Bacteriophage Cocktails in the Post-COVID Rehabilitation

Abstract

Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body. Bacteriophages are promising candidates as potential regulators of the microbiota. In the present study, two complex phage cocktails targeting multiple bacterial species were used in the rehabilitation of thirty patients after COVID-19, and the effectiveness of the bacteriophages against the clinical strain of Klebsiella pneumoniae was evaluated for the first time using real-time visualization on a 3D Cell Explorer microscope. Application of phage cocktails for two weeks showed safety and the absence of adverse effects. An almost threefold statistically significant decrease in the anaerobic imbalance ratio, together with an erythrocyte sedimentation rate (ESR), was detected. This work will serve as a starting point for a broader and more detailed study of the use of phages and their effects on the microbiome.

Adaptive Phage Therapy for the Prevention of Recurrent Nosocomial Pneumonia: Novel Protocol Description and Case Series

“…This may be due to a reduction in the intensity of the inflammatory response due to a decrease in bacterial load. In conducted studies, a decrease in CRP levels during bacteriophage administration was also noted [16,22].…”

Bacteriophages with depolymerase activity in the control of antibiotic resistant Klebsiella pneumoniae biofilms

“…The titers obtained by growing the phages in liquid nutrient medium showed that they could effectively inhibit the growth of K. pneumoniae culture and indicated sufficient virus productivity to obtain high concentrations in the final preparation. A real-time in vitro phage lysis assay showed that the selected phage cocktail could effectively lyse Kl 315 planktonic cells of K. pneumoniae culture and disrupt small microcolonies adhered on the glass surface 19 . Therefore, the cocktail of bacteriophages vB_KpnS_FZ10, vB_KpnP_FZ12 and vB_KpnM_FZ14 was chosen for further studies on more mature biofilms carried out in the present work and vB_KpnP_FZ12 was selected as the most productive on Kl 315 strain to compare the efficacy of a single phage vs three-phage cocktail on K. pneumoniae biofilms.…”

“…The selected bacteriophages were tested in vivo as a part of a broader phage cocktails in published studies 18 , 19 . Real-time in vitro analysis of K.pneumoniae (Kl 315) culture lysis with a cocktail of selected phages was carried out in a previous study using imaging with a 3D Cell Explorer microscope 19 .…”

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

“…Numerous superficially plausible hypotheses may be formulated to seek unification across the many different vulnerability markers, but diet and social geography (in particular as it relates to diet and exposure to pollution and pathogens) have documented effects on host microbiome profiles, which, in turn, have attracted growing attention as possible influences on COVID-19 vulnerabilities [50,52,[160][161][162]165,170,173,183,[190][191][192][193]200,217]. Reasonable interpretations for how such microbe-virus interplay may arise must recognize not only the observations that bacteria use proteases to modulate host physiology in ways that benefit bacterial persistence and replication [171,[237][238][239] and inter-bacterial competition [239][240][241] but also the evidence that bacterial proteolytic action can tangibly modulate viral efficacy [172].…”

“…While substantial research has been devoted to co-pathology among various microbes and the SARS-CoV-2 virus [48][49][50][51][52], this hypothesis aims to assess knowledge of the symbiotic host-protective capacity of some bacteria [50,53] while focusing on putative mechanisms at molecular levels of detail, with potential application to therapeutic development. In particular, a novel hypothesis is rationalized, tying key aspects of host protection to the relative capacity of different bacterial serine proteases to interact with the SARS-CoV-2 Spike protein (and other comparable viral Class I fusion proteins present in various other coronaviruses and retroviruses) in a manner that may interfere with the pathological TMPRSS2-mediated process of Spike cleavage and host-membrane permeation.…”