To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19.
We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for ...studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2. Publication bias was assessed using Egger's test.
43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% 95% CI 78.4–87.7), cough (60.3% 54.2–66.3), and fatigue (38.0% 29.8–46.5) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% 58.2–78.2), decreased lymphocyte count (57.4% 44.8–69.5) and increased lactate dehydrogenase (51.6% 31.4–71.6). Ground-glass opacities (80.0% 67.3–90.4) and bilateral pneumonia (73.2% 63.4–82.1) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4–34.9) and 3.6% (1.1–7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender.
The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.
This study aimed to investigate the influencing factors of delayed clearance of Talaromyces marneffei (T. marneffei) in blood culture of patients with acquired immune deficiency syndrome (AIDS) ...complicated with talaromycosis after antifungal therapy.
The patients with AIDS complicated with talaromycosis were retrospectively enrolled, and divided into two groups according to the blood T. marneffei culture results in two weeks after antifungal therapy. The baseline clinical data were collected and the antifungal susceptibility of T. marneffei was tested.
A total of 190 patients with AIDS and talaromycosis were enrolled, of whom 101 cases remained positive for T. marneffei (Pos-group) while the other 89 cases were negative in blood culture (Neg-group) after two weeks' antifungal treatment. The Pos-group had a higher baseline Aspartate aminotransferase (AST, 78.5 vs. 105 U/L; P = 0.073) and lower CD4+ T cells level (11 vs. 7 cells/μl; P = 0.061). The percentage of isolates with higher MICs of voriconazole (VOR) and fluconazole (FLU) in the Pos-group were significantly higher than those in the Neg-group (χ2 = 12.623, P < 0.001 and χ2 = 9.356, P = 0.002, respectively). By multivariate logistic regression, the MIC value for VOR was identified as the prognostic variable that may influence the clearance of T. marneffei in blood culture after antifungal therapy among AIDS patients with talaromycosis.
The delayed negative conversion of blood T. marneffei-culture may be associated with some factors especially higher MIC of VOR, indicating the possibility of drug resistance of T. marneffei.
For some atypical strains of T. marneffei, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used for identification because it is easy to operate ...even by an inexperienced technician and is time-saving. In a recent study of 283 patients with AIDS, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of Mp1p enzyme immunoassay within 3 days after admission were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively, which was consistent with the gold standard (kappa, 0.729) and superior to GM determination (kappa, 0.603). A significantly lower mortality rate during the 48 weeks was observed in the early ART group (the median period from antifungal therapy to ART initiation was 11 days) when compared to the deferred ART group (the median period from antifungal therapy to ART initiation was 21 days). 2Qin, YHuang, XChen, HLiu, XLi, YHou, J. Burden of Talaromyces marneffei infection in people living with HIV/AIDS in Asia during ART era: a systematic review and meta-analysis.
Since only a few studies have been conducted on the factors associated with different HIV-1 tropisms in low-level viral load HIV-1 infections in China, we investigated the sequences of HIV-1 V3 loop ...in prevalent HIV-1 subtypes and factors related to HIV-1 tropism and immune recovery in HIV-1 infections after 6 months of highly active antiretroviral therapy (HAART) in Guangdong, China.
Plasma samples with HIV-1 RNA of 400-999 copies/mL were collected. We analyzed the amino acid sequence of the V3 loop by
prediction algorithms. Mann-Whitney and Chi-square tests were used for statistical comparison. Furthermore, logistic regression and multiple linear regression were used, respectively, for factors associated with 351 HIV-1 tropism and immune recovery of 67 cases with continued CD4
T cell count during HAART.
There was a lower percentage of HIV-1 R5-tropic virus in CRF01_AE (66.3%) (
< 0.0001) and CRF55_01B (52.6%) (
< 0.0001) compared with both CRF07_BC (96.1%) and CRF08_BC (97.4%), respectively. Compared with the R5-tropic virus, higher proportions of IIe8/Val8, Arg11/Lys11, and Arg18/His18/Lys18 were observed in the X4-tropic virus of CRF01_AE and CRF07_BC (
< 0.0001). The baseline CD4
T cell count (
< 0.0001) and baseline CD4
T/CD8
T ratio (
= 0.0006) of all R5-tropic infections were higher than those in the X4-tropic infection. The baseline CD4
T cell count (odds ratio OR 0.9963,
= 0.0097), CRF07_BC (OR 0.1283,
= 0.0002), and CRF08_BC (OR 0.1124,
= 0.0381) were associated with less HIV-1 X4-tropism. The baseline CD4
T cell count was a positive factor (
< 0.0001) in the recovery of CD4
T cell count during HAART.
R5-tropism represented the majority in low-level viral load HIV-1 infections receiving HAART for more than 6 months in Guangdong, China. The baseline immune level in the HIV-1 R5-tropic infections was higher than that in the X4-tropic infections. The amino acids of the 8th, 11th, and 18th of the HIV-1 V3 loop were more variable in the X4-tropic HIV-1. CRF01_AE, CRF55_01B, and lower baseline CD4
T cell count were associated with more HIV-1 X4-tropism. The immune recovery during HAART was positively related to baseline CD4
T cell count.
Abstract
Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) ...contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others including darunavir, raltegravie, elvitegravir and rilpivirine) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.
