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  • 1
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 10 ( 2023-9-22)
    Abstract: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 ( HMOX1 ; T/T genotype OR 9.9 p   & lt; 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p  = 0.04 and T/T genotype OR 12.9, p   & lt; 0.0001), and rs713400 (eQTL for TMPRSS2 ; C/T + T/T genotype OR 1.86, p  = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 ( CD69 ; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p  = 0.01), rs2660 ( OAS1 ; A/G genotype OR 0.6, p  = 0.08), rs896 ( VIPR1 ; T/T genotype OR 0.4, p  = 0.02) and rs33980500 ( TRAF3IP2 ; C/T + T/T genotype OR 0.3, p  = 0.01) were associated with lower risk of viremia. Conclusion Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2775999-4
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  • 2
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-6-15)
    Abstract: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results A total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with & gt; 1.3 log10 copies/ml) and also in those with at least one IL6 & gt; 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 3
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-2-23)
    Abstract: The use of IL-6 blockers in COVID-19 hospitalized patients has been associated with a reduction in mortality compared to standard care. However, many uncertainties remain pertaining to optimal intervention time, administration schedule, and predictors of response. To date, data on the use of subcutaneous sarilumab is limited and no randomized trial results are available. Methods Open label randomized controlled trial at a single center in Spain. We included adult patients admitted with microbiology documented COVID-19 infection, imaging confirmed pneumonia, fever and/or laboratory evidence of inflammatory phenotype, and no need for invasive ventilation. Participants were randomly assigned to receive sarilumab, a single 400 mg dose in two 200 mg subcutaneous injections, added to standard care or standard care, in a 2:1 proportion. Primary endpoints included 30-day mortality, mean change in clinical status at day 7 scored in a 7-category ordinal scale ranging from death (category 1) to discharge (category 7), and duration of hospitalization. The primary efficacy analysis was conducted on the intention-to-treat population. Results A total of 30 patients underwent randomization: 20 to sarilumab and 10 to standard care. Most patients were male (20/30, 67%) with a median (interquartile range) age of 61.5 years (56–72). At day 30, 2/20 (10%) patients died in the sarilumab arm vs. none (0/10) in standard care (Log HR 15.11, SE 22.64; p = 0.54). At day 7, no significant differences were observed in the median change in clinical status (2 [0–3]) vs. 3 [0–3] , p = 0.32). Median time to discharge (days) was similar (7 [6–11] vs. 6 [4–12] ; HR 0.65, SE 0.26; p = 0.27). No significant differences were detected in the rate of progression to invasive and noninvasive mechanical ventilation. Conclusions and Relevance Our pragmatic pilot study has failed to demonstrate the benefit of adding subcutaneous sarilumab to standard care for mortality by 30 days, functional status at day 7, or hospital stay. Findings herein do not exclude a potential effect of sarilumab in severe COVID-19 but adequately powered blinded randomized phase III trials are warranted to assess the impact of the subcutaneous route and a more selected target population. Trial Registration www.ClinicalTrials .gov, Identifier: NCT04357808.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 4
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-20)
    Abstract: Evidence is scant regarding the long-term humoral and cellular responses Q7 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain. Methods In this single-center prospective observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine. Results A dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8+ T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of PD1 + CD8 + and CD57 + PD1 + CD8 + exhausted T cells compared with those with an increased cellular response both in vivo and in vitro . The proportion of PD1 + CD8 + and CD57 + PD1 + CD8 + exhausted T cells inversely correlated with IFN-γ production. Discussion Our preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients of our study. An additional booster seems to be beneficial in suboptimal vaccine seroconverters, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2023-1-10)
    Abstract: COVID-19 has initially been studied in terms of an acute-phase disease, although recently more attention has been given to the long-term consequences. In this study, we examined COVID-19 as an independent risk factor for long-term mortality in patients with acute illness treated by EMS (emergency medical services) who have previously had the disease against those who have not had the disease. Methods A prospective, multicenter, ambulance-based, ongoing study was performed with adult patients with acute disease managed by EMS and transferred with high priority to the emergency department (ED) as study subjects. The study involved six advanced life support units, 38 basic life support units, and five emergency departments from Spain. Sociodemographic inputs, baseline vital signs, pre-hospital blood tests, and comorbidities, including COVID-19, were collected. The main outcome was long-term mortality, which was classified into 1-year all-cause mortality and 1-year in- and out-of-hospital mortality. To compare