The K⁺/Na⁺innate immune system is involved in the susceptibility to and severity of COVID-19: a systematic review and retrospective cohort study

Abstract Background From single-cellular to multicellular organisms, a natural nonspecific immune system, called the K + /Na + innate immune system, has recently been proposed to play an important role in the process of fighting against viral infection, however, there is little direct research evidence. This study aimed to evaluate whether the changes in serum K + /Na + concentrations are associated with susceptibility and severity of SARS-CoV-2 infection. Methods We systematically searched PubMed, the Web of Science Core Collection, MedRxiv and BioRxiv databases for articles published between Jan 1, 2020 and Dec 14, 2022. We extracted the serum K + /Na + concentration data of patients with COVID-19 from 112 published studies after removing inappropriate articles according to the defined criteria and analyzed the relationship between the serum k + /Na + concentrations and the illness severity of patients. Then we used a cohort of 244 patients with COVID-19 for a retrospective analysis. Results The mean serum k + /Na + concentrations in patients with COVID-19 were 3.99 and 138.0 mmol/L, respectively, which were much lower than the mean levels in the population (4.40 and 142.0, respectively). The mean serum Na + concentration in severe/critical patients (136.8) was significantly lower than those in mild and moderate patients (139.4 and 138.0, respectively). Such findings were confirmed in a retrospective cohort study, of which the mean serum k + /Na + concentrations in all patients were 4.0 and 137.5 mmol/L, respectively. The significant differences in serum Na + concentrations were found between the mild (139.2) and moderate (137.2) patients, and the mild and severe/critical (136.6) patients, which were correlated to the illness severity of patients. Conclusions These findings may indicate the importance of a natural immune system constructed by intracellular potassium and extracellular sodium ions in the fight against viral infection and provide new ideas for the prevention and treatment of COVID-19.