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1.
Environmental Research ; 212:113319, 2022.
Article in English | ScienceDirect | ID: covidwho-1796870

ABSTRACT

Objective This study evaluated the association of the short-term exposure to environmental factors (relative humidity, temperature, NO2, SO2, O3, PM10, and CO) with hospital admissions due to acute viral lower respiratory infections (ALRI) in children under two years before the COVID-19 era. Methods We performed a bidirectional case-crossover study in 30,445 children with ALRI under two years of age in the Spanish Minimum Basic Data Set (MBDS) from 2013 to 2015. Environmental data were obtained from Spain's State Meteorological Agency (AEMET). The association was assessed by conditional logistic regression. Results Lower temperature one week before the day of the event (hospital admission) (q-value = 0.012) and higher relative humidity one week (q-value = 0.003) and two weeks (q-value<0.001) before the day of the event were related to a higher odds of hospital admissions. Higher NO2 levels two weeks before the event were associated with hospital admissions (q-value<0.001). Moreover, higher concentrations on the day of the event for SO2 (compared to lag time of 1-week (q-value = 0.026) and 2-weeks (q-value<0.001)), O3 (compared to lag time of 3-days (q-value<0.001), 1-week (q-value<0.001), and 2-weeks (q-value<0.001)), and PM10 (compared to lag time of 2-weeks (q-value<0.001)) were related to an increased odds of hospital admissions for viral ALRI. Conclusion Short-term exposure to environmental factors (climatic conditions and ambient air contaminants) was linked to a higher likelihood of hospital admissions due to ALRI. Our findings emphasize the importance of monitoring environmental factors to assess the odds of ALRI hospital admissions and plan public health resources.

4.
Emerg Microbes Infect ; 11(1): 676-688, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1672036

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. METHODS AND RESULTS: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042). CONCLUSIONS: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.


Subject(s)
COVID-19 , MicroRNAs , Biomarkers , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , SARS-CoV-2
5.
J Infect Dis ; 225(6): 977-982, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1575292

ABSTRACT

Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2-infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.


Subject(s)
COVID-19 , Chemokine CCL5/genetics , Nasopharynx/virology , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/mortality , Chemokine CCL5/metabolism , Humans , Intensive Care Units , RNA, Viral/genetics , Severity of Illness Index , Viral Load
7.
Front Med (Lausanne) ; 8: 718053, 2021.
Article in English | MEDLINE | ID: covidwho-1472390

ABSTRACT

Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality. Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals. Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis. Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.

8.
J Intern Med ; 291(2): 232-240, 2022 02.
Article in English | MEDLINE | ID: covidwho-1455598

ABSTRACT

BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19 , COVID-19/immunology , COVID-19/mortality , Critical Illness , Humans , RNA, Viral/blood , SARS-CoV-2
9.
Front Med (Lausanne) ; 8: 736028, 2021.
Article in English | MEDLINE | ID: covidwho-1438421

ABSTRACT

Background: Endothelial Activation and Stress Index (EASIX) predict death in patients undergoing allogeneic hematopoietic stem cell transplantation who develop endothelial complications. Because coronavirus disease 2019 (COVID-19) patients also have coagulopathy and endotheliitis, we aimed to assess whether EASIX predicts death within 28 days in hospitalized COVID-19 patients. Methods: We performed a retrospective study on COVID-19 patients from two different cohorts [derivation (n = 1,200 patients) and validation (n = 1,830 patients)]. The endpoint was death within 28 days. The main factors were EASIX [(lactate dehydrogenase * creatinine)/thrombocytes] and aEASIX-COVID (EASIX * age), which were log2-transformed for analysis. Results: Log2-EASIX and log2-aEASIX-COVID were independently associated with an increased risk of death in both cohorts (p < 0.001). Log2-aEASIX-COVID showed a good predictive performance for 28-day mortality both in the derivation cohort (area under the receiver-operating characteristic = 0.827) and in the validation cohort (area under the receiver-operating characteristic = 0.820), with better predictive performance than log2-EASIX (p < 0.001). For log2 aEASIX-COVID, patients with low/moderate risk (<6) had a 28-day mortality probability of 5.3% [95% confidence interval (95% CI) = 4-6.5%], high (6-7) of 17.2% (95% CI = 14.7-19.6%), and very high (>7) of 47.6% (95% CI = 44.2-50.9%). The cutoff of log2 aEASIX-COVID = 6 showed a positive predictive value of 31.7% and negative predictive value of 94.7%, and log2 aEASIX-COVID = 7 showed a positive predictive value of 47.6% and negative predictive value of 89.8%. Conclusion: Both EASIX and aEASIX-COVID were associated with death within 28 days in hospitalized COVID-19 patients. However, aEASIX-COVID had significantly better predictive performance than EASIX, particularly for discarding death. Thus, aEASIX-COVID could be a reliable predictor of death that could help to manage COVID-19 patients.

