COVID does affect pregnant women more severely

As experts evaluate emerging evidence and the pattern of information that comes about, there is a consistent theme that pregnant women are more severely affected by COVID-19, says infectious disease expert Denise Jamieson, MD, MPH, who is the James Robert McCord Professor and Chair of the Department of Gynecology and Obstetrics at Emory University School of Medicine in Atlanta.

Jamieson delivered the Howard Taylor International Lecture: Global Health Threats – Novel Coronavirus & Beyond, during the American College of Obstetricians and Gynecologists’ (ACOG) 2020 Virtual Annual Meeting. Her career has focused on emerging infectious diseases in pregnancy like influenza, ebola, Zika virus, and maternal immunizations. From 1997 to 2017, she was at the Centers for Disease Control and Prevention, where she held a variety of different leadership positions.

Jamieson acknowledged Sonja A. Rasmussen, MD, MS, who serves in the Department of Pediatrics, College of Medicine, Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville.

“Much of what I am going to present represents the evolution of our joint thinking and ideas over many years,” Jamieson said.

She summarized lessons learned from other outbreaks – monkeypox in 2003; SARS in 2003; influenza (Swine flu) in 2009-10; and Zika in 2015-16 – to see what can be applied to the current pandemic.

Monkeypox was a relatively obscure outbreak, but it taught scientists lessons that are relevant now, she said. It began innocuously when a family from Wisconsin adopted a prairie dog from an exotic animal swap meet. But the prairie dog became ill and bit a 3-year-old child in the home. The child became ill with fever and lesions at the site of the bite. The animal dealer then became ill, as did the mother of the child. As it ends up, Gambian pouched rats that had been shipped from Ghana to Texas were the source of the virus. Although the rats had a level of immunity, American prairie dogs did not.

Some of the infected prairie dogs ended up in homes with pregnant mothers. Therefore, there was concern about how to advise pregnant women. “Although there had been at least one reported case of congenital monkeypox, not much was known specifically about monkeypox in pregnancy. However, extrapolating from another pox virus, we knew there was increased morbidity and mortality among pregnant women with smallpox. We also knew that there had been rare cases of fetal vaccinia, vertical transfer of vaccinia virus, the live virus in the smallpox vaccine. Despite these risks, it was recommended that all close contacts with monkeypox be offered vaccination with the smallpox vaccine, regardless of pregnancy status. In other words, pregnant women were not excluded from emergency use of smallpox vaccine.”

Global threats to health may include zoonotic vectors, and that it’s important to rapidly address pregnancy issues during outbreak including use of mitigation measures.

That outbreak has relevance to the ongoing discussions about potential use of COVID-19 vaccine among pregnant patients, she said. SARS in 2003 highlights the case of a super spreader event. After one person in China became ill with it and stayed at a hotel, the virus spread and became the first pandemic of the 21st century. Due to unprecedented scientific, medical and public health collaboration, the global response to SARS was extraordinarily rapid and effective. By July of 2003, SARS had been contained.

“The world was lucky with this first coronavirus pandemic,” Jamieson said. “There were characteristics of the virus that made it easier to control but there also was a coordinated, strong and swift public health response, that included measures such as mandatory quarantine, contact tracing, symptom and fever screening, travel bans, strict infection control procedures at hospitals and universal masking in affected countries.”

The lessons learned from SARS included that global travel represents a major risk for disease transmission. “We also learned that a coordinated public health response can be effective at controlling a pandemic,” she said.

During the influenza and H1N1 pandemic in 2009-2010, the second documented death was an otherwise healthy woman who was pregnant, portending the role that pregnant women would play in that pandemic. “Fairly early on it was clear that pregnant women with influenza were at risk for severe disease,” Jamieson said. An early Lancet paper summarized the cases reported to the Centers for Disease Control and Prevention (CDC).¹

“We found that pregnant women were more likely to be hospitalized with influenza compared to the general population,” she said. A later report found that 5% of all H1N1 deaths were among pregnant women,3 which was a disproportionate number of deaths.

“We also confirmed that early antiviral therapy helped prevent severe disease and death,” Jamieson said. “Only one death occurred in a pregnant woman who received treatment within two days of symptom onset.”

The lessons learned with this pandemic included being reminded that pregnant women may be more vulnerable to severe disease from some emerging pathogens, and, specifically from respiratory pathogens.

Jamieson also covered the Zika virus, which first was identified in 1947 in a monkey in the Zika Forest in Uganda. It would not be until 2015 that Zika was first identified in the Americas. An outbreak occurred in Brazil, then 8 to 9 months later there was an increased incidence of microcephaly in infants born there. By April of 2016 enough evidence had accumulated to conclude that Zika virus in pregnancy could cause a congenital syndrome, which included microcephaly.

Lessons learned from Zika included the role of global travel in importing cases to the United States; it underlined the importance of specifically evaluating pregnancy outcomes as part of infectious disease investigation; it also highlighted the need for having surveillance systems specifically tailored for pregnant women.

“Because the national surveillance systems were set up prior to the realization that Zika caused birth defects, the CDC system did not routinely collect pregnancy status or outcomes. Therefore, we set up several different systems in the US and elsewhere to collect this critically important information.

