Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion

BackgroundB-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution. MethodsAmplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs. Whole genome sequencing was performed on samples from the patients original presentation and 10 months later. ResultsOver the course of almost a year, the virus accumulated a unique in-frame deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Also, minority variants that were identified in the early samples--reflecting the heterogeneity of the initial infection--were found to be fixed late in the infection. Remdesivir and high-titer convalescent plasma treatment were given, and the infection was eventually cleared after 335 days of infection. ConclusionsThe unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants. SummaryWe report an immunocompromised patient with persistent symptomatic SARS-CoV-2 infection for 335 days. During this time, the virus accumulated a unique in-frame deletion in the spike, and a complete deletion of ORF7b and ORF8 which is the first report of its kind in an immunocompromised patient.

Diversity and selection of SARS-CoV-2 minority variants in the early New York City outbreak

High error rates of viral RNA-dependent RNA polymerases lead to diverse intra-host viral populations during infection. Errors made during replication that are not strongly deleterious to the virus can lead to the generation of minority variants. However, accurate detection of minority variants in viral sequence data is complicated by errors introduced during sample preparation and data analysis. We used synthetic RNA controls and simulated data to test seven variant calling tools across a range of allele frequencies and simulated coverages. We show that choice of variant caller, and use of replicate sequencing have the most significant impact on single nucleotide variant (SNV) discovery and demonstrate how both allele frequency and coverage thresholds impact both false discovery and false negative rates. We use these parameters to find minority variants in sequencing data from SARS-CoV-2 clinical specimens and provide guidance for studies of intrahost viral diversity using either single replicate data or data from technical replicates. Our study provides a framework for rigorous assessment of technical factors that impact SNV identification in viral samples and establishes heuristics that will inform and improve future studies of intrahost variation, viral diversity, and viral evolution. IMPORTANCEWhen viruses replicate inside a host, the virus replication machinery makes mistakes. Over time, these mistakes create mutations that result in a diverse population of viruses inside the host. Mutations that are neither lethal to the virus, nor strongly beneficial, can lead to minority variants that are minor members of the virus population. However, preparing samples for sequencing can also introduce errors that resemble minority variants, resulting in inclusion of false positive data if not filtered correctly. In this study, we aimed to determine the best methods for identification and quantification of these minority variants by testing the performance of seven commonly used variant calling tools. We used simulated and synthetic data to test their performance against a true set of variants, and then used these studies to inform variant identification in data from clinical SARS-CoV-2 clinical specimens. Together, analyses of our data provide extensive guidance for future studies of viral diversity and evolution.

The Effect of Cardiac Rehabilitation I Phase Program on Physical Capacity after Coronary Artery Bypass Graft Surgery / 대한스포츠의학회지

The aim of this study was to examine the effect of phase I cardiac rehabilitation program (CRP) on physical capacity in patients with coronary artery bypass graft (CABG). Eighty seven patients who underwent CABG in our hospital were enrolled on the study. Among them, excluding 17 during the study, the results of 70 patients were included in the final data. Subjects were classified into two groups according to the participation in the phase I CRP; participation group (n=35) and non-participation group (n=35). The CR was executed for the participation group until patients' discharge. The variables including resting heart rate (RHR), oxygen saturation, walking distance in 6 minutes, and forced expiration amount were measured at initial phase, discharge and follow-up at 1 month after discharge. From the data, descriptive statistics (mean, standard deviation) were calculated, and differences in each variable before, during, after the treatment and between groups were tested using repeated measure analysis of variance using SPSS ver. 18.0 statistics program for Window. For the effects and results with a statistical significance, post-hoc test was made using t-test. There was statistically significant difference (p<0.05) in the RHR and the walking distance in 6 minutes. While there was no significant difference in the oxygen saturation and the maximum expiration amount. As conclusion, the Phase I CRP after CABG showed a effect on the significant improvement of physical capacity by decreasing the RHR and increasing the walking distance in 6 minutes, exerting a positive influence on the recovery after the CABG operation.

Determination of staphylococcal exotoxins, SCCmec types, and genetic relatedness of Staphylococcus intermedius group isolates from veterinary staff, companion animals, and hospital environments in Korea

The Staphylococcus (S.) intermedius group (SIG) has been a main research subject in recent years. S. pseudintermedius causes pyoderma and otitis in companion animals as well as foodborne diseases. To prevent SIG-associated infection and disease outbreaks, identification of both staphylococcal exotoxins and staphylococcal cassette chromosome mec (SCCmec) types among SIG isolates may be helpful. In this study, it was found that a single isolate (one out of 178 SIG isolates examined) harbored the canine enterotoxin SEC gene. However, the S. intermedius exfoliative toxin gene was found in 166 SIG isolates although the S. aureus-derived exfoliative toxin genes, such as eta, etb and etd, were not detected. SCCmec typing resulted in classifying one isolate as SCCmec type IV, 41 isolates as type V (including three S. intermedius isolates), and 10 isolates as non-classifiable. Genetic relatedness of all S. pseudintermedius isolates recovered from veterinary staff, companion animals, and hospital environments was determined by pulsed-field gel electrophoresis. Strains having the same band patterns were detected in S. pseudintermedius isolates collected at 13 and 18 months, suggesting possible colonization and/or expansion of a specific S. pseudintermedius strain in a veterinary hospital.

Efficacy of Fluvastatin in Patients with Hypercholesterolemia / 대한내분비학회지

Background: Fluvastatin is the first entirely synthetic 3-hydroxy-3-methylglutaryl-coenzyme A(HMG-CoA) reductase inhibitor. Clinical data indicate that this agent exhibits the proven efficacy of its class and also has some theoretical advantages in safety for long-term use because of its unique pharmacololgic property consistent with hepatoselectivity(i.e., low systemic exposure). This study is to evaluate efficacy and safety of fluvastatin in hypercholesterolemic patients in Korea. Methods: An open clinical trial with fluvastatin was conducted in 31 subjects who continued to have high blood cholesterol levels of 6.21 mmol/L(240 mg/dl) or greater after 1 month of lipid-lowering diet plus single blind placebo period. Fluvastatin was administered for 8 weeks with the initial dose of 20 mg per day and if serum cholesterol levels did not fall below 5.20 mmol/L(200 mg/dl) after 4 weeks the dose was increased to 40 mg per day for the second 4 weeks. On each visit every 4 weeks they underwent interview and laboratory tests about side effects and tolerability. Results: The mean % changes in plasma total cholesterol and LDL-cholesterol from baseline were

A Case of Diabetes Insipidus in Patient with Sheehan's Syndrome / 대한내분비학회지

Sheehans syndrome is a known complication of pregnancy, It was described as a syndrome of hypopituitarysm due to acute ischemic necrosis of the anterior pituitary gland secondary to severe postpartum bleeding and shock. The neurophysis is usually preserved. But it can be involved in severe cases manifesting as diabetes insipidus. Because of its rare coexistence with Sheehans syndrome, diabetes insipidus is seldom recognized as a potential postpartum complication. The report describes a patient who developed Sheehans syndrome and diabetes insipidus immediately following delivery. Diabetes insipidus resolved spontaneously after 15 months, while panhypopituitarysm is persistent.