Convalescent plasma for outpatients with early COVID-19

BackgroundConvalescent plasma (CP) for hospitalized patients with COVID-19 has not demonstrated clear benefits. However, data on outpatients with early symptoms are scarce. We aimed to assess whether treatment with CP administered during the first 7 days of symptoms reduced the disease progression or risk of hospitalization of outpatients.MethodsTwo double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of their predefined sample size had been recruited. A Bayesian adaptive individual patient data meta-analysis was implemented. Analyses were done with Bayesian proportional odds and logistic models, where odds ratios (OR)<1.0 indicate a favorable outcome for CP. Fourteen study sites across the Netherlands and Catalonia in Spain participated in the trial. The two studies included outpatients aged ≥50 years and diagnosed with COVID-19 and symptomatic for ≤7days. The intervention consisted of one unit (200-300mL) of CP with a predefined minimum level of antibodies. The two primary endpoints were (a) a 5-point disease severity scale (fully recovered by day 7 or not, hospital or ICU admission and death) and (b) a composite of hospitalization or death.ResultsOf 797 patients included, 390 received CP and 392 placebo. At baseline, they had a median age of 58 years, 1 comorbidity, symptoms for 5 days and 93% tested negative for SARS-CoV-2 S-protein IgG antibodies. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The OR of CP for an improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311). The OR for hospitalization or death was 0.919 (CI 0.592-1.416). The effect of CP on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95% CI 0.394-1.085). CP did not decrease the time to full symptom resolution (p=0.62).ConclusionTreatment with CP of outpatients in the first 7 days of symptoms did not improve the outcome of COVID-19. The possible beneficial effect in patients with ≤5 days of symptoms requires further study.RegistrationNCT04621123 and NCT04589949 on https://www.clinicaltrials.govFunding sourceZONMW, the Netherlands, grant number 10430062010001.SUPPORT-E, grant number 101015756YoMeCorono, www.tomecorono.comThe Fight AIDS and Infectious Diseases Foundation with funding from the pharmaceutical company Grifols S.A

Impacto da hiperidrose primária na qualidade de vida de professores do ensino básico

Objetivou-se analisar o conhecimento, a prevalência e o impacto da Hiperidrose Primária na qualidade de vida de professores do ensino básico de escolas particulares no município de Aracaju/SE. Pesquisa descritiva, exploratória, com abordagem quantitativa. A coleta de dados foi iniciada com a aplicação de um questionário de conhecimento prévio sobre a Hiperidrose Primária e em seguida foi realizada uma palestra sobre a doença. Após a explanação sobre o tema, os professores responderam outros três questionários, foram eles: Critérios Diagnósticos; Hyperhidrosis Disease Severity Scale; e, Qualidade de Vida – Hiperidrose. Pesquisa aprovada pelo Comitê de Ética em Pesquisa da Universidade Tiradentes (3.266.630). A prevalência de HP foi de 8,2% no estudo, onde 78,3% pertenciam ao sexo feminino, 49,2% na faixa etária de 31 a 40 anos e 61,2% pardos. O início da doença ocorreu entre 15 e 20 anos em 27,3%. Foi identificado o desconhecimento da HP por 82,8% dos professores. Houve predominância do grau 02 em 36,4%. Quanto ao sítio anatômico, 45,5% descreveram o palmar e 45,5% o plantar como principais afetados. O diagnóstico da HP por um profissional de saúde foi relatado por 13,6% dos professores. Sobre a qualidade de vida, verificou-se que a pontuação total dos domínios variou de 20 (excelente) a 75 (ruim), com média de 46,7 pontos, onde 3 (13,6%) foram classificados como ruim. Dessa forma, atuar na divulgação de informações sobre a HP é essencial para ampliar os conhecimentos sobre essa doença entre profissionais, alunos, pais e responsáveis.

