A Large Cluster of Parvovirus B19 Aplastic Crisis in Children with Sickle Cell Disease in Atlanta, GA (Dec 2023- July 2024)

Objectives: Parvovirus B19 may cause significant morbidity and severe anemia in individuals with hemolytic anemias, including sickle cell disease (SCD). Beginning in December 2023, we have observed more Parvovirus B19 aplastic crises than expected in children with SCD at our program in Atlanta, GA. We quantified cases per year over a 14.5-year period at our institution and conducted a detailed review of laboratory-confirmed cases of acute Parvovirus infection for the 8-month period from December 2023 – July 2024.

Methods: The Children’s Healthcare of Atlanta Sickle Cell Clinical Database (SCCD) and Epic Sickle Cell Patient Registry were reviewed to identify patients with SCD who also had acute Parvovirus B19 infection. All parvovirus PCR and IgM tests from 2010 - 7/25/2024 were reviewed and categorized as positive or negative, with duplicate tests removed (PCR >199 IU/mL and/or IgM ≥0.91). For recent cases, demographics, SCD genotype, date and age at time of abnormal test result, and clinical characteristics, treatment and outcomes were obtained from the SCCD and review of the medical record. The Institutional Review Board of CHOA approved this study.

Results: There were 245 total Parvovirus cases from 2010-7/25/24. In 2010 -13 and 2015, there was a steady rate of 20 - 24 cases of Parvovirus infection per year. Two larger clusters of Parvovirus B19 infection occurred in 2014 (34 cases) and 2019 (30 cases), with 21 cases from 2016-2018. There were only 2 cases from 7/1/2020 – 9/30/2023. Since December 2023 – July 25, 2024, there have been 42 confirmed cases in 8 months, 29 in 2024 quarter 2.

Within the current cluster, 37% of patients were female, median age 10.1 years (range 8 months – 20 years). SCD genotypes represented were 58% Hb SS, 37% Hb SC, 5% Hb S-b+ thalassemia, and 2% Hb SE. All patients were hospitalized for treatment, with median LOS 3 days (range 1-26). Presenting symptoms included fever (61%), fatigue (33%) and pain (74%). Acute chest syndrome developed in 30%, splenomegaly/splenic sequestration in 14%, and stroke in 5%. Concomitant, other infections were present in 19% through May 2024, most frequently rhino/enterovirus. Thirty-five (81%) patients were treated with red cell transfusion, with a median volume of 12.9 ml/kg (range 5.3– 38.2 ml/kg). Six patients (14%) received intensive care and had lower Hb nadir compared to those not treated in the ICU (median 4.6 vs. 5.8 g/dl), p = 0.04.

Among all SCD patients tested for suspected parvovirus since 2010, patients with positive results had a lower hemoglobin nadir (mean 5.7 g/dl, SD 1.6) compared to patients who tested negative (mean 7.1, SD 1.8), p <0.001. Patients who tested positive also had a lower absolute reticulocyte count (ARC) nadir (mean 34.3 K/ml, SD 49.4) than patients who tested negative (mean 137.3, SD 130.9), p<0.001. Compared to past cases, children in the current cluster were older (mean age 8.2 years, SD 3.7 vs 10.3, SD 4.8), p = 0.01.

In addition to the reported series, there was a suspected case in early December 2023. A 10-year-old girl with Hb SC, who had not had hematology care in >2 years, presented to the emergency department in cardiac arrest and died. Her hematocrit was < 15%. Parvovirus testing was not obtained, and post-mortem exam results were not available. Her 12-year-old brother with Hb SC was subsequently found to have severe anemia (hemoglobin 5.7 vs. baseline 11 g/dL), ARC 7 K/ml, splenomegaly and positive Parvovirus B19 IgM.

Conclusions: Cycles of increased Parvovirus infection are commonly observed in the USA every 3-4 years, particularly in late winter through early summer. Since December 2023, our Center has had a surge of Parvovirus cases. We also suspect that Parvovirus contributed to death in one child. Similar increased Parvovirus incidence has been reported in Northern Europe, affecting pregnant women and people with hemolytic anemia. The older age of the current cluster is likely due to a lack of viral exposure during the COVID-19 pandemic. Clinicians should have high vigilance for early Parvovirus testing and treatment in children with SCD presenting with severe anemia, particularly when ARC is significantly low.