Life-threatening gastrointestinal bleeding caused by cytomegalovirus-induced duodenal ulcer in a patient with AIDS: A case report.

Background: The reasons for gastrointestinal bleeding among patients with acquired immune deficiency syndrome (AIDS) were complex. Here we present an unusual case of life-threatening gastrointestinal bleeding caused by a cytomegalovirus-induced duodenal ulcer in an AIDS patient. Case presentation: A 31-year-old male with AIDS was admitted on July 18, 2023, complaining of abdominal pain for 38 days and intermittent hematochezia for 12 days. During his hospitalization, gastrointestinal endoscopy attributed gastrointestinal bleeding to a giant duodenal ulcer. Furthermore, cytomegalovirus(CMV) infection was confirmed as the reason for the ulcer through metagenomic next-generation sequencing (mNGs), hematoxylin-eosin(HE) staining, and immunohistochemistry (IHC) staining for the biopsy tissue. The patient's gastrointestinal bleeding was stopped by interventional embolization. Following a 4-week course of anti-CMV treatment, the giant duodenal ulcer was cured. Conclusions: For AIDS patients with gastrointestinal bleeding, the CMV-induced gastrointestinal ulcer should be considered. Comprehensive mothods (mNGs, HE staining and IHC staining for biopsy tissue) were benefit for confirmed diagnosis. Beside anti-CMV treatment, the interventional embolization is a choice for hemostasis.

Characteristics of Hepatitis B Virus, Hepatitis C Virus, and Syphilis Coinfection in People With HIV/AIDS Contracted Through Different Sources: Retrospective Study.

BACKGROUND: The burden of hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis coinfections remains disproportionately high among people living with HIV/AIDS. Hubei province is located in central China, where there are distinct regional characteristics of the distribution of people living with HIV/AIDS acquired via diverse transmission routes and the AIDS epidemic itself. OBJECTIVE: We aimed to estimate the magnitude of HBV, HCV, or syphilis coinfections among people living with HIV/AIDS with blood-borne transmission, which includes former paid blood donors, contaminated blood recipients, and intravenous drug users, as well as among people with sex-borne HIV transmission (including heterosexual people and men who have sex with men) and people with mother-to-child HIV transmission. METHODS: From January 2010 to December 2020, people living with HIV/AIDS were tested for hepatitis B surface antigen (HBsAg), HCV antibodies, and syphilis-specific antibodies. The positive patients were further tested for HBV markers, HBV DNA, and HCV RNA, and received a rapid plasma reagin circle card test. All people living with HIV/AIDS were first divided into transmission groups (blood, sex, and mother-to-child); then, people with blood-borne HIV transmission were divided into former paid blood donors, contaminated blood recipients, and intravenous drug users, while people with sex-borne HIV transmission were divided into heterosexual people and men who have sex with men. RESULTS: Among 6623 people living with HIV/AIDS, rates of chronic HCV infection were 80.3% (590/735) in former paid blood donors, 73.3% (247/337) in intravenous drug users, 57.1% (444/777) in contaminated blood recipients, 19.4% (21/108) in people with mother-to-child HIV transmission, 8.1% (240/2975) in heterosexual people, and 1.2% (21/1691) in men who have sex with men. Chronic HBV infection rates were similar among all people with blood-borne HIV transmission. However, compared to heterosexual people, the chronic HBV infection rate was greater in men who have sex with men (213/1691, 12.6% vs 308/2975, 10.4%; χ21=5.469; P=.02), although HBV exposure was less common (827/1691, 48.9% vs 1662/2975, 55.9%; χ21=20.982; P<.001). Interestingly, the combination of HBsAg and hepatitis B e antigen (HBeAg) was found in 11 patients with sex-borne HIV transmission, but in 0 people with blood-borne HIV transmission (11/196, 5.6% vs 0/521, 0%; χ21=29.695, P<.001). In people with sex-borne HIV transmission, the proportions of patients with a syphilis titer ≥1:16 and neurosyphilis were 8.6% (105/1227) and 7.8% (37/473), respectively, whereas these values were 0 in people with blood-borne HIV transmission. CONCLUSIONS: In people living with HIV/AIDS, HCV transmission intensity was significantly associated with specific exposure modes of blood or sexual contact. The rate of chronic HBV infection among men who have sex with men was higher than in any other population. Attention should be paid to the high prevalence of neurosyphilis in people living with HIV/AIDS who contract HIV by sexual intercourse.

Systemic inflammatory response syndrome in patients with severe fever with thrombocytopenia syndrome: prevalence, characteristics, and impact on prognosis.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis. METHODS: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared. RESULTS: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS. CONCLUSIONS: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality.