​Morphological and Molecular Diversity of Botrytis cinerea Infecting Chickpea in India

Background: The Botrytis gray mold (BGM) caused by Botrytis cinerea Pers. ex Fr., has become a major threat for chickpea cultivation in India. In view of monetary significance of this disease and growing its spread into new regions through seed and soil (sclerotia) encouraged us to study variability of this pathogen from diverse regions. Methods: Botrytis cinerea infected chickpea samples were collected from Punjab and Uttarakhand states. Pathogen was isolated using chickpea dextrose agar media. Pathogenicity was proved by inoculation of spore suspension (3x105 spores’mL-1) of the fungus on susceptible cultivar. In vitro studies were conducted for observations of morphological and cultural variability of the fungus. The pathogenic fungus was also identified through molecular characterization using ITS primers. Result: The isolates were categorized into different groups based on growth rate of the pathogen on PDA media. Pathogenicity test proved that B. cinerea isolates from Punjab were showed less disease severity scale compared to Uttarakhand state isolates. The B. cinerea fungus prefers PDA for efficient growth and multiplication than Chickpea Dextrose Agar (CDA) media. There was no conspicuous difference in colour of the colony on PDA and CDA media. The colour of the mycelium were initially white or dirty white or greyish and sporulated culture shown to have as grey with profuse mass on the surface of the mycelium. The fungus B. fabae, a different species was also responsible for causing BGM disease which was confirmed through pathogenicity and ITS sequencing. Twenty-eight isolates were studied for diversity in cultural, morphological and molecular level. The diversity in colony colour, growth type and diameter of mycelial growth, sclerotia initiation, number and pattern of sclerotia formation were observed amongst the isolates. This study would help in designing breeding strategy for development of disease resistant cultivars.

Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41–1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23–1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (−0.14 days (95% CI: −3.19–2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.

Metabolic syndrome and adipokine levels in systemic lupus erythematosus and systemic sclerosis

Introduction Aims of study were to evaluate the prevalence of metabolic syndrome (MetS) in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) patients and to evaluate serum level of adipokines in SLE and SSc patients with and without MetS. Methods Fifty SLE patients and 85 SSc patients were enrolled. The diagnosis of MetS was made according to the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. Clinical assessment and serum levels of adiponectin and resistin were evaluate in SLE and SSc patients. Results Prevalence of MetS was significantly (p<0.0001) higher in SLE patients than SSc patients (36% vs 10.6%). Median values of resistin were significantly (p<0.001) higher in SLE patients with MetS than SLE patients without MetS [4.01 ng/mL (2.7–4.5) vs 1.92 ng/mL (1.2–3)]. Median values of adiponectin were significantly (p<0.05) lower in SLE patients with MetS than SLE patients without MetS [5.64 ng/mL (4.96–8) vs 8.38 ng/mL (6.54–11.01)]. Systemic Lupus Erythematosus Activity Index [8 (6–12) vs 10 (6–13), p<0.01] and Systemic Damage Index [2 (1–3) vs 2 (0–3), p<0.001] were significantly higher in MetS patients than in patients without MetS. In SSc, the median value of disease severity scale was significantly higher (p<0.05) in MetS patients than in patients without MetS [7 (5–7) vs 5 (3–6)]. Conclusion Prevalence of MetS is higher in SLE patients. In SLE patients, MetS showed an association with adipokine levels and inflammation/activity disease scores. In SSc patients, MetS was associated with severity of disease. Key Points• Prevalence of metabolic syndrome is higher in SLE patients than SSc patients.• Resistin is higher in SLE patients with metabolic syndrome.• Adineponectin is lower in SLE patients with metabolic syndrome.• Disease severity scale is higher in SSc patients with metabolic syndrome.

Prevalência e qualidade de vida de escolares com hiperidrose primária no município de Aracaju-Sergipe

