This article is written by Zhuang Shilihe
During the COVID-19 pandemic, how to protect our young children from infection has always been one of the hot issues in research in various countries.
In general, humans want to obtain specific antibodies against a certain kind of antibody in two ways, either through natural infection or through vaccination. However, it is clear that we will not let infants and young children risk getting sick to actively contract a virus, and for infants and young children under 3 years of age, there is currently no COVID-19 vaccine approved in various countries.
Are there other possible ways to get antibodies to infants and even newborns as quickly as possible?
Like the blood magic on Harry Potter, infants and young children also have a natural protection from their mothers - maternal antibodies.
"Inheritance" of antibodies
Before we talk about "bloodline magic", let's talk a little bit about the basics of immunity.
Since its birth, humans have been in a world full of pathogens, including a variety of harmful bacteria, viruses and fungi. To avoid infection, we have a very complex immune system that fights off these pathogens.
This set of immune systems is divided into two parts – innate immunity and adaptive immunity.
The former, also known as non-specific immunity (or innate immunity), is a natural defense gradually established by humans in the process of evolution, which is innate to us and does not target specific pathogens, such as skin, respiratory mucosa and some immune cells (such as macrophages, neutrophils) and so on;
The latter, also called specific immunity (or acquired immunity), is the immunity produced by us against a specific pathogen, specifically the immunity brought about by the natural infection or vaccination of the pathogen, and is divided into humoral immunity mainly mediated by B cells and cellular immunity (cellular immunity) mainly mediated by T cells, the former mainly acts to produce antibodies, and the latter is mainly T cell response.
Source: Reference 3
Some immune cells appear as early as 9 weeks of pregnancy. At 13 weeks' gestation, dendritic cells— an important antigen-presenting cell— can be found on the fetal skin, spleen, thymus, and lungs.
These findings mean that in the early middle and early stages of pregnancy, the fetus's immune system has begun to develop. The problem, however, is that specific immunity can only occur after exposure to pathogens.
So, where do fetal antibodies come from?
Here we have to mention the golden bell hood of the fetus - the blood fetal barrier. The blood-fetal barrier can block many pathogens from entering the fetus and avoid infection, but at the same time allow some of the mother's antibodies (IgG) to enter the fetus, forming the inherent protection of the fetus.
That is to say, the fetus does not need to be exposed to the pathogen to "inherit" the antibody from the mother.
In past studies, we have found that many antibodies can pass through the blood-fetal barrier, including antibodies formed after the mother is vaccinated against influenza.
A 2019 meta-analysis showed that pregnant women who received the influenza vaccine in the third trimester had higher levels of hemagglutinin (the protein on the surface of the influenza virus) in their newborns to inhibit antibodies, and that influenza vaccination in the third trimester was more conducive to delivering antibodies to the fetus.
As a result, in many national guidelines, pregnant women are also the priority group for influenza vaccines – both to protect the mother herself and the baby in her belly.
During the COVID-19 pandemic, the same question has once again attracted attention - can antibodies against the new crown virus be transmitted from mother to child?
In other words, after a mother has been vaccinated against COVID-19 or a natural infection, can she pass on her antibodies to her baby?
Latest research: Vaccination against COVID-19 during pregnancy makes antibodies in the baby last longer
On February 7, 2022, a harvard university study published in JAMA told us the answer.
The study, conducted by Harvard University-affiliated Massachusetts General Hospital and Brigan and Women's Hospital, included pregnant women who had been infected with or vaccinated against COVID-19 at 20 to 32 weeks of pregnancy. This period was chosen because past studies have shown that antibodies are more likely to be transferred to the fetus through the placenta at this time.
The researchers collected blood samples from the mother and cord blood samples from the baby at birth, and collected capillary serum samples from the baby for 2 and 6 months after birth, using the ELISA method to detect the titer of the IgG antibody against the new coronavirus S protein (hereinafter referred to as the antibody). Ultimately, 12 mothers who had been infected with COVID-19 and 72 who had been vaccinated against COVID-19 were included in the study.
