COVID-19 or does my patient have a secondary bacterial pneumonia?” Providing a timely and concrete answer at the bedside has proven difficult. COVID-19 pneumonia shares many of the radiographic, physiologic, and clinical features of severe bacterial pneumonias, often with a protracted course and variable evolution of severity, making objective microbiologic data necessary for the diagnosis of superinfections. However, dedicated diagnostic workup with lower respiratory tract (LRT) sampling has been variably performed, and earlier in the pandemic, it was often avoided because of (now largely allayed) concerns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Consistent with clinical practice guidelines (1), about 85% of critically ill patients with COVID-19 receive systemic antibiotics (2, 3), which are often empiric and of broad spectrum. Such management guided by well-intentioned “best guesses” is destined to offer no benefit in many patients and may even cause harm in some. Empiric antibiotics given to patients with an isolated SARS-CoV-2 infection are not only unnecessary, but may also expose patients to unwarranted adverse effects and promote the selection of resistant pathogens. Furthermore, premature diagnostic closure on presumed secondary pneumonia will neglect investigation of competing etiologies for respiratory decline (eg, pulmonary embolism or congestive heart failure). On the other hand, patients with COVID-19 with a true superinfecting pathogen require the timely initiation of targeted antibiotics of appropriate spectrum and duration (Figure 1).

Given these uncertainties, in this issue of the Journal, Pickens and the NU COVID (Northwestern University COVID-19) Investigators (pp. 921–932) provide influential and practiceinforming data on bacterial superinfection in mechanically ventilated patients with COVID-19 (4). Capitalizing on an institutional practice of routine bronchoscopic sampling in patients after intubation or with clinical suspicion of ventilator-associated pneumonia (VAP), the authors enrolled 179 patients with COVID-19 and captured a comprehensive data set of 389 BAL samples. These samples were collected either early (within 48 h of intubation, n= 133), while looking for a community-or hospital-acquired superinfection, or late (. 48 h, n= 246), while looking for an incident VAP (Figure 1). BAL fluid was analyzed for host cellular composition, as well as for