Studying COVID-19’s Effect on Children’s Kidneys

Infection preventionists (IPs) in children’s hospitals have not been spared by the horrible mayhem caused by coronavirus disease 2019 (COVID-19) just because children are statistically much less likely to get the disease than adults. Some children do get it. Not only that, but some children who get COVID-19 come down with multisystem inflammatory syndrome (MIS-C). According to the Centers for Disease Control and Prevention (CDC), MIS-C “is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs.” It’s how it effects the kidneys, that interests Abby Basalely, MD. Basalely is the attending physician in the pediatric nephrology division at Cohen Children’s Medical Center in New Hyde Park, New York and an investigator at the Feinstein Institutes for Medical Research, the science arm of Northwell Health. Basalely is also one of the authors of a study that recently ran in Kidney International that looked at just how much damage MIS-C can do to children. She tells Infection Control Today® that IPs and other health care workers should test “to see if they have evidence of acute kidney injury” in children that they suspect might have MIS-C. Regarding the function of IPs in children’s hospitals, Basalely has nothing but respect. “To be very honest, my job pales in comparison to what infection preventionists needed to do in order to protect everyone. I salute them.”

Infection Control Today®: Two things scare me about MIS-C. One, it affects kids. Two, it adds credence to those who are concerned about possible long-term effects of COVID-19. What do lay people like me and medical experts need to know about MIS-C?

Abby Basalely, MD: Like you said, multisystem inflammatory syndrome in children is a rare but serious condition that can affect children and is found to be associated with COVID-19. And it can affect different organs: primarily, inflammation in the heart, lungs, brain, eye, skin and gastrointestinal tract. But of interest to me, especially as a nephrologist, is the effect of it on the kidneys. I think overall there have been a little over 2000 cases reported by the CDC in the US to date. And those cases follow COVID-19 spikes in about two to four weeks in succession. What we believe it to be at this point is an inflammatory response to the virus. And what we should know is although it is concerning and it does affect children, the majority of children will recover from MIS-C and we see them thriving and doing well post hospitalization if they need hospitalization for the syndrome.

ICT®: Now recently, there was a study published in a journal Kidney International in which you were one of the coauthors. Could you tell us a little bit about that study? The findings and possible implications of those findings?

Basalely: Sure. We studied the incidence of acute kidney injury, which is an abrupt cessation of kidney function, in a cohort of 152 children that were admitted to four hospitals within the Northwell Health system who essentially had either acute COVID-19 or a defined case of multisystem inflammatory syndrome during the height of the COVID-19 pandemic from March of last year until August. And we found that acute kidney injury occurred in 1 of 10 patients, and the

Abby Basalely, MD

majority of those patients were critically ill. Having acute kidney injury on preliminary analysis was associated with higher markers of inflammation in the body, and also was associated with increased morbidity in the sense that they had an increased length of stay in the hospital of about eight days as compared to their peers who did not have acute kidney injury. So really, what we’re thinking about when we were doing the research was trying to better inform practice and better understand how the reaction affects kidney function in children and whether or not this potentially can inform how pediatricians should be following up the patients. I think it’s an important message that if there was a patient who was admitted for COVID-19, or MIS-C, asking whether or not the kidneys took a hit, so to speak, would be an important question. So that parameters such as blood pressure, or urinary protein loss could be monitored further out to see what those effects may be.

ICT®: You threw a lot of data out there and I heard 1 in 10 children affected have had problems with their kidneys. We’re talking about 1in 10 children who are diagnosed with MIS-C will have…

Basalely: Or acute SARS-CoV-2 infection. So, they had an acute COVID infection. It was not two to four weeks after the viral infection, they had acute COVID. So, instead of saying that they had inflammatory effects of MIS-C.

ICT®: We’ve reported on adults whose immune systems attack COVID-19 but then attacks the persons themselves. Is there any possibility that the two reactions—one that affects children and one that affects adults—can be linked in any way?

Basalely: I think a hyperactivity of the immune system in all cases of COVID-19, whether it’s a delayed response or a few days after the initial infection, definitely contributes to severity of COVID-19 infection in adults. And that’s been shown in a number of adult studies. I think that the data is still out on exactly why specific adults and/or specific children have this hyperactive immune response to the COVID-19 infection, because it doesn’t happen to everyone. And it can be a 30-year-old, it can be a 6-year-old. Determining what the predisposing genetic factors are is something that’s being looked into now, in terms of how immunomodulation has really potentially contributed to these responses.

ICT®: The core of our readership comprises infection preventionists many of who, as you know, have a nursing background. How would the implications of your study affect their jobs? Would they be asking the doctor what’s going on with the kidneys?

Basalely: I think first it would be important to ascertain whether or not somebody has kidney injury and knowing that that’s something that has a higher incidence in these critically ill children who have acute COVID-19 and/or MIS-C. So, doing laboratory testing to see if they have evidence of acute kidney injury will be important. Also, measuring their urine output carefully and making sure that they’re urinating while at the time of admission is important because having a decreased urine output is part of that definition of cessation of kidney function. And then I think moving forward from there, it’s thinking about treatment options in patients who may have kidney injury. Thinking about not utilizing medications that are called nephrotoxic medications that can harm kidneys, would be important. Thinking about either avoiding them or picking another class of drugs, to not put insult to injury that’s already there. And then following up outside of the hospital, if they know and they’re asking the right questions and ascertain that a patient had acute kidney injury. I think carefully monitoring those patients’ blood pressures, making sure that they have yearly uranalysis. It would be important to monitor their kidney health going forward.

