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1.
Intervencni a Akutni Kardiologie ; 21(2):108-111, 2022.
Article in Slovak | EMBASE | ID: covidwho-1887458

ABSTRACT

At the time of the ongoing coronavirus pandemic, we are encountering patients who are Covid-19 positive and have severe coronary artery disease. Patients requiring cardiac surgery are particularly challenging. A multidisciplinary discussion aimed at assessing surgery tolerability and considering the most appropriate approach is important given the higher risk of surgical mortality. We report a case of a high-risk Covid-19 positive symptomatic female patient with an acute coronary syndrome and a critical calcified stenosis of the main stem of the left coronary artery. This patient was not suitable for cardiac surgery and she underwent a percutaneous coronary intervention using a left ventricular mechanical support system and intravascular lithotripsy.

2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333758

ABSTRACT

Repurposing drugs as treatments for COVID-19 has drawn much attention. A common strategy has been to screen for established drugs, typically developed for other indications, that are antiviral in cells or organisms. Intriguingly, most of the drugs that have emerged from these campaigns, though diverse in structure, share a common physical property: cationic amphiphilicity. Provoked by the similarity of these repurposed drugs to those inducing phospholipidosis, a well-known drug side effect, we investigated phospholipidosis as a mechanism for antiviral activity. We tested 23 cationic amphiphilic drugs-including those from phenotypic screens and others that we ourselves had found-for induction of phospholipidosis in cell culture. We found that most of the repurposed drugs, which included hydroxychloroquine, azithromycin, amiodarone, and four others that have already progressed to clinical trials, induced phospholipidosis in the same concentration range as their antiviral activity;indeed, there was a strong monotonic correlation between antiviral efficacy and the magnitude of the phospholipidosis. Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis depends on the gross physical properties of drugs, and does not reflect specific target-based activities, rather it may be considered a confound in early drug discovery. Understanding its role in infection, and detecting its effects rapidly, will allow the community to better distinguish between drugs and lead compounds that more directly impact COVID-19 from the large proportion of molecules that manifest this confounding effect, saving much time, effort and cost. ONE SENTENCE SUMMARY: Drug-induced phospholipidosis is a single mechanism that may explain the in vitro efficacy of a wide-variety of therapeutics repurposed for COVID-19.

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