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Antibody Response Affects COVID-19 Outcomes in Kids and Adults

Posted on by Dr. Francis Collins

Sick child during COVID
Credit: SDI Productions

Doctors can’t reliably predict whether an adult newly diagnosed with COVID-19 will recover quickly or battle life-threatening complications. The same is true for children.

Thankfully, the vast majority of kids with COVID-19 don’t get sick or show only mild flu-like symptoms. But a small percentage develop a delayed, but extremely troubling, syndrome called multisystem inflammatory syndrome in children (MIS-C). This can cause severe inflammation of the heart, lungs, kidneys, brain, and other parts of the body, coming on weeks after recovering from COVID-19. Fortunately, most kids respond to treatment and make rapid recoveries.

COVID-19’s sometimes different effects on kids likely stem not from the severity of the infection itself, but from differences in the immune response or its aftermath. Additional support for this notion comes from a new study, published in the journal Nature Medicine, that compared immune responses among children and adults with COVID-19 [1]. The study shows that the antibody responses in kids and adults with mild COVID-19 are quite similar. However, the complications seen in kids with MIS-C and adults with severe COVID-19 appear to be driven by two distinctly different types of antibodies involved in different aspects of the immune response.

The new findings come from pediatric pulmonologist Lael Yonker, Massachusetts General Hospital (MGH) Cystic Fibrosis Center, Boston, and immunologist Galit Alter, the Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge. Yonker runs a biorepository that collects samples from kids with cystic fibrosis. When the pandemic began, she started collecting plasma samples from children with mild COVID-19. Then, when Yonker and others began to see children hospitalized with MIS-C, she collected some plasma samples from them, too.

Using these plasma samples as windows into a child’s immune response, the research teams of Yonker and Alter detailed antibodies generated in 17 kids with MIS-C and 25 kids with mild COVID-19. They also profiled antibody responses of 60 adults with COVID-19, including 26 with severe disease.

Comparing antibody profiles among the four different groups, the researchers had expected children’s antibody responses to look quite different from those in adults. But they were in for a surprise. Adults and kids with mild COVID-19 showed no notable differences in their antibody profiles. The differences only came into focus when they compared antibodies in kids with MIS-C to adults with severe COVID-19.

In kids who develop MIS-C after COVID-19, they saw high levels of long-lasting immunoglobulin G (IgG) antibodies, which normally help to control an acute infection. Those high levels of IgG antibodies weren’t seen in adults or in kids with mild COVID-19. The findings suggest that in kids with MIS-C, those antibodies may activate scavenging immune cells, called macrophages, to drive inflammation and more severe illness.

In adults with severe COVID-19, the pattern differed. Instead of high levels of IgG antibodies, adults showed increased levels of another type of antibody, called immunoglobulin A (IgA). These IgA antibodies apparently were interacting with immune cells called neutrophils, which in turn led to the release of cytokines. That’s notable because the release of too many cytokines can cause what’s known as a “cytokine storm,” a severe symptom of COVID-19 that’s associated with respiratory distress syndrome, multiple organ failure, and other life-threatening complications.

To understand how a single virus can cause such different outcomes, studies like this one help to tease out their underlying immune mechanisms. While more study is needed to understand the immune response over time in both kids and adults, the hope is that these findings and others will help put us on the right path to discover better ways to help protect people of all ages from the most severe complications of COVID-19.


[1] Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Bartsch YC, Wang C, Zohar T, Fischinger S, Atyeo C, Burke JS, Kang J, Edlow AG, Fasano A, Baden LR, Nilles EJ, Woolley AE, Karlson EW, Hopke AR, Irimia D, Fischer ES, Ryan ET, Charles RC, Julg BD, Lauffenburger DA, Yonker LM, Alter G. Nat Med. 2021 Feb 12.


COVID-19 Research (NIH)

NIH effort seeks to understand MIS-C, range of SARS-CoV-2 effects on children,” NIH news release, March 2, 2021.

Lael Yonker (Massachusetts General Hospital, Boston)

Alter Lab (Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge)

NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute


  • Charlene says:

    Since I can not find answers I thought I would try here and maybe you can refer me to the right person. I had the 1st vaccine moderna and had a severe reaction. Was told by my doctor and an allergist and the dr’s at the emergency room not to get the 2nd shot. I do not know what to do no one has answers. I am asking can doses be mixed? Can I get the J&J vaccine? If so how long do I have to wait between doses? Are there any studies regarding mixes of doses? What are other people doing that had a severe reaction?

