US Pharm. 2022;47(4):22-26.
Do IgA Antibodies Protect Unvaccinated Against COVID-19?
Despite daily contact with COVID-19 patients early in the pandemic, some health professionals avoided falling ill. As a University of Gothenburg study shows, the explanation appears to be an antidote in the immune system: immunoglobulin A (IgA) antibodies to COVID-19.
To understand how the immune system builds up its defenses against COVID-19, a group of researchers at the University’s Sahlgrenska Academy monitored 156 employees at five primary care health centers, belonging to the Nötkärnan group in the Gothenburg area, for 6 months. Recruited during April and May 2020, none of them had been vaccinated against COVID-19, and most of them met infected patients daily.
The reason why some of the staff did not contract the disease seems to have been that IgA was present in their respiratory tract. These antibodies, found naturally in the secretions of mucous membranes in the airways and gastrointestinal tract, can protect the body by binding to viruses and other invading organisms.
The results of the study, published in the European Journal of Immunology, show that a third of the care workers developed antibodies to COVID-19. These subjects fell into two distinct groups based on antibody patterns and COVID-19 incidence.
One group, who had IgA antibodies only, never succumbed to COVID-19. Participants in the other group had both IgG antibodies and T cells and contracted the disease. The acquired immune system also includes IgG antibodies and T cells, which serve to recognize viruses, for example, and protect us against them.
Those responsible for the study were Christine Wennerås, professor of clinical bacteriology at Sahlgrenska Academy, University of Gothenburg, and senior physician at Sahlgrenska University Hospital, and Kristina Eriksson, professor of viral immunology at Sahlgrenska Academy.
“We all have IgA. It’s found on the mucous membranes, and COVID-19 is an infection that spreads via those membranes. We thought it was important to investigate what happened when completely healthy people encountered the coronavirus, before vaccines became available,” Dr. Wennerås says.
“Of the participants in our study, none who contracted COVID-19 required hospitalization. A lot of other research has concerned the most seriously ill patients, who have been hospitalized and in need of intensive care.”
The study focused on identifying health factors that appeared to afford protection against COVID-19. Numerous factors were found by means of extensive questionnaire surveys, blood tests, and more. As soon as a participant had nasal congestion, a cough, red eyes, changes in the sense of taste, or anything else that could be an infection, they had to answer questions and undergo a PCR test.
What the subjects who neither tested positive nor fell ill had in common were IgA antibodies, which bind to the coronavirus. Being female and having a respiratory allergy were other factors affording protection against becoming infected. However, the study provides no support for the idea that people without antibodies against COVID-19 have protective T cells.
“A lot of the COVID-related research has been about IgG antibodies and T cells. The interesting thing is that when we now examine other people’s articles and tables, we find evidence for the conclusion we’ve arrived at about IgA ourselves. But it’s not something those studies have highlighted,” Dr. Wennerås says.
Study: No Increase in Pregnancy Complications After COVID-19 Vaccination
Vaccination against COVID-19 during pregnancy is not associated with a higher risk of pregnancy complications, according to a large-scale registry study from Karolinska Institutet in Sweden and the Norwegian Institute of Public Health published in the journal JAMA.
The study, which comprised almost 160,000 pregnancies, found no increase in the risk of preterm birth, growth retardation, low Apgar scores at birth, or the need for neonatal care after vaccination against COVID-19 during pregnancy.
“The results are reassuring and can hopefully make pregnant individuals more willing to get vaccinated,” says co–first author Anne Örtqvist Rosin, researcher at the Department of Medicine, Karolinska Institutet (Solna).
Earlier studies have shown that pregnant women belong to a risk group for serious COVID-19 requiring intensive care with a higher risk of death than nonpregnant women of a fertile age. Pregnant women with severe COVID-19 are also more likely to have preterm births. Since January 2021, efficacious COVID-19 vaccines have been available in Sweden and Norway, and in May 2021 Sweden recommended all pregnant individuals to have a COVID-19 jab, followed in August by Norway.
“We’re still seeing that vaccination rates are lower than in the rest of the population, so it’s likely that there’s some concern about how the vaccines affect the pregnant individual and the fetus,” explains Dr. Örtqvist Rosin. “When the vaccines were produced, pregnant women were not included in the large clinical studies, and until now there have been no population-based data about any risk there might be to them.”
