DataSheet_1_Causal relationships between susceptibility and severity of COVID-19 and neuromyelitis optica spectrum disorder (NMOSD) in European population: a bidirectional Mendelian randomized study.docx

BackgroundNeurological disorders can be caused by viral infections. The association between viral infections and neuromyelitis optica spectrum disorder (NMOSD) has been well-documented for a long time, and this connection has recently come to attention with the occurrence of SARS-CoV-2 infection. However, the precise nature of the causal connection between NMOSD and COVID-19 infection remains uncertain.MethodsTo investigate the causal relationship between COVID-19 and NMOSD, we utilized a two-sample Mendelian randomization (MR) approach. This analysis was based on the most extensive and recent genome-wide association study (GWAS) that included SARS-CoV-2 infection data (122616 cases and 2475240 controls), hospitalized COVID-19 data (32519 cases and 2062805 controls), and data on severe respiratory confirmed COVID-19 cases (13769 cases and 1072442 controls). Additionally, we incorporated a GWAS meta-analysis comprising 132 cases of AQP4-IgG-seropositive NMOSD (NMO-IgG+), 83 cases of AQP4-IgG-seronegative NMOSD (NMO-IgG−), and 1244 controls.ResultsThe findings of our study indicate that the risk of developing NMO-IgG+ is elevated when there is a genetic predisposition to SARS-CoV-2 infection (OR = 5.512, 95% CI = 1.403-21.657, P = 0.014). Furthermore, patients with genetically predicted NMOSD did not exhibit any heightened susceptibility to SARS-CoV2 infection, COVID-19 hospitalization, or severity.Conclusionour study using Mendelian randomization (MR) revealed, for the first time, that the presence of genetically predicted SARS-CoV2 infection was identified as a contributing factor for NMO-IgG+ relapses.</p

Table_2_Effect of Delayed Diagnosis of Phenylketonuria With Imaging Findings of Bilateral Diffuse Symmetric White Matter Lesions: A Case Report and Literature Review.DOCX

Phenylketonuria is a hereditary metabolic disorder due to the deficiency of tetrahydrobiopterin or phenylalanine hydroxylase. Delayed diagnoses of it manifest a progressive irreversible neurological impairment in the early years of the disease. Guthrie test and tandem mass spectrometry aided in early detection and intervention of phenylketonuria, which significantly decreased the disability of patients as well as reducing the need for diagnosis in adults. This is a case report of a 60-year-old Asian man, characterized by severe visual-spatial disorders and bilateral diffuse symmetric white matter lesions on magnetic resonance imaging, who was diagnosed as phenylketonuria with his congenital mental retardation sibling. Heterozygous mutations exist in gene encoding PAH c.1068C>A and c.740G>T. During the diagnosis, we looked up at other late-onset genetic diseases considered to occur rarely but gradually revealed similar clinical manifestations and significant white matter lesions gaining importance in guiding to correct diagnosis and treatment. We made a comprehensive review of phenylketonuria and other inherited diseases with major prevalence in adulthood with prominent white matter involvement. Our study aims to help neurologists to improve recognition of metabolism-related leukoencephalopathies without neglect of the role of congenital genetic factors.</p

Table_3_Effect of Delayed Diagnosis of Phenylketonuria With Imaging Findings of Bilateral Diffuse Symmetric White Matter Lesions: A Case Report and Literature Review.DOCX

Phenylketonuria is a hereditary metabolic disorder due to the deficiency of tetrahydrobiopterin or phenylalanine hydroxylase. Delayed diagnoses of it manifest a progressive irreversible neurological impairment in the early years of the disease. Guthrie test and tandem mass spectrometry aided in early detection and intervention of phenylketonuria, which significantly decreased the disability of patients as well as reducing the need for diagnosis in adults. This is a case report of a 60-year-old Asian man, characterized by severe visual-spatial disorders and bilateral diffuse symmetric white matter lesions on magnetic resonance imaging, who was diagnosed as phenylketonuria with his congenital mental retardation sibling. Heterozygous mutations exist in gene encoding PAH c.1068C>A and c.740G>T. During the diagnosis, we looked up at other late-onset genetic diseases considered to occur rarely but gradually revealed similar clinical manifestations and significant white matter lesions gaining importance in guiding to correct diagnosis and treatment. We made a comprehensive review of phenylketonuria and other inherited diseases with major prevalence in adulthood with prominent white matter involvement. Our study aims to help neurologists to improve recognition of metabolism-related leukoencephalopathies without neglect of the role of congenital genetic factors.</p

Table_1_Effect of Delayed Diagnosis of Phenylketonuria With Imaging Findings of Bilateral Diffuse Symmetric White Matter Lesions: A Case Report and Literature Review.DOCX

