46 research outputs found

    The reproductive number of COVID-19 is higher compared to SARS coronavirus.

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    Teaser: Our review found the average R0 for 2019-nCoV to be 3.28, which exceeds WHO estimates of 1.4 to 2.5

    IgG Antibodies against Measles, Rubella, and Varicella Zoster Virus Predict Conversion to Multiple Sclerosis in Clinically Isolated Syndrome

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    BACKGROUND:Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called "MRZ reaction" (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI. METHODOLOGY/PRINCIPAL FINDINGS:MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10). MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p=0.04 and p=0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54-94%), which could be further increased by combination with MRI (91%, 95%-CI: 59-99%). CONCLUSIONS/SIGNIFICANCE:Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy

    A DM1 family with interruptions associated with atypical symptoms and late onset but not with a milder phenotype

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    Carriage of interruptions in CTG repeats of the myotonic dystrophy protein kinase gene has been associated with a broad spectrum of myotonic dystrophy type 1 (DM1) phenotypes, mostly mild. However, the data available on interrupted DM1 patients and their phenotype are scarce. We studied 49 Spanish DM1 patients, whose clinical phenotype was evaluated in depth. Blood DNA was obtained and analyzed through triplet‐primed polymerase chain reaction (PCR), long PCR‐Southern blot, small pool PCR, AciI digestion, and sequencing. Five patients of our registry (10%), belonging to the same family, carried CCG interruptions at the 3’ end of the CTG expansion. Some of them presented atypical traits such as a very late onset of symptoms (>50 years) and a severe axial and proximal weakness requiring walking assistance. They also showed classic DM1 symptoms including cardiac and respiratory dysfunction, which were severe in some of them. Sizes and interrupted allele patterns were determined, and we found a contraction and an expansion in two intergenerational transmissions. Our study contributes to the observation that DM1 patients carrying interruptions present with atypical clinical features that can make DM1 diagnosis difficult, with a later than expected age of onset and a previously unreported aging‐related severe disease manifestation

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    The role of anxious distress in immune dysregulation in patients with major depressive disorder

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    Although depression with anxious distress appears to be a clinically relevant subtype of major depressive disorder (MDD), whether it involves specific pathophysiology remains unclear. Inflammation has been implicated, but not comprehensively studied. We examined within a large MDD sample whether anxious distress and related anxiety features are associated with differential basal inflammation and innate cytokine production capacity. Data are from 1078 MDD patients from the Netherlands Study of Depression and Anxiety. In addition to the DSM-5 anxious distress specifier, we studied various dimensional anxiety scales (e.g. Inventory of Depressive Symptomatology anxiety arousal subscale [IDS-AA], Beck Anxiety Inventory [BAI], Beck Anxiety Inventory [BAI, Mood and Anxiety Symptoms Questionnaire Anxious Arousal scale [MASQ-AA]). The specifier was constructed using five self-report items from the IDS and BAI. Basal inflammatory markers included C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-a. Innate production capacity was assessed by 13 lipopolysaccharide (LPS)-stimulated inflammatory markers. Basal and LPS-stimulated inflammation index scores were created. Basal inflammation was not associated with anxious distress (prevalence = 54.3%) in MDD patients, except for a modest positive association for BAI score. However, anxious distress was associated with higher LPS-stimulated levels (interferon-gamma, IL-6, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, matrix metalloproteinase (MMP)-2, TNF-alpha, LPS-stimulated index). Other anxiety indicators (anxious distress specifier score, BAI, MASQ-AA) were also associated with increased innate production capacity. Within a large MDD sample, the anxious distress specifier was associated with increased innate cytokine production capacity but not with basal inflammation. Results from dimensional anxiety indicators largely confirm these results. These findings provide new insight into the pathophysiology of anxious depression
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