Resolving the Microbial Burden with Tailored Immune Modulation in COVID-19 Acute Respiratory Distress Syndrome?

To the Editor:

Nonresolving acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation has been common during the previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks and has had markedly high mortality (1). Therefore, we read with great interest in a recent issue of the Journal the study by Kullberg and colleagues describing the potential role of lung microbiota in nonresolving coronavirus disease (COVID-19)-associated ARDS (2). In this observational cohort study, regularly collected BAL fluids from mechanically ventilated patients with COVID-19 were analyzed for bacteria and fungi using the 16S sequencing technique and related to outcome. We would like to raise three points.

First, the authors reported at the group level that an increased bacterial and fungal load led to a prolonged duration of mechanical ventilation, higher mortality, and more microbiotic dysbiosis such as pneumonia and COVID-19–associated pulmonary aspergillosis. In addition, this microbiotic load was also associated with an increased inflammatory response. Unfortunately, the authors failed to discriminate the patients with a low or high proinflammatory response related to the microbiological burden. This could have played an important role in the outcomes reported. Second, at an individual level, the initial load of bacteria and fungi was insufficiently distinctive for daily clinical practice. Not to mention that 16s sequencing is (not yet) available in all hospital laboratories. Third, the application of selective decontamination of the digestive tract is supposed to be routine care in the Netherlands according to Dutch guidelines (3). However, the results indicate a persistent carrier state of gram-negative bacteria, which is surprising and worrying at the same time.

The authors are to be congratulated on this scientific approach to a relevant clinical problem. But how may we translate this observational study into our daily practice? The strict monitoring of infections, including COVID-19–associated pulmonary aspergillosis in COVID-19–associated ARDS, is correctly stressed, given that early recognition and timely treatment likely improves the patient outcome (4). In addition, the importance of recognition and suppression of a secondary immunological disorder, whether or not caused by a low-grade infection, cannot be emphasized enough (5). Hopefully, the techniques used in this study will enable early diagnosis and treatment of pulmonary infections in the foreseeable future. Until then, we probably need additional approaches, including selective decontamination of the digestive tract and patient-tailored immune modulation to further improve outcomes in COVID-19–associated ARDS.