A68-06 Co-Identification of Staphylococcus Aureus and Candida Albicans in the Lung Microbiome Is Associated With Poor Clinical Outcomes in Invasive Mechanical Ventilation

Abstract Rationale The use of lung metatranscriptome and metagenome tools to diagnose pneumonia and microbe-microbe interactions have been poorly described. We assessed the identification of Candida albicans and Staphylococcus aureus in the lower airway of a critically ill cohort. We hypothesized that the co-identification of Candida albicans and Staphylococcus aureus would be associated with poor clinical outcomes in a cohort of patients with respiratory failure. Methods We analyzed lower airway samples from COVID-19 participants admitted to a medical intensive care unit requiring invasive mechanical ventilation (n = 245 patients). We analyzed clinical events such as mortality, length of hospitalization and mechanical ventilation, APACHE score, days on ventilation, ICU days, and intubation to discharge. We evaluated correlations between the presence of Candida albicans and Staphylococcus aureus reads based upon metatranscriptome sequencing using Illumina NovaSeq. We defined CandidaHi samples as a ratio of C. albicans:S. aureus reads1; We defined StaphHisamples as a ratio C. albicans:S. aureus reads1. The cohort was split between CandidaHi and StaphHi. If any sample was detected as CandidaHi the participant would be considered part of that group, irrespective of other samples. Results We analyzed the presence of Candida albicans and Staphylococcus aureus in lower airway research samples obtained from a cohort requiring invasive mechanical ventilation. We split the samples into CandidaHi(138 samples) or StaphHi(541 samples). C. albicans correlated closely with S. aureus in CandidaHi samples (Fig 1A), conversely, C. albicans did not correlate strongly with S. aureus in StaphHi samples (Fig 1B). We labeled a participant as a CandidaHi participant (n = 79) if any lower airway sample was considered a CandidaHi sample, otherwise, the participant would be grouped with StaphHi participants (n = 164). We found that CandidaHi participants had increased mortality compared to StaphHi participants (Table 1 48% vs. 32% mortality, respectively, p = 0.017). There were no differences in the distribution demographics, or ICU days, ventilation, ventilator-associated pneumonia, ECMO, and immunocompromised status. There was a difference in hospital length of stay likely reflecting late hospitalization mortality in the CandidaHi group. Conclusions The co-identification of S. aureus and C. albicans in the lower airway microbiome may prognosticate worst outcomes. Among a cohort of critically ill, COVID-19 participants, the isolation of C. albicans was closely associated with S. aureus and increased relative mortality by 50%. Further studies are needed to understand the microbe-microbe interactions associated with poor clinical outcomes. This abstract is funded by: Veterans Affairs IK2BX005309-01A2 (BGW); National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number KL2TR001446 (BGW); NYU CTSA grant (TL1 TR001447) from the National Center for Advancing Translational Sciences, National Institutes of Health (CJC);CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease (BGW); R37 CA244775 (LNS, NCI/NIH); R33 GM147800 (LNS, NIGMS/NIH); U01 AG088351 (LNS, NIA/NIH). National Institutes of Health 5R01LM014085 (HL)