Virus World

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has found evidence of small hemorrhages in the brain tissue of fetuses during the peak of COVID-19 cases in the UK. The research, published in Brain, found that the hemorrhages are linked to a reduction in blood vessel integrity. The cause of these hemorrhages is unclear, however possible explanations might be as a direct consequence of the infection or an indirect consequence of the maternal immune response. The study suggests that COVID-19 might affect the fetal brain during the earliest stages of gestation, highlighting a need for further study into the potential impact on subsequent neurological development. The researchers studied 26 samples of human fetal tissue with observed hemorrhages from a total of 661 samples collected between July 2020 and April 2022. It was established that the COVID-19 virus was present in all of the hemorrhagic samples. The majority of the hemorrhagic samples came from donated fetal tissue between the late first and early second trimester of gestation—a particularly important period of human fetal brain development during which the tight junctions between endothelial cells of the blood vessels increase to form the blood brain barrier, the semipermeable barrier that protects the brain from foreign substances.

Upon further study, the integrity of the blood vessels within the hemorrhagic samples was found to be considerably lower than the non-infected samples, ultimately providing an explanation as to why bleeds could be seen in the samples. "While hemorrhages do occasionally occur in developing brains, it is extremely unusual for there to be this many instances within a 21 month period. It is now of the utmost importance that we follow up with children that were prenatally exposed to COVID-19 so that we can establish if there are any long-lasting neurodevelopmental effects," said Dr. Katie Long, the study's lead investigator from King's IoPPN. Marco Massimo, the study's first author from King's IoPPN said, "Our findings suggest that there is an association between the early development of human fetal brain tissue and vulnerability to infection from COVID-19." Professor Lucilla Poston CBE, Professor of Maternal & Fetal Health at King's College London, said, "We know that severe viral infection may influence the fetal brain, but this important study is the first to suggest that this may occur in pregnancies affected by COVID infection. Whatever the cause, a direct effect of the virus or an indirect consequence of maternal infection, this study highlights the need for pregnant women to be vaccinated against COVID-19, thus avoiding complications for both mother and baby." Dr. Long concludes, "While we haven't yet been able to establish clear causation, we certainly feel that it highlights a need for expectant mothers to take extra precautions at a time when cases are on the rise."

Cited study published in Brain (Jan. 16, 2023):

https://doi.org/10.1093/brain/awac372 

Following 803 pregnant and postpartum deaths, authorities have warned women to delay pregnancy as alarm rises.  This month should have been one of the happiest in Letícia Aparecida Gomes’s life. The pregnant 23-year-old Brazilian had been due to marry before delivering her baby, Elloah, in August. Instead, as the Covid-19 pandemic swept Gomes’s country claiming thousands of lives each day, she was taken to hospital having been infected herself. “I felt desperate when I realised it was serious because this is my first pregnancy, my first daughter,” said Gomes, a nursing technician from Maricá, a coastal city an hour’s drive east of Rio de Janeiro. Gomes was lucky. After an agonising week in intensive care, she was discharged and is now recovering at home and preparing to welcome her child.  Others have been far less fortunate. At least 803 pregnant and postpartum women have died from Covid-19 since the pandemic hit Brazil last February, according to a Brazilian taskforce that is studying Covid’s impact on pregnancy. More than half of those deaths, 432, happened this year as Brazil’s pandemic accelerated into by far its deadliest phase. In recent weeks Brazilian newspapers have filled with heartbreaking stories of young mothers killed by the disease including another 23-year-old, Maria Laura Prucoli, who died on Rio’s deprived outskirts last week after her daughter, Lavínia, was delivered by emergency C-section. On 3 April, three days before Gomes was admitted to hospital, a 20-year-old woman who was seven months pregnant died in the midwestern state of Mato Grosso after waiting four days for an intensive care bed.

Concern over the risk Covid poses to pregnant and postpartum women has been expressed around the world, including in the UK where doctors have reported an increase in intensive care admissions and the use of ventilators during the second wave. But experts and activists say the situation in Brazil is particularly alarming, with authorities recently urging women to delay having children until the country’s outbreak loses steam. “We are facing a calamity of maternal deaths here,” said Carla Andreucci, a Brazilian obstetrician and member of the pregnancy taskforce. “There are women dying without finding an ICU bed, without being offered ventilation, without being intubated … It’s like we’re just standing by and watching this happen.” Last July Andreucci’s group published a study suggesting 77.5% of the world’s Covid-related maternal deaths had occurred in the South American country, although they noted that some low-income countries did not release such data. Specialists say a range of factors help explain the high number of pregnant women falling severely ill and losing their lives to Covid in Brazil. They include the way in which the pandemic-induced healthcare collapse deepened historically high rates of maternal deaths. Inadequate access to prenatal care and family planning are longstanding challenges of Brazil’s public health system, with the country suffering rates of maternal deaths more than three times the average of OECD countries even before the pandemic. Some suspect new forms of coronavirus, such as the P1 variant linked to the Brazilian Amazon, may also be partly responsible although there is still no concrete evidence of this. “We don’t have genetic tests but we believe the outbreak of P1 in January played a role in this catastrophe,” Andreucci said, noting that the profile of victims had changed in recent months. Last year, most victims were non-white women from poor areas with risk factors such as diabetes, obesity and cardiovascular disease. This year, white women with no risk factors have been dying as well. Letícia Gomes had been enjoying a healthy pregnancy until she started experiencing coughing fits, tiredness and a temperature in late March and her oxygen levels fell to a worrying 83%. She suspects she was infected making the 20-minute bus journey from her house to the nursing home where she works. During her first night in hospital, Gomes remembered sharing a room with eight other patients: “It was nerve-racking because you saw people in need of oxygen, people dying in front of you, doctors having to choose who had priority.” The next day Gomes was transferred to a specialist unit for pregnant women with Covid at the State Public Servants Hospital in Rio. There, doctors reassured her the illness had not affected her child. “They made me listen to my baby’s heart, so I knew she was fine,” said Gomes, who recalled feeling overjoyed when she called home with news of her discharge over a week in the ICU.

