Characteristics and Outcomes of COVID-19 (SARS-CoV-2)Positive Pregnant Women Admitted to a Dedicated COVID Hospital in Central India: A Single-center Observational Study

DISCUSSION

The effects of COVID-19 on pregnancy are largely unknown; characteristics and facts are constantly changing perhaps due to mutations in the virus itself. Maternal and fetal outcomes in COVID-19 pregnancies can only be defined after a detailed research. WHO has not found a significant difference in clinical symptoms between nonpregnant and pregnant women of reproductive age.^5,6 Pregnant women did not appear to be at higher risk of developing more severe disease as compared to the general population as a whole at that particular time frame. During the study period, a total number of 15,639 antenatal cases were admitted to our non-COVID facility, the Department of Obstetrics and Gynecology, Maharaja Yeshwant Rao Holkar Hospital (MYH), whereas in the Maharaja Tukojirao Holkar Dedicated COVID Hospital, it was 197 so an overall incidence of 1.26 per 1,000 maternities. In a report from UK using UKOSS, the estimated incidence in pregnancy was 4.9 (95% confidence interval 4.5–5.4) per 1,000 maternities.⁷

Disease was recognized on the basis of a galaxy of symptoms, but no single symptom was diagnosed.

In a report from the Center for Disease Control and Prevention (CDC) COVID-19 Response Pregnancy and Infant Linked Outcomes Team by Zambrano et al.:⁸ on 23,000 pregnant and 386,000 nonpregnant females of reproductive age with symptomatic laboratory-confirmed SARS-CoV-2 infection, the frequency percentage of the most common symptoms in each of the pregnant vs nonpregnant groups reported was cough—50.3/51.3, headache—42.7/54.9, muscle aches—36.7/45.2, fever—32.0/39.3, sore throat—28.4/34.6, shortness of breath—25.9/24.8, and new loss of taste or smell—21.5/24.8. Other symptoms that occurred in >10% of each group included nausea, vomiting, fatigue, diarrhea, and rhinorrhea.

In our study during the first wave, majority of women in group A were asymptomatic (84.04%) and the commonest symptom was fatigue (8.51%), while in group B, majority presented with respiratory symptoms (42.72%) and 27.18% were asymptomatic. Reason being in the first wave pregnant women were identified because of compulsory screening if a family member turned out to be positive for SARS-CoV-2. Conservative treatment was given to asymptomatic women remote from term 25/94 in group A, and they delivered later on after recovery from the infection.

Our findings were similar to a systematic review by Allotey et al.⁹ in which 7% of pregnant women universally screened for COVID-19 tested positive, 73% were asymptomatic; they also reported that pregnant women were more likely to be asymptomatic than nonpregnant in the same age-group. In a systematic review by Yanes-Lane et al.,¹⁰ 95% (95% CI 45–100%) of COVID-19 infections in pregnant persons were asymptomatic, while 59% (95% CI 49–68%) remained asymptomatic through follow-up.

After considering symptomatology, specific laboratory parameters were found to be deranged in SARS-CoV-2 infection but at the same time, we must consider that there are changes in laboratory values because of pregnancy. Leukocytosis can be normal in pregnancy, and some of the other laboratory findings overlap with those caused by pregnancy-related disorders (e.g., thrombocytopenia and elevated liver chemistries in preeclampsia with severe features).

In a systematic review by Allotey et al.,⁹ altered laboratory parameters were seen which included raised C-reactive protein levels (49%), lymphopenia (33%), leukocytosis (26%), elevated procalcitonin level (23%), abnormal liver chemistries (15.4%), and thrombocytopenia (6.6%).

In our study in the first wave, i.e., group A changes were seen in laboratory parameters but in group B derangements were more pronounced as majority of women were symptomatic.