    • Merrit says:

      I am not a doctor but am a bio-medical engineer who worked in the diagnostic industry and has followed the COVID literature carefully. There is an ongoing study in the UK [about mixing vaccines] that may help give answers to your questions. In the meantime, you could ask about getting a quantitative COVID antibody test that looks at antibodies to the spike protein (they are currently available …). This will tell you the level of immunity you got from the single dose of the Moderna vaccine.

    • Linda D. says:

      I had bad reactions to first shot, breathing, heart, dizzy, bad headaches… should I get second shot?

    • tdoukas says:

      Research evidence shows that an individual has 80% chance of immunity after only one dose of the Moderna vaccine.

  • Tammy SC says:

    I have Selective IgA Deficiency… How does this disorder factor into what was seen in adult patients with severe Covid reactions? I read one study out of Japan that suggested there are more Covid deaths in the US because there are more patients with Selective IgA Deficiency… so I’m curious if this is related to what the studies referenced here indicate?

  • AJ says:

    What does this mean for people with anti phospholipid antibody syndrome? Sounds like Covid 19 patients are developing APS so are people already diagnosed with APS at higher risk of complications?

  • MaryK. says:

    As a retired MT, I am wondering if there is any connection or studies being done to follow on whether these adverse reactions are an increase in IgA and the subsequent neutrophil/cytokine reactivity?

  • FloM says:

    I had a mild case of COVID 19. I was given the monoclonal antibodies two months ago. Can I get the vaccine?

  • Ivye S. says:

    I had Covid in September 2020 and I recovered. According to the doctors Covid caused a stroke in my left eye. Am I immune to Covid now since I had it? Will I be able to get the vaccine since I am on Prednisone for inflammation in my eye? Will Prednisone and the vaccine react against each other? I don’t know how long I will be on the medication!

  • Diana says:

    I am concerned can any one help me please I got my first covid moderna shot had no reaction and like 8 days ago I got the second one I’ve had severe reactions rash hives on both arms chest back then the next day they Gad away but turn light tan like freckles and I get it over and over the rash also on each side of my neck I have two big lumps went to my doc and he said that I will get this for the next 2 weeks but I don’t think he knows what he is saying can anyone please help me???

    • Diana J. says:

      Diana I got the same thing as u did exactly the same my rash turned ligh tan freckles And I also got two big lumps on each side of my clavicles or shoulders on top they come from ur lymph nodes that’s what I was told I was also told they would be there for 3 months on a article of covid it stated that it’s a good thing that it’s giving u immune to the vaccine I got mine in January and I still have the lumps they are not hard they feel sqweeahy like there’s water in it!! I went to my primary same thing he did not care and then I had a para thyroid test done and it was high I recomend u asking ur doc to draw a parathyroid test from there I’m seeing a specialist.

  • Brittany Russell says:

    Would an adult who had Covid antibodies or recovered from Covid test positive for other antigen or antibody tests?

  • lynne Thomas says:

    Questions but where are the answers? I’m concerned about allergic reactions and answers to questions here.

    • Moderator says:

      Thank you for your comment, Lynne. We encourage you to contact your doctor about any concerns you may have about your individual situation. For answers to Frequently Asked Questions about COVID-19 vaccines, you can also check out this website from the U.S. Centers for Disease Control and Prevention:

      • Lynne says:

        I appreciate your response and link. I was just wondering why there were questions on the website but not many answers. I thought it was sort of like a Q./A. but…no ‘A’. That’s all. Thanks for the information.

  • lynne thomas says:

    Also I want to know where I can find a list of adverse reactions to the 3 vaccines. I’ve been trying to search via CDC Wonder but it’s tedious and difficult. Is there a list of these events?

  • Shirish Chavan says:

    Questions however are the replies? I’m concerned about allergic reactions and answers to inquiries here.

  • Ellen G. says:

    What does a positive serum COVID antibody test result mean? My number was 20.40. I had a delayed breathing reaction to the first Pfizer shot and was advised not to have the second. Am I ok or should I get the Johnson and Johnson when that’s available? Thanks so much!

  • Stephen says:

    Thanks for the great summary. Finding 5 and the stuff about resistance to RBD mutations seems very reassuring.

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