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Respire Inspire – 6th Newsletter – Hot Season Topic

Oct 29, 2020

Coronavirus disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most devastating infectious disease in a century.[1]  With over 43 million cases worldwide to date, and more of us being infected every day, the Covid-19 virus continues to circulate actively and remains a threat to our social life, our health and our jobs.

In this context, it is important to understand what respiratory tract infections are and the importance of prevention. For the moment, as Dr. Deborah Birx, the Nation’s Coronavirus Response Coordinator, stated at the March 31, 2020 White House Coronavirus Task Force Briefing, “There is no magic bullet, no magic vaccine or therapy. It’s just behaviors.”[2]

Prevention is key to limit the spread of respiratory tract infections.



Respiratory tract infections (RTIs) are among the most common and important problems in clinical medicine. RTIs can affect the sinuses, throat, airways or lungs. Mild RTIs get better without treatment, although more severe ones, but also relapses sometimes require medical assistance.

It has long been considered that the upper airways – from the nose to the vocal cords – and the lower airways – below the vocal cords – are distinct anatomical and histological entities and fall under two different specialties as regards to treatment. However epidemiologic, pathophysiologic, and clinical evidence recently revealed the link between upper and lower airways, changing the global pathogenic view of respiratory diseases.

During the second century, Claudius Galenus identified the effect of the upper airway on the lower airway and defined the nose as a “respiratory instrument” in his work “De usu partium.” Nevertheless, the concept of the upper and lower respiratory passages being a continuum and forming a single unified airway has been highlighted only over the last 10-15 years[3].

The concept of united airway disease (UAD) is arguing that any disease process that affects the upper airway is likely to affect the lower airway, and vice versa.



The covid-19 pandemic has raised a lot of questions regarding our immune system and the body’s ability to fight diseases. In addition to vaccine development and approaches that directly target the virus or block viral entry, treatments that address the immunopathology of the infection have become a major focus.

“Immunology is the study of the immune system and is a very important branch of the medical and biological sciences.”[4]   We constantly encounter microorganisms that could harm our health. The immune system defends us against these threats and protects us from infection.

To strengthen our immune system the first line of defense is prevention.

Immunization is recommended as a safe and effective preventive method against respiratory tract infections.

Alternative immunization approaches such as oral immunostimulants may also be efficient. Bacterial lysates have a broad spectrum of action and stimulate both innate and adaptive immunity. This reinforces their rationale of use in prevention of infections, as a complementary approach to vaccination.

The first discovery about Polyvalent Mechanical Bacterial lysates was its ability to activate and mature the dendritic cells at the level of oral mucosa, a major step of the innate immunity allowing an efficient immune answer.In 2019, Pr Guido Ferlazzo (Professor of General Pathology and Immunology – University of Messina, Italy) shared his latest discoveries on bacterial lysates, more specifically PMBL® (Polyvalent Mechanical Bacterial Lysates), and its action on the reinforcement of the airway epithelial barrier in a paper titled «Mucosal Immunity In The Infections Of Airways».

In order to investigate whether the bacterial lysate obtained mechanically can improve the inducible barrier function, they analyzed the expression of the adhesion molecules involved in the cell-cell junctions.

« Following the culture of human bronchial epithelial cells in the presence of the bacterial lysate, we observed a significant increase in the expression of ICAM-1 and E-cadherin on epithelial cells of the respiratory mucosa. The epithelial cells, particularly those of the mucous membranes, are considered as an integral part of the immune response, precisely due to the barrier properties that are readily increased when stimulated by the presence of microorganisms.

(…) Among these anti-microbial peptides, β-defensins are released in high quantities from the respiratory epithelium but not, ad example, from the intestinal one. We then analyzed whether, in the experimental model of respiratory mucosa cells human, it is possible to induce the production of β-defensin a following stimulation by the bacterial lysate obtained for mechanical lysis.  The gene expression of this peptide is induced after only 6 hours of stimulation with the PMBL lysate, indicating that, in the case of sublingual administration (and not swallowing the lysate tablet), the epithelia of the oropharynx they would release peptides with a high anti-microbial action, such as the β-defensin, which would therefore concentrate precisely in the main one entry region of airway pathogens, precisely the oropharyngeal region.

(…) In conclusion, The ability of PMBL to maintain the integrity of the respiratory epithelial barrier, counteracting microbial colonization and, at the same time, stimulate the regeneration of mucous tissue during chronic phlogosis can play an important role in prophylaxis of respiratory airway infections and their recurrence in patients with chronic inflammatory diseases of the respiratory tract.

In a publication from the Department of Biotechnology Development, Institute of Hygiene, Faculty of Medicine in Uruguay, a paper entitled “Characterization of Bacterial Lysates by Use of Matrix-Assisted Laser Desorption–Ionization Time of Flight Mass Spectrometry Fingerprinting” , presents a new analytical method for bacterial lysates characterization is introduced: MALDI-TOF MS (Matrix-Assisted Laser Desorption-Ionization Time of Flight Mass Spectrometry Mass).

The technique allows to obtain a unique mass fingerprint for each microorganism, and is thus ideal for the analysis of monovalent but also polyvalent bacterial lysates products. This reliable and reproducible method is useful to produce protein profiles after cellular extraction and purification.

Polyvalent bacterial lysates obtained by mechanical lysis, PMBL, resulted in a more defined fingerprints, so a more precise characterization as compared to those obtained by chemical alkaline lysis. This result corroborates our precedent findings on PMBL, showing that mechanical lysis allows a better preservation of the proteins/antigens structure as compared to chemical lysis Morandi et al, demonstrated that the better preservation of the antigens structure are 10-100 times more powerful in triggering immune response10.



[1] Gates B. Responding to COVID-19 – a once-in-a-century pandemic? N Engl J Med. 2020;382(18):1677–1679. doi: 10.1056/NEJMp2003762. [PubMed] [CrossRef] [Google Scholar]

[2] Clip of Dr Deborah Birx. C-SPAN. 31 March, 2020. There is no magic bullet – no magic vaccine or therapy. It is just behaviors. [Google Scholar]

[3] Licari A, Castagnoli R, Denicolò CF, Rossini L, Marseglia A and Marseglia GL (2017) The Nose and the Lung: United Airway Disease? Front. Pediatr. 5:44. doi: 10.3389/fped.2017.00044