The battle against SARS-CoV-2 has presented the potential for the use of phage therapy for Covid19 rehabilitation, aiding in patient recovery. This therapeutic approach would aim towards helping patients overcome the damage that the Covid19 infection left behind, in patients who suffered from the coronavirus infection in moderate and severe forms.
Russia’s potential of phage therapy for Covid19 rehabilitation
Russia, currently being one of the few countries in the world that allows open use of phage therapy, has gotten approval from the government on the strategy for preventing the spread of antimicrobial resistance in the Russian Federation up to the year of 2030. The Covid pandemic has significantly exacerbated the already existing problem of antimicrobial resistance which is primarily due to the massive uncontrolled use of antibiotics in outpatient and inpatient settings. Based on studies to dates, the Covid19 virus has an affect on all organs and systems. The totality of various symptoms related to the coronavirus infection, is referred to as Post-Covid Syndrome, which has already been assigned a separate code in the International Classifier of Disease in 2020.
Russia’s Ministry of Health has established that rehabilitation after being infected with Covid19 is compulsory and its duration may vary between 2-3 months, and in some cases, up to 1 year. The goal is to prevent the development of the Post-Covid Syndrome. The syndrome is seen as a consequence in patients that were treated in the intensive care unit mainly caused by the artificial lung ventilation, cognitive limitations and the complex of drug therapy that was administered during the emergency treatment of the patient during their Covid19 infection.
Post-Covid Syndrome rehabilitation and bacteriophages
One of the key aspects of the post-covid rehabilitation is to find a method of restoring the human community of microorganisms, or microecology, as it is the most important regulator of human’s homeostasis. At this stage, there are great prospects of phage therapy for Covid19 rehabilitation. The accumulated clinical experience demonstrates the high efficiency and safety of therapeutic and prophylactic uses of bacteriophages in the treatment of infections in various fields. When using bacteriophages in a complex of therapeutic measures, infectious complications develop much less frequently. In natural conditions, phages are found where there are bacteria homologous to them. They can also be found in the human body, protecting it from microorganisms that cause various purulent-septic processes.
Adaptive phage therapy technology
Today’s circumstances have brought forth potential for a new direction for the use of phage therapy in both the battle of antibiotic resistance in intensive care units, and in rehabilitation departments. The innovation of the scientific approach is found in the development of adaptive phage therapy technology. This is the production of a complex of bacteriophages that are composed for a specific medical institution and is based on the up-to-date collection of the hospital strains of bacteria that are isolated from the biomaterial of patients found in that specific medical institution.
The Academic Council of the Federal Scientific and Clinical Center of Reanimatology and Rehabilitation (FSCC RR) approved this scientific project and the protocol for preclinical and clinical studies are currently being developed. The legal protection has been set and the scientific publications are being prepared. A pilot study has already been completed in order to assess the efficacy and safety of the use of complex bacteriophages in patients presenting serious damage to the brain resulting in disturbance to vital functions. Based on the results of the application of the developed technology of adaptive phage therapy, the following significant results were obtained:
- Reduction of the overall usage of broad-spectrum antibiotics in intensive care units.
- According to data from classic microbiological and molecular research methods; the use of bacteriophages helps reduce the antibiotic resistance of microorganisms in intensive care units.
- The safety and effectiveness of bacteriophages in the treatment of the most severe category of patients in chronic critical conditions have been proved.
To further the development of this project, the concept of Covid19 rehabilitation using the technology of adaptive phage therapy was approved. Three protocols for the rehabilitation of patients who had survived the coronavirus infection, had been developed and approved:
- medical rehabilitation of patients in the conditions of the intensive care unit;
- medical rehabilitation of patients in a sanatorium-resort environment;
- medical rehabilitation of patients on an outpatient basis.
All protocols are based on the use of personalized complex preparations of bacteriophages taken from a collection of pure lines of phages from Micromir (inhalation of Bronchophage; treatment of the skin in the tracheostomy, nasal passages and oral cavity with preparations such as; Otofag, Fagodent, Fagoderm; enteral administration of intestinal bacteriophage.
For the optimization of procedural replication of the technology, a production site on the basis of the FSCC RR is being looked at for the manufacturing of personalized bacteriophage complexes from the collection of clean lines of bacteriophages from Micromir (a production pharmacy based on the FSCC RR).
Phage therapy for Covid19 rehabilitation
Scientific data has changed our understanding of the individual and systematic functions of the human body. The microbiome is one of the most important, invisible to the naked eye, organs that is involved in maintaining homeostasis in the host’s body. A disbalance or dysbiosis of the microbiota is closely related to the development of pathological conditions, for example; microorganisms of the oral cavity and lungs can affect the outcome of many infectious diseases, regulating the immunity of the host mucosa, and disturbed intestinal microbiota contributes to the emergence and progression of viral infection along the gut-lung axis.
Conversely, a viral infection can disrupt the local microbiome, which is manifested by a change in the composition and a disbalance in the microbial community, contributing to a more severe course of the disease. Evidence suggests that infection with the SARS-CoV-2 virus increases the susceptibility of patients to the development of a superinfection, leading to an increase in the severity of illness and mortality. A number of works demonstrate a radical change in the intestinal microbiota of patients undergoing Covid19, characterized by the proliferation of opportunistic microorganisms and the depletion of favorable commensals compared with healthy people. In addition, using the example of patients infected with the influenza virus, it was shown that the restoration of homeostasis of the disturbed intestinal microbiota coincides with the recovery and elimination of the virus. There is a growing body of research that supports the hypothesis that microbiota health is not only a marker of health, but also a therapeutic target.
Bacteriophages play an important role as a regulators of the number of bacterial populations, and phages play the same role in regulating the number of bacteria in the human microbiome. Understanding this role of bacteriophages became the basis for the development of the concept of immunity based on phages found on mucous membranes (Bacteriophage Adherence Immunity). Bacteriophages on mucous membranes are considered as the first line of counteraction to the development of dysbiosis processes in the body, they are included in the process of inhibiting bacterial reproduction even before the reaction of the cellular and humoral mechanisms of the immune system, and also contribute to accelerating the achievement of a new equilibrium point by the microbiome in the event of dysbiosis.
Complex preparations of bacteriophages, purposefully created to ensure high lytic activity against bacterial strains with multiple antibiotic resistance, will allow post-covid patients to reduce the colonization of mucous membranes by pathogenic microorganisms, against which drugs with other mechanisms of action on the microbiota (pre-, pro- and meta biotics) may be powerless. Bacteriophages will help ensure the implementation of the tactics of maximum containment in relation to the excessive use of antibiotics, will allow to abandon the prescription of antibiotics where there are no direct indications (such as an acute purulent-inflammatory process), but only manifestations of pathological colonization are observed. That is why “microbiota rehabilitation” with the help of bacteriophages, aimed at restoring homeostasis in the micro-macroorganism system, can and should be the basis for the comprehensive rehabilitation of patients who have undergone the new coronavirus infection Covid19.