The researchers linked Sweden’s Pregnancy Register and Norway’s Medical Birth Register to each country’s vaccination register to obtain data on if and when pregnant individuals were vaccinated and with which vaccine. The study included a total of 157,521 individuals who gave birth between January 2021 and January 2022, of whom almost one-fifth (18%) had been vaccinated. It was found that vaccinated individuals were at no higher risk than unvaccinated of developing one of the studied complications.
The majority of the pregnant individuals included in the study were vaccinated after week 12 in accordance with current recommendations. Ninety-five percent received an mRNA vaccine (Pfizer-BioNTech or Moderna). This should be taken into consideration when interpreting the results, which were similar for the different mRNA vaccines, irrespective of whether one or two doses were given. Vaccination during the third trimester and vaccination with the Moderna vaccine was associated with a slightly lower risk of neonatal care.
One potential advantage of vaccination during pregnancy is that the antibodies thus formed pass through the placenta, providing the newborn baby with a certain degree of protection against COVID-19.
“We’re now planning to study how long this protection lasts and if SARS-CoV-2 infection or vaccination during pregnancy has any other lasting effects on the child’s health,” says joint last author Professor Olof Stephansson at the Department of Medicine, Karolinska Institutet (Solna).
Leafy Greens Chemical Slows Growth of COVID-19 and Cold Viruses
Researchers at Johns Hopkins Children’s Center report evidence from laboratory experiments that a chemical derived from a compound found abundantly in broccoli and other cruciferous plants may offer a potentially new and potent weapon against the viruses that cause COVID-19 and the common cold. COVID-19 has already killed more than 6 million people worldwide, and studies have shown that common colds cost an estimated economic loss of $25 billion in the United States alone each year.
In a study described March 18 in the Nature journal Communications Biology, the scientists showed that sulforaphane, a plant-derived chemical known as a phytochemical, which is already found to have anticancer effects, can inhibit the replication of SARS-CoV-2—the coronavirus that causes COVID-19—and another human coronavirus in cells and mice.
While the results are promising, the researchers caution the public against rushing to buy sulforaphane supplements available online and in stores, noting that studies of sulforaphane in humans are necessary before the chemical is proven effective and emphasizing the lack of regulation covering such supplements.
Sulforaphane’s natural precursor is particularly abundant in broccoli, cabbage, kale, and Brussels sprouts. First identified as a chemopreventive compound by a team of Johns Hopkins scientists decades ago, natural sulforaphane is derived from common food sources, such as broccoli seeds, sprouts, and mature plants, as well as infusions of sprouts or seeds for drinking. Previous studies, including those at Johns Hopkins Medicine, have shown sulforaphane to have cancer- and infection-prevention properties by way of interfering with certain cellular processes.
“When the COVID-19 pandemic started, our multidisciplinary research teams switched our investigations of other viruses and bacteria to focus on a potential treatment for what was then a challenging new virus for us,” says Children’s Center microbiologist Lori Jones-Brando, PhD, an assistant professor of pediatrics at the Johns Hopkins University School of Medicine and the senior author of the paper. “I was screening multiple compounds for anti-coronavirus activity and decided to try sulforaphane since it has shown modest activity against other microbial agents that we study.” The researchers used purified, synthetic sulforaphane purchased from commercial chemical suppliers in their experiments.
In one experiment, the research team first exposed cells to sulforaphane for 1 to 2 hours before infecting the cells with SARS-CoV-2 and the common cold coronavirus, HCoV-OC43. They found that low micromolar (µM) concentrations of sulforaphane (2.4-31 µM) reduced the replication by 50% of six strains of SARS-CoV-2, including the Delta and Omicron variants, as well as that of the HCoV-OC43 coronavirus. The investigators also observed similar results with cells that had been previously infected with the viruses, in which the protective effects of sulforaphane were seen even with an already established virus infection.
The group also examined the effects of sulforaphane when combined with remdesivir, an antiviral medication used to shorten the recovery of hospitalized adults with COVID-19 infections. In their findings, remdesivir inhibited 50% of the replication of HCoV-OC43 and SARS-CoV-2 at 22 µM and 4 µM, respectively. Further, the research team reports that sulforaphane and remdesivir interacted synergistically at several combination ratios to reduce by 50% the viral burden in cells infected with HCoV-OC43 or SARS-CoV-2. In this context, synergism means that lower doses of both sulforaphane (e.g., 1.6-3.2 µM) and remdesivir (e.g., 0.5-3.2 µM), when combined, are more effective against the viruses than either applied alone.
