The effect of COVID-19 on the cytokine profile, placental function and morphology during pregnancy.

Abstract

The outbreak of COVID-19 in 2019 affected the world globally with a particularly detrimental impact on the healthcare sector. It has now passed; however, the long-term consequences of the infection are yet to be fully elucidated. Inflammation, which is of great concern, has been linked to COVID-19 infections, commonly referred to as the ‘cytokine storm.’ This storm poses a significant risk to mothers and neonates due to its association with gestational complications, along with its role in predisposing infants to disorders. These alterations due to COVID-19, together with its hypoxic nature, have further resulted in concerns for proper placental functioning in these pregnancies, which are yet to be investigated in the Black South African cohort. Thus, for the first time, the present study focuses on the cytokine profile, placental function and morphology in South African pregnancies. These concerns prompted the evaluation of the cytokine profile in the plasma and extracellular vesicles (EVs) of women with these pregnancies, along with assessing the kisspeptin expression and morphology in the placentae from these pregnancies. An altered cytokine profile was identified, suggestive of hyperinflammation in the plasma and EVs from COVID- 19 pregnancies in the South African cohort. Further histopathological analysis revealed that the placentae from these pregnancies presented with severe signs of inflammation and malperfusion, which were considered to be linked to the altered kisspeptin expression we observed in these placentae, thereby suggesting altered placental functioning in COVID-19 pregnancies from the South African cohort. It is clinically evident that pregnant women of South Africa, who already face challenges due to an increased risk of HIV and other gestational complications, were severely negatively impacted during this pandemic. These findings reveal an increased prevalence of complications like preeclampsia, preterm birth, intrauterine growth restriction (IUGR), and stillbirth during pregnancy. In addition to a host of complications in foetal development, these alterations could predispose these neonates to anomalies. Importantly, this study has identified that the cytokine profile was altered in COVID-19 pregnancies. This alteration could possibly have had an impact on the kisspeptin signalling, which would then affect optimal placental functioning, thus suggesting a probable cause for the severe dysfunction observed in the placentae. In addition, this environment did not support ideal foetal development and growth. Therefore, it is believed that the findings from this study warrant monitoring and evaluation of neonates from COVID-19 pregnancies, especially from mothers in the South African cohort, as anomalies or neurodevelopmental disorders can arise due to these alterations observed.