A multinational study of pregnant women and their newborns admitted to hospitals suggests that infection with the SARS-CoV-2 Omicron variant is associated with an elevated risk of severe maternal illness and death, particularly in unvaccinated patients with symptoms.
In the observational study, published yesterday in The Lancet, the INTERCOVID-2022 International Consortium studied the outcomes of 1,545 COVID-infected pregnant women and 3,073 uninfected counterparts admitted to 41 hospitals in 18 countries who delivered from Nov 27, 2021, to Jun 30, 2022, during the Omicron era.
The hospitals were located in Africa, the Americas, Asia, Europe, and the Middle East. Average gestational age among the infected women was 33.1 weeks, and the mothers and newborns were followed until hospital release. The average interval between the first positive COVID-19 test and delivery was 5.5 weeks.
Of all 4,618 participants, 2,886 (63%) had received at least one dose of any COVID-19 vaccine, and 2,476 (54%) had either completed the primary series or received booster doses.
The research was a follow-up to an Apr 22, 2021, JAMA Pediatrics study from the same team that found that pregnant women infected with wild-type SARS-CoV-2 had higher rates of maternal death and admission to an intensive care unit (ICU), and their newborns were at risk for neonatal ICU admission.
Unvaccinated women at greater risk
Overall, infected women were at increased risk for illness and death (MMMI; relative risk [RR], 1.16), Severe Perinatal Morbidity and Mortality Index (SPMMI; RR, 1.21), and Severe Neonatal Morbidity Index (SNMI; RR, 1,23), although the significance of the latter was uncertain.
Among all infected pregnant women, there was a slight significant increase in the risk of preeclampsia (dangerously high blood pressure) and eclampsia (seizures due to preeclampsia), a significant increase of infections requiring antibiotics and higher number of days in an ICU, and an increase of uncertain significance in the risk of maternal death (RR, 3.00; 95% confidence interval [CI], 0.50 to 17.93).
Similarly, unvaccinated women were at higher risk for preeclampsia (RR, 1.54) and maternal death (RR, 5.26). The risk of maternal infections requiring antibiotics, referral to more advanced care, or ICU admission, and fetal distress were also increased.
Relative to infected vaccinated women, infected unvaccinated women were at greater risk for MMMI (RR, 1.36). In all women, severe COVID-19 symptoms increased the risk of severe maternal complications (RR, 2.51), perinatal complications (RR, 1.84), and referral, ICU admission, or death (RR, 11.83). Among unvaccinated women, severe COVID-19 symptoms increased the risk of MMMI (RR, 2.88), and referral, ICU admission, or death (RR, 20.82).
'Universal vaccination is key'
The vaccine effectiveness (VE) of all vaccines against COVID-19 infection was 32% or below, even after a booster dose, while VE against severe complications was 48% (95% CI, 22% to 65%) among those who had completed a primary vaccine series and 76% (95% CI, 47% to 89%) after a booster dose.
Among infected women, the VE of a complete series of all vaccines combined against severe outcomes was 74% (95% CI, 48% to 87%) and 91% (95% CI, 65% to 98%) after a booster. The greatest level of protection against COVID-19 was seen in women who received booster doses of an mRNA vaccine.
Sensitivity analyses revealed a link between being overweight or obese and the increased effects of COVID-19 on MMMI, SPMMI, preeclampsia, complications of preeclampsia, referral, ICU admission, or death among all women but particularly among those who were unvaccinated.
Of 1,577 infants born to COVID-19 patients, 70 (12%) tested positive; their risks were not increased for SNMI, SPMMI, or neonatal ICU stay of 7 days or longer.
"As it is very difficult to predict who is going to develop severe symptoms and complications with the exception of overweight women or women with obesity, universal vaccination is key during pregnancy," the authors wrote.
The findings differ from those described yesterday in BMJ Global Health, which found a sevenfold increase in death rate in infected compared with uninfected pregnant women in a meta-analysis of studies conducted before the period of Omicron dominance. That study did not assess the effects of vaccines.
As it is very difficult to predict who is going to develop severe symptoms and complications with the exception of overweight women or women with obesity, universal vaccination is key during pregnancy.
In a related commentary on the new Lancet study, Sascha Ellington, PhD, and Tara Jatlaoui, MD, MPH, both of the US Centers for Disease Control and Prevention, said the study findings underscore the importance of the vaccination of pregnant women against COVID-19 amid Omicron because it protects both mothers and, by extension, infants up to 6 months old, who are too young to be vaccinated.
"To prevent adverse outcomes associated with SARS-CoV-2 infection during pregnancy, pregnant women should stay up to date with recommended COVID-19 vaccines, including, if available, a bivalent mRNA booster when they are eligible," they wrote.