Clinical features and outcomes in adults with COVID-19 during the pre-Omicron and Omicron waves.

OBJECTIVES: We conducted a single-center retrospective study to compare patient characteristics and death rates during the Omicron (O, December 01, 2021, to September 30, 2022) and pre-Omicron (PO, March 01, 1920, to October 31, 2021) periods. PATIENTS AND METHODS: We retrospectively analyzed the data of 2932 patients (1242 (O) and 1690 (PO)) hospitalized (>24 h) with laboratory-confirmed COVID. RESULTS: Compared to the PO period, O period patients were less frequently men, had a lower body mass index and fewer comorbidities except for immunosuppression and pregnancy. Nosocomial COVID-19 accounted for 18.2 % (O) and 15.4 % (PO) of cases (p = 0.05). Patient mortality rates during the O and PO periods were 11.0 % and 16.9 % (p < 0.001), respectively. Unvaccinated status (p < 0.001), existence of comorbidities, (p < 0.001) and high LDH value at baseline (p = 0.015), but not the period, were identified as factors likely to explain death. CONCLUSION: During the Omicron period, the inpatient death rate remained > 10 %, especially among unvaccinated and comorbid patients. Nosocomial cases were more frequent.

Characteristic and outcome changes in inpatients with COVID-19 during the four pre - Omicron waves.

Background: Four waves of Coronavirus disease 2019 (COVID-19) occurred in France between March 2020 and September 2021. COVID-19 inpatient characteristics change because of the influence of numerous parameters, especially immunization and circulating severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) variants. Methods: This retrospective single-center study analyzed patients with laboratory-proven COVID-19 admitted from 1/3/2020 to 30/6/2020 (wave one), 1/7/2020 to 31/12/2020 (wave two), 1/1/2021 to 30/6/2021 (wave three), and 1/7/2021 to 30/11/2021 (wave four). We compared the outcomes and baseline characteristics between these waves. Results: In our center, 1,762 patients were hospitalized for COVID-19: 666 (37.8 %), 425 (24.1 %), 482 (27.3 %), and 189 (10.7 %) during waves 1, 2, 3, and 4, respectively. Patients during the first wave were hospitalized later after the onset of COVID-19 symptoms, had more severe disease conditions at baseline, and suffered higher intensive care unit (ICU) hospitalization rates. Most patients from waves 1-3 were >70 years old, with 88-93 % having ≥1 comorbidity, whereas those from wave four were younger (68.0 years) with less comorbidities. The first two waves showed higher mortality rates (16.8 % and 20.0 %) than the latter (16.6 % and 9.5 %). Conclusion: Patients during the first wave had more severe disease conditions at baseline and higher mortality and ICU hospitalization rates. Despite the more virulent circulating Delta variant during wave four, the death and hospitalization rates were markedly decreased during wave four. HIPPOKRATIA 2023, 27 (1):1-6.

Evolution of baseline characteristics and severe outcomes in COVID-19 inpatients during the first and second waves in Northeastern France.

OBJECTIVES: Two COVID-19 epidemic waves occurred in France in 2020. This single-center retrospective study compared patients' characteristics and outcomes. PATIENTS AND METHODS: We included all patients with confirmed COVID-19 admitted to Colmar Hospital in March (n=600) and October/November (n=205) 2020. RESULTS: Median ages, sex ratio, body mass index, and number of comorbidities were similar in wave 1 and 2 patients. Significant differences were found for temperature (38°C vs. 37.2), need for oxygen (38.6% vs. 26.8%), high-flow cannula (0% vs. 8.3%), and steroid use (6.3% vs. 54.1%). Intensive care unit (ICU) hospitalizations (25.5% vs. 15.1%, OR: 0.44, 95% CI [0.28; 0.68], P=0.002) and deaths (19.2% vs. 12.7%, OR: 0.61, 95% CI [0.37; 0.98], P=0.04) decreased during the second wave. Except for cardiovascular events (5.5% vs. 10.2%), no change was observed in extrapulmonary events. CONCLUSIONS: Deaths and ICU hospitalizations were significantly reduced during the second epidemic wave.

Predictors of mortality, ICU hospitalization, and extrapulmonary complications in COVID-19 patients.

