As the coronavirus case count ticked up last spring, one worry was on the top of Vanessa Jacoby's mind: pregnancy.
As an obstetrician-gynecologist at the University of California, San Francisco, Jacoby is all too familiar with the fact that pregnant people frequently fare far worse than the greater public during outbreaks of infectious disease. During the H1N1 pandemic in 2009, they made up 5 percent of reported deaths even though they accounted for just one percent of the population. And in the early days of the novel coronavirus pandemic, what little information trickled out about SARS-CoV-2 largely overlooked this high-risk group.
“There were all of these questions that we had no idea what to tell our patients when this started,” Jacoby says. “We knew we needed answers and we needed them very fast.”
Now, in the largest analysis of its kind to date, Jacoby and her colleagues are filling in some of those blanks. They found that COVID-19 symptoms lingered in many of the study participants, which included 594 pregnant or recently pregnant people, most of whom were not hospitalized.
Half of the participants still reported illness after three weeks, while 25 percent were still recovering after two months or longer. (The typical duration for mild cases is two weeks).
The participants' symptoms also manifested differently than those reported in non-pregnant populations, according to the study, which was published October 7 in Obstetrics & Gynecology. For one, fever was uncommon even though it has been a hallmark sign of this disease; it was an initial symptom in just 12 percent of the pregnant individuals and present only in 5 percent after one week of illness. Other signs of COVID-19—cough, loss of smell, fatigue, and shortness of breath—persisted in a small but significant proportion of individuals for up to two months.
Such clues about the progression of COVID-19 during pregnancy can help individuals and their providers better understand when to seek help, and what’s potentially in store for those who fall ill. It also gives another peek into the growing group of so-called COVID-19 “long-haulers” whose months of persistent symptoms have confounded many scientists.
Gemma Maclean was diagnosed with COVID-19 last spring when she was 36 weeks pregnant. "I have not been able to take a deep breath in since May," she tells National Geographic via email. The 26-year-old from Inverclyde, Scotland has also had daily bouts of heart racing, fatigue, gastrointestinal issues, random spikes in temperature, burning pain in her upper back, and blurry vision.
She has struggled to get her voice heard by doctors, who blamed the symptoms on pregnancy and a litany of other conditions. "[They say] it's anxiety, it's health anxiety, then the biggest insult was, It's obviously postnatal depression," she says. As scientists better define long-haul illness, though, fewer patients should have to suffer in silence. The new study is a step in that direction.
Jacoby, who co-led the work with three other researchers, notes that the results are an early snapshot. They hope to do more detailed analyses of the participants in the coming months.
“There’s going to be a lot coming out of this database,” says Sarah Cross, assistant professor in the Division of Maternal-Fetal Medicine at the University of Minnesota Medical School, who wasn’t involved in the study. “I’m very excited to see all that they’re doing.”
Sprint to the start
The work is part of an ambitious project, dubbed the Pregnancy Coronavirus Outcomes Registry or PRIORITY, to build a nationwide database of pregnant women with COVID-19 and track their condition, as well as that of their babies, for up to a year post-pregnancy. As U.S. cases of coronavirus skyrocketed in early spring, along with fears of overcrowded hospitals and shortages of personal protective equipment, Jacoby and her colleagues embarked on a mad scramble to get the database off the ground.
“The work we usually did in three months, we did in about … two and a half weeks,” Jacoby says. “We just really felt this urgent need.”
Pregnancy makes profound changes to how the body functions, which includes making it more susceptible to some infectious diseases. One important change entails a slight suppression of the immune system. The reason is straightforward and mirrors why patients take immune-suppressing drugs to prevent rejection of a transplanted organ, Cross explains. Half of a growing fetus hails from paternal DNA that could register to the immune system as a foreign invader, so the maternal body must adjust its defenses to permit its growth.
Child gestation can also stress the lungs in two ways. As the uterus expands, it presses on the diaphragm, or the flat muscle that controls how much the lungs fill with air. Doing so reduces a person’s respiratory capacity. Meanwhile, the growing fetus also increases the body’s demand for oxygen. Both of these impacts make the status of pregnant people’s lungs “a little more tenuous,” Cross says.
Surprises of COVID-19
The PRIORITY team began enrollment on March 22, and its database now stands at 1,333 people from across the United States. The new study focuses on the first wave of participants—nearly 600 pregnant people with COVID-19—who joined through July 10.
From the start, racial diversity was a central focus for recruitment, Jacoby says. Long before COVID-19 emerged, systemic racism has led to vast disparities in health care and socioeconomic opportunities, which are reflected in pregnancy outcomes. Black women are up to six times more likely to die from complications during pregnancy than white women.
The pandemic magnifies these inequities. Black and Hispanic people are hospitalized for COVID-19 at a rate nearly five times that of white people. Enrolling a diverse group in the PRIORITY study would allow researchers to address questions of disease progression specific to these vulnerable communities. The new report includes 41 percent Black, Indigenous, and people of color—and up to 15 percent of the study group completed the enrollment in a language other than English.
“As we know, language is not a barrier for infection with the virus,” Jacoby says.
Moreover, most past studies on COVID-19 and pregnancy were done with people who were hospitalized, meaning they had moderate to severe illnesses. But 95 percent of PRIORITY’s participants are weathering the disease at home, akin to the vast majority of people in the United States with the disease. The hope was to get a representative sense of how the disease progresses not only among pregnant people, but in communities across the United States.
“They’re your friends and neighbors and family who are living with COVID-19 but are not ill enough to need hospitalization,” she says.
Overall, the results suggest many pregnant people may have prolonged symptoms with COVID-19, but exactly why remains uncertain. The team is working to untangle the underlying factors at play, and they plan to run more comprehensive statistics now that the full PRIORITY study has been recruited.
In general, COVID-19 long-haulers remain a mystery. It’s unclear why their symptoms don’t resolve after two weeks, like typical mild cases, and how common they are in the general population. So far, slight differences in the groups enrolled in long-hauler studies make direct comparisons challenging, Cross notes. She points to one investigation at a French hospital that found two-thirds of adults with mild cases of COVID-19 still reported symptoms up to two months after they began feeling ill. Yet a phone survey conducted by the U.S. Centers for Disease Control and Prevention found that just 35 percent of people had lingering consequences two to three weeks after testing.
The PRIORITY venture itself, like any study, comes with limitations. Jorge Salinas, hospital epidemiologist at the University of Iowa’s Carver College of Medicine, notes that the participants skew more wealthy and more educated than the general population, with 41 percent reporting an income of more than $100,000 per year. That’s in part because pregnant health-care workers comprise a large portion—a third—of the study’s subjects.
“COVID has surprised us every week since it appeared,” Salinas says, noting it hasn’t even been a year since reports emerged of the first case in China. “We will continue learning about the long-term consequences of COVID in years and decades to come.”
Cross notes that the study’s skew toward wealthier backgrounds might mean its overall picture is slightly “rosier” than what is happening in reality nationwide.
“We’re entering a different phase of the pandemic, and we are lucky to have people doing this very important research,” Cross says. “We have some data to fall back on, making us feel a little more comfortable [with] both counseling patients and making management decisions.”