Serum protein biomarkers for HCC risk prediction in HIV/HBV co-infected people: a clinical proteomic study using mass spectrometry.

Background: HBV coinfection is frequent in people living with HIV (PLWH) and is the leading cause of hepatocellular carcinoma (HCC). While risk prediction methods for HCC in patients with HBV monoinfection have been proposed, suitable biomarkers for early diagnosis of HCC in PLWH remain uncommon. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to examine serum protein alterations in HCC and non-HCC patients with HIV and HBV co-infection. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analysis were performed on the differentially expressed proteins (DEPs). The risk prediction model was created using five-cross-validation and LASSO regression to filter core DEPs. Results: A total of 124 DEPs were discovered, with 95 proteins up-regulated and 29 proteins down-regulated. Extracellular matrix organization and membrane component were the DEPs that were most abundant in the categories of biological processes (BP) and cellular components (CC). Proteoglycans in cancer were one of the top three DEPs primarily enriched in the KEGG pathway, and 60.0% of DEPs were linked to various neoplasms in terms of DO enrichment. Eleven proteins, including GAPR1, PLTP, CLASP2, IGHV1-69D, IGLV5-45, A2M, VNN1, KLK11, ANPEP, DPP4 and HYI, were chosen as the core DEPs, and a nomogram was created to predict HCC risk. Conclusion: In HIV/HBV patients with HCC, several differential proteins can be detected in plasma by mass spectrometry, which can be used as screening markers for early diagnosis and risk prediction of HCC. Monitoring protease expression differences can help in the diagnosis and prognosis of HCC.

Case Report: Giant Oral Ulcers Attributed to Cytomegalovirus Infection in a Patient with AIDS.

Oral ulcers are often neglected in patients with AIDS. However, giant oral ulcers are uncommon and are usually suspected to be malignant lesions. Our study presents a case of giant ulcers in an AIDS patient that were initially suspected to be oral cancer. To assist with diagnosis, conventional microbiological tests, metagenomic next-generation sequencing, and a pathological examination were conducted on oral lesion biopsy specimens. The case was finally confirmed via hematoxylin-eosin staining and immunohistochemical staining to be a cytomegalovirus infection.

Prevalence and clinical characteristics of increased pancreatic enzymes in patients with severe fever with thrombocytopenia syndrome.

BACKGROUND AND AIM: The increased pancreatic enzymes have recently been reported in patients with severe fever with thrombocytopenia syndrome (SFTS). However, its significance has not been elucidated clearly. The aim of this study was to explore the prevalence, clinical characteristics of elevated pancreatic enzymes (amylase and lipase) and its association with AP in patients with SFTS. METHODS: Data of demographics, comorbid conditions, clinical symptoms, laboratory parameters and survival time of patients with SFTS were collected. Patients were assigned into the non-AP and AP groups according to the diagnostic criteria of AP. Patients in the non-AP group were divided into the normal (3×ULN) groups according to the serum amylase and lipase levels, and then their clinical data were compared. RESULTS: A total of 284 patients diagnosed with SFTS were retrospectively enrolled, including 248 patients in the non-AP group and 36 patients in the AP group. Patients in the non-AP group were composed of 48, 116 and 84 patients in the normal, EPE and HPE groups, respectively. Compared with patients in the normal and EPE groups, patients in the HPE group had higher serum levels of laboratory parameters referring to liver, kidney, heart and coagulation system injury, as well as higher viral load. The cumulative survival rate of patients in the HPE group was significantly lower than that of patients in the normal group. In addition, patients in the AP group also had higher serum levels of laboratory variables reflecting liver, heart, coagulation dysfunction and viral load than patients in the HPE group. The cumulative survival rate of patients in the AP group was significantly lower than that of patients in the HPE group. CONCLUSION: The increased pancreatic enzymes are very common in patients with SFTS, but they are not always associated with AP. Though AP accounts for the majority of deaths for patients with elevated pancreatic enzymes, patients with pancreatic enzymes >3×ULN except for AP also have a high in-hospital mortality rate.

Characterization of peripheral cytokine-secreting cells responses in HIV/TB co-infection.

Background: Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. Methods: The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Results: Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ+CD4+, IFN-γ+CD8+, TNF-α+CD4+, IL17A+CD4+ T cells and TNF-α+CD14+ monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8+ T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4+, CD8+ T cells and CD14+ monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8+ T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4+ T cells secreting TGF-ß (p<0.001; p=0.001), and CD4+ and CD8+ T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4+ T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8+ T cells secreting TNF-α (p=0.029) was found in the HT group. Conclusion: Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8+ T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.

