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Safety and effectiveness of COVID-19 vaccination during pregnancy
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Safety and effectiveness of COVID-19 vaccination during pregnancy
On July 14, 2023, a research paper titled “Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy” was published by Professor Mary K. Prahl and her team from the Department of Pediatrics at the University of California, San Francisco.
The paper was published in JAMA Netw Open, a monthly open-access journal by the American Medical Association.
The study aimed to evaluate the effectiveness and safety of COVID-19 mRNA vaccines by conducting a year-long follow-up on pregnant women who received the vaccines between December 1, 2020, and December 31, 2021.
Viki Male, an immunologist from Imperial College London, shared the research on social media, intending to present the study findings. Unexpectedly, this sparked controversy among extreme online users who accused her of endorsing the COVID-19 vaccine, leading to irrational personal attacks and insults. The sensitivity surrounding vaccination for pregnant women stems largely from concerns and doubts about vaccine safety.
Despite the official recommendation from the World Health Organization (WHO) for pregnant women to receive the COVID-19 vaccine, many individuals still struggle to make a decision:
Some worry about the potential severe effects on the fetus if they contract COVID-19 during pregnancy and choose not to get vaccinated.
Others opt for vaccination but are concerned about possible intense reactions during pregnancy or adverse effects on infant development.
Although it appears that the COVID-19 pandemic has faded from daily life, it is essential to share relevant research findings to provide a more rational understanding of whether pregnant women should receive the COVID-19 vaccine.
What are the risks of being infected with the new coronavirus during pregnancy?
The researchers conducted a meta-analysis (a statistical analysis method that combines the results of multiple independent clinical studies to quantify the severity of symptoms in 92 pregnant people who were infected with COVID-19 and non-pregnant people who were infected with COVID-19 (matched age/sex). analysis, to provide more reliable evidence for clinical treatment) , it was found that pregnancy would increase the risk of requiring intensive care, mechanical breathing assistance, and extracorporeal membrane oxygenation (ECMO) , but pregnancy did not lead to an overall risk of COVID-19 infection.
increased risk of death. In other words , pregnancy may increase the severity of COVID-19 symptoms .
Someone also conducted a meta-analysis of 111 studies to analyze the pregnancy outcomes of pregnant women infected with COVID-19 and those who were not infected with COVID-19, and found that infection with COVID-19 can lead to premature birth, preeclampsia, stillbirth, neonatal mortality and maternal death risk has increased.
Viraemia (a condition in which the virus enters the blood) is very rare in pregnant COVID-19-infected individuals, and placental co-expression of ACE2 and TMPRSS2 receptors is rare, and placental expression of ACE2 decreases throughout pregnancy .
Although 2019-nCoV infection is rare in the placenta , coagulation and inflammation associated with 2019-nCoV infection also occur , most commonly manifested as intervillous thrombosis and fibrin deposition.
Decidualization of the endometrium is an important feature of implantation and pregnancy. Examination of the decidua of pregnancies infected with COVID-19 revealed localized activation of maternal natural killer cells and T cells, involving the expression of typical genes associated with preeclampsia.
Once the placenta is indeed infected, a more severe inflammatory syndrome, 2019-nCoV placenta, is characterized by histiocytic intervilllitis, perivillous fibrin deposition, and trophoblast necrosis, a risk factor for fetal distress or death .
Many studies have reported that babies born to people infected with the new coronavirus do have the phenomenon of being infected with the new coronavirus .
Some studies have found that the probability of infants being positive for the new coronavirus is 0.9-2.8% through nasopharyngeal swab testing.
However, this detection method cannot indicate that the infant was infected in the womb, because there is a possibility of horizontal transmission of infection shortly after birth.
There are also studies that detect specific IgM in umbilical cord blood in order to more accurately judge vertically transmitted neonatal infections. It was found that in pregnancy with new coronavirus infection, 0% -7.7% of cases can be detected in umbilical cord blood to Spike-specific IgM.
Even if the placenta is not infected with the new coronavirus, if it is infected with the new coronavirus during pregnancy, the levels of inflammatory cytokines in the neonatal cord blood will increase.
What is particularly worrying is that the above-mentioned research data were all collected during the first wave of COVID-19 epidemic.
