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SARS-CoV-2 May Infect Placenta, Trigger Miscarriage

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    Researchers in Switzerland report a case of apparent placental infection by SARS-CoV-2 that may have triggered a second-trimester miscarriage.

    In a report in JAMA, they describe a 28-year-old obese, primigravida woman who presented at 19 weeks' gestation with multiple symptoms, including fever, myalgia, diarrhea, and dry cough for two days. A nasopharyngeal swab was positive for SARS-CoV-2. She was given oral acetaminophen and discharged home.

    Two days later, she presented with severe uterine contractions and fever. An ultrasound showed active fetal movements; fetal tachycardia (180/min); and normal fetal morphology, growth, and amniotic fluid. She was started on prophylactic amoxicillin-clavulanic acid and regional anesthesia.

    The patient wore a mask throughout her labor, as did two healthcare professionals who both tested negative for SARS-CoV-2. Amniotic fluid and vaginal swabs were also negative.

    A stillborn infant was delivered vaginally after 10 hours of labor. Swabs from the axillae, mouth, meconium, and fetal blood obtained within minutes of birth tested negative for both SARS-CoV-2 and bacterial infection.

    Within minutes of placental expulsion, the fetal surface of the placenta was disinfected and incised with a sterile scalpel. Swabs and biopsies obtained close to the umbilical cord and peripheral margin were negative for bacterial infection but positive for SARS-CoV-2.

    At 24 hours, the placenta remained positive for SARS-CoV-2.

    At 48 hours, maternal blood, urine, and vaginal swab were all negative for SARS-CoV-2, although a nasopharyngeal swab remained positive.

    A fetal autopsy showed no malformations, and fetal lung, liver, and thymus biopsies were negative for SARS-CoV-2.

    "The results were surprising because our goal was just to confirm that there was no materno-fetal transmission," Dr. David Baud of Lausanne University Hospital in Switzerland told Reuters Health by email. "Since previous SARS and MERS epidemics (both coronaviruses) induced up to 40% of intra-uterine growth retardation, we expected some changes in the placenta due to the maternal condition, but not induced by the virus itself."

    "The fact that the virus was identified only at the placental level is reassuring," he said. Finding the virus in the fetus "would have been more problematic."

    "At the same time," he added, "it produces many new questions."
    • Is there a window of placental infection by SARS-CoV-2?
    • Is the placenta/pregnancy more susceptible during the first or second trimester?
    • How might the virus reach the placenta? Ascending infection through the vagina is unlikely; thus, most probably through maternal blood, which means maternal viremia. Does this happen frequently, and if so, when?

    Dr. Baud said, "Whether SARS-CoV-2 crosses the placental barrier warrants further investigation. If it does, absence of detection of the virus at the fetal level is not surprising in our case, since by analogy with cytomegalovirus (CMV) or toxoplasmosis infections, the virus is only shed in the amniotic fluid once the fetal kidneys produce sufficient urine (i.e., after 18-21 weeks' gestation) and once sufficient time has elapsed for the virus to breach the placental barrier (at the earliest, 6-8 weeks after infection)."

    "Moreover," he said, "SARS-CoV-2 is an RNA virus, known to be less stable than DNA viruses such as CMV. Placental—and subsequent fetal—infection might only be transient, as we observed with Zika virus (https://bit.ly/3bUhGGZ). "Therefore, the window of infection/detection may be extremely short. This, too, requires further investigation."

    "Pregnant women should avoid any contact with infected people, wash their hands and only go out of home if necessary," he advised. "Clinicians should be aware that pregnant women should be tested in case of symptoms or contact with anybody infected."

    "If a pregnant woman tests positive, we suggest regularly checking fetal growth by ultrasound at least once or twice during the third trimester," he concluded.

    Dr. Baud and colleagues recently developed an algorithm for managing pregnant women at risk of SARS-CoV-2 that was published in The Lancet on March 3.

    —Marilynn Larkin

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