10.
Clin Microbiol Infect ; 27(11): 1678-1684, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1284006

ABSTRACT

OBJECTIVES: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). METHODS: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. RESULTS: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9-10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41-3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26-0.94, p 0.031). CONCLUSIONS: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Adult , Anti-HIV Agents/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , Cross-Sectional Studies , Emtricitabine/therapeutic use , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Prevalence , Reverse Transcriptase Inhibitors/therapeutic use , Seroepidemiologic Studies , Spain/epidemiology , Tenofovir/therapeutic use
11.
Crit Care ; 24(1): 691, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977684

ABSTRACT

BACKGROUND: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. METHODS: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. RESULTS: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). CONCLUSIONS: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.


Subject(s)
COVID-19/complications , RNA, Viral/analysis , Viral Load/immunology , Adult , Aged , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , Chi-Square Distribution , Critical Illness , Female , Humans , Male , Middle Aged , Multivariate Analysis , Polymerase Chain Reaction/methods , RNA, Viral/blood , Statistics, Nonparametric
12.
J Clin Med ; 9(10)2020 Sep 23.
Article in English | MEDLINE | ID: covidwho-906429

ABSTRACT

This study aimed to build an easily applicable prognostic model based on routine clinical, radiological, and laboratory data available at admission, to predict mortality in coronavirus 19 disease (COVID-19) hospitalized patients. METHODS: We retrospectively collected clinical information from 1968 patients admitted to a hospital. We built a predictive score based on a logistic regression model in which explicative variables were discretized using classification trees that facilitated the identification of the optimal sections in order to predict inpatient mortality in patients admitted with COVID-19. These sections were translated into a score indicating the probability of a patient's death, thus making the results easy to interpret. RESULTS: Median age was 67 years, 1104 patients (56.4%) were male, and 325 (16.5%) died during hospitalization. Our final model identified nine key features: age, oxygen saturation, smoking, serum creatinine, lymphocytes, hemoglobin, platelets, C-reactive protein, and sodium at admission. The discrimination of the model was excellent in the training, validation, and test samples (AUC: 0.865, 0.808, and 0.883, respectively). We constructed a prognostic scale to determine the probability of death associated with each score. CONCLUSIONS: We designed an easily applicable predictive model for early identification of patients at high risk of death due to COVID-19 during hospitalization.

13.
Journal of Clinical Medicine ; 9(10):3066, 2020.
Article | MDPI | ID: covidwho-784034

ABSTRACT

This study aimed to build an easily applicable prognostic model based on routine clinical, radiological, and laboratory data available at admission, to predict mortality in coronavirus 19 disease (COVID-19) hospitalized patients. Methods: We retrospectively collected clinical information from 1968 patients admitted to a hospital. We built a predictive score based on a logistic regression model in which explicative variables were discretized using classification trees that facilitated the identification of the optimal sections in order to predict inpatient mortality in patients admitted with COVID-19. These sections were translated into a score indicating the probability of a patient"s death, thus making the results easy to interpret. Results. Median age was 67 years, 1104 patients (56.4%) were male, and 325 (16.5%) died during hospitalization. Our final model identified nine key features: age, oxygen saturation, smoking, serum creatinine, lymphocytes, hemoglobin, platelets, C-reactive protein, and sodium at admission. The discrimination of the model was excellent in the training, validation, and test samples (AUC: 0.865, 0.808, and 0.883, respectively). We constructed a prognostic scale to determine the probability of death associated with each score. Conclusions: We designed an easily applicable predictive model for early identification of patients at high risk of death due to COVID-19 during hospitalization.

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