It was found that placental inflammation, which was rarely seen in people infected with the original strain of COVID-19, with the continuous mutation of COVID-19 virus, in Alpha and Delta variants are becoming more and more common in waves of the pandemic .
That is to say, the impact of infection with new coronavirus variants that may appear in the future on pregnant women or newborns will be different from the conclusions obtained by current research.
Safety of COVID-19 Vaccination During Pregnancy
First of all, we have to clarify a concept, that is, there is a very long and successful history of preventing maternal infection of viruses or conferring passive immunity to newborns through vaccination during pregnancy .
Babies born to mothers vaccinated against smallpox during pregnancy were observed to be immune as early as 1879, as was the case with pertussis and tetanus vaccinations in the mid-20th century.
Influenza vaccination has been recommended during pregnancy in the United States since 1997. Influenza and pertussis vaccines have been routinely offered to pregnant women in the UK since 2010 and 2012.
The United States and Israel were the first countries to provide pregnant women with COVID-19 vaccine, and they provided COVID-19 mRNA vaccine.
Therefore, most of the early data on COVID-19 vaccination during pregnancy come from COVID-19 mRNA vaccine. Among 64,234 pregnant women vaccinated against COVID-19 during pregnancies registered in Canada, among 31,343 deliveries as of October 31, 2021, the rates of stillbirth, preterm birth, or small-for-gestational-age infants were not compared with historical data Increase.
Similar registration studies in other countries have shown that vaccination against COVID-19 during pregnancy does not have serious adverse consequences for pregnant women or childbirth outcomes or newborns .
Scientists found that after receiving COVID-19 vaccine during pregnancy, no specific IgM was detected in the umbilical cord blood, indicating that the maternal vaccination did not trigger an immune response in the fetus, that is, the antigen did not cross the placenta .
Consistent with this, studies have shown that Spike mRNA or protein was not detected in placenta or cord blood .
In addition, studies have found that vaccination during pregnancy has nothing to do with pathological changes in the placenta. These findings suggest that vaccination is unlikely to have a direct effect on fetal development.
However, pregnant women do experience local or systemic immune responses after vaccination with the COVID-19 vaccine at roughly the same rate as in the general population.
In a recent study by Mary K. Prahl, 76 pregnant women were initially immunized with the COVID-19 mRNA vaccine during pregnancy.
Most participants reported local or systemic post-vaccination symptoms such as tenderness or erythema at the injection site, fever/chills, muscle/general/joint pain, fatigue/headache, nausea/vomiting .
Systemic symptoms were more likely after the second vaccination (71%) than after the first vaccination (44%) .
However, none of the participants experienced serious adverse reactions after vaccination.
Reactogenicity of COVID-19 mRNA Vaccine During Pregnancy
Effectiveness of COVID-19 Vaccination During Pregnancy
It is often said that the immune system is weakened during pregnancy, although this claim has not been confirmed by scientific research, but there are differences in the immune system during pregnancy compared to the non-pregnant state.
It has been observed for a long time that cell-mediated autoimmune diseases tend to be in remission during pregnancy, while antibody-mediated diseases are exacerbated.
So we really need to be concerned about whether vaccination during pregnancy will be as effective as vaccination in the normal population.
Two cohort studies from Israel evaluated the effectiveness of the COVID-19 vaccine during pregnancy and found it to be about the same as in the general population .
In a recent study by Mary K. Prahl, they found that all pregnant women who received the COVID-19 mRNA vaccine during pregnancy triggered a strong antibody response that lasted until delivery.
There were no differences in serum IgG titers between 10 pregnant women vaccinated in the first trimester and 36 pregnant women vaccinated in the second trimester.
Thirty pregnant women vaccinated in the third trimester had higher IgG serum titers than those vaccinated in the first or second trimester.
Also, the half-lives of IgG produced by pregnant women vaccinated at three different gestational times were similar.
Antibody responses triggered by inoculation with COVID-19 mRNA at different stages of pregnancy
Mary K. Prahl also assessed the association between symptoms and maternal IgG titers after COVID-19 mRNA vaccination .
After the second vaccination, IgG titers did not differ between pregnant women with and without vaccination symptoms at the injection site, however, IgG titers were higher in pregnant women with systemic vaccination symptoms after the second vaccination than in pregnant women who developed vaccination symptoms at the injection site.
