How likely is it that a virus or bacteria is causing a patient’s symptoms? A new approach to interpret the outcome from multi-pathogen PCR

Background Whether a detected virus or bacteria is a pathogen that may require treatment, or is merely a commensal ‘passenger’, remains confusing for many infections. This confusion is likely to increase with the wider use of multi-pathogen PCR.Objectives To propose a new statistical procedure to analyse and present data from case-control studies clarifying the probability of causality.Methods We conducted a case-control study in US outpatient settings that enrolled patients aged 18 to 75 years with acute lower respiratory tract infection and controls without respiratory symptoms. Patients underwent multi-pathogen PCR testing. The positive etiologic predictive value was calculated to estimate the probability that each potential pathogen was the cause of symptoms. The outcome was illustrated using a modified forest plot and by classifying pathogens into five categories clarifying the probability for causality.Results We enrolled 618 adult cases and 497 asymptomatic controls. The modified forest plot and the classification of risk for causality aimed to facilitate understanding. Pathogens likely to be causative when present included influenza A and B, SARS-CoV-2, rhinovirus, and parainfluenza viruses, while Staphylococcus aureus is almost always commensal. Broad confidence intervals for the positive etiologic predictive value made it difficult to draw conclusions for potential pathogens with low prevalence.Conclusion This pilot study shows that the proposed statistical approach is likely to be practical for analysing larger case-control studies or for a meta-analysis of multiple studies. This method may help when interpreting the results from multi-pathogen PCR.