Exploiting Bacteria for Improving Hypoxemia of COVID-19 Patients
Vito Trinchieri, Massimiliano Marazzato, Giancarlo Ceccarelli, Francesca Lombardi, Alessandra Piccirilli, Letizia Santinelli, Luca Maddaloni, Paolo Vassalini, Claudio Maria Mastroianni, Gabriella D’ettorre
Biomedicines, doi:10.3390/biomedicines10081851
Background: Although useful in the time-race against COVID-19, CPAP cannot provide oxygen over the physiological limits imposed by severe pulmonary impairments. In previous studies, we reported that the administration of the SLAB51 probiotics reduced risk of developing respiratory failure in severe COVID-19 patients through the activation of oxygen sparing mechanisms providing additional oxygen to organs critical for survival. Methods: This "real life" study is a retrospective analysis of SARS-CoV-2 infected patients with hypoxaemic acute respiratory failure secondary to COVID-19 pneumonia undergoing CPAP treatment. A group of patients managed with ad interim routinely used therapy (RUT) were compared to a second group treated with RUT associated with SLAB51 oral bacteriotherapy (OB). Results: At baseline, patients receiving SLAB51 showed significantly lower blood oxygenation than controls. An opposite condition was observed after 3 days of treatment, despite the significantly reduced amount of oxygen received by patients taking SLAB51. At 7 days, a lower prevalence of COVID-19 patients needing CPAP in the group taking probiotics was observed. The administration of SLAB51 is a complementary approach for ameliorating oxygenation conditions at the systemic level. Conclusion: This study proves that probiotic administration results in an additional boost in alleviating hypoxic conditions, permitting to limit on the use of CPAP and its contraindications.
Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Acosta, Garrigos, Marcelin, Vijayvargiya, COVID-19 Pathogenesis and Clinical Manifestations, Infect. Dis. Clin. N. Am,
doi:10.1016/j.idc.2022.01.003Aliberti, Radovanovic, Billi, Sotgiu, Costanzo et al., Helmet CPAP treatment in patients with COVID-19 pneumonia: A multicentre cohort study, Eur. Respir. J,
doi:10.1183/13993003.01935-2020Bao, Tao, Cui, Yi, Pan et al., SARS-CoV-2 induced thrombocytopenia as an important biomarker significantly correlated with abnormal coagulation function, increased intravascular blood clot risk and mortality in COVID-19 patients, Exp. Hematol. Oncol,
doi:10.1186/s40164-020-00172-4Barrett, Bilaloglu, Cornwell, Burgess, Virginio et al., Platelets contribute to disease severity in COVID-19, J. Thromb. Haemost,
doi:10.1111/jth.15534Bonfili, Gong, Lombardi, Cifone, Eleuteri, Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer's Disease, Int. J. Mol. Sci
Brusasco, Corradi, Di Domenico, Raggi, Timossi et al., CPAP-COVID-19 Study Group; Collaborators of the Galliera CPAP-COVID-19 Study Group. Continuous positive airway pressure in COVID-19 patients with moderate-to-severe respiratory failure, Eur. Respir. J,
doi:10.1183/13993003.02524-2020Callapina, Zhou, Schnitzer, Metzen, Lohr et al., Nitric oxide reverses desferrioxamine-and hypoxia-evoked HIF-1α accumulation-Implications for prolyl hydroxylase activity and iron, Exp. Cell Res,
doi:10.1016/j.yexcr.2005.02.018Ceccarelli, Borrazzo, Pinacchio, Santinelli, Innocenti et al., Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study, Front. Nutr
Ceccarelli, Marazzato, Celani, Lombardi, Piccirilli et al., Oxygen Sparing Effect of Bacteriotherapy in COVID-19, Nutrients,
doi:10.3390/nu13082898Chaurasia, Kushwaha, Kulkarni, Mallick, Latheef et al., Platelet HIF-2α promotes thrombogenicity through PAI-1 synthesis and extracellular vesicle release, Haematologica,
doi:10.3324/haematol.2019.217463Chavez, Brady, Gottlieb, Carius, Liang et al., Clinical update on COVID-19 for the emergency clinician: Airway and resuscitation, Am. J. Emerg. Med,
doi:10.1016/j.ajem.2022.05.011D'ettorre, Ceccarelli, Marazzato, Campagna, Pinacchio et al., Challenges in the Management of SARS-CoV-2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19, Front. Med,
doi:10.3389/fmed.2020.00389De Angelis, Mariotti, Rossi, Servili, Fox et al., Arginine Catabolism by Sourdough Lactic Acid Bacteria: Purification and Characterization of the Arginine Deiminase Pathway Enzymes from Lactobacillus sanfranciscensis CB1, Appl. Environ. Microbiol,
doi:10.1128/AEM.68.12.6193-6201.2002Dillon, Holtsberg, Ensor, Bomalaski, Clark, Biochemical characterization of the arginine degrading enzymes arginase and arginine deiminase and their effect on nitric oxide production, Med. Sci. Monit
