Study shows that SARS-CoV-2 infection is associated with an increased risk for maternal morbidity and severe complications

In a recent study published in The Lancet, researchers examined vaccine effectiveness and pregnancy outcomes during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron period.

Background

Previously, the study’s authors reported an association between coronavirus disease 2019 (COVID-19) in pregnancy and increased rates of adverse neonatal and maternal outcomes relative to pregnant individuals without COVID-19. A systematic living review observed that pregnant individuals with COVID-19 are more likely to deliver preterm and have a higher risk of admission to an intensive care unit (ICU) and death than those without COVID-19.

SARS-CoV-2 Omicron was designated a variant of concern (VOC) by the World Health Organization (WHO) in late 2021. Preliminary evidence suggested that Omicron causes a mild disease, despite being more transmissible than earlier variants. THE INTERCOVID-2022 study was initiated to assess the impact of COVID-19 in pregnancy on maternal and perinatal outcomes relative to pregnant individuals without COVID-19.

About the study

In the present study, researchers evaluated vaccine effectiveness against COVID-19 diagnosis, maternal complications, and hospitalization/death in individuals with COVID-19 during pregnancy. This study involved 41 Oxford Maternal and Paternal Health Institute hospitals in 18 countries. Females diagnosed with COVID-19 during pregnancy or delivery were enrolled from November 27, 2021, to June 30, 2022.

Mothers and their neonates were followed up until discharge. Two pregnant individuals without COVID-19 were enrolled at each study site for every individual with COVID-19. Information on the predominant variant was obtained from official reports from hospitals’ catchment areas. Twenty-eight hospitals implemented universal screening for pregnant females at any hospital admission. Data on pregnancy, delivery, and neonates were obtained from medical records.

Vaccination status was determined from medical/primary care records, vaccination registries, maternal oral reports, or vaccination cards. Individuals were considered non-vaccinated if no evidence of vaccination was available from the indicated sources. The primary outcomes were maternal morbidity and mortality (MMMI), severe neonatal morbidity (SNMI), and severe perinatal morbidity and mortality (SPMMI) indices.

The team estimated vaccine effectiveness against COVID-19 diagnosis, moderate/severe symptomatic disease, and severe complications, including maternal referral to higher care, ICU admission, and death. Vaccine effectiveness was defined as a proportionate decline in COVID-19 diagnoses among vaccinated subjects relative to those not vaccinated.

Findings

In total, 4618 pregnant individuals were enrolled; 1545 subjects were diagnosed with COVID-19. The mean gestational age was 33.1 weeks at COVID-19 diagnosis, and the average time between the first positive COVID-19 test and delivery was 5.5 weeks. The proportion of individuals infected with Omicron infection increased sharply in December 2021, with over 80% of cases due to Omicron by January 2022 in all studied regions.

Demographic characteristics and obstetric/gynecologic histories were similar between individuals with and without a COVID-19 diagnosis. Women with a diagnosis had elevated risks of MMMI, SPMMI, SNMI, preterm birth, eclampsia, pre-eclampsia, referral to higher care, ICU admission, and death than those without a diagnosis.

Of the 1577 newborns of mothers with a COVID-19 diagnosis, 570 were tested for SARS-CoV-2 infection due to symptoms, and 70 were positive. The risks for SNMI, SPMMI, or a neonatal ICU stay of seven days or longer, were not increased among test-positive newborns relative to test-negative newborns. Overall, 62% of participants had been vaccinated with at least one dose, and 38% were not vaccinated.

Vaccinated participants were likely to have a higher education level, work outside the home, smoke less, and be married or cohabiting than non-vaccinated subjects. The rate of pre-existing morbidities was marginally higher among vaccinated individuals. Vaccine effectiveness for COVID-19 diagnosis was 32% or below, even after booster vaccination, regardless of vaccine type.

Similarly, it was fairly low against moderate COVID-19. mRNA vaccine booster vaccination showed the highest efficacy of 54% in preventing moderate COVID-19 symptoms. Nevertheless, vaccine effectiveness against severe disease increased and was 48% for two doses and 76% for booster vaccination.

In a sub-sample of individuals with lab-confirmed COVID-19, vaccine effectiveness was substantially improved against severe complications; 74% for a two-dose regimen and 91% after a booster. The risk for vaccine-associated complications did not increase for the mother, fetus, or newborn. Kaplan-Meier curves showed that the cumulative risk of severe complications from the time of the last dose increased until about 200 days post-vaccination.

Conclusions

Taken together, COVID-19 in pregnancy during the first six months after Omicron was declared a VOC was associated with an elevated risk of maternal morbidity and severe complications, mainly in symptomatic and non-vaccinated participants; the risk of pre-eclampsia in those with severe symptoms was also increased. mRNA vaccines conferred the highest protection against severe complications, followed by viral vector vaccines with a booster dose.