AbstractObjectivesAs people across the world suffer from coronavirus disease 2019 (COVID-19), further studies are needed to facilitate evaluating the severity and prognosis of COVID-19 patients. In the study, we aimed to dissect the dynamic profile and clinical implications of hematological findings in hospitalized patients with COVID-19.MethodsWe retrospectively analyzed the hematological findings of 72 patients with COVID-19 admitted from January 21 to February 17, 2020. The final date of follow-up was March 20, 2020. Dynamic profile of vital hematological parameters in severe and non-severe patients was presented at different time points (day 1, 5, 7, 9, 11, 13, 15 after admission), and the correlation of hematological parameters with hospitalization time was indicated.ResultsOf 72 patients with COVID-19, lymphopenia and leukopenia occurred in 39 (54.2%) and 20 (27.8%) patients with COVID-19, respectively. Fifteen (20.8%) patients were defined as severe cases and 57 (79.2%) were non-severe cases. Compared to non-severe patients, leukocyte count, neutrophil count and neutrophil-to-lymphocyte ratio (NLR) were significantly higher, whereas lymphocyte count was declined in severe patients at each time point. A growing trend in platelet count was found in non-severe patients over the follow-up period. In addition, a positive correlation of NLR with hospitalization time was detected from day 5 after admission.ConclusionsDynamic changes in vital hematological parameters from severe and non-severe patients had been characterized in the course of hospitalization. During hospitalization, NLR was found to have certain relevance to the hospitalization days and a role in forecasting disease prognosis for patients with COVID-19.

BackgroundCOVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population.MethodsWe collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays.ResultsWe found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age.ConclusionsWe concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

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The aquaporin 2 (AQP2) plays a critical role in water reabsorption to maintain water homeostasis. AQP2 mutation leads to nephrogenic diabetes insipidus (NDI), characterized by polyuria, polydipsia, and hypernatremia. We previously reported that a novel AQP2 mutation (G215S) caused NDI in a boy. In this study, we aimed to elucidate the cell biological consequences of this mutation on AQP2 function and clarify the molecular pathogenic mechanism for NDI in this patient. First, we analyzed AQP2 expression in Madin-Darby canine kidney (MDCK) cells by AQP2-G215S or AQP2-WT plasmid transfection and found significantly decreased AQP2-G215S expression in cytoplasmic membrane compared with AQP2-WT, independent of forskolin treatment. Further, we found co-localization of endoplasmic reticulum (ER) marker (Calnexin) with AQP2-G215S rather than AQP2-WT in MDCK cells by immunocytochemistry. The functional analysis showed that MDCK cells transfected with AQP2-G215S displayed reduced water permeability compared with AQP2-WT. Visualization of AQP2 structure implied that AQP2-G215S mutation might interrupt the folding of the sixth transmembrane α-helix and/or the packing of α-helices, resulting in the misfolding of monomer and further impaired formation of tetramer. Taken together, these findings suggested that AQP2-G215S was misfolded and retained in the ER and could not be translocated to the apical membrane to function as a water channel, which revealed the molecular pathogenic mechanism of AQP2-G215S mutation and explained for the phenotype of NDI in this patient.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome shows a wide variability in musculoskeletal and cutaneous manifestations, and it is therefore underrecognized and misdiagnosed in the clinic due to a lack of specific markers. In this study, we aimed to identify specific biomarkers by screening serum autoantibodies in SAPHO patients with a 17K human whole-proteome microarray. The serum anti-Sp17 autoantibody was identified and verified to be a specific biomarker in patients with SAPHO syndrome. Indeed, the level of the anti-Sp17 autoantibody was significantly increased in patients with active SAPHO compared to patients with an inactive disease and healthy controls (P < 0.05). Additionally, serum anti-Sp17 autoantibody levels correlated with those of serum hypersensitive C-reactive protein (hsCRP), the erythrocyte sedimentation rate (ESR), and β-crosslaps (β-CTx) in patients with active SAPHO disease. Moreover, anti-Sp17 autoantibody levels were markedly decreased after anti-inflammatory treatment with pamidronate disodium, which downregulated levels of hsCRP and ESR in patients with active SAPHO. Thus, serum levels of the anti-Sp17 autoantibody might serve as a specific biomarker for the diagnosis of SAPHO syndrome or for monitoring the disease status.

A new biflavonoid, (2″ S)-8″-C-methyl-2″,3″-dihydrorobustaflavone-4′-methyl ether (1) and 5 known robustaflavones (2-6) were isolated from the 70% EtOH extract of Selaginella braunii for the first time. The structures of 1 and the known compounds were identified by performing a comprehensive analysis of spectroscopic data including ultraviolet-visible, high-resolution electrospray ionization mass spectrometry, 1-dimensional and 2-dimensional nuclear magnetic resonance, and circular dichroism spectra. Compounds 1-6 were determined for cytotoxic activity against 3 human cancer cell lines (SMMC-7721, MCF-7, and A549). Compound 1 exerted apparent antiproliferative effects on SMMC-7721, MCF-7, and A549 cells, with IC50 values of 18.6, 16.7, and 25.5 μM, respectively.