Background Individual studies have reported widely variable rates for venous thromboembolism ( VTE ) and bleeding among hospitalized patients with coronavirus disease 2019 ( COVID-19 ). Research question What is the incidence of VTE and bleeding among hospitalized patients with COVID-19? Methods In this systematic review and meta-analysis we searched 15 standard and COVID-19 specific sources between January 1, 2020 and July 31, 2020, with no restriction by language. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I 2 statistic. We assessed publication bias using Begg's and Egger's tests. Results The pooled incidence was 17.0% (95% confidence interval [ CI ], 13.4%-20.9%) for VTE, 12.1% (95% CI, 8.4%-16.4%) for DVT, 7.1% (95% CI, 5.3%-9.1%) for PE, 7.8% (95% CI, 2.6%-15.3%) for bleeding, and 3.9% (95% CI, 1.2%-7.9%) for major bleeding. In subgroup meta-analyses, the incidence of VTE was higher when assessed by screening (33.1% vs. 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs. 7.1% in the ward), in prospective studies (25.5% vs. 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs. The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%). Interpretation Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT and subsegmental PE, in critically ill patients, and in prospective studies. Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants, and nature of data collection. Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes.
Objectives To analyse the characteristics and predictors of death in hospitalized patients with coronavirus disease 2019 (COVID-19) in Spain. Methods A retrospective observational study was performed of the first consecutive patients hospitalized with COVID-19 confirmed by real-time PCR assay in 127 Spanish centres until 17 March 2020. The follow-up censoring date was 17 April 2020. We collected demographic, clinical, laboratory, treatment and complications data. The primary endpoint was all-cause mortality. Univariable and multivariable Cox regression analyses were performed to identify factors associated with death. Results Of the 4035 patients, male subjects accounted for 2433 (61.0%) of 3987, the median age was 70 years and 2539 (73.8%) of 3439 had one or more comorbidity. The most common symptoms were a history of fever, cough, malaise and dyspnoea. During hospitalization, 1255 (31.5%) of 3979 patients developed acute respiratory distress syndrome, 736 (18.5%) of 3988 were admitted to intensive care units and 619 (15.5%) of 3992 underwent mechanical ventilation. Virus- or host-targeted medications included lopinavir/ritonavir (2820/4005, 70.4%), hydroxychloroquine (2618/3995, 65.5%), interferon beta (1153/3950, 29.2%), corticosteroids (1109/3965, 28.0%) and tocilizumab (373/3951, 9.4%). Overall, 1131 (28%) of 4035 patients died. Mortality increased with age (85.6% occurring in older than 65 years). Seventeen factors were independently associated with an increased hazard of death, the strongest among them including advanced age, liver cirrhosis, low age-adjusted oxygen saturation, higher concentrations of C-reactive protein and lower estimated glomerular filtration rate. Conclusions Our findings provide comprehensive information about characteristics and complications of severe COVID-19, and may help clinicians identify patients at a higher risk of death.
Highly active antiretroviral therapy (HAART) has been shown to be highly effective in reducing plasma levels of HIV RNA; therefore, these treatments could diminish the risk of transmission. We analyzed 393 steady heterosexual couples, of which one partner had been previously diagnosed with HIV infection (index case) and where the nonindex partner reported his or her sexual relationship with the index case as the unique risk exposure. These couples were consecutively enrolled in the period 1991 through 2003 when the nonindex partners took their first HIV test. HIV prevalence among partners of index cases who had not received antiretroviral therapy was 8.6%, whereas no partner was infected in couples in which the index case had been treated with HAART (P = 0.0123). HIV prevalence among nonindex partners declined from 10.3% during the pre-HAART period (1991-1995) to 1.9% during the late HAART period (1999-2003; P = 0.0061). In the multivariate analysis, this decline held (odds ratio = 0.14, 95% confidence interval: 0.03-0.66) after adjusting for length of partnership, unprotected coitus, and pregnancies as well as gender, CD4 lymphocyte count, AIDS-defining diseases, and sexually transmitted infections in the index case. When HAART became widely available, a reduction of approximately 80% in heterosexual transmission of HIV was observed, irrespective of changes in other factors that affect transmission.
Objective To estimate the risk and probability of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment.
BackgroundVarious patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP).Methodology and Principal FindingsWe re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the “viral dating” (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals.ConclusionsA combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research.
HIV-1 elite controllers (EC) maintain undetectable viral load (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes including a proportion loosing HIV-1 control over time. In this work we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, versus persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1-infection with a longitudinal retrospective study design. Gag-specific T-cell response was assessed by intracellular poly-cytokine production quantified by flow cytometry. Viral diversity and sequence-dating were performed in proviral DNA by PCR amplification at limiting dilution in and genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity and high proinflammatory cytokines levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r=-0.8;=0.02). RANTES was a potential biomarker of transient control. This study identified, virological and immunological factors including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in a better clinical management of these individuals and in the development of future curative approaches. There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work we found differences in virological and immune factors including soluble inflammatory biomarkers between subjects with persistent control of viral replication and EC that will loss the virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose the natural control of viral replication, and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV-infection.
HIV-1 disease progression in elite and viremic controllers is frequent. We propose a baseline clinical score to easily classify these patients according to risk of progression. This score could be instrumental for taking clinical decisions and performing pathogenic studies.
The lipid content and fatty acid (FA) profile have an important impact in human health as well as in the technological transformation and nutritional and organoleptic quality of meat. A genome-wide association study (GWAS) on 144 backcross pigs (25% Iberian × 75% Landrace) was performed for 32 traits associated with intramuscular FA composition and indices of FA metabolism. The GWAS was carried out using Qxpak 5.0 and the genotyping information obtained from the Porcine SNP60K BeadChip (Illumina Inc., San Diego, CA). Signals of significant association considering a false- discovery rate (q-value < 0.05) were observed in 15 of the 32 analyzed traits, and a total of 813 trait-associated SNP (TAS), distributed in 43 chromosomal intervals on almost all autosomes, were annotated. According to the clustering analysis based on functional classification, several of the annotated genes are related to FA composition and lipid metabolism. Some interesting positional concordances among TAS and previously reported QTL for FA compositions and/or other lipid traits were also found. These common genomic regions for different traits suggest pleiotropic effects for FA composition and were found primarily on SSC4, SSC8, and SSC16. These results contribute to our understanding of the complex genetic basis of FA composition and FA metabolism.
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