Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.

COVID-19 Pandemic Clinical Trial

Official title:

Macrophage Migration Inhibiting Factor, Enolase and Caspase-3 as Indicators of Neuronal Insult in Newborns of COVID-19 Positive Mothers.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05175638
• Other study ID #: NER
• Status: Not yet recruiting
• Start date: February 2022
• Est. completion date: October 2022

Study information

• Verified date: January 2022
• Source: Assiut University
• Contact: Rasha Mohammed, MD.
• Phone: 01010024021
• Email: rasha.mohamed94[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The coronavirus disease (COVID- 19) is now a global pandemic that was first reported in China (Wuhan) in December of 2019. Multiple placental abnormalities including fetal and maternal vascular malperfusion have been described in pregnant women infected with (COVID- 19). To date, there are far fewer reports about the specific effects of (COVID- 19) in the newborns delivered for (COVID- 19) positive mothers.

Description:

COVID-19 in pregnant women has important impacts on perinatal and neonatal outcomes. Authors reported positive COVID infection in neonates born to COVID-19 positive mother.

The finding of a recent study suggested that intrauterine or intrapartum transmission is possible and recommended for further investigation. Furthermore, reports showed newborns of COVID-19 positive mother that suffered from catastrophic sequelae of hypoxic ischemic encephalopathy (HIE). These events could be attributed to COVID-19 positive status of the mother.

Neuron specific enolase is a biomarker for neuronal injury and synaptic dysfunction and have been correlated with tissue damage in different experimental models. The increased serum levels of neuron specific enolase are associated with the clinical outcome in patients with anoxic encephalopathy. Neuron specific enolase can be a candidate for a diagnostic/prognostic biomarker for neuroinflammation in COVID-19.

Additionally, the cytokines are candidate biomarkers after hypoxic-ischemic injury. Macrophage migration inhibitory factor (MIF) is a multifunctional protein that has been identified as proinflammatory cytokine and activates the production of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon.

Macrophage migration inhibitory factor plays a central role in controlling the inflammatory and immune response, which may be of particular importance during the development of organ dysfunction in COVID-19 patients. Furthermore, it carries out the apoptosis of the cells. Significant increase of neuronal apoptosis and caspase-3 expression was demonstrated in the brain of neonatal mice exposed to hypoxic injury.

There are a limited number of studies investigating the effect of the pandemic period on the brain of the newborns. With this study, we aim to determine the impact of the COVID-19 outbreak on the neuronal functions in the neonates. The current study searches for a diagnostic/prognostic biomarker for neuroinflammation in neonate born to COVID-19 positive mothers.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: October 2022
• Est. primary completion date: June 2022
• Gender: All
• Age group: N/A to 2 Days

Eligibility

Inclusion Criteria:

• The following inclusion criteria will be used (all necessary): Covid-19 positive mothers, term newborn (>37 completed gestational weeks), free from severe malformations. All infants will be examined generally, systemically and neurologically at birth for clinical assessment of HIE if present and for detection of outcome of these neonates.

Exclusion Criteria:

• free from severe malformations

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pandemic

Intervention

Genetic:
• Gene Expression
the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (15)

Aksakal A, Kerget B, Kerget F, Askin S. Evaluation of the relationship between macrophage migration inhibitory factor level and clinical course in patients with COVID-19 pneumonia. J Med Virol. 2021 Dec;93(12):6519-6524. doi: 10.1002/jmv.27189. Epub 2021 Jul 22. — View Citation

Bleilevens C, Soppert J, Hoffmann A, Breuer T, Bernhagen J, Martin L, Stiehler L, Marx G, Dreher M, Stoppe C, Simon TP. Macrophage Migration Inhibitory Factor (MIF) Plasma Concentration in Critically Ill COVID-19 Patients: A Prospective Observational Study. Diagnostics (Basel). 2021 Feb 17;11(2). pii: 332. doi: 10.3390/diagnostics11020332. — View Citation

Chaparro-Huerta V, Flores-Soto ME, Merin Sigala ME, Barrera de León JC, Lemus-Varela ML, Torres-Mendoza BM, Beas-Zárate C. Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns. Pediatr Neonatol. 2017 Feb;58(1):70-76. doi: 10.1016/j.pedneo.2016.05.001. Epub 2016 May 31. — View Citation

Deng C, Li J, Li L, Sun F, Xie J. Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice. Exp Ther Med. 2019 Jun;17(6):4517-4521. doi: 10.3892/etm.2019.7487. Epub 2019 Apr 15. — View Citation

Florez-Sampedro L, Brandsma CA, de Vries M, Timens W, Bults R, Vermeulen CJ, van den Berge M, Obeidat M, Joubert P, Nickle DC, Poelarends GJ, Faiz A, Melgert BN. Genetic regulation of gene expression of MIF family members in lung tissue. Sci Rep. 2020 Oct 12;10(1):16980. doi: 10.1038/s41598-020-74121-w. — View Citation

Ganti L, Serrano E, Toklu HZ. Can Neuron Specific Enolase Be a Diagnostic Biomarker for Neuronal Injury in COVID-19? Cureus. 2020 Oct 19;12(10):e11033. doi: 10.7759/cureus.11033. — View Citation

Gladkevich A, Kauffman HF, Korf J. Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004 May;28(3):559-76. Review. — View Citation

Golden TN, Simmons RA. Maternal and neonatal response to COVID-19. Am J Physiol Endocrinol Metab. 2020 Aug 1;319(2):E315-E319. doi: 10.1152/ajpendo.00287.2020. Epub 2020 Jun 23. Review. — View Citation

Haque A, Polcyn R, Matzelle D, Banik NL. New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection. Brain Sci. 2018 Feb 18;8(2). pii: E33. doi: 10.3390/brainsci8020033. Review. — View Citation

Hekimoglu B, Aktürk Acar F. Effects of COVID-19 pandemic period on neonatal mortality and morbidity. Pediatr Neonatol. 2021 Oct 27. pii: S1875-9572(21)00219-9. doi: 10.1016/j.pedneo.2021.08.019. [Epub ahead of print] — View Citation

Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125-43. doi: 10.1007/978-94-017-7215-0_9. Review. — View Citation

Jain P, Thakur A, Kler N, Garg P. Manifestations in Neonates Born to COVID-19 Positive Mothers. Indian J Pediatr. 2020 Aug;87(8):644. doi: 10.1007/s12098-020-03369-x. Epub 2020 Jun 5. — View Citation

Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, Feng L. A Case Report of Neonatal 2019 Coronavirus Disease in China. Clin Infect Dis. 2020 Jul 28;71(15):853-857. doi: 10.1093/cid/ciaa225. — View Citation

Wu YT, Liu J, Xu JJ, Chen YF, Yang W, Chen Y, Li C, Wang Y, Liu H, Zhang C, Jiang L, Qian ZX, Kawai A, Mol BW, Dennis CL, Xiong GP, Cheng BH, Yang J, Huang HF. Neonatal outcome in 29 pregnant women with COVID-19: A retrospective study in Wuhan, China. PLoS Med. 2020 Jul 28;17(7):e1003195. doi: 10.1371/journal.pmed.1003195. eCollection 2020 Jul. — View Citation

Zeng L, Xia S, Yuan W, Yan K, Xiao F, Shao J, Zhou W. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr. 2020 Jul 1;174(7):722-725. doi: 10.1001/jamapediatrics.2020.0878. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers.	RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis:	one month