Radiographic imaging is an important aspect of identifying severity of disease in SARS-CoV-2 infection and needs to be done in pregnant women considering the fact that benefit outweighs the risk and a single X-ray chest with shielding, or a CT scan causes only minimal radiation exposure to the fetus, i.e., 0.005 to 0.01 mGy and 0.01 to 0.6 mGy, respectively, noted side effects have been seen to occur from high doses >610 mGy radiation exposures to the fetus.¹¹

Chest radiographs may be normal in early or mild disease. In a systematic review by Oshay et al.¹² in 427 pregnant patients diagnosed with COVID-19, the most frequently encountered pulmonary findings on chest computed tomography were ground-glass opacities (77%), posterior lung involvement (73%), multilobar involvement (72%), bilateral lung involvement (69%), peripheral distribution (68%), and consolidation (41%). Our hospital was converted in emergency to a COVID facility so only X-ray facilities were there. Plain chest radiograph (CXR), although less sensitive than chest CT, is usually the first-line imaging modality used for patients with symptomatic SARS-CoV-2 infection. The relation between radiological changes in CXR and clinical severity of the disease in symptomatic patients with COVID-19 has not been fully studied, but we tried COX-RADS a proposed scoring by De Sanctis et al.¹³ There is no such study on pregnant COVID positive women, and our motive was only to identify the severity of lung involvement, so that individualized treatment may be started.

It was seen that majority of women in group A (61.70%) had normal X-ray findings and a score of 0 as they were asymptomatic. In group B as the severity of COVID-19 infection was more during this period, only 29.2% had a score of 0 while majority (50.50%) women had moderate-to-severe disease.

Gestational age at the time of COVID-19 infection is an important factor in deciding further management. In our management protocol (Flowchart 1), individualized decision-making regarding continuation of pregnancy was the key to successful management. It was made on the basis of severity of infection categorization depending on clinical and imaging findings. In group A, 41.49% of women were reported in labor of which 18/39 delivered vaginally and cesarean section was done in 21/39, almost all were asymptomatic. Those <31 weeks were managed conservatively. But in group B as majority had mild-to-severe disease, the decision of termination was taken in view of maternal benefit in 64/103 cases and conservative management was done in 39/103 cases.

A systematic review by Allotey et al.⁹ including over 11,000 pregnant and recently pregnant women with suspected or confirmed COVID-19 reported that 17% delivered before 37 weeks and 65% delivered by cesarean. Most preterm deliveries were iatrogenic; only 6% were spontaneous. In our study, cesarean section was done in 56.52% in group A in which 10.14% were preterm, while in group B 39.06% in which 20.31% were preterm. Moreover, 2.9 and 12.5% of preterm vaginal deliveries were spontaneous in groups A and B, respectively. Due to severe infection and lung involvement, induction was done in 1.45 and 12.5% of both groups, respectively. During the second wave due to the same reason, there were 12.5% induced abortions in group B.

In viral infections, transmission to the neonate is a major concern during pregnancy as well as during and after birth. With the novel virus, there were many varied reports.

In a systematic review by Kotlyar et al.¹⁴ of infants born to 936 COVID-19 infected mothers, neonatal viral RNA testing was positive in 27/936 (2.9%) nasopharyngeal samples taken immediately after birth or within 48 hours of birth, 1/34 cord blood samples, and 2/26 placental samples; in addition, 3/82 neonatal serologies were immunoglobulin M (IgM) positive for SARS-CoV-2. In addition, in the CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team report by Woodworth et al.¹⁵ of over 5,000 pregnant persons with laboratory-confirmed SARS-CoV-2 infection, 2.6% of the 610 infants with available SARS-CoV-2 test results had a positive test, primarily those born to persons with infection at delivery.

In utero transmission typically occurs via a hematogenous route but sometimes via the ascending route. Viremia rates in patients with COVID-19 may be low (1%) in one study by Penfield et al.,¹⁶ but also found to be higher in severe disease and transient in a study by Patane et al.,¹⁷ suggesting placental seeding and in utero transmission may not be common.

In studies conducted, most of the placentas studied had no evidence of infection, but the virus had been identified in few cases; there are reports of positive vaginal swabs and positive amniotic fluid,^18–22 which may suggest the ascending route of infection and intrapartum transmission through vaginal secretions. Viral shedding in maternal feces has been reported, so fecal contamination of the perineum could theoretically be a source of intrapartum transmission, although there is no evidence of protective effect of cesarean. Postnatal transmission can occur through ingestion of breast milk or from an infected mother (or other caregivers) to her infant through respiratory or other infectious secretions.

In our study, however, all neonates were tested within 12 hours of birth by RT-PCR as negative; no evidence of infection was noted in them on follow-up also. In contrary to this, in a study from South India by Nambiar et al.,²³ 21.42% of babies who delivered vaginally tested positive, while 10.83% of babies delivered by cesarean section were positive.