The first notable finding of this study is the difference in common COVID-19 symptoms between pregnant patients and non-pregnant patients. Well-known symptoms of COVID-19 include fever, cough, and dyspnea; in a previous study on non-pregnant COVID-19 patients, the proportion of those who show each symptom was shown to be 83%, 82%, and 31%, respectively [28]. In our study of pregnant women, the proportions decreased to 57%, 31%, and 11%, indicating relatively mild symptoms. This result was in line with another previous study by Liu et al. that compared pregnant and non-pregnant COVID-19 patients, where more pregnant patients were classified as mild or common [20]. Milder symptoms in pregnant COVID-19 patients may be explained by the younger average age compared to the general COVID-19 patient population; additionally, as there was much fewer comorbidities, symptoms might have appeared to be less profound in the pregnant population.
Unlike common symptoms, various abnormalities of laboratory parameters showed a similar or even increased trend in pregnant women with COVID-19 compared to general patients. A previous meta- analysis using patients with COVID-19 reported that proportions of leukocytosis, lymphopenia, and elevated CRP levels were 17%, 43%, and 58%, respectively [29], while those in our study were 26%, 53%, and 72%. This gap between the pregnant and general patient population was probably attributable to changes in the immune response in pregnancy [11].
Of utmost importance is the effect of COVID-19 infection in pregnant women; in this regard, pregnancy outcomes were observed in the current study. In total, 29% of the study sample exhibited preterm delivery, a strikingly high number compared to the norm, which was reported to be between 5-18% [30]. In previous research on pregnant patients in past coronaviridae outbreaks, namely severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the proportions of pregnant patients that experienced preterm delivery were 29% and 32%, respectively, which were approximately similar to the ratio in pregnant COVID-19 patients [31].
In addition, data on neonates born from COVID-19 patients showed varying tendencies compared to the non-infected. Average Apgar scores at 1 minute and 5 minutes were recorded to be an adequate 8.7 and 9.7, respectively, while average body weight was 3214.7g, which is considered normal. On the other hand, proportions of fetal distress and severe neonatal asphyxia were 11.2% and 2.1%, displaying dissimilarity to those of non-inflicted cases, which were 6.8% and 0.2~2% [32, 33]. While the rate of fetal death in China has been reported to be 0.43%, the present study population exhibited a rate of 1.7%, showing a significant gap as well [34]. Finally, there was no case of neonatal death in our study, which indicated that the presence of COVID-19 in the mother did not seem to result in a higher probability of neonatal death.
Vertical transmission is another crucial issue, primarily as newborns possess an underdeveloped protective system against external sources of potential harm. Yet controversy had existed regarding whether SARS-CoV-2 can be transmitted from the mother to the fetus within the uterus. Research on previous coronavirus outbreaks fail to provide definite evidence for or against vertical transmission in pregnant patients; on the other hand, in other respiratory viruses such as influenza or respiratory syncytial virus (RSV), cases of vertical transmission have been reported [35, 36]. In the present study, a total of four newborns were reported as SARS-CoV-2 positive, suggesting that vertical transmission of COVID-19 may not be negligible. In addition, several case reports have further strengthened this notion; according to Zeng et al [24], among 6 neonates born to the pregnant COVID-19 patients, virus- specific antibodies were detected in neonatal serum samples, although SARS-CoV-2 itself was undetected in the serum or throat swab via reverse transcriptase-polymerase chain reaction (RT-PCR) in the newborns. Among such antibodies, IgM was of particular interest, as it is not usually transferred to the fetus via the placenta due to its large macromolecular structure; interestingly enough, a newborn with elevated IgM numbers was discovered [37]. Combining the data on six neonates covered in the present meta-analysis [24] and that of one neonate in the case report above [37], it was postulated that high levels of IgM in the mother was correlated with high IgM levels in the newborn. Specifically, three neonates exhibited abnormally high IgM levels (33.9 ± 15.6 AU/mL) and so did their mothers (200.1± 102.9 AU/mL). On the other hand, the other four neonates and their mothers showed low average (SD) IgM levels (AU/mL) of 1.7 (1.6) and 14.0 (14.2), respectively. Such data indicates that there might exist a relationship between neonatal and maternal IgM levels.
The present meta-analysis bears a few limitations that should be considered in the interpretation of results. To begin with, the limited number of studies and uniform geographical profile (Chinese) of the selected studies may hinder possibilities of generalization. In addition, in the selected studies, research was conducted on only late term pregnancy cases. As data on COVID-19 infection in different regions and patients accumulate, the results of the present study will be refined and polished to yield more general conclusions. Nevertheless, as a systematic review and meta-analysis on pregnant COVID-19 patients, the current review will serve as an ideal basis for future considerations in the treatment and management of COVID-19 in pregnant women.