Covid–19 in pregnancy was not rare in our area during this first outbreak of Sars-Cov–2. One in 11 women (8.9%) actually entered in contact with the virus. To note, being the pandemic still ongoing, this proportion is expected to rise in the next future, i.e. when the duration of exposure to the outbreak will be longer (we exclusively recruited women who delivered, thus those who were exposed only in the last three months of pregnancy). On the other hand, the clinical course of the disease appeared mostly unremarkable. Sixty-one percent did not report any symptom, prompt preterm delivery because of Covid–19 complications was necessary only in one case and pregnancy outcome was not markedly influenced. The robustness of these latter conclusions is however modest because they emerged from secondary and underpowered analyses.
Interestingly, the rate of infected women observed in our study is very similar to the prevalence observed in a concomitant survey performed in our area and focusing on blood donors. Specifically, Valenti et al. evaluated the presence of antibodies against the nucleocapsid protein and reported for April 2020 a prevalence of 7.1% (95%CI: 4.4–10.8%), thus in line with our findings 12. In contrast, our reassuring clinical findings are somehow in disagreement with recent evidence from large case series of affected pregnant women. Savasi et al. reported on an Italian multicenter case series of 77 women hospitalized for Covid–19 and highlighted that one in five delivered urgently for respiratory compromise or were admitted to an intensive care unit 9. Based on a retrospective case series in the USA, 7 out of 46 pregnant women with Covid–19 necessitated hospitalization 7. This rate resulted even higher (69%) in a Spanish cases series of 60 pregnant infected subjects 8. In a large case series from China, only 6 out of 119 pregnant women (5%) were asymptomatic and in 9 cases (8%) the course of the disease was severe 5. Last but not least, Hantoushzadeh et al. described 9 cases of maternal death due to Covid–19 in Iran 6. As already pointed out in the introduction, the most plausible explanation for the discrepancy with our findings is a selection bias. The denominator is radically different. By mainly focusing on the presence of antibodies, we were able to study an unselected population. In contrast, published case series reported on women who were mainly identified because of Covid–19 related symptoms. Our data could better reflect the real impact of Covid–19 in pregnancy. Nonetheless, we cannot definitely rule out that differences in the characteristics of the population, local environmental conditions and genetic variants of the virus may have also impacted on clinical relevance and could play a role in explaining these inconsistencies.
Some limitations of our study should be acknowledged. Firstly, the reliability of the diagnostic tests is still a source of debate. Even if Covid–19 was investigated using three different modalities, the accuracy of all the tests used is yet uncertain. The nasopharyngeal swab could detect only ongoing infections and the sensitivity in affected cases was reported to be only 63% 13. Preliminary evidence is comforting for the other two tests employed to detect antibodies against Sars-Cov–2 but available studies for validation are not optimal. In particular, no attempts have yet been made to investigate the accuracy of these tests for asymptomatic or poorly symptomatic cases. Inferring results obtained in patients with moderate or severe forms of the disease to the whole population is arguable. More in general, the clinical and biological significance of the different type of antibodies remain to be ascertained 10,14,15. Noteworthy, in our experience, agreement between the two tests was not excellent since only 17 women were found to be positive to both tests while 7 were positive only to one of the two.
Secondly, even if women referred from other hospitals because of Covid–19 were excluded, we cannot rule out some other selection biases. On one hand, some healthy women with unremarkable history may have decided to deliver in other hospitals to avoid an Institution with Covid–19 affected cases while, on the other hand, some women with mild symptoms suggestive for the infection could have been more likely to refer to our hospital. Both biases could lead to overestimate the detected frequency of Covid–19. However, the high proportion of asymptomatic cases tends to rule out a major role of these confounders.
Finally, since Covid–19 related symptoms were retrospectively collected, one cannot exclude a recall bias. In this regard, it has however to be underlined that women were blinded to the results of the antibodies tests when interviewed and that the investigated period of time was limited to only three months. Even if episodes of mild symptoms could be overlooked, it is unlikely that more significant health troubles could be omitted.
In conclusion, women in the second half of pregnancy do not appear to be more susceptible to Covid–19; the observed prevalence overlaps with the non-pregnant population of the same area. In addition, the study suggests that the course of the disease is mostly unremarkable. However, this latter observation warrants confirmation in larger studies.