ABSTRACT
Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population who experienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province-that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe-via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sex and risk factors. We genotyped 1195 individuals and replicated the association at the 3p21.31 locus with severity, but with a stronger effect size that further increased in gravely ill patients. Transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. We also identified 17 loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility.
ABSTRACT
BACKGROUND AND PURPOSE: Heparin is widely used for acute stroke to prevent thrombus propagation and/or multiple emboli generation, although there is, as yet, no demonstrated efficacy. However, all of the available clinical studies allowed long intervals from stroke to treatment. The purpose of this study was to try an intravenous regimen of unfractionated heparin the acute cerebral infarction starting treatment within the first 3 hours of the onset of symptoms. METHODS: The study was an outcome evaluator-blind design trial. Patients had to display signs of a nonlacunar hemispheric infarction. Selected patients were randomly allocated to receive intravenous heparin sodium or saline. Heparin was infused at a rate to maintain activated partial thromboplastin time ratio 2.0 to 2.5 x control for 5 days. The primary end point was recovery of a modified Rankin score zero to 2 at 90 days of stroke at phone interview by a single physician blind to treatment. Safety end points were death, symptomatic intracranial hemorrhages, and major extracranial bleedings by 90 days of stroke. RESULTS: A total of 418 stroke patients were included. In the heparin group, there were more self-independent patients (38.9% versus 28.6%; P=0.025). In addition, in the same group, there were fewer deaths (16.8% versus 21.9%; P=0.189), more symptomatic brain hemorrhages (6.2% versus 1.4%; P=0.008), and more major extracerebral bleedings (2.9% versus 1.4%; P=0.491). CONCLUSIONS: Intravenous heparin sodium could be of help in the earliest treatment of acute nonlacunar hemispheric cerebral infarction, even keeping into account an increased frequency of intracranial symptomatic brain hemorrhages.
