ORIGINAL RESEARCH
Changes in amino acid profile of cord blood plasma and amniotic fluid of mothers with COVID-19
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
Correspondence should be addressed: Natalia A. Lomova
Oparina, 4, Moscow, 117997; ur.xednay@avomol-ahsatan
Funding: the study was supported by RFBR grant №. 20-04-60093.
Author contribution: Lomova NA — analysis of clinical data, systematic analysis, manuscript writing; Chagovets VV — mass spectrometry-based metabolome analysis, statistical analysis of the results, manuscript editing; Dolgopolova EL — collection and preparation of biological matrix samples in the red zone, statistical analysis of the results; Novoselova AV — mass spectrometry-based metabolome analysis, mass spectrometry data processing; Petrova UL — collection and preparation of biological matrix samples in the red zone; Shmakov RG — analysis of clinical data in the red zone, systematic analysis, manuscript editing; Frankevich VE — preparation of the study, systematic analysis, manuscript writing and editing.
Compliance with ethical standards: the study was approved by the Ethics Committee of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. I. Kulakov (protocol № 13 dated December 10, 2020); the study met the requirements of the Declaration of Helsinki, International Conference on Harmonization (ICF), Good Clinical Practice (GCP), and Federal Law № 323-FZ “On the Basics of Protecting Citizens' Health in the Russian Federation” of November 21, 2011; the informed consent was submitted by all patients.
Neonates born to mothers with COVID-19 are at risk for infection, they may have high risk of complications during the neonatal period, and long-term health consequences. The study was aimed to define the amino acid profile of blood plasma and amniotic fluid in patients with COVID-19 in order to assess the relationship between the COVID-19 infection during the antenatal period, and metabolomic alterations in the “intrauterine” patient. The levels of 31 amino acids in the samples of amniotic fluid and cord blood plasma of pregnant women with COVID-19, obtained during delivery, were assessed by high-performance liquid chromatography-mass spectrometry. The index group included 29 patients with confirmed diagnosis of COVID-19, and the control group included 17 healthy women with uncomplicated pregnancies. There were significant (p < 0.05) differences in the concentrations of eight amino acids between the studied groups. Logistic regression models were developed (sensitivity 0.84; specificity 1) making it possible to define, whether the assessed amniotic fluid was obtained from COVID-19 patients. Significant differences in the concentrations of four amino acids were observed in the umbilical cord blood. The models developed made it possible to define whether the studied cord blood plasma belonged to controls or to COVID-19 patients (sensitivity and specificity 1). Three amino acids were detected, and their levels were significantly different in COVID-19 patients simultaneously in two points (amniotic fluid and cord blood plasma), depicting the fetal metabolome in a holistic manner. The impact of the virus on those infected results in pronounced metabolomic alterations in the amniotic fluid and the fetal cord blood plasma, which may lead to impaired programming of protein production, but never show up at birth.
Keywords: COVID-19, amino acid analysis, cord blood plasma, amniotic fluid, markers of neonatal condition