COVID-19
Unlike SARS-CoV and MER-CoV, the risk of severe COVID-19 disease in the pregnant population compares favorably to the general population.116 Recently, a World Health Organization mission group studied 147 pregnant women with COVID-19, 65 confirmed and 82 presumed, of whom 8% had severe disease, and 1% were critical with multiorgan failure (Table 8). As the rate of adverse events seemed less compared to the general population (13.8% severe and 6.1% critical), the mission concluded that pregnant women might not be at increased risk.142 However, this determination may evolve with more data (Table 9 )
Table 9 Obstetrics and gynecology manifestations of SARS-CoV, MERS-CoV and COVID-19.
SARS (only studies with large study population included)
Study Robertson et al (2004)N = 1, confirmed cases (19 weeks)Case report Wong et al (2004)N = 12, confirmed casesRetrospective study Lam et al (2004)N = 10 pregnant, 40 nonpregnant confirmed casesCase-control study Stockman et al (2004)N = 1, confirmed case (7 weeks)Case report Ng et al (2009)7 placentasClinicopathologic study
Clinical features Healthy infant at term via C-section (due to placenta previa) • Spontaneous miscarriage (57%) in first trimester pregnancies (confounded by treatment with Ribavirin)
• Preterm delivery (80%) in >24 weeks gestation
• IUGR (16.6%) • ICU admission: 60% (pregnant) vs. 18% (nonpregnant) (P = 0.01)
• Renal failure: 30% vs. 0 (P = 0.01)
• Sepsis: 20% vs 0 (P = 0.04)
• DIC: 20% vs 0 (P = 0.04)
• Death: 30% vs 0 (P = 0.01)
(2/3 in second and third trimesters)• Hospital stay longer in pregnant patients (P = 0.01) • Spontaneous PROM
• Healthy infant via C-section (due to fetal distress) • Preterm birth (delivery in acute infection)
• IUGR, oligohydramnios, SGA (convalescent after third trimester infection)
Key findings on investigations N/A Newborns tested negative for SARS ↑LDH in pregnant patients(P = 0.04, <0.0001) Cord blood, placenta, breast milk negative for antibodies N/A
Histopathology N/A N/A N/A N/A Convalescent, infection in third trimester: Extensive fetal thrombotic vasculopathy (FTV), sharply demarcated areas of necrotic villi
Key study findings and message Healthy mother and infant, no vertical transmission No perinatal SARS infection Physiologic pregnancy related changes in immune system and respiratory mechanics • No vertical transmission
• Antibody formation may be influenced by gestation at infection FTV possibly due to pro-thrombotic state, induced directly by virus, or hypoxia
MERS
Study Alserehi et al (2016)N = 1, confirmed case (32 weeks)Case report Assiri et al (2016)N = 5, confirmed cases (all ≥22 weeks)Case series, retrospective Jeong et al (2017)N = 1, confirmed caseCase report, review Alfaraj et al (2019)N = 2, confirmed cases (6 weeks and 24 weeks)Case report, review
Clinical features Healthy infant at 32 weeks via C-section • All required ICU
• 1 stillbirth, 1 neonatal death
• 2 patients died • Asymptomatic patient
• Healthy infant at 37 weeks via C-section due to placental abruption • Asymptomatic patients
• ICU care (54%)
• Death (27%) (1 infected in second trimester, 2 in third)
• Infant death rate: 27%
• Case fatality rate: 35% (similar to nonpregnant, P = 0.75)
Key findings on investigations Infant negative for MERS-CoV N/A No neonatal IgG N/A
Key study findings and message Younger age, infection in later gestational period and immune response may contribute to successful outcome Infection may be associated with maternal and perinatal death and disease Healthy mother and infant, benign course Case fatality similar to nonpregnant cases
COVID-19
Study Chen et al (2020)N = 9, confirmed casesRetrospective study WHO-China Joint Mission (2020)N = 147 pregnant (64 confirmed cases, 82 suspected,1 asymptomatic) Zhu et al (2020)N = 10 neonates, 9 mothers (1 twin)Retrospective study Liu et al (2020)N = 13 confirmed cases (2 < 28weeks)Retrospective study Schwartz (2020)N = 38, confirmed casesReview Chen et al (2020)N = 118, confirmed or suspectedRetrospective study