The findings suggest:
- Compared to naturally infected mothers, vaccinated mothers have higher levels of antibodies in their bodies or in their umbilical cord blood during childbirth.
- In babies born to vaccinated mothers, protective antibodies are detectable in 98% after 2 months of life.
Similarly, antibody levels are more persistent in babies born to vaccinated mothers: 57% of babies still have detectable antibodies after 6 months of life, compared to only 8% of babies born to mothers who are naturally infected with the new coronavirus.
Source: Reference 1
This study means that mothers who are vaccinated against COVID-19 at the time of pregnancy not only transfer antibodies to the baby's body, but also transfer the quality of antibodies to better than mothers who are naturally infected with COVID-19.
The persistence of antibodies is a very important issue.
The reason why the "6 months" time point was chosen is because there is currently no COVID-19 vaccine approved for use in children under 3 years of age (the largest clinical trial is only for children ≥6 months), and even if the influenza vaccine is very mature, the lower age limit for approval is 6 months.
Therefore, for babies at 0 to 6 months, antibodies passed down from their mothers are crucial to defending against the new crown virus.
After birth, the mother still has a special way to continuously transmit antibodies to the baby - breastfeeding.
On November 10, 2021, a study by New York University and the University of Rochester published in JAMA Pediatrics showed that high levels of IgA antibodies or IgG antibodies were found in the milk of 77 mothers (47 in the infected group and 30 in the vaccine group) that could neutralize the virus in both live viruses and in trials.
Source: Reference 2
IgA is the absolute workhorse in breast milk, accounting for 90% of all antibodies, called secretory IgA (SIgA), and is the highest in colostrum.
SIgA enters the gastrointestinal tract of newborns and infants with milk, and since it is mainly in a binary form, the two IgAs are connected by secretory components (Sc), which prevent SIgA from being protected from the action of proteinases.
Thus, SIgA can be destroyed by gastric acid and digestive enzymes, but adheres to its intestinal mucosa, absorbs it directly into the infant's blood circulation through the mucosa, and is secreted through the mucosal epithelial cells of various systems - such as the respiratory mucosa, the urinary tract mucosa, thereby preventing infection of the corresponding parts.
This study by JAMA Pediatrics shows that the new crown antibodies in the mother's body can be transmitted not only through the blood-fetal barrier to the baby, but also through breastfeeding.
Although the amount of protection that breast milk's COVID-19 antibodies will give to your baby is still being studied, these studies together show one thing :
The mother, through all her means, strives to pass on the antibodies that protect herself to the baby.
Do pregnant women have to be vaccinated against COVID-19?
In addition to effectiveness, pregnant women also need to consider the safety of the new crown vaccine.
Researchers at the University of British Columbia published the largest COVID-19 vaccine safety analysis for pregnant women in medRxiv.
The study data came from CANVAS (Canada's National Vaccine Safety Network), where researchers emailed vaccinators about adverse reactions within 7 days of vaccination, particularly significant health events (referring to absenteeism/absenteeism or need to see a doctor due to health problems).
The study collected information on women aged 15 to 49 years who received two mRNA vaccines (Pfizer and Moderna) during pregnancy in CNVAS and established unvaccinated pregnant women as a control group. The findings suggest:
- 4.0% (226/5597) of pregnant women had an important health event after the first dose of mRNA vaccine, while 7.3% (227/3108) occurred after the second dose, compared with 3.2% (11/339) of unvaccinated pregnant women;
- Compared with unvaccinated pregnant women, pregnant women are more likely to have an important health event after receiving the second dose of The Moderna vaccine (adjusted odds ratio 4.4), but not the first dose of the Moderna vaccine or any of the Pfizer vaccines.
- Pregnant women are less likely to have an important health event after receiving any one dose of mRNA vaccine compared to women who are not pregnant, with the first dose of aOR 0.63 and the second dose of aOR 0.62.
