ABSTRACT
Pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of "preeclampsia-like syndrome". Preeclampsia is a systematic syndrome that affects 5% of people worldwide and is the leading cause of maternal mortality. It is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension and neurological disturbances. Here, we used whole-transcriptome, spatial profiling of placental tissues to analyse the expression of genes between placentae from pregnant participants who contracted SARS-CoV-2 and those prior to the pandemic. Our analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-eclampsia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress. This study illustrates how spatially resolved transcriptomic analysis can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce "preeclampsia-like syndrome". Our study highlights the benefits of spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in "preeclampsia-like syndrome."
Subject(s)
Hypertension , Nervous System Diseases , Inflammation , Pre-EclampsiaABSTRACT
Background. Robust biomarkers that predict disease outcomes amongst COVID19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods. We conducted a multi cohort observational study to investigate the biology and the prognostic role of interferon alpha inducible protein 27 (IFI27) in COVID19 patients. Findings. We show that IFI27 is expressed in the respiratory tract of COVID19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 swine influenza virus infection, IFI27 like genes were highly upregulated in the blood samples of severely infected patients. Interpretation. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet to be discovered respiratory virus.