Clinical features • Similar to other COVID-19 patients, no severe pneumonia or death
• Fetal distress in 2
• All live births, no complications • 8% severe disease (general: 13.8%)
• 1% critical (general: 1%) Mothers: Similar to other COVID-19 patientsNeonates:• Intrauterine distress, PROM
• 4 FT, 6 premature
• 2 SGA, 1 LGA
• Shortness of breath (6)
• Fever
• Vomiting
• Pneumothorax
• ↑HR Mothers:• Similar to other COVID-19 patients, 1 asymptomatic
• 7.6% required ICU care (general 5%)
Neonates:• Preterm labor (46%)
• C-section (77%)
• Fetal distress 3/10
• PROM 1/10
• Stillbirth 1/10) No maternal deaths Outcomes:• Live births: 70/7
• Preterm: 14/68 (iatrogenic 8/14)
• Spontaneous abortion: 9 (8%)
• C-section due to COVID concerns: 38/62
Neonates:• Deaths: 0
• Asphyxia: 0
• Median APGAR score: 8-9
Key findings on investigations Amniotic fluid, cord blood, breastmilk, neonate negative for virus N/A Neonates:Thrombocytopenia with abnormal liver function N/A N/A N/A
Message No vertical transmission in patients with COVID-19 in late pregnancy Pregnant women do not appear to be at higher risk No vertical transmission detected Infection may increase risk to mothers and neonates No maternal-fetal transmission (30-40 weeks of gestation) • No increased risk of severe disease in pregnant women.
• Exacerbation of respiratory symptoms in postpartum period likely related to pathophysiological changes.
DIC, disseminated intravascular coagulation; FT, full term; Hb, hemoglobin; HR, heart rate; ICU, intensive care unit; IUGR, intrauterine growth restriction; LDH, lactate dehydrogenase; LGA, large for gestational age; MERS-CoV, middle east respiratory syndrome coronavirus; PROM, premature rupture of membranes; SARS-COV, severe acute respiratory syndrome coronavirus; SGA, small for gestational age.
There are a few case reports and mini case series discussing the late trimester pregnancy and COVID-19. A study on 38 third trimester pregnant women did not show any severe pneumonia requiring mechanical ventilation or maternal deaths, despite co-morbid conditions. There were also no fetal or neonatal deaths.143 Another study (13 women in the second and third trimesters) reported 1 ARDS and septic shock case with a stillbirth at 34 weeks of gestation.144 Other reports on women with gestational ages of 25-39 weeks raise concern for an increased risk of preterm rupture of membranes and preterm delivery.144, 145, 146 However, in contrast, a retrospective study of 16 pregnant women infected with COVID-19 compared with 45 noninfected pregnant women showed no differences in preterm labor or preterm delivery, though the youngest gestational age included was only 35 weeks. Also, there was no difference in birth weight between the 2 groups.143 Pathophysiology in obstetric patients could be due to naturally suppressed cell-mediated immunity and physiologic respiratory changes.133 A noteworthy observation by Abbas et al has been an increasing incidence of hydatiform moles with the onset of the pandemic. The majority of these cases were primigravidae without other risk factors. They suggest an immune mediated mechanism triggered by the virus and recommend COVID testing in all women with hydatiform moles.65
Currently, there is no evidence of vertical transmission of COVID-19, as confirmed by negative viral PCR in 30 neonates.143 One study of 6 women showed no detectable virus in amniotic fluid, cord blood and breastmilk, nor on a neonatal throat swab.146 There is a paucity of data regarding COVID-19 infection in the first and second trimesters.
A study investigating the possibility of sexual transmission of COVID-19 found no virus in the vaginal discharge of 35 COVID-19-infected nonpregnant patients, possibly due to the lack of ACE2 expression in the vagina.147