Fig. 2

Case-based analysis of 15 critically ill patients with COVID-19 with depicted clinical diagnoses, plasma microbial cell-free DNA metagenomics and survival outcomes. The Y-axis margin indicates two groups of clinical diagnoses: Group A includes 11 patients who received antibiotics for either microbiologically-confirmed (n = 3) or clinically-suspected infections despite negative microbiologic workup (n = 8), whereas Group B includes four patients with low clinical suspicion for secondary infection and no antibiotic therapies at time of sampling. The Y-axis ticks denote each patient sample and the x-height of each stacked bar represents the number of microbial cell-free DNA molecules per plasma microliter (MPMs) by metagenomic sequencing, with different colors for the top 10 microbes by ranked abundance. The “other” category (shown in grey) represents the sum of lower abundance taxa of commensal origin. Five out of 11 subjects of Group A (45%, Subjects 1–5) had high MPM signal for probable respiratory pathogens, whereas in the remaining 6/11 subjects there was no evidence of co-infecting bacterial pathogens. Subject 7 was clinically-diagnosed with culture-negative sepsis and treated with prolonged course of empiric broad-spectrum antibiotics while on extracorporeal membrane oxygenation support for refractory hypoxemic respiratory failure from COVID-19; the high mcfDNA signal for C.tropicalis (2,490 MPMs) is concerning for undiagnosed invasive Candidiasis, corroborated by persistent growth of yeast organisms (not further speciated) from clinical bronchoalveolar lavage samples obtained on days 5, 9 and 14 after the research sample acquisition. Two out of four patients of Group B (subjects 12 and 13) who did not survive and had not received empiric antimicrobials were found to have high mcfDNA signal (> 4000 total MPMs) of probable respiratory pathogens, indicative of undiagnosed (and untreated) secondary infections