Pulmonary surfactant and COVID-19: A new synthesis

Abstract

Chapter 1: COVID-19 pathogenesis poses paradoxes difficult to explain with traditional physiology. For instance, since type II pneumocytes are considered the primary cellular target of SARS-CoV-2; as these produce pulmonary surfactant (PS), the possibility that insufficient PS plays a role in COVID-19 pathogenesis has been raised. However, the opposite of predicted high alveolar surface tension is found in many early COVID-19 patients: paradoxically normal lung volumes and high compliance occur, with profound hypoxemia. That ‘COVID anomaly’ was quickly rationalised by invoking traditional vascular mechanisms–mainly because of surprisingly preserved alveolar surface in early hypoxemic cases. However, that quick rejection of alveolar damage only occurred because the actual mechanism of gas exchange has long been presumed to be non-problematic, due to diffusion through the alveolar surface. On the contrary, we provide physical chemical evidence that gas exchange occurs by an process of expansion and contraction of the three-dimensional structures of PS and its associated proteins. This view explains anomalous observations from the level of cryo-TEM to whole individuals. It encompasses results from premature infants to the deepest diving seals. Once understood, the COVID anomaly dissolves and is straightforwardly explained as covert viral damage to the 3D structure of PS, with direct treatment implications. As a natural experiment, the SARS-CoV-2 virus itself has helped us to simplify and clarify not only the nature of dyspnea and its relationship to pulmonary compliance, but also the fine detail of the PS including such features as water channels which had heretofore been entirely unexpected.

Mouth breathing, dry air, and low water permeation promote inflammation, and activate neural pathways, by osmotic stresses acting on airway lining mucus

“…The water that condenses on the upper airways on exhalation may then contain molecular and structural elements of nano-bubble forms in the alveolar region of the lungs and promote another "salt effect" on the composition of the condensation layer that we do not consider in our study. That is, nano-bubbles are stabilized at a critical salt concentration of approximately 0.17M (75,78), slightly above isotonic salt concentration, while this number is suppressed with convection (79), as occurs along the surface of airway lining fluid in the upper airways. Should nano-bubbles exist in the condensation layer, the elevation of salt concentration that occurs on dehydration (Fig 2b) might trigger their stabilization and contribute to the lowering of surface tension and the frothiness of upper airway condensation layer that is observed to occur when the upper airways are dry (Fig.…”

“…The analysis does not, therefore, explicitly address the substructure of matter, leaving unaddressed the molecular composition of the condensation layer in the upper airways. Recent discoveries (Ninham et al , 2022 ) of the role played by pulmonary surfactant in the movement of gases between the alveolar lumen and the systemic circulation suggest that the absorption of oxygen and nitrogen from inhaled air may significantly occur by way of nano-bubbles of oxygen and nitrogen formed in a lattice of pulmonary surfactant, on inhalation, seemingly transitioning to carbon dioxide and water on exhalation (Ninham et al , 2022 ). Such nano-bubbles have an even better documented role in the endothelial surface layer (Reines and Ninham, 2019 ), where they reside within the glycocalyx (Reines and Ninham, 2019 ) and facilitate the oxygenation of blood.…”

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

“…The glycocalyx layer is known to contain an abundance of proteins that affect vascular function (e.g., syndecans) that can be degraded and affect the vasculature like metalloproteinases (MMP), heparanase, and hyaluronidase through the action of cytokines (IL-1β and others) [22,23]. This process of respiration is dependent on membrane thickness and gas solubility of O2, N2 and CO2 nanobubbles [24] (see Figure 1). Type II pneumocytes are responsible for epithelial cell repair and renewal and are specialized secretory cells that produce surfactant consisting of 90% lipids (mainly saturated phospholipids) and 10% pulmonary surfactant proteins (SP) that contribute to the surface tensile maintenance utilizing dipalmitoylphosphatidylcholine (DPPC), and other SP, that are synthesized in the type II pneumocytes endoplasmic reticulum SP-A,SP-B, SP-C, SP-D. SP-B and SP-C are hydrophobic proteins with SP-A and SP-D possessing hydrophilic components intermixed that participate in pulmonary host defense.…”

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

“…The glycocalyx layer is known to contain an abundance of proteins that affect vascular function (e.g., syndecans) that can be degraded and affect the vasculature like metalloproteinases (MMP), heparanase, and hyaluronidase through the action of cytokines (IL-1β and others) [20,21]. This process of respiration is dependent on membrane thickness and gas solubility of O2, N2 and CO2 nanobubbles [22] (see Figure 1). Type II pneumocytes are responsible for epithelial cell repair and renewal and are specialized secretory cells that produce surfactant consisting of 90% lipids (mainly saturated phospholipids) and 10% pulmonary surfactant proteins (SP) that contribute to the surface tensile maintenance utilizing dipalmitoylphosphatidylcholine (DPPC), and other SP, that are synthesized in the type II pneumocytes endoplasmic reticulum SP-A,SP-B, SP-C, SP-D. SP-B and SP-C are hydrophobic proteins with SP-A and SP-D possessing hydrophilic components intermixed that participate in pulmonary host defense.…”