Modulation of NBAS-Related Functions in the Early Response to SARS-CoV-2 Infection.

Upon infection, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is predicted to interact with diverse cellular functions, such as the nonsense-mediated decay (NMD) pathway, as suggested by the identification of the core NMD factor upframeshift-1 (UPF1) in the SARS-CoV-2 interactome, and the retrograde transport from the Golgi to the endoplasmic reticulum (ER) through the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where coronavirus assembly occurs. Here, we investigated the expression and localization of the neuroblastoma-amplified sequence (NBAS) protein, a UPF1 partner for the NMD at the ER, participating also in retrograde transport, and of its functional partners, at early time points after SARS-CoV-2 infection of the human lung epithelial cell line Calu3. We found a significant decrease of DExH-Box Helicase 34 (DHX34), suppressor with morphogenetic effect on genitalia 5 (SMG5), and SMG7 expression at 6 h post-infection, followed by a significant increase of these genes and also UPF1 and UPF2 at 9 h post-infection. Conversely, NBAS and other genes coding for NMD factors were not modulated. Known NMD substrates related to cell stress (Growth Arrest Specific 5, GAS5; transducin beta-like 2, TBL2; and DNA damage-inducible transcript 3, DDIT3) were increased in infected cells, possibly as a result of alterations in the NMD pathway and of a direct effect of the infection. We also found that the expression of unconventional SNARE in the ER 1, USE1 (p31) and Zeste White 10 homolog, ZW10, partners of NBAS in the retrograde transport function, significantly increased over time in infected cells. Co-localization of NBAS and UPF1 proteins did not change within 24 h of infection nor did it differ in infected versus non-infected cells at 1 and 24 h after infection; similarly, the co-localization of NBAS and p31 proteins was not altered by infection in this short time frame. Finally, both NBAS and UPF1 were found to co-localize with SARS-CoV-2 S and N proteins. Overall, these data are preliminary evidence of an interaction between NBAS and NBAS-related functions and SARS-CoV-2 in infected cells, deserving further investigation.

The impact of maternal SARS-COV-2 infection in early stages of newborn neurodevelopment: preliminary results in a multicenter Spanish study

Introduction: The consequences for the COVID-19 pandemic in the newborns of affected mothers remains unknown. Previous clinical experiences with other infections during pregnancy lead to considered pregnant women and their offspring especially vulnerable for SARS-COV-2. That is, the underlying physiopathological changes caused by the infection (e.g. storm of cytokines, micro-coagulation in placenta or vertical transmission) could clearly compromise fetal neurodevelopment. Objective(s): To analyze the impact of maternal SARS-COV-2 infection during pregnancy in early neurodevelopment of infants gestated during the COVID-19 pandemic period compared to those gestated immediately prior (2017-2021). Method(s): 212 pregnant women (14% infected) were followed throughout their pregnancy and postpartum, including newborn development. SARS-COV-2 infection was serologically confirmed during pregnancy. The Brazelton Neonatal Assessment Scale (NBAS) was administered at 6 weeks old by a trained neonatologist to evaluate neurological, social and behavioral aspects of newborn's functioning. Differences in NBAS scores between cases and controls were tested by ANOVAs. All the analysis were adjusted for maternal age, sociodemographic status, anxious-depressive symptomatology, infant's sex and gestational age at birth and NBAS, and for the period of gestation (previous or during COVID-19 pandemic). Result(s): NBAS social interactive dimension was significantly decreased in those infants exposed to prenatal SARS-COV-2 (F= 4.248, p=.043), particularly when the infection occurred before the week 20 of gestation. Gestation during COVID-19 pandemic did not alter NBAS subscales. Conclusion(s): SARS-COV-2 infection during pregnancy seems to be associated with lower NBAS scores on social dimension in 6 weeks old exposed newborns.