both the patients with COVID-19 vs. patients without COVID-19 and to compare survival vs non-survival, two main statistical analyses were performed, namely, a longitudinal analysis (Cox regression) and a logistic regression analysis. Results Between 12 March 2020 and 30 September 2021, a total of 3,107 patients were included in the study, with 2,594 patients without COVID-19 and 513 patients previously suffering from COVID-19. The mortality rate was higher in patients with COVID-19 than in patients without COVID-19 (31.8 vs. 17.9%). A logistic regression showed that patients previously diagnosed with COVID-19 presented higher rates of nursing home residency, a higher number of breaths per minute, and suffering from connective disease, dementia, and congestive heart failure. The longitudinal analysis showed that COVID-19 was a risk factor for mortality [hazard ratio 1.33 (1.10–1.61); p & lt; 0.001]. Conclusion The COVID-19 group presented an almost double mortality rate compared with the non-COVID-19 group. The final model adjusted for confusion factors suggested that COVID-19 was a risk factor for long-term mortality.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711781-9
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  • 6
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 10 ( 2023-4-18)
    Abstract: Nowadays, there is no gold standard score for prehospital sepsis and sepsis-related mortality identification. The aim of the present study was to analyze the performance of qSOFA, NEWS2 and mSOFA as sepsis predictors in patients with infection-suspected in prehospital care. The second objective is to study the predictive ability of the aforementioned scores in septic-shock and in-hospital mortality. Methods Prospective, ambulance-based, and multicenter cohort study, developed by the emergency medical services, among patients ( n  = 535) with suspected infection transferred by ambulance with high-priority to the emergency department (ED). The study enrolled 40 ambulances and 4 ED in Spain between 1 January 2020, and 30 September 2021. All the variables used in the scores, in addition to socio-demographic data, standard vital signs, prehospital analytical parameters (glucose, lactate, and creatinine) were collected. For the evaluation of the scores, the discriminative power, calibration curve and decision curve analysis (DCA) were used. Results The mSOFA outperformed the other two scores for mortality, presenting the following AUCs: 0.877 (95%CI 0.841–0.913), 0.761 (95%CI 0.706–0.816), 0.731 (95%CI 0.674–0.788), for mSOFA, NEWS, and qSOFA, respectively. No differences were found for sepsis nor septic shock, but mSOFA’s AUCs was higher than the one of the other two scores. The calibration curve and DCA presented similar results. Conclusion The use of mSOFA could provide and extra insight regarding the short-term mortality and sepsis diagnostic, backing its recommendation in the prehospital scenario.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2775999-4
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2020-11-10)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2020-11-10)
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2737824-X
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  • 8
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2022-7-22)
    Abstract: The coronavirus disease 2019 (COVID-19) pandemic has been a worldwide stress test for health systems. 2 years have elapsed since the description of the first cases of pneumonia of unknown origin. This study quantifies the impact of COVID-19 in the screening program of chronic viral infections such as human papillomavirus (HPV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) along the six different pandemic waves in our population. Each wave had particular epidemiological, biological, or clinical patterns. Methods We analyzed the number of samples for screening of these viruses from March 2020 to February 2022, the new infections detected in the pandemic period compared to the previous year, the time elapsed between diagnosis and linking to treatment and follow-up of patients, and the percentage of late HIV diagnosis. Moreover, we used the origin of the samples as a marker for quantifying the restoration of activity in primary care. Results During the first pandemic year, the number of samples received was reduced by 26.7, 22.6, and 22.5% for molecular detection of HPV or serological HCV and HIV status respectively. The highest decrease was observed during the first wave with 70, 40, and 26.7% for HPV, HCV, and HIV. As expected, new diagnoses also decreased by 35.4, 58.2, and 40.5% for HPV, HCV, and HIV respectively during the first year of the pandemic. In the second year of the pandemic, the number of samples remained below pre-pandemic period levels for HCV (−3.6%) and HIV (−9.3%) but was slightly higher for HPV (8.0%). The new diagnoses in the second year of the pandemic were −16.1, −46.8, and −18.6% for HPV, HCV, and HIV respectively. Conclusions Undoubtedly, an important number of new HPV, HCV, and HIV infections were lost during the COVID-19 pandemic, and surveillance programs were disrupted as a consequence of collapse of the health system. It is a priority to reinforce these surveillance programs as soon as possible in order to detect undiagnosed cases before the associated morbidity-mortality increases. New pandemic waves could increase the risk of reversing the achievements made over the last few decades.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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