ABSTRACT
The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.
ABSTRACT
AIMS: In patients with coronavirus disease 2019 (COVID-19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model. METHODS AND RESULTS: This retrospective cohort study included patients with confirmed COVID-19 from Wuhan Tongji Hospital (Wuhan, China). Data were compared between those with and without myocardial injury. Kaplan-Meier analysis and Cox regression models were used to describe the association between myocardial injury and poor prognosis. Simple correlation analyses were used to find factors associated with high-sensitivity cardiac troponin I levels. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with myocardial injury. The area under the receiver operating characteristic curve was used to determine the predictive value of the model. Of 353 patients included in the study, 79 presented myocardial injury. Patients with myocardial injury had higher levels of inflammation markers, poorer liver and kidney function, and more complications compared with patients without myocardial injury. High-sensitivity cardiac troponin I levels were significantly associated with neutrophil/lymphocyte ratio, creatinine, d-dimer, lactate dehydrogenase, and inflammatory cytokines and negatively associated with oxygen saturation. It was significantly associated with poor prognosis after adjusting for age, sex, and complications. Multivariate regression showed that myocardial injury was associated with a high neutrophil/lymphocyte ratio (odds ratio 2.30, 95% CI 1.11-4.75, per standard deviation increase, P = 0.02), creatinine (3.58, 1.35-8.06, P = 0.01), and lactate dehydrogenase (3.39, 1.42-8.06, P = 0.01) levels. Using a predictive model, the area under the receiver operating characteristic curve was 0.92 (0.88-0.96). CONCLUSIONS: In patients with COVID-19, neutrophil/lymphocyte ratio, creatinine, and lactate dehydrogenase are blood markers that could help identify patients with a high risk of myocardial injury at an early stage.
ABSTRACT
The SARS-CoV-2 epidemic starting in Wuhan in December, 2019 has spread rapidly throughout the nation. The control measures to contain the epidemic also produced influences on the transport and treatment process of patients with acute myocardial infarction (AMI), and adjustments in the management of the patients need to be made at this particular time. AMI is characterized by an acute onset with potentially fatal consequence, a short optimal treatment window, and frequent complications including respiratory infections and respiratory and circulatory failure, for which active on-site treatment is essential. To standardize the management and facilitate the diagnosis and treatment, we formulated the guidelines for the procedures and strategies for the diagnosis and treatment of AMI, which highlight 5 Key Principles, namely Nearby treatment, Safety protection, Priority of thrombolysis, Transport to designated hospitals, and Remote consultation. For AMI patients, different treatment strategies are selected based on the screening results of SARS-CoV-2, the time window of STEMI onset, and the vital signs of the patients. During this special period, the cardiologists, including the interventional physicians, should be fully aware of the indications and contraindications of thrombolysis. In the transport and treatment of AMI patients, the physicians should strictly observe the indications for patient transport with appropriate protective measurements of the medical staff.