OBJECTIVE: A major coronavirus disease 2019 (COVID-19) outbreak occurred in Northeastern France in spring 2020. This single-center retrospective observational cohort study aimed to compare patients with severe COVID-19 and those with non-severe COVID-19 (survivors vs. non-survivors, ICU patients vs. non-ICU patients) and to describe extrapulmonary complications. PATIENTS AND METHODS: We included all patients with a confirmed diagnosis of COVID-19 admitted to Colmar Hospital in March 2020. RESULTS: We examined 600 patients (median age 71.09 years; median body mass index: 26.9 kg/m2); 57.7% were males, 86.3% had at least one comorbidity, 153 (25.5%) required ICU hospitalization, and 115 (19.1%) died. Baseline independent factors associated with death were older age (>75 vs. ≤75 years), male sex, oxygen supply, chronic neurological, renal, and pulmonary diseases, diabetes, cancer, low platelet and hemoglobin counts, and high levels of C-reactive protein (CRP) and serum creatinine. Factors associated with ICU hospitalization were age <75 years, oxygen supply, chronic pulmonary disease, absence of dementia, and high levels of CRP, hemoglobin, and serum creatinine. Among the 600 patients, 80 (13.3%) had an acute renal injury, 33 (5.5%) had a cardiovascular event, 27 (4.5%) had an acute liver injury, 24 (4%) had venous thromboembolism, eight (1.3%) had a neurological event, five (0.8%) had rhabdomyolysis, and one had acute pancreatitis. Most extrapulmonary complications occurred in ICU patients. CONCLUSION: This study highlighted the main risk factors for ICU hospitalization and death caused by severe COVID-19 and the frequency of numerous extrapulmonary complications in France.

[Difficulties experienced at work by patients with multiple sclerosis]. / Difficultés ressenties au travail par les patients atteints de sclérose en plaques.

AIM: Multiple sclerosis (MS) is a disease of the central nervous system that affects young adults at a time when they launch into the workforce. The disease often has a great impact on working life. The objective of this survey was to identify the problems faced by people with multiple sclerosis in the context of their work. METHODS: To describe the difficulties experienced at work by patients with multiple sclerosis, we carried out in 2010 a regional survey including neurology and functional rehabilitation centers. RESULTS: Two hundred and seven MS patients of working age responded to the survey. The employment rate was 67.6%. Among difficulties expressed by patients, physical and mental fatigue appeared as the issues affecting work. For 41% of respondents, preventive measures at work could help maintain or resume employment. CONCLUSION: Problems of fatigability put forward by MS patients are elements that can predict a loss of employment.

Mycophenolate mofetil in multiple sclerosis: a multicentre retrospective study on 344 patients.

OBJECTIVES: Mycophenolate mofetil (MMF) is an immunosuppressive agent, sometimes used as a disease-modifying therapy for multiple sclerosis (MS). Several studies have reported the relative safety of this treatment but, to date, its efficacy has rarely been described. We performed a retrospective study to assess the safety and efficacy of MMF in patients with MS. METHODOLOGY: Three French MS centres included all of their patients treated by MMF. The main outcome criterion was annualised relapse rate (ARR) in the 1 year period after onset of MMF compared with the 1 year control period. Treatment with another immunosuppressive drug, such as mitoxantrone or cyclophosphamide, in the 2 years preceding initiation of MMF was included in a subgroup analysis. MMF safety and progression of the Expanded Disability Status Scale (EDSS) score were also assessed. RESULTS: 344 patients were included; 149 patients were previously treated with another immunosuppressant (IS group). Mean MMF treatment duration was 25.3±1.1 months. During the 1 year control period, ARR was 1.11±0.08, and for the 1 year treatment period, ARR was reduced significantly to 0.35±0.05 (p<0.0001, Wilcoxon paired test). Adverse events (occurring in 11% of patients) were mainly digestive disorders, benign infections, asthenia and transitory lymphopenia. Concerning the progression of disability, in the subgroup of patients without previous immunosuppressant treatment, EDSS remained stable between initiation and 1 year after the beginning of MMF. INTERPRETATION: Our results suggest that MMF can improve or stabilise MS patients and can be used as an alternative therapy.

A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

[Multiple sclerosis without treatment: characteristic features of 70 untreated patients in a cohort of 1187 patients]. / Sclérose en plaques sans traitement de fond : analyse des caractéristiques de 70 patients non traités sur une cohorte de 1187 patients.

INTRODUCTION: First treatment protocols for multiple sclerosis (MS) have been established in France for over 15 years. Presently, a large majority of patients are treated, or has been treated in the past years, with one or more disease modifying drugs. However, despite a long-term follow-up, a certain patients remain untreated. OBJECTIVE: The aim of this study was to determine in a large cohort the proportion of patients who never received any medication for MS and to analyze their profiles and reasons for no treatment. PATIENTS AND METHODS: We studied a cohort of 1187 MS patients followed in a French (Alsace) cohort, all included in the EDMUS (European database for Multiple Sclerosis). We then performed a retrospective study on patients followed from at least 5 years (724 patients) and retained those who had never received MS medication. RESULTS: Seventy patients (9.8% of the whole cohort) corresponded to the inclusion criteria. They were 57 women and 13 men, mean age 54.9 years (range 33-81). The mean duration of the disease was 20.6 years (range 5-56). MS was of relapsing remitting type in 46 patients (65.7%), primary progressive in 11 patients (15.7%) and secondary progressive in 13 patients (18.6%). In patients with relapsing remitting disease, the annualized relapse rate was 0.33 (range 0.08-1). Mean EDSS was 3.4 after a mean follow-up of 20.6 years. Progression index was 0.16 without any differences between progressive and relapsing remitting forms (0.15 and 0.16 respectively). Reasons for not treating were: lack of disease activity (65.8%), very slow disease progression (10%), patient's initial decision followed by very slow progression (14.2%), contraindication for treatment in patients with longstanding progressive disease (10%). There were also patients (4.3%) whose initially well-stabilized disease recently became active again, leading to reconsideration about starting treatment. CONCLUSION: After a mean follow-up of 20 years, the proportion of treatment-free patients was around 10%. Most of these patients had a relapsing remitting form with a low rate of relapse or a progressive form with very slow progression.

Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis.

"Disease activity free" in relapsing-remitting multiple sclerosis (RRMS) is a new concept introduced by the results of the AFFIRM study. Our objective was to analyze the clinical and radiological efficacy of natalizumab treatment in actual clinical practice and compare it with the post hoc analysis of the AFFIRM study. All patients with RRMS who began treatment with natalizumab at our two French MS centres between April 2007 and May 2008 were included and followed-up for at least 2 years. No measurable disease activity ("disease activity free") was defined as no activity on clinical measures (no relapses and no sustained disability progression) and radiological measures (no gadolinium-enhancing lesions and no new T2-hyperintense lesions on cerebral MRI). A total of 193 patients were included. Natalizumab was discontinued in 25.9% of cases before the completion of 2 years of treatment. In our cohort, we observed patients with more severe disease than in the AFFIRM study. The proportion of patients remaining free of clinical activity during 2 years of treatment was lower than in the AFFIRM study (37.8% vs. 64.3%). The proportion of patients remaining free of radiological activity during 2 years of treatment was higher than in the AFFIRM study (68.9% vs. 57.7%), while the proportion of patients remaining free of disease activity during 2 years of treatment was comparable to the AFFIRM study (33.3% vs. 36.7%). Natalizumab seems to be as effective in a real-life setting as in pivotal and post hoc studies. The confirmation of such benefits is important because of the progressive multifocal leukoencephalopathy risk.

Demographic and clinic characteristics of French patients treated with natalizumab in clinical practice.

Natalizumab is the first selective adhesion molecule inhibitor indicated for treatment of active relapsing-remitting multiple sclerosis (RRMS). Natalizumab has been available in France since April 2007. The aims of this study are to analyze demographic, clinical, and tolerance data from French patients with RRMS treated with natalizumab in actual clinical practice and to draw comparisons with patients in the pivotal AFFIRM study. All patients with RRMS in the Nord-Pas de Calais and Alsace regions of France treated with natalizumab at any time since April 2007 were included. Variables analyzed included previous treatments; disability status [Expanded Disability Status Scale (EDSS) score]; annualized relapse rate (ARR) at baseline and after 12 months of treatment; and adverse events. Data from 384 patients (72% female) were evaluated. Mean baseline EDSS score was 3.53 and mean baseline ARR was 2.19, both significantly greater than in AFFIRM. One hundred twenty-seven patients completed 12 months of treatment; mean EDSS score in this group was 3.02 (14% reduction) and mean ARR was 0.59 (73% reduction). Although these patients had significantly different baseline characteristics and greater disability compared with patients receiving natalizumab in AFFIRM, average disability remained stable and ARR declined by 73%. Tolerability was similar to that observed in AFFIRM.

Vitamin D-binding protein gene polymorphism association with IA-2 autoantibodies in type 1 diabetes.

BACKGROUND: Vitamin D-binding protein (DBP) is the main systemic transporter of 1.25(OH)2D3 and is essential for its cellular endocytosis. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: GAT-->GAG substitution replaces aspartic acid by glutamic acid in codon 416; and ACG-->AAG substitution in codon 420 leads to an exchange of threonine for lysine. These DBP variants lead to differences in the affinity for 1.25(OH)2D3. Correlations between DBP alleles and type 1 diabetes have been described in different populations. Therefore, we investigated the polymorphism in codon 416 of the DBP gene for an association with autoimmune markers of type 1 diabetes. DESIGN AND METHODS: The present analysis was a case control study. 110 patients, 68 controls, and 115 first-degree relatives were genotyped for the DBP polymorphism in codon 416. DNA typing of DBP locus was performed by the PCR-restriction fragment length polymorphism method (RFLP). RESULTS: The frequencies of the Asp/Glu and Glu/Glu were significantly increased in diabetic subjects with detectable IA-2 antibodies (P < 0.01). On the contrary, the DBP Glu-containing genotype was not accompanied by differences in the prevalence of GAD65 antibodies. These finding supports a role of the vitamin D endocrine system in the autoimmune process of type 1 diabetes.

