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Proteomics Confirms Vertical Transmission of SARS-CoV-2 From Mother to Fetus

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A study published in Viruses documents a case of vertical SARS-CoV-2 transmission from a mother to a fetus in the second trimester of pregnancy.1

The diagnosis was confirmed using a mass spectrometry-based method developed by researchers at the Skoltech Institute of Science and Technology. It marks the first published research of its kind in which a proteomics method – high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) – has been used to confirm SARS-CoV-2 proteins in an infected placenta.  

What is vertical transmission?

Our current knowledge of how SARS-CoV-2 infection can impact pregnancy outcomes is limited, largely due to the fact the outbreak of the virus is still recent. Individual case studies from across the globe are contributing to our understanding of SARS-CoV-2 vertical transmission.

"Vertical transmission is when the mother's infection overcomes the barrier that the placenta must create, and the fetus becomes infected. In this case, it is the SARS-CoV-2 virus," says Evgeny Nikolaev, professor at the Center for Computational and Data-Intensive Science and Engineering at Skoltech and one of the authors of the study.

Whether or not vertical transmission of SARS-CoV-2 can occur has been debated since the start of the COVID-19 global pandemic. "Most studies have found no evidence of vertical transmission of SARS-CoV-2 from an infected mother to the fetus or newborn, " the authors write in the paper. "However, mostly the infection in the third trimester has been studied until now. Data on the possibility of vertical transmission and the effects of SARS-CoV-2 on the fetus in the 1st and 2nd trimesters remain very limited."

SARS-CoV-2 and pregnancy outcomes: A case study

The new study explores the case of a healthy 27-year-old woman that became "moderately sick" with COVID-19 in the 21st week of her pregnancy – the second trimester.

Prior to a diagnosis of COVID-19, the pregnancy had developed normally. Two weeks after illness, an ultrasound scan detected abnormalities in the fetus, as described in the paper: "Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation." The authors note that, apart from the SARS-CoV-2 infection, there were no other possible reasons as to why such severe placental insufficiency had developed.

The child was delivered prematurely at the 26th week of gestation and passed away after one day and 18 hours. “The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS-CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case,” the paper states.

Why was a proteomics-based method a suitable approach for making the diagnosis? Nikolaev explains, "The proteomics-based method is not only suitable but also the most reliable one since it allows you to identify virus proteins with 100% confidence, which is not given by the PCR method. Proteins are detected by identifying the unique peptides they contain (and we know for sure that the rest of the proteins in the entire biological world do not have these unique peptides)."

The key findings of the study are two-fold: It demonstrates that transplacental transmission of SARS-CoV-2 is possible in earlier stages of pregnancy and highlights the potential utility of mass spectrometry in this type of research.

The proteomics method, which is available in The Journal of Proteome Research, can be adopted by any team that has an appropriate mass spectrometer, Nikolaev says.2 "We cut the N and S proteins isolated from the virus using a particular enzyme (trypsin) and detect them on a mass spectrometer. We use a standard ionization method -- electrospray. Then, we search for the specific sequence of amino acids in mass-spectrometry data, using standard proteomic techniques," he describes.

How can the information from one case study can be used to further understand SARS-CoV-2 transmission and outcomes? "We plan to analyze all the future cases that may occur, but, of course, it would've been so much better if we didn't have to," Nikolaev says.

The researchers' efforts will now be focused on speeding up the analysis method.

Evgeny Nikolaev was speaking to Molly Campbell, Science Writer for Technology Networks.


1.       Sukhikh G, Petrova U, Prikhodko A, et al. Vertical transmission of SARS-CoV-2 in second trimester associated with severe neonatal pathology. Viruses. 2021;13(3). doi:10.3390/v13030447.

2.       Nikolaev EN, Indeykina MI, Brzhozovskiy AG, et al. Mass-spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via nucleocapsid n protein. J Proteome Res. 2020;19(11):4393-4397. doi:10.1021/acs.jproteome.0c00412.