SARS-CoV-2 delta and omicron variants alter trophoblast cell fusion and syncytiotrophoblast dynamics: new insights into placental vulnerability
Bibliographic record
Abstract
Pregnancy is associated with an increased risk of severe COVID-19. In addition, SARS-CoV-2 infection during gestation has been linked to adverse obstetrical outcomes and placental abnormalities. Nevertheless, the susceptibility of early trophoblast cells to SARS-CoV-2 and the potential consequences of infection on trophoblast function remain unclear. In this study, we assessed the permissiveness of first trimester trophoblast cells to SARS-CoV-2 infection and its impact on trophoblast cells fusion. To address this, we isolated primary cytotrophoblast (CTB) cells from first trimester human placentas and allow their differentiation into STB in vitro. These cells were infected with SARS-CoV-2 variants of concern, including Delta and Omicron (BA.1, BA.2, BA.5). Viral replication was assessed by RT-qPCR and immunofluorescence, while host cell responses, including expression of viral entry receptors and innate immunity genes, were measured by RT-qPCR. Trophoblast fusion was evaluated by staining and calculating the fusion index. In parallel, placental tissues from SARS-CoV-2-infected pregnancies were analyzed by immunohistochemistry to quantify syncytial knots (SK) formation in vivo. Our results demonstrate that both first trimester CTB and STB are permissive to SARS-CoV-2 infection in a variant- and donor-dependent manners, with Delta exhibiting higher replication efficiency compared to Omicron variants. In STB, viral replication did not correlate with the induction of entry receptors or type III interferon responses. However, in CTB, viral replication was significantly associated with enhanced cell fusion. In parallel, an increased number of SK was observed in infected placental areas in vivo compared to non-infected regions from the same placenta and to gestational age-matched controls. Altogether, these in vitro and in vivo results suggest that SARS-CoV-2 infection in early pregnancy may alter STB turnover, potentially contributing to placental dysfunction and adverse pregnancy outcomes.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".