Adverse pregnancy outcomes associated with antiretroviral therapy initiated before pregnancy and during pregnancy: a retrospective study in Hubei province, China.

Background: Antiretroviral therapy (ART) initiation before pregnancy was reported to have an increased risk of adverse pregnancy outcomes (APOs) than ART initiation during pregnancy. However, the risks of APOs associated with different ART regimens initiated before or during pregnancy remain unknown. Methods: Pregnant women living with HIV (PWLHIV) from Hubei Province, China, were retrospectively enrolled between January 1, 2004, and December 31, 2021. The trends of ART initiation time and application of different ART regimens were evaluated over time, separately. Using no ART exposure before and during pregnancy as control, the risks of APOs associated with protease inhibitor (PI) based regimens and non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens initiated before pregnancy were analyzed; and the risks of APOs associated with PI-based regimens, NNRTIs based regimens and zidovudine (AZT) monotherapy initiated during pregnancy were analyzed. APOs, including low birthweight (LBW), stillbirth, preterm birth (PTB) and early miscarriage, were reviewed. Results: Among 781 PWLHIV including 1,010 pregnancies, 522 pregnancies (51.7%) were exposed to ART before or during pregnancy. Of them, the proportion of ART initiation before pregnancy per year increased from around 20% in the early period to more than 60% after 2019. Efavirenz (EFV)-nucleoside reverse transcriptase inhibitors (NRTIs) (32.2%), LPV/r-NRTIs (31.2%), and nevirapine (NVP)-NRTIs (27.4%) were the most commonly used regimens, and the proportion of LPV/r-NRTIs used per year has increased to around 50.0% in recent years. LPV/r-NRTIs was associated with higher risks of LBW whether initiated before pregnancy [adjusted OR (aOR) = 2.59, 95%CI 1.04-6.45, p = 0.041] or during pregnancy (aOR = 2.19, 95%CI 1.03-4.67, p = 0.041), compared with no exposure to ART before and during pregnancy. However, no matter initiated before or during pregnancy, LPV/r-NRTIs had no significantly increased risks of stillbirth, PTB and early miscarriage, and EFV /NVP-NRTIs and AZT monotherapy had no significantly increased risks of LBW, stillbirth, PTB and early miscarriage when compared with no exposure to ART before and during pregnancy. Conclusion: Our data suggests that LPV/r-NRTIs has been widely used among PWLHIV in recent years. However, the potential risk of LBW should be continuously monitored among PWLHIV whether LPV/r-NRTIs is initiated before or during pregnancy.

Frequency and functional profile of circulating TCRαß+ double negative T cells in HIV/TB co-infection.

BACKGROUND: Increased frequency of circulating double negative T (DNT, CD4-CD8-CD3+) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαß+ DNT cells was further investigated in HIV/TB co-infection. METHODS: A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαß+ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry. RESULTS: Significantly increased frequency of TCRαß+ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαß+ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas+TCRαß+ DNT cells had no significant difference. TCRαß+ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαß+ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαß+ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4+ T cells but similar to CD8+ T cells. CONCLUSIONS: Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαß+ DNT cells in HIV/TB co-infection. TCRαß+ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection.

The Role of CD4+CD8+ T Cells in HIV Infection With Tuberculosis.

Background: Tuberculosis (TB) is an important opportunistic infection in acquired immunodeficiency diseases (AIDS). Although the frequency of CD4+CD8+ double-positive (DP) T cells has been observed to increase in pathological conditions, their role (phenotypic and functional) is poorly described, especially in human immunodeficiency virus (HIV) infection with TB (HIV/TB (HT) coinfection). Methods: The percentage and phenotypic and functional properties of peripheral blood DP T cells in patients with HT coinfection in comparison to uninfected controls and to patients with HIV or TB mono-infection were analyzed by direct intracellular cytokine staining (ICS). Results: Total and CD4lowCD8high DP T cells were significantly increased in patients with both HIV and TB mono-infection, especially in patients with HT coinfection. Compared with healthy controls (HCs), the percentage of DP T cells expressing chemokine receptor 5 (CCR5) in patients with HT coinfection was significantly higher. Compared with HCs and patients with TB, a lower percentage of tumor necrosis factor α (TNF-α) secreting DP T cells and a higher percentage of granzyme A-secreting DP T cells were observed in patients with HIV mono-infection and HT coinfection, respectively. In addition, DP T cells expressed more cytolytic markers (granzyme A and perforin) than CD4+ T cells, but similarly to CD8+ T cells in patients with HT coinfection. Conclusions: Our data suggested that HT coinfection resulted in a marked increase in DP T cells, especially the CD4lowCD8high subpopulation. DP T cells may be susceptible to HT coinfection, and have the same cytotoxic function as CD8+ T cells.

