COVID-19

Active research and clinical experience have shown that the uncontrolled immune response to Sars-Cov-2 is characterized in many cases by a devastating cytokine storm (Chaolin Huang 2020). Morbidity and mortality are in part a consequence of this inflammatory response in the body (Ye Q 2020). The course of the disease is known to be more severe in pregnant women (Kathryn M Moore 2021), however, the effect of SARS-CoV-2 on the developing fetus is currently unclear. Case studies show that vertical transmission is rare, however, several studies support that placental and fetal infections may occur (Chen H 2020), (Dong L 2020), (Patanè L 2020). Several clinical manifestations of Covid-19 infection in the nervous system have also been reported recently (Desforges M. 2020), (Bohmwald K. 2018). 

The purinergic P2X7 receptor plays a key role in the inflammatory response of innate immunity to various exogenous and endogenous effects (DAMP and PAMPs) and pro-inflammatory cytokine production (Solle M 2001), (Horváth G 2019), which are capable of affect fetal brain development, thus affecting neuro- and gliogenesis, neuronal migration, synaptogenesis, and elimination of synapses during development, thereby leading to the formation of abnormal cortical and cerebellar neural networks (Benjamin E Deverman 2009). In a recent study, P2X7 receptor concentration has been shown to be elevated in the plasma of COVID-19 patients (Julio García-Villalba 2022). All of this may lead to the conclusion that COVID-19 infection during pregnancy and the associated inflammatory conditions during fetal development can potentially result in long-term abnormalities in the offspring. Increased maternal immune activation in both humans (Ousseny Zerbo 2016), and rodents (Myka L Estes 2016), (Irene Knuesel 2014) induced by viral infection at a specific time during central nervous system development has been shown to increase the prevalence of several neurodevelopmental disorders, such as autism spectrum disorder or schizophrenia. We investigate the effect of SARS-CoV-2 infection during pregnancy on the developing fetal central nervous system, especially how phenotypes and brain morphological abnormalities in mice change upon mouse-adapted SARS-CoV-2 maternal infections compared with the clinical symptoms, cytokine changes, and lung pathology observed in the mother animals.

 

 

References:

 

Benjamin E Deverman, Paul H Patterson. „Cytokines and CNS development.” Neuron. 64, 1. szám (2009): 61-78.

 

Bohmwald K., Galvez N., Ríos M., Kalergis A.M. „Neurologic alterations due to respiratory virus infections.” Front. Cell. Neurosci. 386 (2018): 12.

 

Chen H, Guo J, Wang C, et al. „Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records.” Lancet. 395, 10226. szám (2020): 809-815.

 

Desforges M., Le Coupanec A., Dubeau P. „Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?” Viruses. 14 (2020): 12.

 

Dong L, Tian J, He S, et al. „Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn.” JAMA. 323, 18. szám (2020): 1846-1848.

 

Horváth G, O.L., Beko K, Baranyi M, Kittel Á, Fritz-Ruenes PA, Sperlágh B. „P2X7 Receptors Drive Poly(I:C) Induced Autism-like Behavior in Mice.” J Neurosci. 39, 13. szám (2019): 2542-2561.

 

Irene Knuesel, Laurie Chicha, Markus Britschgi, Scott A Schobel, Michael Bodmer, Jessica A Hellings, Stephen Toovey, Eric P Prinssen. „Maternal immune activation and abnormal brain development across CNS disorders.” Nat Rev Neurol. 10, 11. szám (2014): 643-60.

 

Julio García-Villalba, Laura Hurtado-Navarro, Alejandro Peñín-Franch, Cristina Molina-López, Laura Martínez-Alarcón, Diego Angosto-Bazarra, Alberto Baroja-Mazo, Pablo Pelegrin. „Soluble P2X7 Receptor Is Elevated in the Plasma of COVID-19 Patients and Correlates With Disease Severity.” Front Immunol., 2022.

 

Kathryn M Moore, Mehul S Suthar. „Comprehensive analysis of COVID-19 during pregnancy.” Biochem Biophys Res Commun. 538 (2021): 180-186.

 

Myka L Estes, A Kimberley McAllister. „Maternal immune activation: Implications for neuropsychiatric disorders.” Science. 353, (6301). szám (2016): 772-7.

 

Ousseny Zerbo, Yinge Qian, Cathleen Yoshida, Judith K. Grether, Judy Van de Water, Lisa A. Croen. „Maternal Infection during Pregnancy and Autism Spectrum Disorders.” J Autism Dev Disord. 45, 12. szám (2016): 4015–4025.

 

Patanè L, Morotti D, Giunta MR, et al. „Vertical transmission of COVID-19: SARS-CoV-2 RNA on the fetal side of the placenta in pregnancies with COVID-19 positive mothers and neonates at birth.” American Journal of Obstetrics & Gynecology MFM., 2020: 100145.

 

Solle M, Labasi J, Perregaux DG, Stam E, Petrushova N, Koller BH, Griffiths RJ, Gabel CA. „Altered cytokine production in mice lacking P2X(7) receptors.” J Biol Chem., 2001: 125-32.

 

Ye Q, Wang B, Mao J. „The pathogenesis and treatment of the `Cytokine storm' in COVID-19.” J. Infect. 80, 6. szám (2020): 607-613

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