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| Situs Inversus and Early Gestation SARS-CoV-2 Infection: A Link? |
Inversion of position, whether total or partial, is an uncommon congenital condition characterized by the reversal of visceral organization compared to typical organ development. Interestingly, our research has unveiled a significant rise in fetal inversion cases diagnosed via ultrasound shortly after the "zero COVID" policies were eased in China.
We decided to investigate the incidence of fetal reversal from January 2014 to July 2023, drawing from clinical data from two distinct obstetric centers in China. During the initial seven months of 2023, the number of inversion cases at these centers was four times higher than the average annual incidence rate observed between 2014 and 2022 (refer to Figure 1, Figure S1, and Table S1 in the Supplementary Appendix on NEJM.org). The peak incidence was noted in April 2023 and sustained until June 2023. In total, we identified 56 cases of positional inversion from January 2023 to July 2023, encompassing 52 cases of total positional inversion and 4 cases of partial positional inversion.
This surge coincided with an increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases following the suspension of anti-COVID-19 policies. This upswing, affecting approximately 82% of the Chinese population, initiated in December 2022, peaked around December 20, 2022, and subsided in early February 2023. While we cannot definitively establish causality, our observations indicate a potential association between SARS-CoV-2 infection and fetal inversion, warranting further investigation.
Congenital positional inversion has previously been associated with abnormal morphogen distribution and cilia dysfunction during the early stages of pregnancy. Although the vertical transmission of SARS-CoV-2 remains a subject of debate, the possibility of fetal infection in the early stages of pregnancy impacting the visceral aspect cannot be ruled out. Alternatively, maternal inflammatory responses mediated by SARS-CoV-2 may indirectly affect the functioning of the left-right organizer and hinder visceral lateralization. Further research is required to rule out the contribution of genetic abnormalities in genes linked to primary ciliary dyskinesia that might not have been detected during prenatal genetic screening and to assess potential environmental factors. Remarkably, despite the spike in infection cases in our centers amid the spread of SARS-CoV-2, site-reversed diagnoses have remained exceedingly rare.
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