“Historically, we have learned that the combination of multiple compounds in a treatment regimen is an ideal strategy to treat viral infections,” says Alvaro Ordonez, MD, the first author of the paper and an assistant professor of pediatrics at the Johns Hopkins University School of Medicine. “The fact that sulforaphane and remdesivir work better combined than alone is very encouraging.”
The researchers then conducted studies in a mouse model of SARS-CoV-2 infection. They found that giving 30 mg of sulforaphane per kilogram of body weight to mice before infecting them with the virus significantly decreased the loss of body weight that is typically associated with virus infection (7.5% decrease). Further, the pretreatment resulted in a statistically significant decrease in both the viral load, or amount of virus, in the lungs (17% decrease) and upper respiratory tract (9% decrease) as well as the amount of lung injury (29% decrease) compared with infected mice that were not given sulforaphane. The compound also decreased inflammation in the lungs, protecting the cells from a hyperactive immune response that seems to be one of the driving factors that has caused many people to die from COVID-19.
“What we found is that sulforaphane is antiviral against HCoV-OC43 and SARS-CoV-2 coronaviruses while also helping control the immune response,” Dr. Ordonez says. “This multifunctional activity makes it an interesting compound to use against these viral infections, as well as those caused by other human coronaviruses.”
The team plans to conduct studies in humans to evaluate if sulforaphane can be effective in preventing or treating these infections.
“Despite the introduction of vaccines and other medications that can have side effects, effective antiviral agents are still necessary to prevent and treat COVID-19, particularly considering the potential effects of new coronavirus variants arising in the population,” Dr. Jones-Brando says. “Sulforaphane could be a promising treatment that is less expensive, safe, and readily available commercially.”
Children’s Antibody Responses to COVID-19 Stronger Than Adults’
Infants and toddlers who experienced community infection with SARS-CoV-2, the coronavirus that causes COVID-19, had significantly higher levels of antibodies against the virus compared with adults, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health in collaboration with the CDC.
The new study suggests that children tend to have strong antibody responses after SARS-CoV-2 infection. Understanding antibody responses to SARS-CoV-2 at different ages can inform COVID-19 vaccine strategies and policies. The findings were published online in the journal JCI Insight.
This analysis is based on samples taken at enrollment from 682 children and adults in 175 Maryland households who participated in a household surveillance study of SARS-CoV-2 infection and had not yet received a COVID-19 vaccine. Participants ranged in age from 0 to 62 years, and enrollment samples were collected between November 2020 and March 2021.
The researchers found evidence of SARS-CoV-2 antibodies, indicating prior infection with the virus, in 56 people at the time of enrollment. Of these 56 people with antibody evidence of previous SARS-CoV-2 infection, 15 were children aged 0 to 4 years, with the youngest aged 3 months; 13 were children aged 5 to 17 years; and 28 were adults aged 18 years or older. Antibodies to a key site on the virus’s outer spike protein—the receptor-binding domain (RBD)—were present at much higher levels in children compared with adults: more than 13 times higher in children aged 0 to 4 years, and nearly nine times higher in children aged 5 to 17 years. And levels of SARS-CoV-2 neutralizing antibodies, which may help to predict protection against severe COVID infection, were nearly twice as high in children aged 0 to 4 years compared with adults.
In most households where both children and adults had antibody evidence of SARS-CoV-2 infection, children aged 0 to 4 years had the highest levels of SARS-CoV-2 RBD and neutralizing antibodies of all infected household members.
“This study demonstrates that even children in the first few years of life have the capacity to develop strong antibody responses to SARS-CoV-2 infection, which in some cases exceed adult responses,” says Ruth Karron, MD, lead investigator and a professor in the Department of International Health and director of the Johns Hopkins Vaccine Initiative at the Bloomberg School.
Dr. Karron and colleagues set up their prospective household surveillance study, known as SARS-CoV-2 Epidemiology And Response in Children (SEARCh), to learn more about SARS-CoV-2 infection in children younger than age 5 years, a relatively understudied population. To be included in the study, each household had to have at least one child aged 4 years or younger and agree to approximately 8 months of follow-up for evidence of SARS-CoV-2 infection.
