SARS-CoV-2 infection and immunity during pregnancy and fetal development

The current pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in approximately 5.42 million deaths and over 286 million confirmed cases. The first cases of COVID-19 were reported in Wuhan, Hubei Province, China, in December 2019, where the majority of those affected had worked in a wholesale seafood market. Patients had fever, cough, chest discomfort, and pneumonia, necessitating hospitalization and the use of ventilators for assistance, some of whom died.

Patients’ samples were submitted for isolation in cell culture, followed by RT-qPCR and next-generation sequencing (NGS), indicating coronavirus (CoV) as the causative agent. Immune disorders, gastrointestinal disorders and long-term post-COVID-19 disorders have all become clinical symptoms since then. There is now no cure or preventative treatment to prevent infection, but various vaccines have been developed and distributed worldwide to minimize the number of serious illness and mortality. SARS-CoV-2 variants have recently emerged, raising concerns about vaccine and treatment efficacy.

There has also been great interest in finding out how infection affects pregnancy and fetal development, but there are still many unknowns. As a result, a review conducted by a team of researchers from the Icahn School of Medicine at Mount Sinai, the University of Colorado and Active Motif, Incorporated Information on SARS-CoV-2 virology, collects in utero transmission from infected pregnant mothers to fetuses , new findings on possible methods for SARS-CoV-2 cellular trade through exosomes and the transcriptomic effects of SARS-CoV-2 infection to inform future studies aimed at a better understanding of COVID-19 and the development of therapeutic solutions against SARS -CoV-2.

This review article is published in Journal of Developmental Biology.

The study

SARS-CoV-2 was discovered to be a member of the Coronaviridae family, of the genus Betacoronavirus (which includes MERS-CoV, which was the cause of outbreaks of respiratory diseases in the Middle East in 2012), and the subgenus sarbecovirus, of which SARS-CoV (associated with the 2002-2003 pandemic and first identified in Guangdong Province, China) is also a member. Although SARS-CoV-2 and SARS-CoV are both sarbecoviruses, SARS-CoV-2 was found to be more closely related to other bats SARS-like beta-coronavirus. Bats have been postulated as the reservoir of the virus because of their genetic similarity; other animals, such as pangolins, have been suggested as potential intermediate hosts due to their genomic sequence similarity.

Reported effects of SARS-CoV-2 infection on fetuses through pregnant mothers and on children. Abbreviations: MISC multisystem inflammatory syndrome in children. “?” indicates that the transmission mechanism is not clearly understood.

COVID-19 transmission from infected pregnant mothers to fetuses has been documented, albeit rarely. COVID-19 cases in children have been reported with fatal results. Long COVID, a severe infection outcome in which the symptoms last for five weeks or longer after an acute SARS-CoV-2 infection, has been described in children in the same way as it has been in adults. Children have also been diagnosed with Pediatric Inflammatory Multisystem Syndrome (PIMS-TS), which has been linked to COVID-19. Compared to older children and adults, children under 5 years of age with mild to moderate COVID-19 have more SARS-CoV-2 viral RNA in their nasopharynx, which may affect transmission.

Transmission electron microscopy (TEM) of SARS-CoV-2-infected Vero E6 cells. Exosomes and / or a SARS-CoV-2-like particle can be seen (inserted) inside an MVB. Evs — extracellular vesicles, PM — plasma membrane, MVB — multivesicular bodies.

Infection with SARS-CoV-2 causes fetal discomfort as well as significant morbidity and death in infants. There is insufficient evidence to indicate adverse effects on future generations as a result of individuals who tested positive for COVID-19 during pregnancy. However, the results of multisystem inflammatory syndrome in children (MIS-C) and other complications suggest that more research is needed to fully understand the full range of COVID-19 effects in children, in utero development and on SARS-CoV. 2 cellular trafficking mediated by exosomes during the in utero and perinatal stages of development.

Although it is clear that SARS-CoV-2 infection triggers an immune response in pregnant women, the effects on fetal immune responses are still a hot topic of discussion. A recent study examined 205 babies born to COVID-19-positive mothers. While only 10% of neonates tested positive for COVID-19, the majority of SARS-CoV-2-infected infants produced immunoglobulin G and M (IgG, IgM) antibodies. No placental viral RNA was found in COVID-19 positive pregnant women in another study.

Furthermore, there do not appear to be verified examples of SARS-CoV-2 infection transmitted from mothers to their fetuses during pregnancy. Although serious illness has been documented in infants under one year of age, such cases have shown underlying comorbidity. These data show that vertical infection is unusual and that infants born to COVID-19-positive women have innate passive immunity.

Exosomes are released by each cell type that has been studied so far. Exosomes from the mesenchymal, endothelial and trophoblastic lines have been studied relative to the placental line and have been shown to reduce T cell expression. The role of extermination in utero and its significance in SARS-CoV-2 infections and the subsequent establishment of an immune response in neonates were investigated in this study.

Exosomes are endocytically-derived extracellular nanospheres that pack cellular content. They are thought to help maintain cellular homeostasis, although the mechanism of their formation is unknown. SARS-CoV-2 infections via exosomes or in utero immunity development appear to be two possible ideas for exosomal contribution in utero and fetal development. While viral RNA has been identified in exosomes, there appears to be little or no viral replication during pregnancy. This finding rejects the first notion that exosomes could cause viral infection in the womb.

Implications

The effects of SARS-CoV-2 on the transcriptome provide a wealth of data to be utilized efficiently. The transcriptomic profiles reveal which genes are upregulated or downregulated by the infection, making it possible to target them therapeutically to reverse the effect. These profiles can also be used as biomarkers to determine the severity of infection ranging from mild to severe. Finally, these profiles provide further insight into how SARS-CoV-2 infection affects cellular development and programming.

To fill knowledge gaps in understanding maternal-fetal transmission mechanisms, hereditary patterns of epigenetic imprints can be compared between cells from COVID-19-infected mothers and their offspring. It will be interesting to see if the mother’s epigenetic changes caused by SARS-CoV-2 infection are transmitted to her offspring. Overall, this review aims to broaden the perspective on several elements of COVID-19, which will help in understanding other viral infections and help us better prepare for future outbreaks.

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