Nanoantidote for repression of acidosis pH promoting COVID‐19 infection

Abstract

Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID‐19) infection and is associated with increased mortality in critically ill COVID‐19 patients. It remains unclear whether acidosis further promotes SARS‐CoV‐2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis‐related pH of 6.8 increases SARS‐CoV‐2 receptor angiotensin‐converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS‐CoV‐2 pseudovirus infection. Based on this, we synthesized polyglutamic acid‐PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO3‐NPs) nanoantidote to neutralize excess hydrogen ions (H+), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO3‐NPs effectively prevented the heightened SARS‐CoV‐2 infection efficiency due to pH 6.8. Our study reveals that acidosis‐related pH promotes SARS‐CoV‐2 infection, which suggests the existence of a positive feedback loop in which SARS‐CoV‐2 infection‐induced acidosis enhances SARS‐CoV‐2 infection. Therefore, antacid therapy for acidosis COVID‐19 patients is necessary. CaCO3‐NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

Approaching Personalized Medicine: The Use of Machine Learning to Determine Predictors of Mortality in a Population with SARS-CoV-2 Infection

“…In our study, these data are reinforced by the fact that the estimated glomerular filtration rate is also among the most relevant parameters, as it has been shown in other studies to be a good predictor of admission mortality in COVID-19. In addition, our study showed a high relevance of FiO2, closely related to acute hypoxic respiratory failure-, and potassium and pH as predictors of a poor outcome and mortality, which is compatible with the results obtained by Satici et al [48], Noori et al [49], or Liu et al [50]. Interestingly, hypokalemia has also been shown to be an indicator of a poorer prognosis and longer days of negative nucleic acid conversion.…”

Effect of COVID-19 on Glycemic Control, Insulin Resistance, and pH in Elderly Patients With Type 2 Diabetes

“…Moreover, COVID-19 promotes respiratory acidosis among critically ill patients [27]. As a way to quickly reverse acute acidemia, the previous pole of therapy placed great assertiveness on intravenous sodium bicarbonate, which significantly reduces the primary composite outcome and mortality in patients with acute kidney injury [28]. We observed a decrease in pH in elderly patients with type 2 diabetes, which was reversed following complete remission from COVID-19.…”

“…In parallel, acidosis enhances COVID-19 infection by increasing cell membrane ACE2 expression. Therefore, acidosis promotes further infection and difficulty in recovery from COVID-19 [28].…”

Hydrogen Ion Capturing Hydrogel Microspheres for Reversing Inflammaging

“…Preparation of MNP: First, the poly(ethylene glycol)-poly(glutamic acid) (PEG-P(Glu)) block copolymer was synthesized and obtained using Fuchs-Farthing reaction as previously reported. [22] 1 H-NMR hydrogen spectrum (300 MHz; solvent: D 2 O) was used to determine the substitution ratio of P(Glu). Then, 1 mL Tris-HCl buffer (10 mm, pH 7.6) containing 10 mg CaCl 2 , 3 μg TGF-𝛽, 300 μg CAT, 10 mg mPEG-P(Glu) polymer.…”