BACKGROUND. Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19. METHODS. In this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China. RESULTS. The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4⁺ T cells, and CD8⁺ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 10⁶/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 10⁶/L, respectively). The expression of IFN-γ by CD4⁺ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%). CONCLUSION. The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4⁺ and CD8⁺ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4⁺ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19. TRIAL REGISTRATION. This is a retrospective observational study without a trial registration number. FUNDING. This work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

BACKGROUND. The coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease’s long-term effects on the brain still need to be explored. METHODS. We recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed. RESULTS. Compared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6. CONCLUSION. Indirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19–related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19. FUNDING. Natural Science Foundation of China.

Background: Since late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. Methods: In this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. Results: Of the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (0.7 × 10□/L) than moderate cases (1.1 × 10□/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4 ⁺ T cells and CD8 ⁺ T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 × 10 ⁶ /L) than moderate cases (676.5, 359.2 and 272.0 × 10 ⁶ /L). The expressions of IFN-γ by CD4 ⁺ T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). Conclusion: The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4 ⁺ T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.

BACKGROUND: After the initial surge in COVID-19 cases, large numbers of patients were discharged from a hospital without assessment of recovery. Now, an increasing number of patients report postacute neurological sequelae, known as “long COVID” — even those without specific neurological manifestations in the acute phase. METHODS: Dynamic brain changes are crucial for a better understanding and early prevention of “long COVID.” Here, we explored the cross-sectional and longitudinal consequences of COVID-19 on the brain in 34 discharged patients without neurological manifestations. Gray matter morphology, cerebral blood flow (CBF), and volumes of white matter tracts were investigated using advanced magnetic resonance imaging techniques to explore dynamic brain changes from 3 to 10 months after discharge. RESULTS: Overall, the differences of cortical thickness were dynamic and finally returned to the baseline. For cortical CBF, hypoperfusion in severe cases observed at 3 months tended to recover at 10 months. Subcortical nuclei and white matter differences between groups and within subjects showed various trends, including recoverable and long-term unrecovered differences. After a 10-month recovery period, a reduced volume of nuclei in severe cases was still more extensive and profound than that in mild cases. CONCLUSION: Our study provides objective neuroimaging evidence for the coexistence of recoverable and long-term unrecovered changes in 10-month effects of COVID-19 on the brain. The remaining potential abnormalities still deserve public attention, which is critically important for a better understanding of “long COVID” and early clinical guidance toward complete recovery. FUNDING: National Natural Science Foundation of China.

Background: Cuproptosis is a copper-triggered modality of mitochondrial cell death and cuproptosis process may play important roles in gastric cancer development. However, little is known about cuproptosis-related lncRNAs in gastric adenocarcinoma (STAD). This study is aimed to investigate the potential prognostic signatures of cuproptosis-related lncRNAs in STAD.Methods: The Cancer Genome Atlas (TCGA) database were used to obtain gene expression profiles, clinicopathological, and OS information for STAD. Cuproptosis-related genes were collected based on previous studies and cuproptosis-related lncRNAs were screened out by co-expression analysis. The nomogram constructed by Cox regression analysis with the minimum absolute contraction and selection operator (lasso) algorithm. In addition, the potential response of ICB therapy and immune evasion incidence were estimated with Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Immune checkpoint expressions associated with risk scores were also analyzed. The correlation of immune checkpoint CD209 and HAVCR2 expressions associated with risk scores were experimentally testified by RT-qPCR, Western Blot, and IHC. Results: Patients were classified into high-risk and low-risk groups based on the risk score calculated in this model. The Kaplan–Meier survival curve analysis revealed that the high-risk group was associated with poor prognosis. Multivariate Cox regression analysis suggested that this lncRNA prediction model was an independent risk factor affecting the OS rate. Furthermore, ROC curve indicates that the nomogram was superior to traditional clinicopathological features in predicting STAD prognosis. Finally, functional enrichment analysis and immune checkpoint investigation revealed that the nomogram is notably associated with cholesterol metabolism and immune functions, RT-qPCR and Western Blotting demonstrated the co-expression relationship of LINC01150 with CD209 and HAVCR2.Conclusion: A novel cuproptosis-related lncRNAs signature impacts on the prognosis and immunological features of GC.