“Everyone was surprised and cried. I cried too,” Gomes said. Her wedding will finally happen on 21 May. A domestic outcry over the plight of Brazilian pregnant and postpartum women saw the health ministry this week include them in the priority vaccination group. So far, however, fewer than 10% of Brazilians have received two doses meaning most pregnant women will face a long wait. In the meantime, the leftist congresswoman Sâmia Bomfim, who is seven months pregnant with her first child, is proposing new legislation that would allow expectant mothers to work from home during the pandemic. “I am able to socially isolate and work from home, but the majority of pregnant women in Brazil don’t have this privilege”, Bomfim said. A total of 8.5 million Brazilian women have left the workforce since the epidemic began last February. Raíssa Perlingeiro, an infectious disease specialist at the Covid centre in Rio, said that over the past three months, as Brazil’s outbreak intensified, her unit had become busier and their shifts more demanding. Patients were arriving with more serious conditions than before. “It is very tough work and it’s very hard to watch women go through this – particularly because I’m seven months pregnant myself,” Perlingeiro said. The 32-year-old doctor said she had decided to continue working at the unit after being vaccinated as part of a campaign to protect frontline healthworkers. “I couldn’t be away from work at such a difficult time, the team is already small,” Perlingeiro said. “I had to do my part.”

BACKGROUND

Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy.

METHODS

From December 14, 2020, to February 28, 2021, we used data from the “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons.

RESULTS

A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases).

CONCLUSIONS

Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

Published in NEJM (June 17, 2021):

https://doi.org/10.1056/NEJMoa2104983 

See also NEJM (June 17, 2021):

https://doi.org/10.1056/NEJMe2107070 

The COVID-19 infection rate among pregnant women was estimated to be 70% higher than in similarly aged adults in Washington state, according to a new study published today in American Journal of Obstetrics and Gynecology. Other key findings include: The study also showed that the number of COVID-19 infections in pregnant patients from nearly all communities of color in Washington was high. There was a twofold to fourfold higher prevalence of pregnant patients with COVID-19 infections from communities of color than expected based on the race-ethnicity distribution of pregnant women in Washington in 2018. A high number of pregnant women with COVID-19 received their medical care in a language other than English. This indicates that public health outreach to enhance vaccination rates in these communities is crucial.  COVID-19 vaccine allocation is based priority lists set by each state's department of health, which can vary. In some states, pregnancy is considered a high-risk health condition for COVID-19 vaccine allocation in Phase 1B. Texas, New Hampshire, New Mexico and Alaska are among the states that prioritize pregnant women for COVID-19 vaccines in schedule Phase 1B. "The vaccine distribution plans vary quite a bit, state-by-state, and pregnant women are written out of the allocation prioritization in about half of U.S. States. Many states are not even linking their COVID-19 vaccine allocation plans with the high-risk medical conditions listed by the CDC - which include pregnancy, Adams Waldorf said.

"The higher infection rates in pregnant patients, coupled with an elevated risk for severe illness and maternal mortality due to COVID-19, suggests that pregnancy should be considered a high-risk health condition for COVID-19 vaccine allocation in Phase 1B all across the United States," she added. "The time to act is now." She said this study is unique in the United States because it is the first to address the question of infection rates in pregnancy in a large population that represents the majority of pregnancies in the state. The data can inform vaccine policy and guide public health workers and physicians in trying to mitigate COVID-19 in vulnerable populations.  The multisite study included 35 hospitals and clinics that compose the Washington State COVID-19 in Pregnancy Collaborative led by Adams Waldorf and Erica Lokken, an epidemiologist at the UW School of Public Health. The group identified 240 pregnant women who acquired COVID-19 from March through June 2020. This number represents all such known cases at the collaborating sites, which account for 61% of births in the state each year. "Higher infection rates in pregnant patients may be due to the overrepresentation of women in many professions and industries considered essential during the COVID-19 pandemic - including healthcare, education, service sectors," said Lokken. Pregnant women may also have larger households, children in daycare or playgroups, and be caregivers within an extended family, she added.

This study data fills critical gaps and provides an important estimate of regional COVID-19 infection rates in the pregnant population, Waldorf said. The Centers for Disease Control and Prevention's estimated infection rates may not be representative, she said. "COVID-19 case reports are missing pregnancy status in up to 65% of reports for women of reproductive age. As a result, the number of pregnant patients infected with COVID-19 was likely underrepresented in national numbers," the authors concluded. "When the data is woefully incomplete for specific groups, like pregnant women, it is easy to assume that they haven't been impacted by the pandemic. This was not the case," said Adams Waldorf. Pregnant healthcare workers have received the COVID-19 vaccine, and Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, has reported no "red flags" in preliminary data about post-vaccination well-being of this population. Adams Waldorf urges pregnant women to discuss the risks and benefits of COVID-19 vaccination with their prenatal care provider. More ob-gyns have begun recommending that pregnant women take the vaccine. "We want to use information from this study to be more prepared for the next pandemic and to not brush pregnant women to the side. They need to have a seat at the table when it comes to vaccine trials and vaccine allocation," Adams Waldorf said.

American Journal of Obstetrics and Gynecology (Feb. 9, 2021):

https://doi.org/10.1016/j.ajog.2021.02.011