The youngest mothers were two 26-years-old women with GA of 9 3/7 and 31 2/7. The former was still pregnant when this case series was being reported. She presented to our center, and her chief complaint was fever accompanied by headache, body pain, and blood work-ups revealed leukocytosis (17.3×10⁶/L) and lymphopenia (4.6%). The nasopharyngeal RT-PCR test confirmed the COVID-19 diagnosis, and we did not perform HRCT to reduce the unnecessary radiation dose exposure. She was admitted to our specialized COVID-19 ward without the development of hypoxia and dyspnea. She was discharged from our hospital and was alive until the present time.

The oldest mother was 43 years-old woman with the GA of 39 5/7, brought to the Hazrat -E- Rasoul  Akram Hospital with the cough. She refused to receive a RT-PCR test, and the typical features of COVID-19 were detected on HRCT images. A day after hospital admission, she developed dyspnea and fetal distress, therefore, normal vaginal delivery was (NVD) done. Both the mother and the baby were alive until three months after the delivery.

Two mothers (14.28%) were admitted to ICU and treated with High-flow oxygen (HF O₂). If symptoms includes non-invasive refractory hypoxia, loss of consciousness, hemodynamic instability, respiratory fatigue and hypercapnia persist, patients were admitted to the ICU according to the Iranian National Guideline to Diagnosis and Treatment of Covid Disease in Pregnancy [12]. The cesarean section (C/S) was done following O₂ saturation reduction and fetal distress. The first mother was a 39 years-old female with the GA of 30 2/7 and had dry coughs at the time of admission. She was intubated in the ICU for seven days after C/S and was treated with Atazanavir, Favipiravir, Chloroquine, and broad-spectrum antibiotic and Steroid, medical treatment was performed based on the Iranian national guideline COVID 19 on pregnant women and discharged after complete recovery. The second mother was in her late 40s with the GA of 33 4/7 and intubated in the ICU. Unfortunately, despite receiving the previously mentioned drugs, she died of pneumomediastinum on the second day after C/S. Both infants were discharged from the NICU in good general condition.

As shown in Table 2, 13 neonates were born, and the 11^th mother was still pregnant. The median of GA at the time of hospital admission was 32 2.5/7 (IQR: 30.75 0.75/7- 36.25 4.25/7). The median Apgar score was nine and ten after one and five minutes, respectively. The former had an IQR of 8-9.5, while the last had an IQR of 9-10. All born neonates had negative RT-PCR tests, and only two out of 13^th born babies (15.38%) were admitted to the NICU. Happily, all neonates (100%) were in proper clinical conditions.

Discussion

In this study, 12 out of 14 pregnant women were in the third trimester, and the two were in the first and second trimester. None of the mothers had high blood pressure, diabetes, or cardiovascular disease (data were not shown). Two out of fourteen women under study were admitted to the intensive care unit, and one of them died. Two out of the 13 newborn babies were born through the NVD, and the rest were by the C/S. In a systematic review study conducted by Zaigham et al., on the pregnancy evaluated of 108 women and showed the superiority of third-trimester involvement as reported in our study [13]. Nakamura et al., believed that the increased mortality rate in pregnant mothers was partly due to the high rate of obesity and pre-eclampsia in the third trimester [14].

During this case series study, we confirmed the COVID-19 diagnosis via HRCT in 11 pregnant women (78.57%), and RT-PCR tests were positive in only 4 cases (27.43%). The 13^th mother had a positive RT-PCR test and typical feature of COVID-19 on HRCT images. Similar studies have emphasized the importance of CT findings compared to RT-PCR [8]. A review article of 7 studies conducted by Kucirka et al., indicated that the false-negative rate of the RT-PCR test varied according to the time trends of the disease; it ranged from 100% to 67% within the four days before the symptoms evolved. During the symptomatic phase, the median false-negative rate of the RT-PCR test showed a biphasic trend; it decreased from 38% (on the first day of being symptomatic) to 20% (during the eighth day) and then increased up to 66% on day 21 [15]. Therefore, we had to evaluate the patients via HRCT to confirm the COVID-19 diagnosis and assess the lung-involvement severity.

Overall, eleven neonates were born via C/S; three mothers gave birth to their babies via C/S due to their concerns after COVID-19, which led them not to cooperate in NVD. One other neonate was in the breech position, and for the other seven mothers, C/Ss were done due to the previous C/S. Studies from China report higher rates of C/S in mothers with Covid-19, while in Spain, in a cohort study, 53% of patients had NVDs, and 47% had a cesarean section [16]. Moreover, Cai et al., designed a systematic review study to determine whether the MOD could affect the COVID-19 vertical transmission between the mothers and their babies. They have concluded that the vertical transmission was not affected by the MOD, and the physicians must choose the proper MOD based on the obstetric indications and the disease severity [17]. Although, some case report studies showed the possibility of vertical transmission [18, 19].

Myalgia and fatigue were the most common symptoms among mothers at the time of hospitalization. However, in most studies, cough and fever were the first common symptoms [6]. In this study, two women had severe disease and resulted in intubation and the subsequent maternal death in one pregnant woman. As shown in the result section, pneumomediastinum was the leading cause of maternal death, and multiple studies have been conducted reporting the possible effect of COVID-19 in pneumomediastinum development [20-22]. Panahi et al., showed no differences in the COVID-19-related signs and symptoms between the pregnant and non-pregnant women which is inconsistent with our case series study [23]. This discrepancy might result from our low sample size and the case series nature of the study.

In contrast to the symptoms frequency’s similarities, the Center for Disease Control and Prevention (CDC) declared that COVID-19 had more severe clinical trends in pregnant women and resulted in higher hospitalization and ICU admission rates and the subsequent more severe adverse outcome [24].

Conclusion

This study shows that most of the maternal involvement occurred during the third trimester of pregnancy, and despite the severe involvement, neonatal COVID-19 involvement or mortality was not reported. Although the pregnant women still need to be closely monitored to prevent and decrease the maternal and neonatal mortality rate and adverse events. Moreover, the COVID-19 diagnosis must have relied on patients’ clinical symptoms and lung CT findings due to the false-negative results of the RT-PCR test.

Ethical Approval: This study was approved by the ethics committee of the Faculty of Medicine, Hazrat -E- Rasoul  Akram Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran from March 8, 2020 to December 28, 2020byethics code PH.REC.1399.009.

Funding Support: None declared.

Acknowledgement: None declared.

Conflict of Interests: None declared.