Objetivo: Estabelecer a prevalência de hiperidrose primária (HP) e sua interferência na qualidade de vida de estudantes, de uma escola de Aracaju-SE. Métodos: Estudo transversal, descritivo, exploratório e quantitativo com avaliação de 211 escolares de 8 a 17 anos do ensino fundamental e médio no período de abril a junho de 2019. Utilizou-se três questionários validados e autoaplicáveis que abordam os critérios de diagnóstico para HP, o grau de intensidade Hyperhidrosis Disease Severity Scale (HDSS), e a qualidade de vida em relação à HP. Os dados foram apresentados com média, desvio padrão, frequência absoluta e relativa. Utilizou-se o Qui-Quadrado de Pearson e Teste t de Student (p<0,05). Resultados: De 202 escolares inclusos, a prevalência da HP foi de 27,8%, sem diferença entre o sexo e etnias. Ocorreu em sítios combinados e o sítio isolado palmar foi prevalente. O início dos sintomas deu-se na infância com níveis entre leve e moderada, com HDSS 2 e 3. Conclusão: A prevalência de HP foi alta, com caráter familiar significativo. Acomete, principalmente, as regiões palmo-plantar com início na infância, acarretando ansiedade, constrangimento, danos nas atividades escolares e nas relações interpessoais, aumentando em situações de tensão e preocupação, com impacto negativo na qualidade de vida.

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.

Incidence and phenotypical variation of outer retina-associated hyperreflectivity in macular telangiectasia type 2

BackgroundMacular telangiectasia type 2 (MacTel) is a neurodegenerative disease resulting in photoreceptor loss. Optical coherence tomography (OCT) reveals outer retina-associated hyperreflectivity (ORaH) as part of this process. The purpose of this study was to describe the incidence and phenotypical variation of ORaH.MethodsDifferent parameters of ORaH were analysed: OCT characteristics (Spectralis SD-OCT), correlation with vascular changes (OCT angiography; OCTA 3×3 mm Optovue) and correlation with hyperpigmentation (autofluorescence/fundus images). ORaH was also evaluated regarding the grade of severity of photoreceptor loss (Disease Severity Scale).ResultsOf 220 eyes with MacTel type 2, 106 demonstrated ORaH. On OCT, the size, the extension into the inner retina and the contact with retinal pigment epithelium (RPE) of the ORaH were variable. On OCTA neovascularisation (NV) in the outer retina (OR) was present at the location of the ORaH in 97.6%. Increasing size of NV correlated with progressive photoreceptor loss. In 86.6% with NV, the flow signals were visible between the OR and the choriocapillaris. In 85.7%, the ORaH was associated with hyperpigmentation on autofluorescence and fundus colour images.ConclusionsThe presence of ORaH is associated with increasing photoreceptor loss and disease severity. In these more advanced cases of the present study, a variable presentation of ORaH in respect to size and form was seen, but in most cases, ORaH was in contact to the RPE. Additionally, ORaH was associated with hyperpigmentation and OR NV on OCTA. These results are consistent with the concept of ORaH representing fibrovascular OR-NV with RPE proliferation after contact with the RPE.

Prevalence of Diabetic Retinopathy and its Associated Factors among Diabetic Patients in Primary Care Clinics, Kuantan, Pahang

Introduction: Diabetic retinopathy (DR) is one of the commonest complications of diabetes mellitus. This study was to determine the prevalence of DR and its association with chronic kidney disease (CKD), high HbA1c and dyslipidemia among diabetic patients in government primary care clinics. Materials and Methods: A cross sectional study was carried out. The respondents were selected from diabetic registry at two government primary care clinics in Kuantan, Pahang via stratified random sampling method during the study period from May 2010 to April 2011. The respondents were interviewed and assessed clinically using a structured questionnaire. Retinal examination was performed by accredited staff using non-mydratic retinal imaging and DR was classified according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Results: Out of 400 respondents, 58.8% were diagnosed with diabetes less than 5 years and 51.0% had uncontrolled blood pressure (>130/80 mmHg). The prevalence of DR and maculopathy were 33.5% and of 17.8% respectively. Most of these patients (22.3%) had mild non-proliferative DR. DR patients had higher percentages CKD (17.9% vs. 6.8%; p<0.001) and a higher mean of HbA1C (8.69 vs. 8.11; p=0.015) compared to non-DR patients. The study revealed that DR was independently associated with CKD {OR: 3.46, 95% CI (1.76, 6.80)} and high HbA1c {OR: 1.12, 95% CI (1.02, 1.23)}. Those with dyslipidemia however, has 39% less risk of DR {OR: 0.61, 95% CI (0.39, 0.94)}. Conclusion: This study showed that diabetic patients with CKD and high HbA1c have greater risks to develop DR but has protective risk with dyslipidemia.