Methods

We enrolled 15 critically-ill patients with COVID-19 (confirmed by nasopharyngeal qPCR for SARS-CoV-2) in a prospective ICU cohort study [3]. Following informed consent, we obtained plasma samples for conducting mcfDNA-Seq with the Karius Test (Karius, Inc. Redwood City, CA)[4]. We evaluated detection of mcfDNA in the context of clinical diagnoses and prescribed antimicrobial therapies by the treating physicians, and examined for associations with clinical outcomes.

Results

Of 15 patients analyzed (median age 63, 53% females, 73% mechanically-ventilated), six (40%) died within 30 days from enrollment. Samples were obtained at a median (interquartile range-IQR) of 10 (4–12) days from COVID-19 symptoms onset, and each sample contained a median of 837 (111–4638) total mcfDNA molecules per microliter (MPMs) and 2 (1–4) identified organisms. Of the total 92,791 MPMs reported across 15 samples, 90% belonged to typical pathogenic bacteria (eg E. coli and K. Pneumoniae), with the remainder MPMs aligned to commensal bacteria (5%, eg oral Streptococcus species), fungi (4%, Candida species) and DNA viruses (1%). Compared to survivors, non-survivors had higher total mcfDNA (p= 0.04), higher pathogenic bacteria MPMs (p= 0.02) and a trend for a higher number of identified organisms per sample (p= 0.06).(Fig. 1).