Pregnant women without symptoms of vaccination were 65.5% higher. Overall, IgG titers were 6.3 times higher in pregnant women with any vaccination symptoms after the second vaccination than in pregnant women without any vaccination symptoms.
Reactogenicity and immunogenicity of COVID-19 mRNA vaccine administered during pregnancy
Placental transfer of antibodies provides immune protection to newborns
We all know that maternal IgG produced through vaccination during pregnancy crosses the placenta, and at birth, maternal IgG can be detected in the cord blood and is still detectable in the blood of a 6-month-old newborn.
Scientists have long discovered that the transfer of IgG through the placenta after tetanus and pertussis vaccination can provide immune protection for babies, and by analogy, vaccination with COVID-19 during pregnancy should also provide immunity for babies against new coronavirus infection.
Early research data show that in terms of the effectiveness of preventing neonatal infection of newborns less than 6 months old, the effectiveness of vaccination after 20 weeks of pregnancy can reach 80%, while the effectiveness of vaccination before 20 weeks of pregnancy is only 32% .
Mary K. Prahl found that pregnant women who received COVID-19 mRNA vaccine at different stages of pregnancy showed IgG placental transfer.
There were no differences in maternal and cord blood IgG titers at delivery in the first- and late-gestational vaccination groups.
Cord blood IgG titers of pregnant women vaccinated in the second trimester were higher than maternal IgG titers.
The IgG transfer rate of pregnant women vaccinated with COVID-19 mRNA vaccine at different stages will also be different, but regardless of the stage of gestation, all infants have umbilical cord blood IgG titers higher than the baseline level.
Placental transfer of maternal IgG antibodies triggered by COVID-19 mRNA vaccine during delivery
Mary K. Prahl found that most infants born to pregnant women who received COVID-19 mRNA vaccine in the second and third trimesters maintained positive IgG titers for at least 5 to 6 months, and the rate of antibody decay within 30 days was significantly slower than that of newborn infants. Maternal .
They also found that IgG/IgA titers in breast milk of mothers vaccinated during pregnancy decreased from colostrum to 5/6 months after birth.
Changes in antibody titers in breast milk of pregnant women vaccinated with COVID-19 mRNA vaccine
Through the above-mentioned various studies, we know that the occurrence of new coronavirus infection during pregnancy poses a major risk to pregnant women and fetuses.
Vaccination with COVID-19 mRNA vaccine will cause some local or systemic vaccination symptoms in pregnant women. This symptom is usually related to the effective vaccine.
Sex-related, however, will not cause very serious adverse consequences in pregnant women, nor will it have any adverse effects on pregnancy outcomes.
COVID-19 mRNA vaccine antigen will not be passed to the fetus through the placenta to trigger an immune response.
The effectiveness of vaccination during pregnancy was similar to that in the general population.
Antibodies in the mother are passed on to the newborn through the placenta, providing immune protection for at least five or six months, and IgG/IgA antibodies can be detected in breast milk.
Although WHO recommends that pregnant women can receive COVID-19 mRNA vaccine, the vaccination rate of COVID-19 vaccine during pregnancy is still very low in many countries, and it is completely understandable that people are cautious about the safety of vaccination at this stage.
Due to the widespread misinformation about COVID-19 vaccination, it is necessary to convey the conclusions of relevant scientific research to the general public, so as to help people make better rational choices during the outbreak.
Of course, before getting COVID-19 vaccine, pregnant women should consult their doctor or midwife to understand whether they are suitable for vaccination and which vaccine they should choose.
Different countries and regions may have different policies and guidelines. After vaccination, pregnant women should also pay attention to observe their own body reactions, and seek medical treatment in time if they feel unwell.
Finally, when it comes to maternal antibodies, there are actually two sides.
On the one hand, maternal antibodies can provide early immune protection for newborns and prevent many pathogenic infections. The immune response is suppressed.
In the next issue, we will talk about whether maternal antibodies to the new coronavirus can suppress the immune response triggered by the baby’s vaccination.
SARS-CoV-2 infection and COVID-19 vaccination in pregnancy
Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy
Safety and effectiveness of COVID-19 vaccination during pregnancy
(source:internet, reference only)