Background
High cytokine levels have been associated with severe COVID-19 disease. Although many cytokine studies have been performed, not many of them include combinatorial analysis of cytokine ...profiles through time. In this study we investigate the association of certain cytokine profiles and its evolution, and mortality in SARS-CoV2 infection in hospitalized patients.
Methods
Serum concentration of 45 cytokines was determined in 28 controls at day of admission and in 108 patients with COVID-19 disease at first, third and sixth day of admission. A principal component analysis (PCA) was performed to characterize cytokine profiles through time associated with mortality and survival in hospitalized patients.
Results
At day of admission non-survivors present significantly higher levels of IL-1α and VEGFA (PC3) but not through follow up. However, the combination of HGF, MCP-1, IL-18, eotaxine, and SCF (PC2) are significantly higher in non-survivors at all three time-points presenting an increased trend in this group through time. On the other hand, BDNF, IL-12 and IL-15 (PC1) are significantly reduced in non-survivors at all time points with a decreasing trend through time, though a protective factor. The combined mortality prediction accuracy of PC3 at day 1 and PC1 and PC2 at day 6 is 89.00% (p<0.001).
Conclusions
Hypercytokinemia is a hallmark of COVID-19 but relevant differences between survivors and non-survivors can be early observed. Combinatorial analysis of serum cytokines and chemokines can contribute to mortality risk assessment and optimize therapeutic strategies. Three clusters of cytokines have been identified as independent markers or risk factors of COVID mortality.
Abstract
Background
Trichuris trichiura
(human whipworm) infects an estimated 477 million individuals worldwide. In addition to
T. trichiura
, other
Trichuris
species can cause an uncommon zoonosis ...and a number of human cases have been reported. The diagnosis of trichuriasis has relied traditionally on microscopy. Recently, there is an effort to use molecular diagnostic methods, mainly qPCR. LAMP technology could be an alternative for qPCR especially in low-income endemic areas.
Trichuris muris
, the causative agent of trichuriasis in mice, is of great importance as a model for human trichuriasis. Here, we evaluate the diagnostic utility of a new LAMP assay in an active experimental mouse trichuriasis in parallel with parasitological method by using stool and, for the first time, urine samples.
Methods
Stool and urine samples were collected from mice infected with eggs of
T. muris
. The dynamics of infection was determined by counting the number of eggs per gram of faeces. A LAMP based on the
18S
rRNA gene from
T. muris
was designed. Sensitivity and specificity of LAMP was tested and compared with PCR. Stool and urine samples were analysed by both LAMP and PCR techniques.
Results
Trichuris muris
eggs were detected for the first time in faeces 35 days post-infection. LAMP resulted specific and no cross-reactions were found when using 18 DNA samples from different parasites. The detection limit of the LAMP assay was 2 pg of
T. muris
DNA. When testing stool samples by LAMP we obtained positive results on day 35 p.i. and urine samples showed amplification results on day 20 p.i., i.e. 15 days before the onset of
T. muris
eggs in faeces.
Conclusions
To the best of our knowledge, we report, for the first time, a novel LAMP assay (Whip-LAMP) for sensitive detection of
T. muris
DNA in both stool and urine samples in a well-established mice experimental infection model. Considering the advantages of urine in molecular diagnosis in comparison to stool samples, should make us consider the possibility of starting the use urine specimens in molecular diagnosis and for field-based studies of human trichuriasis where possible. Further studies with clinical samples are still needed.
Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor ...outcomes in COVID-19 patients.
A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0.
A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI-(1.28-42.4),
= 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results.
A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.
Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity ...of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank:
= 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665),
< 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878),
= 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.
Abstract Background Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by ...SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. Methods A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. Results Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. Conclusion : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.
Strongyloidiasis is a parasitosis that represents a public health problem, in tropical regions. The present study aimed to investigate the anthelmintic effects of several extracts of Argemone ...mexicana, as well as its main component berberine (Ber) against the third-stage larvae (L3) of Strongyloides venezuelensis in-vitro experiments. Also, the anti-hemolytic activity of the extract, fractions, and Ber were tested in human erythrocytes. A dose-response anthelminthic bioassay demonstrated Ber as the most effective component, followed by methanolic subfraction (Fr3) and finally the crude extract of A. mexicana (Am) showing LC50 response values of 1.6, 19.5, and 92.1 μg/mL, at 96 h respectively. Also, Am, Fr3, and Ber did not produce significant hemolysis against human erythrocytes (p ≤ 0.05). Am and Fr3 showed erythrocyte protection effect capacity at the membrane level (p ≤ 0.05). Furthermore, Ber was found to have an antioxidant activity of 168.18 μg/mL. According to the results, the Fr3 of A. mexicana, and particularly Ber, exhibited potent in-vitro effects against L3 of S. venezuelensis, without hemolytic activity against human erythrocytes and presented good antioxidant capacity. In conclusion, the extracts of A. mexicana and the main component have activity against S. venezuelensis, nevertheless, further studies are required to elucidate the mechanism of action.
Display omitted
•Anthelmintic activity of A. mexicana methanolic extract, active fraction, and it ‘s main component.•Development of a new alternative to a conventional anthelmintics.•The capacity of the berberine alkaloid is reported, which has a response against the viability of S. venezuelensis (L3).•The safety of the methanolic extract, active fraction, and berberine, was evaluated by an in-vitro hemolytic bioassay.
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