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ObjectivesComorbidities have significant indications for the disease outcome of COVID-19, however which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard for defining the recovery of COVID-19 infections. To dissect the underlying diseases that could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in the Zhongnan Hospital of Wuhan University, Wuhan, China between Jan 5 and Feb 25, 2020. MethodologyWe comprehensively analyzed demographic, clinical and laboratory data, as well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression modelling were employed to identify factors influencing the viral clearance negatively. ResultsWe found that increasing age, male gender, and angiotensin-converting enzyme 2 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) adversely affected the viral clearance. Furthermore, analysis by a random forest survival model pointed out hypertension, cortisone treatment, gender, and age as the four most important variables. ConclusionsWe conclude that patients at old age, males, and/or having diseases associated with high expression of ACE2 will have worse prognosis during a COVID-19 infections.
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BackgroundViral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Previous studies have pointed out that suboptimal T and B cell responses can delay viral clearance in MERS-CoV and SARS-CoV infected patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined. MethodsFrom January 26 to February 28, 2020, an observational study was launched at the Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. To investigate the factors that contribute to the viral clearance, we comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. FindingsIn 25 enrolled COVID-19 patients, lymphopenia was a common feature. After the treatment, 14 out of the 25 enrolled patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cells and B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. ConclusionsBy comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidance as a criterion for releasing and discharging patients.
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Objective:To investigate the relationship between positive rate and titer of hepatitis B surface antibody (anti-HBs) and CD4 + T lymphocyte count level in human immunodeficiency virus (HIV) infected patients after hepatitis B virus (HBV) exposure. Methods:A total of 4 893 HIV-infected patients were admitted to Zhongnan Hospital of Wuhan University from January 2010 to December 2018. The demographic data, HIV-related diagnosis, treatment information, CD4 + T lymphocyte count and serum markers of HBV infection of HIV infected patients were retrospectively analyzed. The patients were grouped according to the CD4 + T lymphocyte count and serum markers of HBV infection, and the differences of anti-HBs positive rate and HBV exposure rate in patients with different CD4 + T lymphocyte counts were compared.The differences of CD4 + T lymphocyte count in patients with different titer of anti-HBs were compared. Statistical analysis was performed using chi-square test, analysis of variance or t test. Results:Patients with HIV infection were divided into CD4 + T lymphocyte count<200/μL group (3 293 cases), 200-500/μL group (1 200 cases) and CD4 + T lymphocyte count>500/μL group (400 cases). The HBV exposure rates in the three groups were 78.0%(2 569/3 293), 77.0%(924/1 200) and 76.2%(305/400), respectively. The anti-HBs positive rates were 38.2%(1 258/3 293), 53.8%(645/1 200) and 62.5%(250/400), respectively. The anti-HBs titers were (120.00±36.45) IU/L, (148.00±26.40) IU/L and (212.00±92.08) IU/L, respectively. The exposure rates of HBV in the three groups were similar ( χ2=0.992, P=0.609), but the positive rates and titers of anti-HBs were significantly different ( χ2=146.779 and F=45.362, respectively, both P<0.01). When the patients were grouped by anti-HBs titer, 2 740 cases were divided into anti-HBs negative group (<10 IU/L), 1 220 cases in low anti-HBs group (10-99 IU/L), 693 cases in medium anti-HBs group (100-499 IU/L) and 240 cases in high anti-HBs group (≥500 IU/L). The CD4 + T lymphocyte count levels of the four groups were (150.00±8.42)/μL, (185.00±7.08)/μL, (243.00±12.07)/μL and (308.00±22.60)/μL, respectively. The overall CD4 + T lymphocyte count levels among the four groups were significantly different ( F=68.479, P<0.01). Among the 90 HIV infected patients who received anti-retroviral therapy (ART), the anti-HBs titer increased from (91.96±21.87) IU/L to (200.76±56.43) IU/L after treatment, and the anti-HBs level before and after treatment was significantly different ( t=-2.542, P=0.035). Among 208 patients with negative HBV markers, no patients had hepatitis B surface antigen switched to positive when monitored for an interval time of (26.2±5.3) months. Conclusions:The risk of HBV exposure in patients with HIV infection is not significantly related to the disease stage, but the positive rate and titer of anti-HBs are significantly positively correlated with CD4 + T lymphocyte count level. The monitoring of anti-HBs and the serum markers of HBV infection in the same individual is conducive to the in-depth understanding of the protective effect of anti-HBs and the scientific evaluation of the risk of infection after HBV exposure.
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Autophagy is a physiological process of normal cells that is activated in response to accumulation of abnormal proteins, damaged organelles, and cell starvation and involves their transport to lysosomes for degradation and recycling, enabling the mainte-nance of cellular homeostasis. Oncolytic viruses, which are obtained from naturally occurring or genetically modified viruses, specifical-ly target and kill tumor cells. Despite receiving much attention, the mechanisms underlying this process remain unclear, although re-cent studies have implicated autophagy in the phenomenon. Here we outline how oncolytic viruses cause cell death via autophagy and how they can be exploited for the treatment of cancer.
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To investigate the clinical and pathological significance of melanin content and cyclin D1 expression in malignant melanoma. Methods: Melanin content and cyclin D1 expression were detected by immunohistochemical staining in one tissue micro-array containing 189 specimens of malignant melanoma between January 2001 and December 2014. Results: There were 76 cases (40.2%) of high melanin content among 189 malignant melanoma patients, and 80 cases (45.7%) of high expression of cyclin D1. The content of melanin was not correlated with the patients＇age, gender, tumor tissue source, and lymph node metastasis, but instead, it was correlated with tumor invasion depth (P=0.001) and clinical stage (P=0.038). The melanin content was much lower in advanced malignant melanoma (stageⅢandⅣor T3 and T4) than in non-advanced melanoma (stageⅠandⅡor T1 and T2). Regarding cyclin D1 expression, there was no significant difference in age, gender, invasion depth (T stage), clinical stage, lymph node metastasis, and tumor tissue source. Melanin content was negatively correlated with cyclin D1 expression in 58 cases of lymph node metastatic malig-nant melanoma (r=-0.271, P=0.039). Conclusions: Melanin content in melanoma tissues may be involved in the invasion, progression, and metastasis of malignant melanoma. The results will provide new evidence for the prognosis and pathological diagnosis of malig-nant melanoma.
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Objective To observe the specific humoral and cellular immune response in BALB/c mice injected with pS and p18S. Methods pS and p18S were constructed separately by inserting HBsAg gene fragment and the fusion gene fragment of HBsAg and mouse interleukin 18(IL 18) into the reading frame of pcDNA3.1+. Mice were injected with either plasmid intramuscularly in a total dose of 300 ?g per mouse. Every serum sample was detected for anti HBs using enzyme linked immunosorbent assay(ELISA). Furthermore, HBsAg specific cytotoxic T lymphocytes activity was measured. Results The expression of HBsAg was demonstrated by ELISA in p815 cells transfected with pS and p18S. pS can stimulate a positive antibody response. The average level was 135 mIU/ml, with the highest level of 530 mIU/ml. p18S could elicit relatively lower antibody response which was 20 mIU/ml. HBsAg specific CTL activities were 37.1% and 34% separately in pS and p18S immunized mice. It was only 13.2% when detected in pcDNA3.1+ immunization. Conclusion pS is effective to stimulate a humoral and cellular response in H 2d mice. IL 18 gene can not enhance the immune response when fused with HBsAg gene. Conversely, it seems to inhibit an immune response.
