BackgroundSome studies of community-acquired pneumonia (CAP) have reported that human rhinovirus (HRV) is the most common virus in viral pneumonia in immunocompetent adults. Secondary bacterial and fungal infections are increasingly recognized complications of HRV infection that have substantial morbidity and mortality. We report a novel case of a co-infection of Streptococcus pneumoniae (S. pneumoniae) associated with HRV pneumonia that had successful diagnosis with combined target next generation sequencing (NGS) and percutaneous lung puncture biopsy (PLPB).Case presentationA 62-year-old female was admitted with productive cough, dyspnea and respiratory failure. She was initially diagnosed with severe pneumonia caused by HRV infection by targeted NGS from bronchial-alveolar lavage fluid. After initial clinical improvement treated by high flow nasal cannula (HFNC) and antibiotics, the patient''s condition worsened again after her discharge, with persistent dyspnea and refractory hypoxemia. Chest computed tomography showed areas of consolidation and ground glass opacification. Despite empirical antibiotics for a suspected secondary co-infection, her condition showed no significant improvement. A PLPB was performed, and targeted NGS for the lung tissue was positive only for S. pneumoniae. Targeted NGS of her sputum was positive for S. pneumoniae, Aspergillus fumigatus and type A HRV. The patient was treated with linezolid, voriconazole and methylprednisolone. HFNC was weaned on day 57, and she was discharged with good lung recovery.ConclusionsOur case demonstrates the diagnostic utility of combined targeted NGS and CT-guided PLPB in resolving refractory pneumonia with overlapping viral and bacterial etiologies. Co-infection with these two pathogens should be considered in the differential diagnosis of patients with consolidation, wheezing and respiratory failure following severe HRV infection. The combination of targeted NGS and CT-guided PLPB should be reserved for diagnostically challenging cases refractory to conventional methods.