Companion diagnostic for the chloroquine use in the treatment of COVID-19: systems biology report of candidate markers.

Abstract BACKGROUND Chloroquine is used for the treatment of COVID-19 patients. However, efficacy of the chloroquine has been under discussion. Variability of clinical outputs of the drug application requires implementation of a companion diagnostic that would allow monitoring responsiveness to chloroquine. The first line of such markers would be markers already used in clinics. Analysis of reported mechanisms of COVID-19 and chloroquine may lead to such markers. METHODS Systemic analysis of molecular mechanisms and markers engaged by chloroquine and COVID-19 virus was performed. The networks of regulatory mechanisms were explored for an intersection and relevance to clinical markers. RESULTS Reported here systemic analysis describes the intersection of molecular mechanisms of chloroquine and processes engaged by COVID-19. 266 nodes provide insight into the mechanisms of chloroquine impact on the infection and represent a pool of companion diagnostic markers. As an example, an intersection with the markers of heart arrhythmia retrieved 19 nodes. Thirteen of them were reported in human plasma: levels of albumin, amyloid precursor protein, and endoglin correlate with adverse cardiac effects. CONCLUSIONS Reported nodes are the candidate markers for companion diagnostic of the chloroquine application to COVID-19 patients. Some of these markers are already used in the clinic and their interpretation may contribute to monitoring for adverse effects of chloroquine.