She ended with a short review of COVID-19 and some of what has been learned so far.

There are key questions, she said, with COVID-19 and pregnancy. Are pregnant women more susceptible to becoming infected with SARS-CoV-2 or at an increased risk for severe disease? Second, is there perinatal transmission? And third, what are the effects of the virus on the pregnancy, including the fetus/neonate?

On susceptibility, “we have no data,” she said. “Once asymptomatic infection was recognized, many labor and delivery units started universal testing of all women admitted for delivery.” (See related Figure “Universal screening of pregnant women presenting to labor and delivery in the U.S.) “You can see here a wide range of overall prevalence of positive test results, depending on time and place of testing, as well as whether women were symptomatic or asymptomatic. However, since we don’t have reliable estimates of overall prevalence in non-pregnant populations, we cannot conclude anything about susceptibility.”

As regards severity in pregnancy, the best data are from the CDC. Its Morbidity and Mortality Weekly Report (MMWR) summarizes data from the CDC surveillance system, which includes case reports submitted by the 50 states, the District of Columbia, and New York City. (See related Figure “Women of reproductive age (WRA) with SARS-CoV-2 infection by pregnancy status – Jan 22-June 7”).

“Although there is a large amount of missing data, I think this report is the best information we’ve had to date about severity of COVID in pregnancy. When adjusted for age and comorbidities, pregnant women were more likely to be hospitalized, admitted to the ICU, and require mechanical ventilation compared to non-pregnant women. There was not an increased risk of death.” (See related figure “Hospitalization, ICU admission, mechanical ventilation, and death among pregnant women and nonpregnant WRA with SARS-CoV-2 infection”).

“It will be important to look at updated data from the CDC surveillance system, which should include case reports beyond June 7 and hopefully with more complete information about pregnancy status,” Jamieson said.

In terms of transmission risk of the virus to the fetus (known as vertical transmission), the story of this possibility has been unfolding over time, she said. “There were some initial reports of possible perinatal transmission. There were early reports of infants with elevated IgM at birth. Since IgM does not readily cross the placenta, this suggested possible perinatal transmission. However, there are multiple problems with using IgM assays to diagnose congenital infections, including possible fetal-maternal leakage of IgM and inaccurate test results. There were also some reports of several infants testing positive several days after birth. In these cases, it was hard to sort out intrauterine or intrapartum transmission from postnatal transmission. Therefore, it is important to use carefully defined criteria to address perinatal transmission.”

She cited criteria used by Dean A. Blumberg, MD, and colleagues, from their editorial “Vertical Transmission of SARS-CoV-2: What is the optimal definition?”² from the American Journal of Perinatology.

“They suggested that you need three things: the mother needs to be positive around the time of birth; you need evidence of early exposure, as well as persistence,” she said. Evidence of early exposure means that virus is detected in any of the following: swab of neonatal respiratory tract in the first 24 hours of life; amniotic fluid; umbilical cord blood; neonatal blood sample in the first 24 hours of life. With persistence, you can have either of the following: swab of the respiratory is positive more than 24 hours after the start of life; or the neonate has a positive SARS-CoV-2 IgM assay in the first 7 days of life.

“I think there are now a handful of cases that meet these criteria, and are likely intrauterine transmission,” she said.

As more data becomes available, the impact to pregnant women will become more and more clear, she said. As she noted, there is a consistent pattern that pregnant women are more severely affected by COVID, although she does not think it is as severe as the other diseases she covered.

One audience member asked if Jamieson thought pregnant women should be offered the COVID vaccine, even if there is no safety data.

“Should pregnant women be prioritized? Because they’re at an increased risk for severe disease, and that is that prioritization scheme that is being worked on, whether they should be prioritized. I don’t think we have enough data to really address that piece,” she said. “But the way I would look at it is, ‘Should pregnant women be excluded from the opportunity to be vaccinated based on their pregnancy status? So if you are a pregnant healthcare worker and you’re in the top priority to be vaccinated, should you be categorically excluded from the opportunity to be vaccinated just because you happen to be pregnant? My answer would be, emphatically, no. I think with careful counseling about what we know and what we don’t know about the vaccine and depending on what vaccine is available, pregnant women should be given the opportunity to be vaccinated, with careful counseling about what we know and what we don’t know. And just of note there are some of the vaccine platforms that are in Phase III trials that we know quite a bit about, some we know much less about. But I think whatever the safety and efficacy data is we owe it to our patients to talk to them about the vaccine and to be able to offer the vaccine.”

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Editor’s Note: Contemporary OB/GYN will soon publish a fuller article from Jamieson’s presentation, including more related studies.

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1. Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. The Lancet. 2009; 374(9688): 451-458. doi.org/10.1016/S0140-6736(09)61304-0
2. Blumberg DA, Underwood MA, Hedriana HL, Lakshminrusimha S. Vertical Transmission of SARS-CoV-2: What is the Optimal Definition? Am J Perinatol. 2020 Jun;37(8):769-772. doi: 10.1055/s-0040-1712457. Epub 2020 Jun 5. PMID: 32503058; PMCID: PMC7356079.