COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient’s condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a “cytokine storm”. In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

A modification is proposed for the Hill equation, which describes the cooperative binding of a ligand by a macromolecule. A relative coefficient of cooperativity was introduced as a new parameter in the equation to ensure the conjugation of the Hill coefficient with the number of interacting subunits in the oligomer. This makes it possible to clarify the physical meaning of the Hill coefficient and explains the nature of its non-integer values. Normalization of the relative coefficient of cooperativity additionally provides the opportunity to compare the coefficient values for oligomers with different numbers of protomers. The relative coefficient of cooperativity may be useful in solving a wide range of problems where coordinated interactions of elements are described at all levels of the spatial organization of proteins, nucleic acids, their complexes, and receptors with their mediators.

The study of hemoglobin oxygenation, starting from the classical works of Hill, has laid the foundation for molecular biophysics. The cooperative nature of oxygen binding to hemoglobin has been variously described in different models. In the Adair model, which better fits the experimental data, the constants of oxygen binding at various stages differ. However, the physical meaning of the parameters in this model remains unclear. In this work, we applied Hill’s approach, extending its interpretation; we obtained a good agreement between the theory and the experiment. The equation in which the Hill coefficient is modulated by the Lorentz distribution for oxygen partial pressure approximates the experimental data better than not only the classical Hill equation, but also the Adair equation.

—This paper presents an overview of the best-known models that describe the binding of oxygen to hemoglobin. A formal criteria-based approach was designed to find the optimal mathematical and physical models of cooperative oxygen binding by hemoglobin. The main models of oxygenation, which are based on power and exponential dependencies, were compared using regression and cluster analyses of experimental data on oxyhemoglobin dissociation. Adair’s, Bernard’s, and Hill’s power-law models were shown to be superior to exponential models in describing the ligand binding by an oligomeric protein. The sequential four-stage Koshland–Némethy–Filmer model, which corresponds to the Adair equation, was found to most accurately describe the experimental data.