Duca, Memaj, Zanardi, Preti, Alesi et al., Severity of respiratory failure and outcome of patients needing a ventilatory support in the Emergency Department during Italian novel coronavirus SARS-CoV-2 outbreak: Preliminary data on the role of Helmet CPAP and Non-Invasive Positive Pressure Ventilation, eClinicalMedicine,
doi:10.1016/j.eclinm.2020.100419Fernández-Ferreiro, Formigo-Couceiro, Veiga-Gutierrez, Maldonado-Lobón, Hermida-Cao et al., Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial, Nutrients,
doi:10.3390/nu14010228Forcados, Muhammad, Oladipo, Makama, Meseko, Metabolic Implications of Oxidative Stress and Inflammatory Process in SARS-CoV-2 Pathogenesis: Therapeutic Potential of Natural Antioxidants, Front. Cell. Infect. Microbiol,
doi:10.3389/fcimb.2021.654813Ito, Sono, Ito, Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation, Antioxidants,
doi:10.3390/antiox8030072Kosanovic, Sagic, Djukic, Pljesa-Ercegovac, Savic-Radojevic et al., Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings, Antioxidants,
doi:10.3390/antiox10071126Król, Kepinska, Human Nitric Oxide Synthase-Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases, Int. J. Mol. Sci,
doi:10.3390/ijms22010056Lundquist, Artursson, Oral absorption of peptides and nanoparticles across the human intestine: Opportunities, limitations and studies in human tissues, Adv. Drug Deliv. Rev,
doi:10.1016/j.addr.2016.07.007Mussini, Falcone, Nozza, Sagnelli, Parrella et al., Therapeutic strategies for severe COVID-19: A position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT), Clin. Microbiol. Infect,
doi:10.1016/j.cmi.2020.12.011Okabe, Toyofumi, Yoshikawa, Yoneyama, Yokoyama et al., Mammalian enteral ventilation ameliorates respiratory failure, Med,
doi:10.1016/j.medj.2021.04.004Radovanovic, Rizzi, Pini, Saad, Chiumello et al., Helmet CPAP to Treat Acute Hypoxemic Respiratory Failure in Patients with COVID-19: A Management Strategy Proposal, J. Clin. Med,
doi:10.3390/jcm9041191Riccia, Bizzini, Perilli, Polimeni, Trinchieri et al., Anti-inflammatory effects of Lactobacillus brevis (CD2) on periodontal disease, Oral Dis,
doi:10.1111/j.1601-0825.2006.01291.xShen, Wang, Effects of hypoxia on platelet activation in pilots, Aviat. Space Environ. Med
Singhal, Shah, Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine, J. Biol. Chem,
doi:10.1074/jbc.REV120.011188Sundararaman, Ray, Ravindra, Halami, Role of probiotics to combat viral infections with emphasis on COVID-19, Appl. Microbiol. Biotechnol,
doi:10.1007/s00253-020-10832-4Wischmeyer, Tang, Ren, Bohannon, Ramirez et al., Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial,
doi:10.1101/2022.01.04.21268275Wozniak, Rubino, Tan, Jones, Webb et al., Positive role of continuous positive airway pressure for intensive care unit patients with severe hypoxaemic respiratory failure due to COVID-19 pneumonia: A single centre experience, J. Intensiv. Care Soc,
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'abstract': '<jats:p>Background: Although useful in the time-race against COVID-19, CPAP cannot provide '
'oxygen over the physiological limits imposed by severe pulmonary impairments. In previous '
'studies, we reported that the administration of the SLAB51 probiotics reduced risk of '
'developing respiratory failure in severe COVID-19 patients through the activation of oxygen '
'sparing mechanisms providing additional oxygen to organs critical for survival. Methods: This '
'“real life” study is a retrospective analysis of SARS-CoV-2 infected patients with hypoxaemic '
'acute respiratory failure secondary to COVID-19 pneumonia undergoing CPAP treatment. A group '
'of patients managed with ad interim routinely used therapy (RUT) were compared to a second '
'group treated with RUT associated with SLAB51 oral bacteriotherapy (OB). Results: At '
'baseline, patients receiving SLAB51 showed significantly lower blood oxygenation than '
'controls. An opposite condition was observed after 3 days of treatment, despite the '
'significantly reduced amount of oxygen received by patients taking SLAB51. At 7 days, a lower '
'prevalence of COVID-19 patients needing CPAP in the group taking probiotics was observed. The '
'administration of SLAB51 is a complementary approach for ameliorating oxygenation conditions '
'at the systemic level. Conclusion: This study proves that probiotic administration results in '
'an additional boost in alleviating hypoxic conditions, permitting to limit on the use of CPAP '
'and its contraindications.</jats:p>',
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