Respiratory viral co-detection in the multiplex era: a critical perspective on diagnostic stewardship and anti-infective decision-making

INTRODUCTION: Respiratory viral co-detection has become increasingly frequent with the widespread use of multiplex molecular panels. However, detecting two or more respiratory viruses in a single sample does not necessarily indicate active coinfection, etiologic equivalence, or the need to escalate antiviral or antibacterial therapy. AREAS COVERED: This critical perspective examines respiratory viral co-detection as a diagnostic stewardship and anti-infective decision-making challenge. It proposes an interpretive framework that distinguishes molecular co-detection from probable coinfection, sequential infection, prolonged nucleic acid shedding, and clinically actionable co-detection. The article discusses how symptom timing, syndromic compatibility, local viral circulation, host vulnerability, and therapeutic availability should guide interpretation. It also addresses the limitations of Ct values as surrogate markers of viral burden, the potential contribution of host-response biomarkers, the influence of vaccination and immunoprophylaxis, and the implications of viral interactions for clinical reasoning and antiviral trial design. EXPERT OPINION: Multiplex panels provide the greatest value when interpreted as tools for therapeutic prioritization, antibacterial stewardship, infection control, and risk stratification rather than as flat lists of equivalent etiologies. Future antiviral studies should incorporate co-detection as a prespecified modifier of clinical and treatment outcomes.