ICT®: Again, this is outside the boundaries of your study, but I’m sure you’re tracking progress being made on getting a vaccine for children under 16. Do you see possibly that helping eliminate MIS-C, or at least lowering the chances of the risk of it?

Basalely: From what we understand, 99% of cases of MIS-C have evidence of previous SARS-CoV-2 infection. So, eliminating that virus would in theory, again, decrease the risk of MIS-C or acute COVID infection because if you’re immune to it, the likelihood of you having that virus, hopefully would mean that you don’t have this inflammatory response.

ICT®: What was the hardest part of doing this study? I ask this of a lot of medical experts who have to deal with people in dire straits. You’re dealing with little people in dire straits. I guess you have to emotionally distance yourself from that kind of thing?

Basalely: I think the one thing that was surprising about this study is a lot of the children who came in and had evidence of acute kidney injury and had MIS-C actually came out with—when we measured their kidney function at discharge—it had to return to baseline and they really had, so to speak, bounced back and done well. So, I think from that standpoint, working with children and thinking toward the end and not thinking about it while at the time of acute illness when you’re seeing someone so sick, I think that’s the hope and beauty of pediatric nephrology. And I think that’s why [I’m glad to be a] pediatric nephrologist because we see pretty happy outcomes and helping someone through that time. We’re working toward those, the majority of those cases where we see recovery?

ICT®: Are you worried about the so-called long-hauler effect on these children?

Basalely: As a nephrologist, what we do know is that having an acute kidney injury that is moderate to severe, potentially will increase risk of high blood pressure, chronic kidney disease in the future. I think the concept of long COVID, or the effects following of it on the kidney are unknown. And I’m not sure if they would be separate from what we already know about acute kidney injury and children, or if they will be unique to COVID-19 viral infection, which is something we’re kind of following as we follow these patients over time. My colleague, Christine Capone, [MD, MPH], who's a co-author on the paper is one of the pediatric cardiologists here is following these patients. She and Elizabeth Mitchell, [MD], are following these patients and actually studying prospectively how they are doing over time to determine whether or not there’s really long-term effects from this MIS-C or if they’re having long COVID-19 effect.

ICT®: You ran down the list of organs that this can affect in the body. Is it primarily the kidneys that—and I know you that’s your specialty—but is it primarily the kidneys that people are worried about? Or maybe there haven’t been enough studies to tell.

Basalely: I think that sometimes the kidneys are less popular as an organ system to discuss. We found about 18% of children, in only the MIS-C cohort, had evidence of kidney dysfunction. Whereas a majority of them had fevers. There’s a very strong cardiology component where there’s evidence of systolic dysfunction, which means cardiac dysfunction. It’s not pumping as well—the heart. Or there’s evidence of some coronary aneurism or debilitation of the arteries that feed the heart. So that’s something that’s even more common in these children. And gastrointestinal symptoms are also very common.

ICT®: How would this look on the ground as far as an infection preventionist’s job is concerned?

Basalely: I salute them. They’re doing a great job. Since the beginning of COVID-19 pandemic, I think that the guidance that they were receiving and the amount of how they had to be dynamic in terms of changing what was going to in terms of protecting staff, in terms of protecting patients, in terms of protecting visitors, from potential COVID-19 infection. It was one of those kinds of situations where we knew nothing, and everyone had to think 24/7 fast on your feet as more information came out. Understanding what kind of masks to use, what kind of hand washing to do. Who was allowed in the hospital? To be very honest, my job pales in comparison to what infection preventionists needed to do in order to protect everyone. I salute them.

ICT®: I just became aware of MIS-C maybe about three or four weeks ago. Is it one of those underreported stories? Have you been aware of it for a while and it just wasn’t reported on because everything was going crazy and people were just trying to keep people alive?

Basalely: Are you referring to MIS-C or COVID in children?

ICT®: MIS-C.

Basalely: I think overall because it has a low incidence it was … I don’t believe it was underreported. I also think that at the same time as we want to best serve children who are affected by this, we don’t want to sound the alarm so to speak in terms of concern over children. It’s a very low risk of developing this syndrome and understanding that it exists at the same time. As you know, the flu has worse impact on overall pediatric care. I think the media has, to a large extent, covered it. And I’ve seen it reported, but because we don’t want to sound alarm—and it is such a rare occurrence in children and the children overall do well—we want the children to return back to schools in a safe way. I think balancing that would be important. And recognizing that this happens, we need to care for the children that it happens to and make sure that they have long-term follow-up, at the same time recognizing that 2000 cases in all of the U.S. is a pretty limited amount.

ICT®: I read somewhere that MIS-C was surging in February?

Basalely: It always surges. And surge is always relative, right? But in terms of if you look at when the COVID-19 spike happens, oftentimes because this is thought to be a post-infectious inflammatory response, it surges about two to four weeks after there’s been a high prevalence of COVID for some time in the population. We saw this as well, during the COVID-19 pandemic, where April, May, June, we were seeing more kids with MIS-C, because in March and April even maybe late February was when we were seeing significant infection throughout the community.

ICT®: Is there anything I neglected to ask you, doctor, that you think is pertinent to this conversation?

Basalely: I think what is important is that acute kidney injury in children is an under-evaluated problem. And oftentimes, like I was saying before, clinicians can try to mitigate this process and/or prevent it by not utilizing medications that are nephrotoxic or can cause harm to kidneys. And thinking about long-term effects overall of kidney health in children is an important as we’re seeing an increase in high blood pressure in these children and an increase in the epidemiology of this process and whether or not there’s a component of acute kidney injury there.That is important to think about moving forward.

This interview has been edited for clarity and length.