A case of hepatic tuberculosis with acquired immune deficiency syndrome.

Hepatic tuberculosis (TB) is a rare type of extrapulmonary TB. Due to the nonspecific clinical symptoms and imaging manifestations, hepatic TB with human immunodeficiency virus (HIV) infection is easy to be misdiagnosed. We report a case of hepatic TB with acquired immune deficiency syndrome (AIDS), which was initially misdiagnosed as general bacterial liver abscess even after the patient received needle biopsy. In subsequent process, pathogenic tests using washing solution of punctured liver tissue sample were proved feasible, convenient, and specific for pathogenic diagnosis in resource-limited areas of China. For liver abscess in patients with HIV, the pathogens are more complex than HIV negative patients. Some uncommon pathogens, such as TB and fungi, should also be taken into consideration. For the hepatic TB without abscess formation, pathogenic test using washing solution of punctured liver tissue sample should be attached importance.

Electrocardiogram manifestations of hyponatraemia.

Electrolytes play a vital role in myocardial electrophysiological activities in the human body. Electrolyte disturbances can affect depolarisation and repolarisation of myocardial cells and thus result in arrhythmia. The most common electrolyte disturbance among hospitalised patients is hyponatraemia. We report on a case of an acquired immune deficiency syndrome patient with decompensated cirrhosis, who developed sinus arrest from hyponatraemia. The electrocardiogram manifestations at different sodium concentrations were also recorded in subsequent therapeutic processes.

Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.

The indicative role of markers for liver injury on the severity and prognosis of coronavirus disease 2019 patients.

BACKGROUND: Liver injury in coronavirus disease 2019 (COVID-19) patients was poorly understood. METHODS: The markers of liver injury, severity of disease and prognosis among 495 COVID-19 patients in Zhongnan Hospital of Wuhan University from 1st January 2019 to 11th March 2019 were retrospectively analyzed. RESULTS: The levels of aspartate aminotransferase (AST) (50.1 ± 38.4 vs. 31.4 ± 39.1, P < 0.001), gamma-glutamyl transpeptidase (GGT) (70.3 ± 70.2 vs. 34.1 ± 34.7, P < 0.001) and fibrinogen-to-albumin-ratio (FAR) (13.4 ± 4.0 vs. 10.4 ± 3.4, P < 0.001) were greater than mild COVID-19 patients, whereas the levels of albumin(35.0 ± 6.2 vs. 39.9 ± 3.7, P < 0.001) and albumin/globulin (A/G) ratio (1.21 ± 0.24 vs. 1.50 ± 0.31, P < 0.001) were lower in severe COVID-19 patients. By comparing the changes of liver injury markers 7-10 days after hospitalization, the level of albumin deteriorated from 35.0 ± 6.2 to 30.20 ± 5.5 (P < 0.001), A/G ratio from 1.21 ± 0.24 to 1.06 ± 0.25 (P < 0.001), and FAR from 13.4 ± 4.0 to 15.4 ± 2.9(P < 0.001) in severe COVID-19 patients, while the changes of albumin, A/G ratio and FAR showed opposite patterns in mild COVID-19 patients. FAR > 12 [2.566 (1.410-4.670), P = 0.012) on admission and changes of albumin >5g/l [22.489 (6.422-78.757), P = 0.001] were two risk factors for death, and the sensitivity and specificity for the poor prognosis were 80.8% and 64.0%, 82.6% and 76.3%, respectively. CONCLUSION: The levels of AST, GGT, albumin and FAR are correlated with disease severity after severe acute respiratory syndrome coronavirus-2 infection. FAR > 12 on admission and changes of albumin > 5 g/l were good predictors for the prognosis of COVID-19 patients.

Risk factors for delayed negative conversion of SARS-CoV-2 in patients with COVID-19 pneumonia: a retrospective cohort study.

The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11-25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.

Clinical Characteristics and Outcomes of Older Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Single-Centered, Retrospective Study.

