Impact of COVID-19 Pandemic in Children with CKD or Immunosuppression

• chronic kidney disease
• COVID-19
• immunosuppression
• kidney transplantation
• glomerular disease
• children

Infections are a major concern in children on KRT and with CKD. Risk factors include immunosuppression, multiple contacts in dialysis units, and hospital visits (1).

Italy was one of the countries most affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak (2). Although adults with CKD and kidney transplant recipients are known to be at greater risk for disease severity due to immunosuppression and comorbidities (3), little is known about the equivalent pediatric population.

We report data from a nationwide observational study performed by the Italian Society of Pediatric Nephrology during the lockdown period in order to better understand the clinical effect of coronavirus disease 2019 (COVID-19) in children with immunosuppression or CKD. Data were collected by means of a phone-based structured questionnaire between April 13 and 24, 2020, and data referred to the whole period from the detection of first cases to the pandemic peak in Italy (February 20 to April 15, 2020). The primary objective was to identify patients with severe COVID-19 as defined by any of the following: death, admission to Pediatric Intensive Care Unit, mechanical ventilation, and the need to change ongoing immunosuppressive treatment due to a documented SARS-CoV-2 infection. The presence of fever, respiratory, gastrointestinal, or flu-like symptoms and adherence to lockdown measures were also assessed. Inclusion criteria were age <18 years and one of the following diagnoses: primary or secondary GN and idiopathic nephrotic syndrome requiring long-term immunosuppressive therapy, CKD stages 3–5, dialysis, or kidney transplant. National rates of participation were calculated estimating the number of prevalent cases. Data regarding COVID-19 swab testing in the enrolled population were compared with those of the general Italian population for the same age range and time period. The study was approved by the local ethics committees of each participating center.

A total of 1572 patients (median age, 11.1 years; interquartile range, 7.2–14.7) were included. Patient characteristics are summarized in Table 1. According to the estimated number of children with CKD and chronic GN and the prevalence of patients with transplants and patients on dialysis from all Italian pediatric kidney transplant centers and the Italian Registry of the Pediatric Chronic Dialysis, respectively, the enrolled patients represented 67% of the entire Italian pediatric population with the aforementioned kidney diseases. The majority (71%) are considered at risk for viral infections because of immunosuppression, with 14% receiving three or more agents. On the other hand, 29% of patients had CKD stages 3–5, with 93 on dialysis. Hypertension was present in 20% of children, and 20% of the total cohort was on renin-angiotensin-aldosterone system blockers. Nonspecific infectious symptoms were identified in 12%. Patients were quarantined at home in 83% of cases, yet 35% underwent at least one hospital visit during the observation, and 51% had parents working outside, including health care workers (Table 1).

No patients fulfilled the criteria for the presence of severe COVID-19.

Nevertheless, swab tests were performed in 84 patients, mostly symptomatic children (46 of 84) or those with a confirmed familial SARS-CoV-2 case (four of 84). A significantly higher percentage of patients underwent swab testing compared with the healthy Italian pediatric population (5% versus 1%; P=0.005); however, the percentage of positive tests was not significantly different (4% versus 2%; P=0.43). Only three patients (0.19%) tested positive for SARS-CoV-2, all living in the worst-affected Italian region (Lombardy). One was on immunosuppressive therapy for Henoch–Schönlein purpura, and the other two had CKD secondary to congenital abnormalities of kidneys and urinary tract. Two had symptoms (fever and skin rash); the other was asymptomatic and was tested because of family exposure. None had leukopenia or required x-ray. Baseline therapies were not modified, and each child had a mild clinical course, in line with previous patient series in a similar population (4,5).

Severity of COVID-19 in the adult population seems to be associated with the presence of comorbidities, including immunosuppression, hypertension, and CKD. Even with similar characteristics, no patient in our fragile population had severe COVID-19. The absolute risk of SARS-CoV-2 infection was not significant, and the ratio of positive to performed tests is comparable with the general pediatric population.

Our study has some limitations, including potential recall bias from the survey and the overall small number of swab tests performed. We did not aim to assess the prevalence of SARS-CoV-2 infection because of the very strict swab testing policy in place in Italy during the worst phase of the pandemic, limiting the screening to only symptomatic children. Instead, we planned a pragmatic study in order to clarify the real effect of the disease and elucidate clinical recommendations in those times of uncertainty.

Although the reason is unclear, the incidence of COVID-19 is known to be low in the pediatric population, with a generally benign clinical trend. Considering the exposure to hospital environment in over a third of patients, our data show that even children in the advanced stages of CKD or on immunosuppressive therapy are at low risk of clinically relevant COVID-19.

• Copyright © 2021 by the American Society of Nephrology