Low-coverage whole genome sequencing for a highly selective cohort of severe COVID-19 patients (preprint)

Despite advances in identifying genetic markers associated to severe COVID-19, the full genetic characterisation of the disease remains elusive. This study explores the use of imputation in low-coverage whole genome sequencing for a severe COVID-19 patient cohort. We generated a dataset of 79 imputed variant call format files using the GLIMPSE1 tool, each containing an average of 9.5 million single nucleotide variants. Validation revealed a high imputation accuracy (squared Pearson correlation {approx}0.97) across sequencing platforms, showing GLIMPSE1\'s ability to confidently impute variants with minor allele frequencies as low as 2% in Spanish ancestry individuals. We conducted a comprehensive analysis of the patient cohort, examining hospitalisation and intensive care utilisation, sex and age-based differences, and clinical phenotypes using a standardised set of medical terms developed to characterise severe COVID-19 symptoms. The methods and findings presented here may be leveraged in future genomic projects, providing vital insights for health challenges like COVID-19.

Genomic Determinants of Long COVID (preprint)

Around 5–10% of adults may experience persistence of symptoms/signs beyond 4 to 12 weeks after acute SARS-CoV-2 infection. According to the World Health Organization, up to 40 million people suffer from Long COVID in Europe and the USA alone. The Centers for Disease Control and Prevention have encouraged the recognition of predictors for Long COVID. Any genetic markers associated to the disease have remained elusive to date. Here we explore the potential contribution of genetic traits to Long COVID. We used a well characterized cohort of 50 individuals with definitive diagnostic criteria for Long COVID from an initial set of patients of more than 1,200 with suspected Long COVID. All were attended at Hospital Puerta de Hierro, a large regional hospital in Madrid, Spain. All subjects had tested positive for SARS-CoV-2 RNA and/or antibodies, showed clinical manifestations for more than 6 months, and developed more than 5 persistent symptoms/signs. Low pass whole genome sequencing was performed in blood specimens for our selected cohort. From hundreds of polygenic risk scores (PRS) recorded at the PGS Catalog, we tested in our selected cohort a total of 12 PRS that passed our filtering criteria. Selected PRS encompassed distinct medical conditions, including cancers, hematologic, cardiovascular, endocrine, immunologic and neurological disorders. The calculated PRS in our patients produced a distribution of scores that was compared to a control ancestry-matched general population. We found significant differences for the PRS of traits ‘Tiredness/lethargy in the last 2 weeks’ and suggestive significance for ‘Depression’ when comparing Long COVID patients and controls. Our results strongly support a genetic susceptibility for Long COVID, with those scoring high in genetic predisposition for ‘tiredness’ as more likely to develop the disease. Results shed new light into the physiopathological basis for Long COVID, contrary to opinions considering it a subjective condition.

Impact of COVID-19 pandemic in surgical training of Junior Residents in general surgery.

Background: The pandemic caused by SARS-CoV2 has had a huge impact on our health system. Due to both cancellation of elective surgery and restructuring in departments at most medical centers, surgical residents face a potential training deficit in their specialty.This study aims to objectively analyze and quantify the impact of the pandemic on the surgical activity of residents, in the setting of emergency and elective surgery, to assess whether this period has really supposed a training deficit. Material and methods: A descriptive analysis is proposed, comparing the number of procedures performed by residents of our department during the year prior to the pandemic and during the pandemic, clustering them into different subgroups. Results: The results give an optimistic outlook. In the first place, in elective surgery, despite the lower procedures performed in absolute numbers, the proportional participation of residents in the scheduled surgeries increased in all the subgroups analyzed, finding statistically significant differences and finally approaching the total number of procedures in both periods, without relevant differences in the comparison. As for emergency surgery, residents also increased their proportional participation in most subgroups, in this case reaching more total procedures, even in absolute numbers. Conclusion: Therefore, the results seem to indicate that the teaching effort made by staff surgeons of the department has managed to palliate, in most of the subgroups analyzed, the decrease in surgical activity that the pandemic has produced, so, at least in the area of surgical practice, the impact of the pandemic has probably been reduced comparing to previous expectations.