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. In this study, we aimed to describe the clinical course and outcomes of older patients with COVID-19. METHODS: This is a retrospective investigation of hospitalized older patients with confirmed COVID-19 at Zhongnan Hospital of Wuhan University from January 1, 2020, to February 10, 2020. RESULTS: In total, 203 patients were diagnosed with COVID-19, with a median age of 54 years (interquartile range, 41-68; range, 20-91 years). Men accounted for 108 (53.2%) of the cases, and 55 patients (27.1%) were more than 65 years of age. Among patients who were 65 years and older, the mortality rate was 34.5% (19/55), which was significantly higher than that of the younger patients at 4.7% (7/148). Common symptoms of older patients with COVID-19 included fever (94.5%; n = 52), dry cough (69.1%; n = 38), and chest distress (63.6%; n = 35). Compared with young patients, older patients had more laboratory abnormalities and comorbidities. Through a multivariate analysis of the causes of death in older patients, we found that males, comorbidities, time from disease onset to hospitalization, abnormal kidney function, and elevated procalcitonin levels were all significantly associated with death. CONCLUSIONS: In the recent outbreak of COVID-19, our local hospital in Wuhan found that patients aged 65 and older had greater initial comorbidities, more severe symptoms, and were more likely to experience multiorgan involvement and death, as compared to younger patients.

Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19.

BACKGROUND: Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. METHODS: A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. RESULTS: 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P = 0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR = 16.04; 95% CI, 1.14 to 224.95; P = 0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR = 1.10; 95% CI, 1.02 to 1.19; P = 0.016). CONCLUSIONS: NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.

Multi-part and scale adaptive visual tracker based on kernel correlation filter.

Accurate visual tracking is a challenging issue in computer vision. Correlation filter (CF) based methods are sought in visual tracking based on their efficiency and high performance. Nonetheless, CF-based trackers are sensitive to partial occlusion, which may reduce their overall performance and even lead to failure in tracking challenge. In this paper, we presented a very powerful tracker based on the kernelized correlation filter tracker (KCF). Firstly, we employ an intelligent multi-part tracking algorithm to improve the overall capability of correlation filter based tracker, especially in partial-occlusion challenges. Secondly, to cope with the problem of scale variation, we employ an effective scale adaptive scheme, which divided the target into four patches and computed the scale factor by finding the maximum response position of each patch via kernelized correlation filter. With this method, the scale computation was transformed into locating the centers of the patches. Thirdly, because the small deviation of the central function value will bring the problem of location ambiguity. To solve this problem, the new Gaussian kernel functions are introduced in this paper. Experiments on the default 51 video sequences in Visual Tracker Benchmark demonstrate that our proposed tracker provides significant improvement compared with the state-of-art trackers.

Elevated expression of miR-146a correlates with high levels of immune cell exhaustion markers and suppresses cellular immune function in chronic HIV-1-infected patients.

Functional exhaustion of immune cells is a defining characteristic of HIV-1 chronic infections, exhibiting dysregulation of cellular immune responses and expression of co-inhibitory receptors. Although the molecular mechanisms controlling immune-cell exhaustion retains largely unknown, immune checkpoint blockade strategy has shown inspiring potential to reinvigorate T cell functions in chronic infections. In this study, we investigated peripheral blood mononuclear cells (PBMCs) exhaustion markers from 109 chronic HIV-1-infected patients and found they correlated positively with microRNA-146a, which was inversely correlated with CD4+ T cell count. Intriguingly, ex vivo neutralization of miR-146a in PBMCs from chronic HIV-1 infection exhibited an elevated antiviral cytokines production as well as the expression of GZMB and perforin, while simultaneously, decreased the inhibitory receptors expression such as PD-1, CTLA-4, TIM-3 and LAG-3. These results highlight the importance of miR-146a to HIV-1 induced immune cell exhaustion, and uncover a novel layer of HIV/AIDS pathogenesis and provide potential targets for improved immune intervention.

CRISPR/Cas9-mediated deletion of miR-146a enhances antiviral response in HIV-1 infected cells.

The human immunodeficiency virus type 1 (HIV-1) causes persistent infection in human and induces miR-146a expression in infected cells. miR-146a represses the innate immune response by inhibiting the expression of TRAF6 and IRAK1 genes, thus negatively controls the NF-κB-related cytokines and interferon stimulated genes. Here we reported that lentiviral CRISPR/Cas9 system was highly efficient in introducing mutations in the precursor miR-146a genomic sequences, resulting in a loss of miR-146a expression and function. miR-146a ablation led to increasing cytokines production in LPS-stimulated A549 cells. Moreover, miR-146a knockout in HIV-1 infected MT2 cells markedly increased the expression of cytokines and HIV-1 restriction factors and reversed T cell exhaustion markers expression, thus influencing HIV-1 replication. Our study indicates that lentiviral CRISPR/Cas9-mediated gene editing is an effective approach to abrogate miR-146a expression, which consequently inhibits HIV-1 replication as well as proviral reactivation by enhancing the expression of cytokines and HIV-1 restriction factors.