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The cases of two women with COVID-19 who delivered babies who tested positive for the SARS-CoV-2 virus suggest the possibility of in utero transmission, but Italian researchers speaking at the Virtual COVID-19 Conference 2020 stopped short of declaring that outright.
"Evidence is stacking up and accumulating that it is indeed possible, though rare," said Claudio Fenizia, PhD, immunology specialist at the University of Milan. Still, none of this should affect the way clinicians practice — at least not yet, he added.
The scientific community needs to assess "the real risk of getting infected during pregnancy. It could be that it's a marginal risk with marginal consequences," he told Medscape Medical News.
In one of the cases, SARS-CoV-2 was detected in the placenta, vaginal tract, and maternal blood of an Italian woman and in the umbilical cord blood of her infant. The virus has been seen before in the placenta, or the maternal blood, or the vaginal tract of women, but rarely has it all been seen in the same woman, with an infant whose nasopharyngeal swab tested positive at birth.
Testing Pregnant Women
Fenizia and his colleagues assessed 31 women with SARS-CoV-2 who gave birth at three Italian hospitals in the early days of the COVID-19 pandemic. All the women were in their final trimester of pregnancy.
"At the time — and I'm saying at the time like it was years ago; it was actually 5 months, not even the length of a pregnancy — we had no data at all about pregnancy," he explained.
"We just started collecting all the samples we could and storing them the best way we could," he reported. The team came in "during the weekend and during the night to process the placenta and other tissue to store the samples in an appropriate way."
They didn't know what they'd do with the samples, they just knew they had to keep them. "We were just starving for information," he said.
In addition to saving samples from the placenta, maternal blood, umbilical cord blood, and vaginal secretions, and the umbilical cord itself, the researchers tested the mother and infant for immunoglobulin (Ig)M and IgG antibodies against SARS-CoV-2, as well as for inflammatory markers. After birth, each infant was tested for the virus with a nasopharyngeal swab; if it was positive, the test was repeated.
This is a strength of the study, Fenizia said.
"It's not the case of IgM in one study, a case of placenta in another one," he explained. "This is collective reporting that is quite a deep analysis on six or seven different kinds of specimens from each delivery."
The researchers only included viral RNA results in the study if they were able to find the entire genome of the virus, not fragments that couldn't possibly replicate. However, they didn't culture the virus to see if it was infectious. This fits with many other studies that have not reported on the ability of the virus they find to infect cells, he said.
The virus was detected in only two samples of maternal placenta, and both those women had infants with a positive nasopharyngeal swab at birth.
Differentiating the Two Cases
One of those women had severe COVID-19 symptoms and her body was awash in the virus at the time of delivery. SARS-CoV-2 was present in her blood, in vaginal swabs, and in the placenta, and she had both IgM and IgG antibodies in her blood. The virus was detected in umbilical cord blood, and there were IgG antibodies in her infant's cord blood, but not IgM antibodies. About a week after birth, the infant's SARS-CoV-2 test was negative.
The other woman had been sick for a longer period — 17 days vs 6 days — but her symptoms were mild and she did not require hospitalization. IgM and IgG antibodies were detected in her own blood and in her infant's cord blood.
"IgM antibodies are not normally transferred from the placenta, so that presence is a consequence of direct exposure of the fetus to the virus," Fenizia said.
Although her nasopharyngeal swab tested positive for SARS-CoV-2, the woman didn't have the virus in her blood or vagina at the time of delivery. At first, the researchers classified her placenta as negative for SARS-CoV-2, but on further testing, they detected the virus in some of her placental tissue.
This is intriguing, Fenizia explained. If the woman had had a spike in the virus weeks earlier, with viremia in the blood, and then the fetus was exposed through the placenta, both she and her infant would have antibodies. Although the infant's nasopharyngeal swab was positive at birth, it was negative 2 days later.
The researchers didn't have breast milk data for either woman.
With just 31 cases, analyses of data on vertical transmission are limited, "but two out of 31 is 6%," he noted. "I would say that's quite rare. We don't know how rare because we don't have enough numbers to define that, but it's not even 10%."
Evaluating the Findings
In contrast, rates of mother-to-child transmission of HIV is 10% to 20%, said Lynne Mofenson, MD, senior HIV technical advisor at the Elizabeth Glaser Pediatric AIDS Foundation in Washington, DC, who has spent decades studying how HIV moves through the placenta to infect a fetus, or not.
Since the emergence of COVID-19, she's been tracking the disease in pregnant women and following case reports of potential vertical transmission. The Italian study adds to the literature but is not conclusive, she explained.
For one thing, as hard as medical staff work to keep delivery suites sterile, when an infant presses on the intestines during vaginal birth, fecal matter often comes out. And studies have shown that SARS-CoV-2 can be present in fecal matter, so there's a chance of incidental exposure during childbirth.
Plus, nasopharyngeal testing is much more likely to identify SARS-CoV-2 transmitted to the infant during childbirth than in utero, unless samples of amniotic fluid also show the presence of SARS-CoV-2, she said. And this study, for all its thoroughness, lacked such data.
Besides, SARS-CoV-2 in the cord blood and placenta isn't the definitive proof of transmission that it might seem.
"With HIV, we did not use cord blood because there was potential for contamination with maternal blood," she said. "If cord blood was used, you needed confirmatory neonatal blood samples. And as we also discussed with HIV, you can have a positive placenta but not necessarily an infected infant. So positive placenta just means there was maternal viremia and it made it into the placenta, but not necessarily the infant."
Data on the Italian woman who experienced severe COVID-19 symptoms make a strong case for vertical transmission, said Mofenson. However, she said she would categorize transmission for the second woman as likely "transient contamination" at birth that resolved in 48 hours
This doesn't mean she thinks vertical transmission is a myth, though. Another case of purported vertical transmission — reported but not yet subjected to the peer-review process — is the most definitive so far, if it stands up to vetting.
Those researchers found SARS-CoV-2 in the amniotic fluid, placenta, maternal blood, and newborn's blood. In addition, the infant was intubated and the bronchoalveolar lavage as a result of that procedure was positive for SARS-CoV-2.
But Mofenson said she agrees with Fenizia that vertical transmission is likely rare. Unlike HIV, where an untreated virus guarantees virus in the blood, viremia with SARS-CoV-2 is uncommon.
"Mothers don't usually have virus in the blood" with SARS-CoV-2, she told Medscape Medical News. "That's the first hurdle. And if you don't clear that first hurdle, there's just no way" for transmission to occur.
Virtual COVID-19 Conference 2020. Track A 11384. Presented July 10, 2020.
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Cite this: Possible In Utero SARS-CoV-2 Transmission - Medscape - Jul 10, 2020.
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