Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine.

OBJECTIVE: To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine. PATIENTS AND METHODS: Cross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded. RESULTS: 169 (4,45%) patients had Covid-19 infection, of which 12 (7.1 %) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P < .05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P < .05). CONCLUSION: There is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19.

OBJETIVO: Analizar la incidencia de la enfermedad del coronavirus 19 (COVID-19) en pacientes consumidores crónicos de hidroxicloroquina. PACIENTES Y MÉTODOS: Estudio multicéntrico observacional retrospectivo transversal en Áreas de Salud de Castilla La-Mancha y distritos sanitarios de Andalucía. De los 4.451 participantes incluidos en el primer reclutamiento se seleccionaron 3.817 sujetos con datos válidos. La variable principal del estudio ha sido la presencia o ausencia de infección por la COVID-19 por diagnóstico clínico, serológico o por reacción en cadena de la polimerasa. Se registraron variables sociodemográficas, clínicas y tratamientos y comorbilidades concomitantes. RESULTADOS: Ciento sesenta y nueve (4,45%) pacientes presentaron infección por la COVID-19, de los cuales fallecieron 12 (7,1%) y 32 (18,9%) requirieron ingreso hospitalario. La enfermedad respiratoria previa se relacionó con la infección por la COVID-19 (p < 0,05). La maculopatía aparece en un 5,3% de los pacientes y está relacionada significativamente con la dosis de hidroxicloroquina consumida (p < 0,05). CONCLUSIÓN: No existe relación entre consumo crónico de hidroxicloroquina e incidencia de la COVID-19.

Incidencia de la COVID-19 en pacientes en tratamiento crónico con hidroxicloroquina / Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine

Objetivo: Analizar la incidencia de la enfermedad del coronavirus 19 (COVID-19) en pacientes consumidores crónicos de hidroxicloroquina.Pacientes y métodosEstudio multicéntrico observacional retrospectivo transversal en Áreas de Salud de Castilla La-Mancha y distritos sanitarios de Andalucía. De los 4.451 participantes incluidos en el primer reclutamiento se seleccionaron 3.817 sujetos con datos válidos. La variable principal del estudio ha sido la presencia o ausencia de infección por la COVID-19 por diagnóstico clínico, serológico o por reacción en cadena de la polimerasa. Se registraron variables sociodemográficas, clínicas y tratamientos y comorbilidades concomitantes.ResultadosCiento sesenta y nueve (4,45%) pacientes presentaron infección por la COVID-19, de los cuales fallecieron 12 (7,1%) y 32 (18,9%) requirieron ingreso hospitalario. La enfermedad respiratoria previa se relacionó con la infección por la COVID-19 (p<0,05). La maculopatía aparece en un 5,3% de los pacientes y está relacionada significativamente con la dosis de hidroxicloroquina consumida (p<0,05).ConclusiónNo existe relación entre consumo crónico de hidroxicloroquina e incidencia de la COVID-19. (AU)

Objective: To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine.Patients and methodsCross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded.Results169 (4,45%) patients had Covid-19 infection, of which 12 (7.1%) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P<.05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P<.05).ConclusionThere is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19. (AU)

[Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine]. / Incidencia de la COVID-19 en pacientes en tratamiento crónico con hidroxicloroquina.

OBJECTIVE: To analyze the incidence of Covid-19 in patients who are chronic users of hydroxychloroquine. PATIENTS AND METHODS: Cross-sectional retrospective observational multicenter study in health areas and districts from Castilla La-Mancha and Andalucia. Of the 4451 participants included in the first recruitment, 3817 with valid data were selected. The main variable of the study is the presence or absence of Covid-19 infection by clinical, serological or polymerase chain reaction diagnosis. Sociodemographic and clinical variables and treatment and concomitant comorbidities were recorded. RESULTS: 169 (4,45%) patients had Covid-19 infection, of which 12 (7.1%) died and 32 (18.9%) required hospital admission. Previous respiratory pathology was related to Covid-19 infection (P<.05). Maculopathy appears in 5.3% of patients and is significantly related to the dose of hydroxychloroquine consumed (P<.05). CONCLUSION: There is no relationship between chronic use of hydroxychloroquine and the incidence of Covid-19.

Author Correction: Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Quantification of Immune Dysregulation by Next-generation Polymerase Chain Reaction to Improve Sepsis Diagnosis in Surgical Patients.

OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis. METHODS: Expression of 6 neutrophil protease genes (MMP8, OLFM4, LCN2/NGAL, LTF, PRTN3, MPO) and also of 5 genes involved in the immunological synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in blood from 101 surgical patients with sepsis, 53 uninfected surgical patients, and 16 blood donors by using ddPCR. Areas under receiver operating characteristic curves (AUROC) and multivariate regression analysis were employed to test individual genes and gene ratios to identify sepsis, in comparison with procalcitonin. RESULTS: Sepsis-induced overexpression of neutrophil protease genes and depressed expression of immunological synapse genes. MMP8/HLA-DRA, LCN2/HLA-DRA outperformed procalcitonin in differentiating between patients with sepsis and surgical controls in the AUROC analysis: LCN2/HLA-DRA: 0.90 (0.85-0.96), MMP8/HLA-DRA: 0.89 (0.84-0.95), procalcitonin: 0.80 (0.73-0.88) (AUROC, confidence interval 95%), and also in the multivariate analysis: LCN2/HLA-DRA: 8.57 (2.25-32.62); MMP8/HLA-DRA: 8.03 (2.10-30.76), procalcitonin: 4.20 (1.15-15.43) [odds ratio (confidence interval 95%)]. Gene expression levels of HLA-DRA were an independent marker of hospital mortality. CONCLUSIONS: Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.

Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73-0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78-0.91], <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82-32.29], 0.006; PCT: 4.21 [1.15-15.43] 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22-995.08], 0.038; PCT: 5.52 [0.40-75.78], 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.

Transcriptomic correlates of organ failure extent in sepsis.

OBJECTIVES: Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients. METHODS: Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score. RESULTS: The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality. CONCLUSIONS: The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.