The HLA-DQB alleles and amino acid variants of the vitamin D-binding protein in diabetic patients in Alsace.

BACKGROUND: The HLA-DQB1 chain, in particular the amino acid in position 57, and genetic variants of the vitamin D-binding protein (DBP) have been reported to be associated with type 1 diabetes. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: codons 416 GAT --> GAG (Asp --> Glu) and 420 ACG --> AAG (Thr --> Lys). We compared distribution of DQB1 alleles and amino acid variants of DBP in type 1 diabetic patients (n = 44) in the Alsacian population and in healthy controls (n = 58). METHODS: The second exon of the DQB1 gene and exon 11 of DBP were analyzed by restriction mapping after polymerase chain reaction. RESULTS: A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) was observed in diabetic subjects as compared to controls (94.3 vs. 32.8%; p < 0.001). Combinations other than Ala/Ala carried the highest relative risk (OR = 52; p < 0.001). The analysis of the polymorphism in exon 11 of DBP showed a significant difference in the allele frequency of the HaeIII site, but not of the StyI site between patients and controls. Allele frequencies of HaeIII in diabetic subjects were 36% and 64% for Asp and Glu respectively (p < 0.001; chi(2) = 29.5). The frequency of Asp/Asp and Glu/Glu genotypes was increased in controls and diabetic subjects respectively. DBP alleles in individuals carrying the DQB1 NA combination revealed that 46.6% of diabetics were DBP Asp/Glu, but this was not statistically significant using the Fisher exact test (16/31 vs. 0/3; p = 0.23). CONCLUSIONS: The study of the DQB1 chain confirmed the value of alleles encoding for an amino acid different from Asp in position 57 (NA) in the susceptibility to type 1 diabetes. The allele frequency of the HaeIII site, but not of the StyI site, differed between patients and controls (HaeIII p < 0.001; StyI p > 0.05).

Sensitivity at diagnosis of combined beta-cell autoantibodies in insulin-dependent diabetic children. French Registry of IDDM in Children Study Group.

The purpose of this study was to test for the presence (alone or in combination) of 4 autoantibodies directed against beta cells in the sera of children at diagnosis of the overt clinical phase of insulin-dependent diabetes mellitus. Children recorded in 1989 in the population-based French Registry of Incidence of Insulin-Dependent Diabetes Mellitus were included in the present study. One hundred and thirty-eight sera were tested for islet cell antibodies (ICA), insulin autoantibodies (IAA) and antibodies against glutamic acid decarboxylase (GAD-Ab) and tyrosine phosphatase (IA2-Ab). IAA showed significantly lower sensitivity (36%) than the other antibodies (ICA: 84%; GAD-Ab: 74%; IA2-Ab: 81%). In the age-range of the registry, the prevalence rates for the 4 antibodies were not significantly affected by age. IAA and GAD-Ab were significantly associated with ICA, whereas GAD-Ab and/or IA2-Ab was(were) associated with 93% sensitivity at diagnosis. Sensitivity was 100% with the 4 antibodies combined. No significant association was found between the antibodies and HLA DR phenotypes. This study shows that a combination of the 4 major autoantibodies allows all children with insulin-dependent diabetes to be identified.

Anti-37kDa antibodies are associated with the development of IDDM in individuals with islet cell antibodies.

Antibodies directed against a beta-cell specific antigen with a molecular weight of 37 kDa have recently been described. These anti-37kDa antibodies were measured by the immunoprecipitation technique in individuals at risk for insulin-dependent diabetes mellitus (IDDM), with islet cell antibodies (ICA) greater than 20 Juvenile Diabetes Foundation units (JDFU). These subjects were recruited from large population-based cohorts at various degrees of risk for developing the disease before adulthood. Anti-37kDa antibodies were measured in 25 ICA-positive first degree relatives with ICA greater than 20 JDFU, identified from a baseline cohort of 1,185 relatives (age: 0-75 years). Four relatives were positive for anti-37kDa antibodies since the first determination onwards. These relatives developed IDDM in a 2-year follow-up period. We included 300 children with an IDDM parent, and aged less than 7 years, in a prospective survey for the prediction of IDDM. Five (1.6%) showed ICA greater than 20 JDFU. None of them were found to be positive for anti-37kDa antibodies, and none have progressed to diabetes during a 2-year follow-up. Among a baseline cohort of 13,380 schoolchildren (age: 6-17 years), 28 (0.2%) were found to have ICA greater than 20 JDFU. One boy was positive for anti-37kDa antibodies on two consecutive occasions and developed IDDM after a 10-month follow-up. No other schoolchildren with ICA greater than 20 JDFU were found to be positive for anti-37kDa antibodies. Altogether 40 other ICA-positive sera (with titres < 20 JDFU) were found to be negative for anti-37kDa antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)