In this study, the authors describe the first therapeutic use of phages for the secondary
bacterial infections in COVID-19 patients and the first clinical application of NEPT strategy to preview bacterial anti-phage resistance.
Some take home points:
In this study, despite the in vitro proof of synergistic effect between ɸAb124 and ɸAb121, phage resistance was observed in 4 out of 6 treatments. Nevertheless, the bacterial gain of anti-phage resistance might be accompanied by losing advantages in other respects such as virulence. Patient 1 and Patient 2 who saw clinical improvement in chest radiographs were finally discharged from the hospital. In contrast, conventional antibiotic treatment had been tried previously and failed to suppress CRAB infection or improve the condition of these patients. Suggesting that phage therapy may have contributed to the recovery of the patients.
Compared to antibiotic treatment, the rapid lysis of bacteria by phages leads to less endotoxin release from gram-negative organisms and does not increase the innate inflammatory response [18, 19]. However, Patient 1 experienced an incident resembling a dramatic wave in IL-6 and IL-8 at four hours post-ɸAb124 inhalation, which is distinguished from the previously described patterns of a cytokine storm. Risk prevention measures against the cytokine storm should be considered during phage therapy.
PHAGElogist 