Severe parvovirus B19 infection in patients with sickle cell disease hospitalized in intensive care units

Abstract

Parvovirus B19 infection can lead to severe complications in patients with chronic hemolysis. The aim of this study was to describe severe parvovirus B19 infections in adult patients with sickle cell disease (SCD). In this multicenter, retrospective, observational cohort study, adult patients with SCD admitted to intensive care units (ICUs) between 2011 and 2024 with acute parvovirus B19 infection were included. Unsupervised analysis was performed including clinical and biological characteristics to identify clusters of patients with different outcomes. Clinical phenotypes were defined based on patient clustering. Parvovirus B19 genomes from ICU (n = 15) and non-ICU control patients (n = 15) admitted to the hospital during the same period were sequenced and compared. Sixty-one patients (52% female; median age, 29 years [interquartile range, 24-38]) from 8 ICUs in France were included. Three clusters of patients were identified. From these clusters, 3 groups of patients with distinct clinical phenotype were identified: erythroblastopenia (n = 26), bone marrow necrosis (BMN) and fat cerebral embolism syndrome (CFE; n = 17), and other vaso-occlusive manifestations (n = 18). Length of stay in the ICU and hospital was longer in patients with BMN/CFE. There was no difference in parvovirus B19 genotype or NS1 or VP1/2 amino acid diversity between the groups. Similar results were observed between patients who were admitted to the ICU and those who were not. ICU patients with SCD and acute parvovirus B19 infection presented 3 clinical phenotypes associated with different initial severity and outcome but with similar parvovirus B19 clades and amino acid diversity.

Graphical abstract

Figure 1.

Time course of ICU admission of patients with SCD and acute parvovirus B19 infection (n = 61). Note that the inclusion period ended in May 2024.

Figure 2.

SOMs of unsupervised analysis of the clinical and biological characteristics of 61 patients with SCD and acute parvovirus B19 infection. Unsupervised analysis of the clinical and biological characteristics of the 61 patients with SCD and parvovirus B19 infection. Patients with similar characteristics are located by the SOM algorithm closely on the maps, within one of the small groupings (“districts”). Each individual map shows the mean values or proportions per district for each characteristic: blue indicates the lowest average values, red the highest, with numbers shown for a selection of representative districts in each SOM. For instance, patients with erythroblastopenia were more frequently located in the lower left districts and had SS genotype, lower baseline hemoglobin, higher platelet counts, and less requirement for vasopressors and mechanical ventilation. 1, cluster 1; 2, cluster 2; 3, cluster 3; ACP, acute cor pulmonale; ARDS, acute respiratory distress syndrome; FiO₂, fraction of inspired O₂; Hb, hemoglobin; HR, heart rate; IMV, invasive mechanical ventilation; LOS, length of stay; RR, respiratory rate; SpO₂, oxygen peripheral saturation.

Figure 3.

Phylogenetic tree of NS1-VP1 sequence in patients with parvovirus B19 infection and different clinical conditions. This figure shows NS1-VP1 genome phylogenetic analysis including sequences from contextual references (eg, JN689428), and sequences from ICU and non-ICU patients (eg, ICU13 or non-ICU10). All patients from this cohort presented with genotype 1a (genotype 1a, 1b, 2, and 3 sequences are colored in orange, red, green, and pink, respectively). Samples from ICU and non-ICU patients did not form separate clusters, and the 3 phenotypes of ICU patients (ie, erythroblastopenia in blue; BMN/CFE in lilac, and other vaso-occlusive manifestations in pink) were equally distributed within the ICU-related viral sequences.

Figure 4.

Viral amino acidic variations in NS1 and VP1/2 viral proteins from patients admitted or not to the ICU. Shannon entropy calculated for (A) NS1 and (B) VP1/2 viral proteins (lower panels) and between ICU and non-ICU sequences (upper panels). The upper entropy graph shows differences between ICU and non-ICU subsets (purple: not significant). The lower entropy graph shows single viral amino acid variations within the ICU-related viral sequences (purple) and non-ICU–related viral sequences (green). Low entropy differences between protein sequences from ICU and non-ICU subsets suggest conserved proteins and no viral evolution.