Risultati per: L’eparina inibisce la proteina spike del virus SARS-Cov-2

Studi in vitro e su animali ne mostrano la capacità

Objective
COVID-19 would kill fewer people if health programmes can predict who is at higher risk of mortality because resources can be targeted to protect those people from infection. We predict mortality in a very large population in Mexico with machine learning using demographic variables and pre-existing conditions.

Design
Cohort study.

Setting
March 2020 to November 2021 in Mexico, nationally represented.

Participants
1.4 million laboratory-confirmed patients with COVID-19 in Mexico at or over 20 years of age.

Primary and secondary outcome measures
Analysis is performed on data from March 2020 to November 2021 and over three phases: (1) from March to October in 2020, (2) from November 2020 to March 2021 and (3) from April to November 2021. We predict mortality using an ensemble machine learning method, super learner, and independently estimate the adjusted mortality relative risk of each pre-existing condition using targeted maximum likelihood estimation.

Results
Super learner fit has a high predictive performance (C-statistic: 0.907), where age is the most predictive factor for mortality. After adjusting for demographic factors, renal disease, hypertension, diabetes and obesity are the most impactful pre-existing conditions. Phase analysis shows that the adjusted mortality risk decreased over time while relative risk increased for each pre-existing condition.

Conclusions
While age is the most important predictor of mortality, younger individuals with hypertension, diabetes and obesity are at comparable mortality risk as individuals who are 20 years older without any of the three conditions. Our model can be continuously updated to identify individuals who should most be protected against infection as the pandemic evolves.

Background
COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19.

Methods
Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality.

Results
90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control–treatment) in cumulative overall health was –37.4 (95% CI –157.2 to 82.3), p=0.53 on a scale of 0–2100. No clinically or statistically significant differences were seen in any secondary outcomes.

Interpretation
In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility.

Trial registration number
NCT04780061.

Introduction
Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression. Biomarkers that predict both iRAEs and rejection while allowing individualisation of immunosuppression exposure are lacking. Although plasma viral DNA levels of torque teno virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in newly transplanted KTRs within the first year after transplant, its role for prevalent KTRs on stable immunosuppression is less clear.
This study aims to determine the prognostic value of TTV levels for severe infections (defined as infections requiring hospitalisation) in prevalent KTRs on stable immunosuppression for at least 3 months and compare it against that of other commonly available biomarkers. The study also aims to explore the relationship between TTV levels and factors affecting the ‘net state of immunosuppression’ as well as other clinical outcomes.

Methods and analysis
This is a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured using the TTV R-GENE kit upon recruitment when study subjects are admitted and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The relationship between TTV load and clinical outcomes such as severe infections will be analysed and compared against that from other common biomarkers and previously published predictive scores.

Ethics and dissemination
The study was approved by the SingHealth Centralised Institutional Review Board (2023/2170). The results will be presented at conferences and submitted for publication in peer-reviewed journals.

Trial registration number
NCT05836636.

E’ un giovane di 25 anni. Condizioni cliniche in miglioramento

Objective
Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction.

Design
Metabolic state, exhaustion and transcriptome of virus-specific CD8+ T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52) were determined ex vivo and during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were tested in vitro. Intrahepatic virus-specific CD8+ T cells were analysed by scRNA-Seq in a HBV-replicating murine in vivo model of acute and chronic infection.

Results
HBV-specific (core18-27, polymerase455-463) and HCV-specific (NS31073-1081, NS31406-1415, NS5B2594-2602) CD8+ T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase455-463 -specific CD8+ T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core18-27-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8+ T cells in a murine model of chronic infection.

Conclusion
Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.

Recently, we read the article by Ng et al with great interest,1 which identified several gut microbiota harbour the potential to improve immune response and reduce adverse events following COVID-19 vaccines, and demonstrated that gut microbiota has the potential to complement the effectiveness of vaccines. Together with several recent studies, gut microbiota plays a key role in modulating immune responses of vaccination2–4 and is related to the severity of COVID-19 patients,5 6 however, the comprehensive assessment of host’s response, particularly the role of gut microbiota in antibodies production is limited and should be seriously considered because the vaccination of SARS-CoV-2 is the most promising approach for curbing the COVID-19 pandemic.4 7 Therefore, we recruited 30 young volunteers (20–23 years old), including 15 male and 15 female volunteers, and collected 143 faecal and 120…

Dufour et al highlighted that the effect of COVID-19 in patients with cirrhosis is derived from the prevaccination era and suggested that the impact of Omicron infection in patients with cirrhosis needs to be elucidated.1 We agree with the author that previous studies have reported significant morbidity and mortality in patients with cirrhosis infected with SARS CoV-2 in the prevaccination era.2–7 To our knowledge, no studies have assessed the impact of Omicron infection in patients with cirrhosis. Therefore, we aimed to compare the outcomes of Omicron infection among patients with cirrhosis and without cirrhosis. We retrospectively included non-cirrhotic (NC) patients and patients with cirrhosis from 1 January 2022 to 1 March 2022 diagnosed with Omicron infection. Omicron BA.1 variant was identified based on the S-gene dropout on the reverse transcriptase PCR test. In the absence…

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 148, Issue 11, Page 908-909, September 12, 2023.

Circulation, Volume 148, Issue 11, Page 910-911, September 12, 2023.

Circulation, Volume 148, Issue 11, Page 906-907, September 12, 2023.

Con i corvi, rappresentano indicatore di malattia in un’area

To the Editor In their recent systematic review and meta-analysis, Dr Tsampasian and colleagues reported risk factors associated with post−COVID-19 condition (PCC). According to the study analysis, female sex, older age, higher body mass index, smoking, preexisting comorbidities, and previous hospitalization or intensive care admission were significantly associated with developing PCC, and SARS-CoV-2 vaccination with 2 doses was associated with a lower risk of PCC. Although this article presents a topical research subject with a strong potential effect, 2 key issues need to be clarified before more robust conclusions can be made.

In Reply We thank Dr Yang and colleagues for their interest in our study and for highlighting that post−COVID-19 condition (PCC) is of important public health interest. They mention specific studies and rightly ask why these were not included in our meta-analysis. For the purposes of transparency, our inclusion and exclusion criteria were clearly listed in the Methods section of the article. Reviewing the suggested studies against our criteria easily demonstrates that none met the inclusion criteria we outlined. Those studies either did not clearly report the duration of symptoms since the acute COVID-19 infection—whereas we followed the World Health Organization definition, which requires a symptom duration of greater than 3 months; or they investigated the effect of vaccination on the resolution of PCC symptoms (vs identifying the association of risk of developing PCC and vaccination which was our study aim); or they discussed how vaccination affected the various PCC symptoms. Hence, we confirm that none of the proposed studies fulfilled the inclusion criteria for the specific purpose of our systematic review and meta-analysis.