Successive onset of Vogt-Koyanagi-Harada syndrome in father and son.

BACKGROUND: Vogt‒Koyanagi‒Harada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. CASE PRESENTATION: A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. CONCLUSIONS: To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied.

Complete genome sequencing and molecular genetic evolution analysis of Guangxi mutant of porcine epidemic diarrhea virus

In order to understand the genomic characteristics and molecular genetic diversity of porcine epidemic diarrhea virus(PEDV) in Guangxi in recent years, 11 pairs of specific primers were designed to detect the whole genome of PEDV GXNN isolated from porcine diarrhea in Nanning, Guangxi, China, and similarity comparison, genetic evolution, gene variation and S gene recombination were also analyzed. The results showed that full length of the GXNN strain was 28 035 bp, had similar genomic characteristics with other PEDV isolates, about 96.4%-98.7% nucleotide similarity with different reference strains, and the nucleotide similarity of S, ORF3, M and N genes was 93.7%-98.9%, 90.9%-99.4%, 97.4%-99.7% and 95.6%-99.2%;the amino acid similarity of them was 92.9%-99.5%, 91.3%-99.1%, 97.4%-99.1% and 96.4%-99.5%. GXNN is closely related to most domestic isolates in recent years. Phylogenetic tree showed that GXNN closely related to most strains isolated in China recent years, belonged to GII-b subtype. However, it was low relatedness to classic vaccine strains, domestic early epidemic strains, foreign epidemic strains and Guangxi CH-GX-2015-750 A, they belong to different subtypes. Compared with the 5 vaccine strains, the S gene of GXNN stain has a large variation, by inserting amino acid Q at positions 118 844 and 905 sizes, four unique amino acid mutations in the core neutralizing epitope(COE)region and the main epitope region, and 14 mutations in other regions. 126 T/A, 199 A/V and 103 T/A site mutations of ORF3, M and N genes were happened at position 126, 4 D4 region and PN-D4 region, respectively. Recombination analysis revealed that there was a potential recombination region in the hypervariable region of S gene at 826-3 142 nt. This study successfully obtained the complete genome sequence of a PEDV strain, and analyzed its genetic variation and provided a reference for PEDV molecular epidemiology research and new vaccine development.

Ionization of D571 Is Coupled with SARS-CoV-2 Spike Up/Down Equilibrium Revealing the pH-Dependent Allosteric Mechanism of Receptor-Binding Domains.

As a type I viral fusion protein, SARS-CoV-2 spike undergoes a pH-dependent switch to mediate the endosomal positioning of the receptor-binding domain to facilitate viral entry into cells and immune evasion. Gaps in our knowledge concerning the conformational transitions and key intramolecular motivations have hampered the development of effective therapeutics against the virus. To clarify the pH-sensitive elements on spike-gating the receptor-binding domain (RBD) opening and understand the details of the RBD opening transition, we performed microsecond-time scale constant pH molecular dynamics simulations in this study. We identified the deeply buried D571 with a clear pKa shift, suggesting a potential pH sensor, and showed the coupling of ionization of D571 with spike RBD-up/down equilibrium. We also computed the free-energy landscape for RBD opening and identified the crucial interactions that influence RBD dynamics. The atomic-level characterization of the pH-dependent spike activation mechanism provided herein offers new insights for a better understanding of the fundamental mechanisms of SARS-CoV-2 viral entry and infection and hence supports the discovery of novel therapeutics for COVID-19.

Metagenomic Next-Generation Sequencing in the Diagnosis of HHV-1 Reactivation in a Critically Ill COVID-19 Patient: A Case Report.

Background: Secondary infections pose tremendous challenges in Coronavirus disease 2019 (COVID-19) treatment and are associated with higher mortality rates. Clinicians face of the challenge of diagnosing viral infections because of low sensitivity of available laboratory tests. Case Presentation: A 66-year-old woman initially manifested fever and shortness of breath. She was diagnosed as critically ill with COVID-19 using quantitative reverse transcription PCR (RT-qPCR) and treated with antiviral therapy, ventilator and extracorporeal membrane oxygenation (ECMO). However, after the condition was relatively stabled for a few days, the patient deteriorated with fever, frequent cough, increased airway secretions, and increased exudative lesions in the lower right lung on chest X-rays, showing the possibility of a newly acquired infection, though sputum bacterial and fungal cultures and smears showed negative results. Using metagenomic next-generation sequencing (mNGS), we identified a reactivation of latent human herpes virus type 1 (HHV-1) in the respiratory tract, blood and gastrointestinal tract, resulting in a worsened clinical course in a critically ill COVID-19 patient on ECMO. Anti-HHV-1 therapy guided by these sequencing results effectively decreased HHV-1 levels, and improved the patient's clinical condition. After 49 days on ECMO and 67 days on the ventilator, the 66-year-old patient recovered and was discharged. Conclusions: This case report demonstrates the potential value of mNGS for evidence-based treatment, and suggests that potential reactivation of latent viruses should be considered in critically ill COVID-19 patients.

Quarantine at home may not enough!-from the epidemiological data in Shaanxi Province of China.

OBJECTIVES: A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. RESULTS: 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.