing pro‐inflammatory cytokines and maintaining immune homeostasis of thalidomide, we introduced this drug for treatment of the patients with critical/severe COVID‐19 pneumonia for whom the efficacy of antiviral drugs might remain unsatisfactory or insufficient, especially in the late stage. Here, we report the protective effect of thalidomide in combination with antiviral drugs and low‐dose short‐term glucocorticoid on lung injury and immunological dysfunction caused by critical COVID‐19. On 31 January 2020, a 45‐year‐old woman was admitted to a fever clinic of Wencheng County People's Hospital, in Wenzhou city, Zhejiang province, with a 5‐day history of cough, fever, fatigue, and diarrhea. She denied any recent travel to Wuhan, China, or close contact with infected persons or suspected cases. The patient exhibited no dyspnea. She was first treated with ofloxacin and oseltamivir, but the condition deteriorated. The swab specimen was tested positive for SARS‐CoV‐2 by real‐time reverse‐transcriptase polymerase chain reaction (rRT‐PCR) on 1 February 2020. Chest computerized tomography indicated signs of the subpleural effusions in the left upper and left lower lung (Figures? 1A and? 1B ). Therefore, the patient was diagnosed with COVID‐19, and treated with lopinavir/ritonavir. Due to the persistent hyperpyrexia, she was transferred to the isolation ward in our hospital on 3 February 2020 for further treatment. The patient was healthy before this outbreak. Physical examination revealed a body temperature of 38.1°C, blood pressure of 117/78?mmHg, pulse rate 92 beats per minute, and a respiratory rate of 20 breaths per minute. On admission, the patient's vital signs were initially stable. This patient continued to have a high fever, dyspnea, and was obviously fatigued, accompanied by nausea and vomiting. Treatment during this period was primarily supportive and antiviral therapy. However, on hospital day 2 (illness day 6), oxygen saturation decreased to 93% while the patient was treated by nasal cannula delivery of oxygen at 3?L/min, and arterial blood gas analysis indicated a deterioration of the oxygenation index (PaO _(2)/FiO _(2): 220?mmHg). According to Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the sixth edition), the patient was classified into the critical phenotype. FIGURE 1 Chest computed tomography images. A and B, Subpleural exudation opacities in the lower right, left upper lung and left lower lung, on 2 February 2020. C and D, Fibrous lesions in the lower right, left upper lung, and left lower lung, on 11 February 2020. E and F, Fibrous lesions in the lower right, left upper lung and left lower lung, on 17 February 2020 Laboratory testing revealed a significantly increased level of C‐reactive protein at 90.0?mg/L and cytokine levels including IL‐6 at 102.95?pg/mL, IL‐10 at 24.84?pg/mL, and IFN‐γ at 38.16?pg/mL (Figure? 2A ). Lymphocytopenia appeared, as well as a significantly decreased T?cell absolute value (254/T?cell μL), including CD4+ T?cells (163/μL), CD8+ T?cells (83 /μL), NK cells (44 /μL), and B cells (76 /μL) (Figure? 2B ). These results indicated that cytokine surg
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