Frequency and prognosis of CVD and myocardial injury in patients presenting with suspected COVID-19 - The CoV-COR registry.

Background: The COVID-19 pandemic led to an alteration of algorithms in emergency medicine, which may influence the management of patients with similar symptoms but underlying cardiovascular diseases. We evaluated key differential diagnoses to acute COVID-19 infection and the prevalence and the prognosis of myocardial injury in patients presenting for suspected COIVD-19 infection. Methods: This prospective observational study includes patients presenting with symptoms suggestive of COVID-19 infection during the pandemic. In patients without COVID-19, leading diagnoses was classified according to ICD-10. Myocardial injury was defined as elevated high-sensitivity Troponin I with at least one value above the 99th percentile upper reference limit and its prevalence together with 90-days mortality rate was compared in patients with vs without COVID-infection. Results: From 497 included patients (age 62.9 ± 17.2 years, 56 % male), 314 (63 %) were tested positive on COVID-19 based on PCR-testing, while another cause of symptom was detected in 183 patients (37 %). Cardiovascular diseases were the most frequent differential diagnoses (40 % of patients without COVID-19), followed by bacterial infection (24 %) and malignancies (16 %). Myocardial injury was present in 91 patients (COVID-19 positive: n = 34, COVID-19 negative: n = 57). 90-day mortality rate was higher in patients with myocardial injury (13.4 vs 4.6 %, p = 0.009). Conclusion: Cardiovascular diseases represent the most frequent differential diagnoses in patients presenting to a tertiary care emergency department with symptoms suggestive of an acute infection. Screening for cardiovascular disease is crucial in the initial evaluation of symptomatic patients during the COVID pandemic to identify patients at increased risk.Trial Registration:Clinicaltrials.gov Identifier: NCT04327479.

Chain length dependence of antimicrobial peptide-fatty acid conjugate activity.

The rise of resistant bacteria has prompted the search for new antimicrobial agents. Antimicrobial membrane lytic peptides have potential as future microbial agents due to their novel mode of action. Recently conjugation of a fatty acid to antimicrobial peptides has been explored as a method to modulate the activity and selectivity of the peptide. Our work further explores these phenomena by testing two peptides, YGAAKKAAKAAKKAAKAA (AKK) and LKKLLKLLKLLKL (LKK), conjugated to fatty acids of varying length for their activity, structure, solution assembly properties and the ability to bind model membranes. We found that increasing the length of fatty acids conjugated to peptide AKK, up to a 16 carbons in length, increases the antimicrobial activity. Peptide AKK appears to lose activity when the minimal active concentration is higher than the critical miscelle concentration (CMC) of the molecule. Thus, if the CMC of the peptide conjugate is too low the activity is lost. Peptide LKK has no activity when conjugated to lauric acid and appears to aggregate at very low concentrations. Conjugation of AKK with a fatty acid increases its affinity to model supported lipid membranes. It appears that the increased hydrophobic interaction imparted by the fatty acid increases the affinity of the peptide to the surface thus increasing its activity. At concentrations above the CMC, solution self-assembly inhibits binding of the peptide to cell membranes.

Promotion of peptide antimicrobial activity by fatty acid conjugation.

Three peptides, YGAA[KKAAKAA](2) (AKK), KLFKRHLKWKII (SC4), and YG[AKAKAAKA](2) (KAK), were conjugated with lauric acid and tested for the effect on their structure, antibacterial activity, and eukaryotic cell toxicity. The conjugated AKK and SC4 peptides showed increased antimicrobial activity relative to unconjugated peptides, but the conjugated KAK peptide did not. The circular dichroism spectrum of AKK showed a significantly larger increase in its alpha-helical content in the conjugated form than peptide KAK in a solution containing phosphatidylethanolamine/phosphotidylglycerol vesicles, which mimics bacterial membranes. The KAK and AKK peptides and their corresponding fatty acid conjugates showed little change in their structure in the presence of phosphatidylcholine vesicles, which mimic the cell membrane of eukaryotic cells. The hemolytic activity of the KAK and AKK peptides and conjugates was low. However, the SC4 fatty acid conjugate showed a large increase in hemolytic activity and a corresponding increase in helical content in the presence of phosphatidylcholine vesicles. These results support the model of antimicrobial peptide hemolytic and antimicrobial activity being linked to changes in secondary structure as the peptides interact with lipid membranes. Fatty acid conjugation may improve the usefulness of peptides as antimicrobial agents by enhancing their ability to form secondary structures upon interacting with the bacterial membranes.