The characteristic of human immunodeficiency virus type 1 (HIV-1) is its susceptibility to erroneous replication and recombination, which plays a crucial role in the diverse and dynamic variation of ...HIV-1. The spread of different subtypes in the same population often leads to the emergence of circulating recombination forms (CRFs). At present, the main recombinant subtypes of HIV-1 in China are CRF07_BC, CRF01_AE, CRF08_BC and B' subtypes, while CRF55_01B has become the fifth major epidemic strain in China after rapid growth in recent years since it was first reported in 2013. In this study, we obtained five nearly full-length genomes (NFLGs) and one half-length genome from five different cities in Guangdong. Here, we focused on analyzing their characteristics, parental origin and drug resistance.
Plasma samples were collected from six HIV-1 infected patients in Guangdong Province who had no epidemiological association with each other. The NFLGs of HIV-1 were amplified in two overlapping segments by the near-terminal dilution method. The positive products were sequenced directly to obtain genomic sequences. The recombinant patterns and breakpoints of the NFLGs were determined using the Simplot software and confirmed by the maximum likelihood trees for segments using the IQ-TREE and BEAST software. The genotypic resistance profiles of the protease reverse transcriptase and integrase were resolved by the Stanford HIV drug resistance database.
The six genomes shared highly similar recombinant pattern, with the CRF55_01B backbone substituted by CRF07_BC segments, therefore assigned as CRF156_0755. The evolutionary analysis of the segments showed that CRF07_BC segments were not clustered with the Chinese MSM variants in the CRF07_BC lineage. All the five NFLGs were identified with the non-nucleoside reverse-transcription inhibitors (NNRTIs) resistance mutation V179E.
With the accumulation and evolution of recombination between CRF55_01B and CRF 07_BC, the prevalence of more recombinant strains of CRF55_01B and CRF 07_BC may occur. Therefore, it is necessary to strengthen the identification and monitoring of the recombination of CRF55_01B and CRF 07_BC.
Previous studies have shown positive association between HIV-related stigma and depression, suicidal ideation, and suicidal attempt among people living with HIV/AIDS (PLWH). But few studies have ...examined the mechanisms among HIV-related stigma, depression, and suicidal status (suicidal ideation and/or suicidal attempt) in PLWH. The current study examined the relationships among perceived and internalized stigma (PIS), depression, and suicidal status among PLWH in Guangzhou, China using structural equation modeling.
Cross-sectional study by convenience sampling was conducted and 411 PLWH were recruited from the Number Eight People's Hospital from March to June, 2013 in Guangzhou, China. Participants were interviewed on their PIS, depressive symptoms, suicidal status, and socio-demographic characteristics. PLWH who had had suicidal ideation and suicidal attempts since HIV diagnosis were considered to be suicidal. Structural equation model was performed to examine the direct and indirect associations of PIS and suicidal status. Indicators to evaluate goodness of fit of the structural equation model included Chi-square Statistic, Comparative Fit Index (CFI), Root Mean Square Error of Approximation (RMSEA), Standardized Root Mean Square Residual (SRMR), and Weighted Root Mean Square Residual (WRMR).
More than one-third (38.4%) of the PLWH had depressive symptoms and 32.4% reported suicidal ideation and/or attempt since HIV diagnosis. The global model showed good model fit (Chi-square value = 34.42, CFI = 0.98, RMSEA = 0.03, WRMR = 0.73). Structural equation model revealed that direct pathway of PIS on suicidal status was significant (standardized pathway coefficient = 0.21), and indirect pathway of PIS on suicidal status via depression was also significant (standardized pathway coefficient = 0.24). There was a partial mediating effect of depression in the association between PIS and suicidal status.
Our findings suggest that PIS is associated with increased depression and the likelihood of suicidal status. Depression is in turn positively associated with suicidal status and plays a mediating role between PIS and suicidal status. Therefore, to reduce suicidal ideation and attempt in PLWH, targeted interventions to reduce PIS and improve mental health status of PLWH are warranted.
Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic ...methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with
Talaromyces marneffei
(TSM group, n = 93) and those without
Talaromyces marneffei
(non-TSM group, n = 190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4+ counts of < 50 cells/µL compared to those with CD4+ counts ranged from 50–100 cells/µL. The Mp1p EIA has the advantage of assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4+ counts.
Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among ...HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong.
The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015.
A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed.
There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.
Comprehensively elucidating the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) latency is a priority to achieve a functional cure. As current 'shock' agents failed to efficiently ...reactivate the latent reservoir, it is important to discover new targets for developing more efficient latency-reversing agents (LRAs). Here, we found that TRIM28 potently suppresses HIV-1 expression by utilizing both SUMO E3 ligase activity and epigenetic adaptor function. Through global site-specific SUMO-MS study and serial SUMOylation assays, we identified that P-TEFb catalytic subunit CDK9 is significantly SUMOylated by TRIM28 with SUMO4. The Lys44, Lys56 and Lys68 residues on CDK9 are SUMOylated by TRIM28, which inhibits CDK9 kinase activity or prevents P-TEFb assembly by directly blocking the interaction between CDK9 and Cyclin T1, subsequently inhibits viral transcription and contributes to HIV-1 latency. The manipulation of TRIM28 and its consequent SUMOylation pathway could be the target for developing LRAs.
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