Throughout the COVID-19 pandemic, people have had to figure out what it means to keep themselves and their families safe amid a “new normal” of a spreading virus. For families with children who are immunodeficient, navigating this safely took on even greater importance.
Physicians and researchers at Johns Hopkins All Children’s Hospital and the University of South Florida (USF) Morsani College of Medicine are examining how children with immune deficiency and immune dysregulation — both rheumatology patients, as well as immunology patients from the USF Pediatric Allergy/Immunology Program at Johns Hopkins All Children's Hospital — are affected by COVID-19.
“The more information we have available, the better and easier it is to make decisions,” says Jessica, whose 2-year-old son, Easton, was diagnosed with an immunodeficient condition in September 2019 — about six months before the pandemic became a daily reality in the United States. “It’s hard especially when you don’t know a lot about a disease or disorder.”
As part of a study, the physicians screen children attending rheumatology and immunology clinics for the presence of COVID-19 antibodies. For those children who test positive for COVID-19, the evaluation includes their overall immune response, as well as specific tests of their immune system’s ability to neutralize the virus. Their research will compare this response to the immune response in the general population. In addition, with the Pfizer COVID-19 vaccine now available for children ages 12 and above, the team’s research is also examining the quality of the antibody response from the vaccine to the spike protein of the virus, among those patients for whom parents agree to participate in the additional blood collection and testing for the research.
The study, which is approved by the Johns Hopkins All Children’s Institutional Review Board and funded by an Institutional Research Award from the Johns Hopkins All Children’s Foundation, began several months ago and will run for at least a year.
The purpose of the study is to begin to establish a better understanding of how the live virus and/or immunization affect children who have conditions that impact their immune systems. Immunodeficiency disorders are ones in which the immune system’s ability to fight infection is compromised. Immune dysregulation disorders are conditions in which the immune system malfunctions in a way that may affect multiple systems in the body. The immune system may be overactive, causing inflammation or organ damage, or underactive, putting the child at greater risk for serious infection.
While a lot has been learned in this area in the past year in adult patients, “this particular pediatric patient population hasn’t been comprehensively studied yet,” says principal investigator Ann Szymanski, M.D., pediatric rheumatologist at Johns Hopkins All Children’s Hospital. Most of the information in the medical literature has been based on very few cases. The team’s work will help build on the knowledge in this area of pediatric care.
“COVID-19 is further exposing how intricate the immune system is, and how individualized and personalized each person’s immune response is,” Szymanski says. “It’s illustrating how the immune system plays a role in nearly every infection we get and how that response influences how sick a person may become.”
‘We Don’t Know What Will Happen’
Jessica’s son Easton was diagnosed with an inherited condition called X-linked agammaglobulinemia, an immune system disorder with complete absence of antibodies that inhibits his ability to fight bacterial infections effectively. He receives an infusion of immunoglobulins (which is a purified fraction of the plasma from thousands of healthy donors) to fight infection every two weeks. He has stayed largely healthy since beginning the infusions, with any illnesses being thankfully short-lived.
But at the beginning of the pandemic, Jessica says, “it was pretty scary because we were still relatively new to what being immunodeficient meant and what his diagnosis meant.”
In February, first Jessica, then Easton, and then her husband tested positive for COVID-19. They worried what this meant for Easton, but thankfully he didn’t have many symptoms, the most persistent being a cough that stayed with him for some time.
His physician is Jolan Walter, M.D., Ph.D., division chief of the USF Pediatric Allergy/Immunology Program at Johns Hopkins All Children’s Hospital, working with her clinical team, which includes Panida Sriaroon, M.D., directing fellows (physicians who are training in the specialty) and clinical coordinators. They treated him with an infusion of a cocktail of monoclonal antibodies specific to the virus — an emergency-use approved, lab-made protein that mimics the body’s immune response in patients with suppressed immune systems, to help them fight infections. The infusion helped to shorten his COVID-19 illness, and Walter monitors his immune system over time to watch for any long-term effects of the virus.
