Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

Abstract

A hypothesis concerning the potential utility of surfactant supplementation for the treatment of critically ill patients with COVID-19 is proposed, along with a brief summary of the data in the literature supporting this idea. It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in pre-term infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system stimulation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. Therefore, it is suggested that surfactant preparations containing phosphatidylglycerol be tested for their ability to improve lung function in critically ill patients with COVID-19.

CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2

“…Another large group of anti-viral genes were found to participate in the phosphatidylglycerol biosynthetic process (NES =-1.94, FDR =0.007). Interestingly, phosphatidylglycerol was reported to regulate the innate immune response in lungs [58] and consequently was suggested as a treatment against SARS-CoV-2 infection by restoring the lung tissue [59]. The current results suggest also that phosphatidylglycerols may play a supporting role in SARS-CoV-2 infection.…”

Use of exogenous pulmonary surfactant in acute respiratory distress syndrome (ARDS): Role in SARS-CoV-2-related lung injury

“…COVID-19 causes lung damage and ARDS, so the use of pulmonary surfactant as Curosurf® could be hypothesized for the treatment of this viral infection, therefore be beneficial if applied in the early stages of the treatment strategy against pulmonary insufficiency. Furthermore the therapeutic combination of surfactant and ambroxol could be a potential approach an urgent and immediate COVID-19 clinical trial ( Bollag and Gonzales, 2020 ).…”

“…Theoretically, type 2 phenotype is due to the disease’s natural evolution and initial respiratory management, according to Gattinoni et al and non-ARDS type may transit to ARDS-type by self-inflicted or ventilator-induced lung injury ( Gattinoni et al (2020) ). Interestingly, Schousboe et al, starting from Gattinoni’s hypothesis, compared ARDS in SARS-CoV-2 to neonatal respiratory distress syndrome, caused by surfactant deficiency, suggesting an assessment of surfactant levels to the evaluation of COVID-19 patients ( Bollag and Gonzales, 2020 ).…”

Surfactants – Compounds for inactivation of SARS-CoV-2 and other enveloped viruses

“…The effect was attributed to the surfactant inhibiting alveolar collapse and diffuse alveolar damage in the lungs, thereby preserving lung function for oxygenation. [ 149 ] Similarly, phosphatidylglycerol combined with lung surfactant has been advanced for potential treatment of COVID-19 patients, for instance with respect to restoring lung surfactant damaged by infection [ 150 ]. However, this is beyond the scope of this review that focuses on the interactions between surfactants and viruses, even if it is of great potential importance.…”