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Despite intensive characterization of immune responses after COVID-19 infection and vaccination, research examining protective correlates of vertical transmission in pregnancy are limited. Herein, we profiled humoral and cellular characteristics in pregnant women infected or vaccinated at different trimesters and in their corresponding newborns. We noted a significant correlation between spike S1–specific IgG antibody and its RBD-ACE2 blocking activity (receptor-binding domain–human angiotensin-converting enzyme 2) in maternal and cord plasma (P <.001, R > 0.90). Blocking activity of spike S1–specific IgG was significantly higher in pregnant women infected during the third trimester than the first and second trimesters. Elevated levels of 28 cytokines/chemokines, mainly proinflammatory, were noted in maternal plasma with infection at delivery, while cord plasma with maternal infection 2 weeks before delivery exhibited the emergence of anti-inflammatory cytokines. Our data support vertical transmission of protective SARS-CoV-2–specific antibodies. This vertical antibody transmission and the presence of anti-inflammatory cytokines in cord blood may offset adverse outcomes of inflammation in exposed newborns. [ABSTRACT FROM AUTHOR]

Background: Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these cells that are not directly infected has not been extensively studied. Herein, we profiled gene expression in HBCs and CTBs isolated from placentae of recovered pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy, placentae from subjects with active infection, SARS-CoV-2 vaccinated subjects, and those who were unexposed to the virus. Methods: Placentae were collected within 4 h post-delivery and membrane-free tissues were enzymatically digested for the isolation of HBCs and CTBs. RNA extracted from HBCs and CTBs were sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) were identified by DESeq2 package in R and enriched in GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Gene Sets, and Canonical Pathways. Protein-protein interactions among the DEGs were modelled using STRING and BioGrid. Results: Pregnant subjects (n = 30) were recruited and categorized into six groups: infected with SARS-CoV-2 in i) the first (1T, n = 4), ii) second (2T, n = 5), iii) third (3T, n = 5) trimester, iv) tested positive at delivery (Delivery, n = 5), v) never infected (Control, n = 6), and vi) fully mRNA-vaccinated by delivery (Vaccinated, n = 5). Compared to the Control group, gene expression analysis showed that HBCs from infected subjects had significantly altered gene expression profiles, with the 2T group having the highest number of DEGs (1,696), followed by 3T and 1T groups (1,656 and 958 DEGs, respectively). These DEGs were enriched for pathways involved in immune regulation for host defense, including production of cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, and cell migration/adhesion. Protein-protein interaction analysis mapped these DEGs with oxidative phosphorylation, translation, extracellular matrix organization, and type I interferon signaling. Only 95, 23, and 8 DEGs were identified in CTBs of 1T, 2T, and 3T groups, respectively. Similarly, 11 and 3 DEGs were identified in CTBs and HBCs of vaccinated subjects, respectively. Reassuringly, mRNA vaccination did not induce an inflammatory response in placental cells. Conclusions: Our studies demonstrate a significant impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal HBCs, with limited effect on lining CTB cells isolated from pregnant subjects infected and recovered from SARS-CoV-2. The pathways associated with these DEGs identify potential targets for therapeutic intervention. Author summary: During the coronavirus disease 2019 (COVID-19) pandemic, our understanding of human immunity to SARS-CoV-2 infection and vaccination has increased markedly, but little is known about immunity against SARS-CoV-2 in pregnant subjects. In this study, we isolated Hofbauer cells and cytotrophoblasts from placentae of pregnant subjects infected with SARS-CoV-2 during all trimesters of pregnancy and profiled gene expression in these cells. Our gene expression analysis showed a significant and surprising impact of indirect SARS-CoV-2 infection on gene expression of inner mesenchymal Hofbauer cells, with limited effect on lining cytotrophoblasts isolated from pregnant subjects infected and recovered from SARS-CoV-2. Our data also support immunizing pregnant subjects with mRNA vaccination. [ABSTRACT FROM AUTHOR]

Aim: This study is a comprehensive review with the purpose of collecting the most relevant data in several sections including current treatment guidelines in the paediatric population. Methods: Literature was systematically searched in different databases. Results were limited to 2019+ and English, French and Spanish language. Results: Children can exhibit mild and less severe COVID‐19 disease than adults and also have asymptomatic carriage of SARS‐CoV‐2, while severe disease is more frequently noted during infancy (<1 year). SARS‐CoV‐2 binds the angiotensin‐converting enzyme 2 (ACE‐2) receptor; age‐, racial‐, and gender‐specific differences in ACE‐2 expression need to be elucidated in order to explain the differential clinical profiles between children and adults. Multisystem inflammatory syndrome in children (MIS‐C) is an important condition to recognise in children. The decision to use antiviral or immunomodulatory therapy in a child or adolescent should be individualised based on the clinical scenario. Remdesivir is the only FDA‐approved therapy available for children older than 12 years old who require hospitalisation for COVID‐19. Conclusion: Further studies are urgently required to address prevention and treatment in at‐risk and infected children, especially with underlying comorbidities. The chapter on the overall impact of COVID‐19 in children has not yet been written. Nevertheless, SARS‐CoV‐2 has now joined a long list of human pandemics, which may forever change the world's history. [ABSTRACT FROM AUTHOR]

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection. [ABSTRACT FROM AUTHOR]