In children with insufficient immune response to COVID-19 infection and/or immunization, the team is exploring many questions, Walter says. Those questions include the following: How long does it generally take for these patients to develop antibodies? Are there additional risk factors that would put children with compromised immune systems at greater risk? When would they be protected, and how long would that protection last? Are they at a particular risk for reinfection?
Families with children who have compromised immune systems have had to grapple with the same calculations a lot of families have had throughout the pandemic concerning whether it’s safe to go to school, or work, or to spend time with another family outside the home. But these calculations can take on a more intense level of importance when your child is immunocompromised, Walter says.
Feeling the Effects of Isolation
One of the most challenging immune conditions is severe combined immunodeficiency (SCID), a primary (genetic) immunodeficiency disease that causes profound weakening of the immune system. A SCID diagnosis means families must completely isolate from the time of their child’s diagnosis, throughout treatment and until their new immune system has come in — a reality that has been compounded by the pandemic, says Heather Smith, founder of SCID Angels for Life. The Lakeland, Florida-based group provides support and resources to families affected by SCID, some of whom are patients of the USF immunology program at Johns Hopkins All Children’s Hospital.
In 1993, Smith’s first child, Brandon, was 7 months old when he died from complications from SCID after coming down with a cold just a few weeks before. With genetic testing, the family was able to determine their second child, Taylor, would also have SCID, and in 1995, Taylor had the first-ever in-utero stem cell transplantation to treat SCID before he was even born. He’s now 26.
For infants with SCID, before and during treatment, Smith says, “any little germ — not just one but any — could turn out to be catastrophic because your child doesn’t have their own functioning immune system yet and are relying on what little, if any, protection was passed on from the mother. So, they’re extremely vulnerable.” Even after treatment, introducing them into the world is a slow, steady process, and patients with SCID must be careful about protecting themselves from infectious diseases as much as possible well into adulthood.
Almost all the families involved in SCID Angels for Life opted to keep their children home and go to school virtually throughout the pandemic. For some families, both parents have had to quit their jobs when remote work has not been possible and the risk of potentially exposing their immunocompromised child to the coronavirus was too great.
“It’s a big struggle for our families. They have all managed to do their best with their kids this year, but they’re missing their friends and that interaction,” Smith says. “They’re seeing that more and more of their friends are being allowed to have small playdates, and they’re not, so they’re really feeling the effects of isolation.”
“It’s been scary for people who are healthy and have a fully functioning immune system — they’re not always doing well with this virus,” she says. “Imagine how frightening this is” for those with an immune deficiency.
Expanding Knowledge, Helping Families
More information about how COVID-19 may impact children who are immunodeficient would be crucial, Jessica says. “It really shapes the decisions we make as parents, and what we’re going to do or not do with our children. Can we take them to the playground? Or take them to the grocery store?” Their family has also been cautious about being around other family members or participating in family gatherings, as they are mindful of the risk that exposure could bring.
The team is also looking at the different medications the children are currently taking as part of their regular treatment for immune deficiency and immune dysregulation. Early data suggest that patients on maintenance immune suppressive medications may fare better than those who are not, because of the impact of the medications on COVID-19. For instance, these medications counter hyperinflammation induced by coronavirus infection, says Joseph Dasso, M.D., Ph.D., scientist with the Children’s Research Institute, a joint effort of USF and Johns Hopkins All Children’s Hospital.
“People make a lot of assumptions that children and adults with immune deficiency would be extremely susceptible to COVID-19, but it’s much more complicated than that,” Dasso says.
“With our technologies and collaborative network, we have the ability to interrogate the immune response of children with immune defects of all kinds who are exposed to the live virus or immunization,” Walter says. “We will not only better understand their immune system but also, through the lens of the pandemic, we have the opportunity to assess their level of protection and risk for severe disease.”