COVID-19 Disease in Pediatric Solid Organ Transplantation from Alpha to Omicron: A High Monocyte Count in the Preceding Three Months Portends a Risk for Severe Disease

Importance: Planning for future resurgences in SARS-CoV-2 infection is necessary for providers who care for immunocompromised patients. Objective: to determine factors associated with COVID-19 disease severity in immunosuppressed children. Design: a case series of children with solid organ transplants diagnosed with SARS-CoV-2 infection between 15 March 2020 and 31 March 2023. Setting: a single pediatric transplant center. Participants: all children with a composite transplant (liver, pancreas, intestine), isolated intestine transplant (IT), isolated liver transplant LT), or simultaneous liver kidney transplant (SLK) with a positive PCR for SARS-CoV-2. Exposure: SARS-CoV-2 infection. Main outcome and measures: We hypothesized that children on the most immunosuppression, defined by the number of immunosuppressive medications and usage of steroids, would have the most severe disease course and that differential white blood cell count in the months preceding infection would be associated with likelihood of having severe disease. The hypothesis being tested was formulated during data collection. The primary study outcome measurement was disease severity defined using WHO criteria. Results: 77 children (50 LT, 24 intestine, 3 SLK) were infected with SARS-CoV-2, 57.4 months from transplant (IQR 19.7–87.2). 17% were ≤1 year post transplant at infection. 55% were male, 58% were symptomatic and ~29% had severe disease. A high absolute lymphocyte count at diagnosis decreased the odds of having severe COVID-19 disease (OR 0.29; CI 0.11–0.60; <i>p</i> = 0.004). Conversely, patients with a high absolute monocyte count in the three months preceding infection had increased odds of having severe disease (OR 30.49; CI 1.68–1027.77; <i>p</i> = 0.033). Steroid use, higher tacrolimus level, and number of immunosuppressive medications at infection did not increase the odds of having severe disease. Conclusions and relevance: The significance of a high monocyte count as predictor of severe disease potentially confirms the importance of monocytic inflammasome-driven inflammation in COVID-19 pathogenesis. Our data do not support reducing immunosuppression in the setting of infection. Our observations may have important ramifications in resource management as vaccine- and infection-induced immunity wanes.