- If limited to events requiring medical attention, there was no significant difference across all cohorts.
On the question of whether the vaccine causes miscarriage/stillbirth, studies have shown that most pregnancy loss occurs in the first trimester (73/83,88%), and there is no significant difference between pregnant women (1.5%) within 7 days of receiving either vaccine and pregnant women who are not vaccinated (2.1%). Other adverse pregnancy events, such as vaginal bleeding, fetal heart rate abnormalities, and decreased fetal motility, are rarely reported within 7 days of either MRNA vaccination.
The results show that mRNA vaccine has good safety for pregnant women.
In terms of inactivated vaccines widely vaccinated in the mainland, on December 17, 2021, Coxing and IQVIA Brazil published a preprinted article study on the medRxiv platform, collecting a total of 3333 suspected abnormal reactions to vaccination from April 2021 to August 2021 from the Brazilian Suspected Abnormal Response Monitoring System for Vaccination (SI-EAPV).
Results showed that the overall incidence of adverse events in pregnant women was 309.4 per 100,000 doses (95% CI: 297.23, 321.51), of which 90.65% were non-serious events. The incidence of maternal events was 4.78%, including spontaneous abortion (2.37%), pregnancy bleeding (0.76%), and neonatal mortality (0.52%).
The study showed that among the four vaccines in Brazil (Coxing, Pfizer, AstraZeneca, Johnson & Johnson), the Cogener COVID-19 inactivated vaccine had the lowest incidence of adverse events (74.08/100,000 doses, 95% CI: 63.47, 84.69).
However, for pregnant women to vaccinate against COVID-19, it is necessary to consider the type of vaccine and the risk of local outbreaks, and follow local vaccination strategies.
Currently, the CDC recommends that pregnant women, breastfeeders, and people who are trying to conceive or may become pregnant in the future receive COVID-19 vaccinations, "pregnant women should complete the COVID-19 vaccination on time, including the new crown booster injection on time." The WHO also said that pregnant women, those who are trying to conceive and those who breastfeed can be vaccinated against COVID-19.
According to the Technical Guidelines for COVID-19 Vaccination (First Edition) released by the mainland on March 29, 2021, it is recommended for women of childbearing age and lactating age that if they are pregnant after vaccination or if they are vaccinated in the case of an unknown pregnancy, it is not recommended to terminate their pregnancy; for women with pregnancy preparation plans, it is not necessary to delay the pregnancy plan just because of the new crown virus vaccination.
At the same time, it is recommended to vaccinate lactating women (such as medical staff, etc.) who are at high risk of new coronavirus infection. Breastfeeding is recommended after breastfeeding women have been vaccinated against COVID-19.
Lightning on the forehead
The body's immune system is very complex, and to date, the mechanism by which we deliver these antibodies is still not fully understood.
The mother's antibodies protect the baby. Rationally, this is a mechanism by which the immune system fights foreign pathogens; emotionally, it is the most primitive and powerful care of the mother for her child.
While these studies provide an important reference for COVID-19 vaccination, they also show how Homo sapiens, who have spent hundreds of thousands of years finally at the top of the food chain, can protect their pups with all the power of their lives.
Just like Lily's blood magic for Harry Potter repelled Voldemort's most vicious Awada Spell — in this world, the first person to fight off all kinds of demons for you was your mother. (Planner: z_popeye, Producer: Gyouza)
Image source: Screenshot of the Harry Potter movie
Acknowledgements: This article has been professionally reviewed by the co-author @Halogen Vaccine
Source: Screenshot of the Harry Potter movie
Resources:
[1] Shook LL, Atyeo CG, Yonker LM, et al. Durability of Anti-Spike Antibodies in Infants After Maternal COVID-19 Vaccination or Natural Infection. JAMA. Published online February 07, 2022. doi:10.1001/jama.2022.1206
[2] Young BE, Seppo AE, Diaz N, et al. Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination. JAMA Pediatr. 2022;176(2):159–168. doi:10.1001/jamapediatrics.2021.4897