Más difícil todavía: tratar una glomerulonefritis rápidamente progresiva grave en el seno de una neumonía por COVID-19

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.     

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

脊髓小脑共济失调2型家系ATXN2基因中间重复病例表型与分子遗传学特征

目的探讨脊髓小脑共济失调2型(SCA2)致病基因ATXN2异常等位基因中间重复个体的表型和分子遗传学特点。方法针对2005—2018年中日友好医院神经科运动障碍与神经遗传病研究中心收集的1383个常染色体显性遗传共济失调家系的先证者和部分家系成员,采用荧光标记毛细管电泳片段分析方法进行动态突变检测,对携带ATXN2基因中间重复的个体进行临床表型和遗传特征分析。结果共检出163个家系(包含先证者和家系成员共203人)携带异常扩展的ATXN2基因CAG重复序列,其中93个家系中有107例的异常扩展等位基因重复次数在29~34次之间。在其中的20个亲子对中,父系遗传16个,异常等位基因的代间扩展增加0~28次,母系遗传4个,异常等位基因的代间扩展增加0~4次。结论对于临床拟诊SCA2家系患者,需对其亲代或成年子代个体进行ATXN2基因检测,以免漏诊。动态突变基因检测有助于识别中间重复的个体,对明确家系致病基因和遗传咨询至关重要。     

Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T₂-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T₂-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T₂-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T₂ relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T₂ was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T₂ relaxation time was derived (R² = 0.98): T₂ (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T₂-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T₂-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.     

Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

SARS-CoV-2 host diversity: An update of natural infections and experimental evidence

Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat. This virus is supposed to be spread by human to human transmission. Cellular angiotensin-converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. Moreover, a recent study predicted that dogs might be secondary hosts during the evolution of SARS-CoV-2 from bat to human. Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets. There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks. Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne routes. Based on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to humans; needs to be deeply investigated. Humans showing clinical symptoms of respiratory infections have been undergoing for the COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic. In this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field. This review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for seroprevalence studies, especially in companion animals.     

Clinical manifestations and radiological features by chest computed tomographic findings of a novel coronavirus disease-19 pneumonia among 92 patients in Japan

IntroductionThe novel coronavirus disease (COVID-19) could cause a severe acute respiratory infectious disease, showing a high mortality rate of 12–45% among cases who required intensive care unit admission. COVID-19 pneumoniaPatients and methodsFor the purpose of identifying clinical manifestations and radiological findings of COVID-19 pneumonia, we reviewed all cases of COVID-19 pneumonia which were published by the homepage of the Japanese Association for Infectious Diseases from Feb 5 2020 until April 30 2020, including our cases. All patients were diagnosed based on positive results of the novel coronavirus-real-time RT-PCR with chest computed tomography (CT) findings.ResultsA total of 92 patients were enrolled in this study. The median age was 66 years (range 16–92 years). For all, 50 (54%) were males. The most common underlying disease was hypertension in 32 (36%). Any comorbidity was seen in 60 (67%). The mortality rate was 4 (6%). In terms of clinical symptoms on an initial visit, fever and cough were confirmed in 66 (72%) and 37 (40%). Forty-three (47%) had no respiratory symptoms. As for radiological findings by chest CT scan, ground-glass opacities (GGO)s, peripheral distribution, bilateral lung involvements were seen in 88 (96%), 76 (83%) and 78 (85%), respectively.ConclusionIt is difficult to diagnose as COVID-19 pneumonia due to poor respiratory symptoms. Chest CT findings typically show GGO, peripheral and bilateral shadows. Patients should have chest CT performed if suspected for early diagnosis and therapeutic intervention, resulting in a favorable outcome and prevention of secondary nosocomial transmitted infection.     

Evaluation of six anti-SARS-CoV-2 antibody test kits and practical approaches to optimize the diagnostic performance

In an investigation of six anti-SARS-CoV-2 antibody kits with different target antigen and methodology, each kit showed comparable performance. As false-positive reactions occurred independently with different kits, specificity increased to 100% when pairs of kits were used. With three-kit combination, both sensitivity (99.1%) and specificity (100%) increased.