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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329353

ABSTRACT

Background: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and defence strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months.MethodsWe established a cohort of 769 health professionals including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2. We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. Findings: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time.Interpretation: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 13 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. Funding Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04;NCT04885478)

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317390

ABSTRACT

Background: The steroids are currently used as standard treatment for severe COVID-19. However, the evidence is weak. Our aim is to determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Methods: A secondary analysis derived from multicenter, observational study of adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). The primary outcome was ICU mortality. We performed a Multivariate analysis after propensity score full matching (PS), Cox proportional hazards (CPH), Cox covariate time interaction (TIR), Weighted Cox Regression (WCR) and Fine-Gray analysis(sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: : A total of 2,017 patients were analyzed, 1171(58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR:1.0,95%CI:0.98-1.15). Corticosteroids were administered in 298/537(55.5%) patients of “A” phenotype and their use was not associated with ICU mortality (HR=0.85[0.55-1.33]). A total of 338/623(54.2%) patients in “B” phenotype received corticosteroids. The CPH (HR =0.65 [0.46-0.91]) and TIR regression (1- 25 day tHR=0.56[0.39-0.82] and >25 days tHR=1.53[1.03-7.12]) showed a biphasic effect of corticosteroids due to proportional assumption violation. No effect of corticosteroids on ICU mortality was observed when WCR was performed (wHR=0.72[0.49-1.05]). Finally, 535/857(62.4%) patients in “C” phenotype received corticosteroids. The CPH (HR=0.73[0.63-0.98]) and TIR regression (1- 25 day tHR=0.69[ 0.53-0.89] and >25 days tHR=1.30[ 1.14-3.25]) showed a biphasic effect of corticosteroids and proportional assumption violation. However, wHR (0.75[0.58-0.98]) and sHR (0.79[0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate-high dose. Only patients with the highest severity could benefit from steroid treatment although this effect on clinical outcome was minimized during ICU stay.

3.
Lancet Reg Health Eur ; 11: 100243, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1500123

ABSTRACT

BACKGROUND: It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. FINDINGS: As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p<0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p<0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p<0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p<0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. INTERPRETATION: Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. FUNDING: Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYUC.

4.
Med Intensiva ; 2021 Oct 26.
Article in Spanish | MEDLINE | ID: covidwho-1482804

ABSTRACT

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational studySetting: Critical Care UnitsPatients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: corticosteroids vs no corticosteroidsMain variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a Multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis(sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2,017 patients were analyzed, 1171(58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR:1.0,95%CI:0.98-1.15). Corticosteroids were administered in 298/537(55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85[0.55-1.33]). A total of 338/623(54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72[0.49-1.05]). Finally, 535/857(62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75[0.58-0.98]) and sHR (0.79[0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

5.
Front Cell Infect Microbiol ; 11: 709893, 2021.
Article in English | MEDLINE | ID: covidwho-1403459

ABSTRACT

Highlights: Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome. Background: Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity. Methods: We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death. Results: Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity. Conclusion: We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care.


Subject(s)
COVID-19 , Neopterin , Critical Illness , Humans
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