Systematic review of host genetic association with Covid-19 prognosis and susceptibility: What have we learned in 2020?

Biomarker identification may provide strategic opportunities to understand disease pathophysiology, predict outcomes, improve human health, and reduce healthcare costs. The highly heterogeneous Covid-19 clinical manifestation suggests a complex interaction of several different human, viral and environmental factors. Here, we systematically reviewed genetic association studies evaluating Covid-19 severity or susceptibility to SARS-CoV-2 infection following PRISMA recommendations. Our research comprised papers published until December 31st , 2020, in PubMed and BioRXiv databases focusing on genetic association studies with Covid-19 prognosis or susceptibility. We found 20 eligible genetic association studies, of which 11 assessed Covid-19 outcome and 14 evaluated infection susceptibility (five analyzed both effects). Q-genie assessment indicated moderate quality. Five large-scale association studies (GWAS, whole-genome, or exome sequencing) were reported with no consistent replication to date. Promising hits were found on the 3p21.31 region and ABO locus. Candidate gene studies examined ACE1, ACE2, TMPRSS2, IFITM3, APOE, Furin, IFNL3, IFNL4, HLA, TNF-ɑ genes, and ABO system. The most evaluated single locus was the ABO, and the most sampled region was the HLA with three and five candidate gene studies, respectively. Meta-analysis could not be performed. Available data showed the need for further reports to replicate claimed associations.

Obstetric and perinatal outcomes in cases of congenital Zika syndrome.

OBJECTIVE: To describe obstetric and perinatal outcomes in cases of congenital Zika syndrome (CZS). METHODS: A dual prospective and retrospective cohort study involving 102 pairs of mothers and fetuses/children with CZS whose infection was confirmed by testing for the Zika virus in amniotic fluid, umbilical cord blood, and fragments from the placenta of the newborn infant (confirmed CZS), or by intrauterine imaging tests (neurosonography), and/or postnatal computed tomography (presumed CZS). RESULTS: Suspicion of CZS was investigated by ultrasonography during pregnancy in 52.9% of cases. The principal prenatal imaging findings were ventriculomegaly (43.1%) and microcephaly (42.2%). Median gestational age at delivery was 39 weeks, with 15.7% being premature. Mean head circumference at birth was 30.0 ± 2.3 cm, with 66% of cases being classified as having microcephaly. Arthrogryposis was found in 10 cases (9.8%). There were no fetal deaths; however, nine neonatal deaths were recorded, and three autopsies were performed. CONCLUSION: Neonatal mortality was high, almost 10%. Regarding the abnormalities of CZS, microcephaly, although common, was not present in all cases and intracranial findings need to be taken into consideration for diagnosis. Therefore, ultrasound screening during pregnancy should be systematized and expanded in endemic zones.

Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus macaques.

Infection with Simian Immunodeficiency Virus (SIV) leads to high viral loads and progression to Simian AIDS (SAIDS) in rhesus macaques. The viral accessory protein Nef is required for this phenotype in monkeys as well as in HIV-infected humans. Previously, we determined that HIVNef binds HIVGagPol and Alix for optimal viral replication in cells. In this study, we demonstrated that these interactions could correlate with high viral loads leading to SAIDS in the infected host. By infecting rhesus macaques with a mutant SIV(mac239), where sequences in the nef gene that are required for these interactions were mutated, we observed robust viral replication and disease in two out of four monkeys, where they reverted to the wild type genotype and phenotype. These two rhesus macaques also died of SAIDS. Two other monkeys did not progress to disease and continued to harbor mutant nef sequences. We conclude that interactions between Nef, GagPol and Alix contribute to optimal viral replication and progression to disease in the infected host.