P-1520. Immune Depression Associated with Viral DNAemia in Pediatric Sepsis

TL;DR

This study shows that viral DNA in the blood of children with sepsis is linked to weakened immune responses and a higher risk of secondary infections.

Contribution

The study identifies viral DNAemia as a novel indicator of immune depression and secondary infection risk in pediatric sepsis.

Findings

Viral DNAemia is associated with early and persistent lymphopenia and neutropenia in pediatric sepsis.

Patients with both viral DNAemia and persistent lymphopenia are at highest risk for secondary infections.

EBV and HHV6 DNAemia are independently linked to increased secondary infection rates.

Abstract

Sepsis remains a significant cause of pediatric mortality and morbidity. We recently reported that viral DNAemia was associated with increased mortality in pediatric sepsis, and that persistent lymphopenia early in the course of sepsis was independently associated with subsequent development of secondary infection. This study aims to further understand the immunologic alterations associated with these findings.Adjusted association of viral DNAemia with early markers of immune depressionPatients with viral DNAemia during their course were more likely to have multiple markers of immune depression after adjusting for age, max organ failure index on day 0, PRISM, and immunocompromised status. Persistent lymphopenia was also independently associated with secondary infection in prior analyses. IPMOF: Immunoparalysis-associated multiorgan failure.Adjusted association of secondary infection with viral DNAemiasAfter adjusting for persistent lymphopenia and persistent neutropenia (independently associated with secondary infection in all patients and immunocompromised patients, respectively), patients with secondary infection were more likely to have had EBV DNAemia, HHV6 DNAemia, or DNAemia of any of the listed viruses.

Adjusted association of viral DNAemia with early markers of immune depression

Patients with viral DNAemia during their course were more likely to have multiple markers of immune depression after adjusting for age, max organ failure index on day 0, PRISM, and immunocompromised status. Persistent lymphopenia was also independently associated with secondary infection in prior analyses. IPMOF: Immunoparalysis-associated multiorgan failure.

Adjusted association of secondary infection with viral DNAemias

After adjusting for persistent lymphopenia and persistent neutropenia (independently associated with secondary infection in all patients and immunocompromised patients, respectively), patients with secondary infection were more likely to have had EBV DNAemia, HHV6 DNAemia, or DNAemia of any of the listed viruses.

Secondary analysis of 401 pediatric sepsis patients from 9 Pediatric Intensive Care Units. Samples were tested by PCR for EBV, CMV, HSV, adenovirus, HHV6, BKV, and parvovirus B19. Culture information was recorded daily for the first 28 days. Associations between DNAemia, immune depressions markers, and stringently defined secondary infection were assessed with multivariable logistic regression.Time to secondary infection by DNAemia and persistent lymphopenia statusPatients with both DNAemia and persistent lymphopenia were most likely to develop secondary infection during their course.

Time to secondary infection by DNAemia and persistent lymphopenia status

Patients with both DNAemia and persistent lymphopenia were most likely to develop secondary infection during their course.

Patients with viral DNAemia during their course were more likely to have had early lymphopenia (aOR 1.95, p=0.006), persistent lymphopenia (aOR 1.79, p=0.013), early neutropenia (aOR 3.52, p=0.007), or persistent neutropenia (aOR 3.01, p=0.007) after adjusting for age, max organ failure index on day 0, PRISM, and immunocompromised status (Fig 1). Patients who developed secondary infections of any type were more likely to have had DNAemia (77% vs 45%, aOR 3.5, p=0.003) after adjusting for persistent lymphopenia and persistent neutropenia (Fig 2). Similar findings were seen for EBV (34% vs 11%, aOR 3.7, p=0.001) and HHV6 (43% vs 21%, aOR 2.4, p=0.018). Risk of secondary infection was greatest in those who had both DNAemia and persistent lymphopenia (Fig 3). The largest proportion of secondary infections was viral in both groups (No DNAemia: 5/8, 62%; DNAemia: 12/27, 48%) followed by bacterial (3/8, 38%; 9/27, 33%) and fungal (0, 0%, 5/27, 19%), and this was not significantly different in those who did or did not have DNAemia (p=0.56).

Patients who were found to have DNAemia demonstrated multiple markers of immune depression and were more likely to develop secondary infections. Viral DNAemia is associated with immune derangements in sepsis and are likely indicative of an immune depressed state.

All Authors: No reported disclosures

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