The analysis of these samples also found that:
• In the majority of households with SARS-CoV-2–positive children aged 0 to 4 years and other affected household members, the children aged 0 to 4 years had the highest levels of anti-RBD and neutralizing antibodies.
• Fifty-six (8.2%) of the blood samples, from 22 households (12.6%), contained detectable antibodies against the SARS-CoV-2 (original Wuhan variant) spike protein RBD, indicating prior infection with the virus. Half of the 56 previously infected individuals were children.
• Only about half of those with RBD antibodies had been previously told by a healthcare provider that they may have SARS-CoV-2 infection, indicating that many milder or asymptomatic SARS-CoV-2 infections in the community may not be recognized and counted as infection cases. None of the individuals in the study with previously suspected SARS-CoV-2 infection were hospitalized because of their infections.
“Very young children in our study developed high titers of antibody to the SARS-CoV-2 spike protein, which is the target antigen for COVID vaccines,” Dr. Karron says. “These findings should provide some reassurance that with the appropriate vaccine doses we can effectively immunize very young children against SARS-CoV-2.”
Few studies have looked at antibody responses to SARS-CoV-2 in both children and adults. A study of hospitalized patients found that adults mounted higher neutralizing antibody responses than children. In contrast, several community-based studies found that children mounted robust responses. Findings from this study expand on those from previous community-based studies.
Children aged 5 to 17 years are currently eligible for the Pfizer-BioNTech mRNA COVID-19 vaccine, and studies of the vaccine in younger children are ongoing.
Dr. Karron and colleagues are continuing to analyze follow-up specimens from these 56 individuals, as well as individuals infected during the SEARCh study, to learn more about the quality of their SARS-CoV-2 antibody responses and to see how durable their antibody responses are over time.
Booster Proves Benefit of Vaccination After COVID-19 Recovery
When our immune system comes into contact with the SARS-CoV-2 coronavirus, it fights back and produces antibodies. A similar immune response is triggered by coronavirus vaccines. However, there are still little data available on the strength and durability of immune protection.
A team led by Professor Carsten Watzl from the Leibniz Research Centre for Working Environment and Human Factors Institute for Occupational Research (IfADo), in cooperation with the Max Planck Institute of Molecular Physiology (MPI) and the Klinikum Dortmund in Germany, has now been able to detect high levels of neutralizing antibodies in test persons even 300 days after a coronavirus infection with the original variant of the coronavirus. And what’s more: After complete vaccination, the recovered probands showed antibody levels about five times higher than those vaccinated without prior infection. This would provide much better protection against a severe course of the disease in the event of a new infection with other coronavirus variants.
Our immune protection is provided by two systems working hand in hand. When infected with a virus, the immune system reacts by producing antibodies that can prevent the virus from infecting further cells. At the same time, so-called T-killer cells can recognize the foreign virus components and kill already infected cells. During the immune reaction, the antibodies constantly improve and are finally tailor-made for the pathogen. The amount of these neutralizing antibodies indicates how well a new infection can be fought off by the body.
One of the main targets of the immune system is the spike protein, which is used by the virus to bind to human cells and then infect them. “We have been able to produce a part of this protein, or more precisely the area that docks with the cell, in high purity in the test tube,” reports Jan-Erik Hoffmann, head of protein production at the MPI Dortmund. With this exact copy and blood samples from the Klinikum Dortmund, the researchers at IfADo were able to develop a reliable and meaningful detection system for coronavirus antibodies. In close exchange with the Dortmund health department and the Dortmund hospital, the scientists used this system to perform a study with about 140 volunteers from a Dortmund health facility with several documented cases of SARS-CoV-2 infection at the beginning of the pandemic in March 2020.
Effective amounts of neutralizing antibodies against the spike protein could be detected in almost all of the subjects who tested positive for SARS-CoV-2. And even after 300 days, the antibody levels had hardly decreased in three out of four subjects. However, test persons were infected with the original variant of the coronavirus, and neutralizing antibodies against the original spike protein were measured. As we know, the virus has now evolved in such a way that immunity to the original virus currently offers significantly less protection. Therefore, the researchers also investigated the effect of vaccination with the vaccines from AstraZeneca and BioNTech on the immune system. The result: After complete vaccination, recovered test persons developed up to five times more neutralizing antibodies than vaccinated persons without prior infection. This should also provide better protection against current variants.
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