Lutz, W. | bioRxiv Science

bioRxiv2022

Trans-synaptic dwelling of SARS-CoV-2 particles perturbs neural synapse organization and function

SARS-CoV-2 infection is associated with short- and long-term neurological and psychiatric complications, referred to as neuroCOVID. These symptoms are relatively heterogenous and fluctuating, hampering the discovery of molecular mechanisms underlying viro-induced brain perturbations. Here, we show that the human cerebral cortex poorly supports SARS-CoV-2 dissemination using post-mortem COVID-19 patient samples, ex vivo organotypic cultures of human brain explants and stem cell-derived cortical organoids. Despite restricted infection, the sole exposure of neural cells to SARS-CoV-2 particles is sufficient to induce significant perturbations on neural synapse organization associated to electrical activity dysfunction. Single-organoid proteomics revealed that exposure to SARS-CoV-2 is associated to trans-synaptic proteins upregulation and unveiled that incoming virions dwell at LPHN3/FLRT3-containing synapses. Our study provides new mechanistic insights on the origin of SARS-CoV-2-induced neurological disorders. One-Sentence SummarySARS-CoV-2 modulates neural plasticity and electrical activity as viral particles lodge at the trans-synaptic interface.

microbiology↗

bioRxiv2019

The persistent influence of caste on under-five mortality: Factors that explain the caste-based gap in high focus Indian states

ObjectiveAlthough under-five mortality (U5M) is declining in India, it is still high in a few selected states and among the scheduled caste (SC) and scheduled tribe (ST) population of the country. This study re-examines the association between castes and U5M in high focus Indian states following the implementation of the countrys National Rural Health Mission (NRHM) program. In addition, we aim to quantify the contribution of socioeconomic determinants in explaining the gap in U5M between the SC/ST population and non-SC/ST population in high focus states in India.\n\nData and methodUsing data from the National Family Health Survey (NFHS), we calculated the under-five mortality rate (U5MR) by applying a synthetic cohort probability approach. We applied a binary logistic regression model to examine the association of U5M with the selected covariates. Further, we used Fairlies decomposition technique to understand the relative contribution of socioeconomic variables on U5M risk between the caste groups.\n\nFindingsIn high focus Indian states, the parallel gap in U5M between well-off and deprived caste children has disappeared in the post-NRHM period, indicating a positive impact in terms of reducing caste-based inequalities in the high focus states. Despite the reduction in U5M, particularly among children belonging to STs, children belonging to the SC and ST population still experience higher mortality rates than children belonging to the non-SC/ST population from 1992 to 2016. Both macro level (district level mortality rates) and individual (regression analysis) analyses showed that children belonging to SCs experience the highest likelihood of dying before their fifth birthday. A decomposition analysis revealed that 78% of the caste-based gap in U5M is due to the effect of womens level of educational attainment and household wealth between the SC/ST and non-SC/ST population. Program indicators such as place of delivery and number of antenatal care (ANC) visits also contributed significantly to widening caste-based gaps in U5M.\n\nConclusionThe study indicates that there is still scope to improve access to health facilities for mothers and children belonging to deprived caste groups in India. Continuous efforts to raise the level of maternal education and the economic status of people belonging to deprived caste groups should be pursued simultaneously.

epidemiology↗