Phenylketonuria is a hereditary metabolic disorder due to the deficiency of tetrahydrobiopterin or phenylalanine hydroxylase. Delayed diagnoses of it manifest a progressive irreversible neurological impairment in the early years of the disease. Guthrie test and tandem mass spectrometry aided in early detection and intervention of phenylketonuria, which significantly decreased the disability of patients as well as reducing the need for diagnosis in adults. This is a case report of a 60-year-old Asian man, characterized by severe visual-spatial disorders and bilateral diffuse symmetric white matter lesions on magnetic resonance imaging, who was diagnosed as phenylketonuria with his congenital mental retardation sibling. Heterozygous mutations exist in gene encoding PAH c.1068C>A and c.740G>T. During the diagnosis, we looked up at other late-onset genetic diseases considered to occur rarely but gradually revealed similar clinical manifestations and significant white matter lesions gaining importance in guiding to correct diagnosis and treatment. We made a comprehensive review of phenylketonuria and other inherited diseases with major prevalence in adulthood with prominent white matter involvement. Our study aims to help neurologists to improve recognition of metabolism-related leukoencephalopathies without neglect of the role of congenital genetic factors.</p

Table_2_Milder symptoms and shorter course in patients with re-positive COVID-19: A cohort of 180 patients from Northeast China.XLSX

China experienced another widespread Coronavirus disease 2019 (COVID-19) outbreak recently caused by the Omicron variant, which is less severe but far more contagious than the other COVID-19 variants, leading local governments to focus efforts on eliminating the spread of the disease. Previous studies showed that after “recovering” from the virus, some patients could re-test positive for COVID-19 with nucleic acid tests, challenging the control of disease spread. In this study, we aimed to analyze the clinical and laboratory characteristics of re-positive COVID-19 patients in Northeast China. We retrospectively analyzed data from confirmed reverse transcription polymerase chain reaction (RT-PCR) re-positive COVID-19 patients who were admitted to the First Hospital of Jilin University, Jilin Province, China, from March to June 2022. Detailed clinical symptoms, medical history, anti-Corona Virus (CoV) IgG and IgM levels, and CoV nucleic acid cycle threshold (Ct) values during the re-positive period were collected and analyzed. A total of 180 patients were included in this study, including 62 asymptomatic cases and 118 mild cases. The cohort included 113 men and 67 women, with an average age of 45.73 years. The median time between recovery from the virus and re-positivity was 13 days. Our results showed that the proportion of re-positive patients with symptoms was lower, and the nucleic acid test-positive duration was shorter during the re-positive period. Furthermore, in patients with underlying disease, the proportion of patients with symptoms was higher, anti-CoV IgG levels were lower, and the total disease duration was longer. In conclusion, during the re-positive period, the symptoms were milder, and the CoV nucleic acid test-positive course was shorter. The concomitant underlying disease is an important factor associated with clinical symptoms, and the overall course of COVID-19 re-positive patients may be associated with lower anti-CoV IgG levels. Large-scale and multicenter studies are recommended to better understand the pathophysiology of recurrence in patients with COVID-19.</p

Table_1_Milder symptoms and shorter course in patients with re-positive COVID-19: A cohort of 180 patients from Northeast China.DOCX

China experienced another widespread Coronavirus disease 2019 (COVID-19) outbreak recently caused by the Omicron variant, which is less severe but far more contagious than the other COVID-19 variants, leading local governments to focus efforts on eliminating the spread of the disease. Previous studies showed that after “recovering” from the virus, some patients could re-test positive for COVID-19 with nucleic acid tests, challenging the control of disease spread. In this study, we aimed to analyze the clinical and laboratory characteristics of re-positive COVID-19 patients in Northeast China. We retrospectively analyzed data from confirmed reverse transcription polymerase chain reaction (RT-PCR) re-positive COVID-19 patients who were admitted to the First Hospital of Jilin University, Jilin Province, China, from March to June 2022. Detailed clinical symptoms, medical history, anti-Corona Virus (CoV) IgG and IgM levels, and CoV nucleic acid cycle threshold (Ct) values during the re-positive period were collected and analyzed. A total of 180 patients were included in this study, including 62 asymptomatic cases and 118 mild cases. The cohort included 113 men and 67 women, with an average age of 45.73 years. The median time between recovery from the virus and re-positivity was 13 days. Our results showed that the proportion of re-positive patients with symptoms was lower, and the nucleic acid test-positive duration was shorter during the re-positive period. Furthermore, in patients with underlying disease, the proportion of patients with symptoms was higher, anti-CoV IgG levels were lower, and the total disease duration was longer. In conclusion, during the re-positive period, the symptoms were milder, and the CoV nucleic acid test-positive course was shorter. The concomitant underlying disease is an important factor associated with clinical symptoms, and the overall course of COVID-19 re-positive patients may be associated with lower anti-CoV IgG levels. Large-scale and multicenter studies are recommended to better understand the pathophysiology of recurrence in patients with COVID-19.</p

Table1_Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.xlsx

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264–0.892, p = 0.020; OR = 0.323, 95% CI = 0.107–0.972, p = 0.044; OR = 1.492, 95% CI = 1.111–2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.</p

DataSheet1_Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.docx

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264–0.892, p = 0.020; OR = 0.323, 95% CI = 0.107–0.972, p = 0.044; OR = 1.492, 95% CI = 1.111–2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.</p

Table3_Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.xlsx

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264–0.892, p = 0.020; OR = 0.323, 95% CI = 0.107–0.972, p = 0.044; OR = 1.492, 95% CI = 1.111–2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.</p

Table2_Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.xlsx

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264–0.892, p = 0.020; OR = 0.323, 95% CI = 0.107–0.972, p = 0.044; OR = 1.492, 95% CI = 1.111–2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.</p