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1.
Preprint in English | medRxiv | ID: ppmedrxiv-20186213

ABSTRACT

BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19. MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 30 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (183,112 sera) and in France (18,316 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 234,881 and 26,056 sera). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population. ResultsThe mean serum apolipoprotein-A1 levels in these populations began decreasing in January 2020, compared to the same 30 weeks in 2019. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 30 weeks, in both France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0;P=0.04). ConclusionApolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population with no new blood sample, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test. NCT01927133, CER-2020-14. Key Points QuestionDoes serum apolipoprotein-A1 decrease could be a very early biomarker of SARS-CoV-2 pandemic? FindingsDuring the 30 weeks of 2020 we observed in two large cohorts of patients at risk of liver fibrosis a highly significant decrease of serum apolipoprotein-A1, not observed in previous years. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases, including the recovery period. MeaningApolipoprotein-A1 could be used as a sentinel of the pandemic in existing routine surveillance of the general population.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-20090118

ABSTRACT

BackgroundPrognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. MethodsFrench single-center prospective cohort study of 152 patients with positive Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay, hospitalized in a medical ward. Multivariable models and a simplified scoring system assessed predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death). A validation was performed on an external sample of 132 patients. FindingsAt D14, the probability of ICU transfer or death was 32% (95% CI 25-40). Older age (OR 2{middle dot}61, 95% CI 0{middle dot}96-7{middle dot}10), poorer respiratory presentation (OR 4{middle dot}04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1{middle dot}76-9{middle dot}25), higher CRP-level (OR 1{middle dot}63 per 100mg/L increment, 95% CI 0{middle dot}98-2{middle dot}71) and lower lymphocytes count (OR 0{middle dot}36 per 1000/mm3 increment, 95% CI 0{middle dot}13-0{middle dot}99) were associated with an increased risk of ICU requirement or death. A 8-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. InterpretationIn this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, 32% were transferred to ICU or died. A simplified scoring system at admission predicted the outcome at D14. FundingNo funding.

3.
Arthritis Res Ther ; 14(5): R221, 2012 Oct 17.
Article in English | MEDLINE | ID: mdl-23075451

ABSTRACT

INTRODUCTION: Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels [25(OH)D] was also shown. METHODS: In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation (100,000 IU of cholecalciferol per week for 4 weeks, followed by 100,000 IU of cholecalciferol per month for 6 months.) in 20 SLE patients with hypovitaminosis D. RESULTS: Serum 25(OH)D levels dramatically increased under vitamin D supplementation from 18.7±6.7 at day 0 to 51.4±14.1 (p<0.001) at 2 months and 41.5±10.1 ng/mL (p<0.001) at 6 months. Vitamin D was well tolerated and induced a preferential increase of naïve CD4+ T cells, an increase of regulatory T cells and a decrease of effector Th1 and Th17 cells. Vitamin D also induced a decrease of memory B cells and anti-DNA antibodies. No modification of the prednisone dosage or initiation of new immunosuppressant agents was needed in all patients. We did not observe SLE flare during the 6 months follow-up period. CONCLUSIONS: This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials.


Subject(s)
B-Lymphocytes/pathology , Dietary Supplements , Homeostasis/drug effects , Lupus Erythematosus, Systemic/pathology , T-Lymphocytes/pathology , Vitamin D/administration & dosage , Vitamin D/pharmacology , Adult , Antibodies, Anti-Idiotypic/blood , B-Lymphocytes/drug effects , Cholecalciferol/administration & dosage , Cholecalciferol/pharmacology , Cholecalciferol/therapeutic use , Comorbidity , DNA/immunology , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Longitudinal Studies , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/epidemiology , Prospective Studies , T-Lymphocytes/drug effects , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/pathology , Th1 Cells/drug effects , Th1 Cells/pathology , Th17 Cells/drug effects , Th17 Cells/pathology , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D/therapeutic use , Vitamin D Deficiency/blood , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology
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