Predicted risk of heart failure pandemic due to persistent SARS-CoV-2 infection using a three-dimensional cardiac model, 2023, Masumoto et al

Predicted risk of heart failure pandemic due to persistent SARS-CoV-2 infection using a three-dimensional cardiac model

Highlights

• Persistent SARS-CoV-2 infection model of human cardiac tissue was established
• Hypoxic stress to the persistent infection model led to cardiac dysfunction
• ACE2 and SARS-CoV-2 S protein expression were elevated after the hypoxic stress
• This research may predict a “heart failure pandemic” in the post COVID-19 era

Summary

Patients with chronic cardiomyopathy may have persistent viral infections in their hearts, particularly with SARS-CoV-2, which targets the ACE2 receptor highly expressed in human hearts. This raises concerns about a potential global heart failure pandemic stemming from COVID-19, an SARS-CoV-2 pandemic in near future. Although faced with this healthcare caveat, there is limited research on persistent viral heart infections, and no models have been established.

In this study, we created an SARS-CoV-2 persistent infection model using human iPS cell-derived cardiac microtissues (CMTs). Mild infections sustained viral presence without significant dysfunction for a month, indicating persistent infection. However, when exposed to hypoxic conditions mimicking ischemic heart diseases, cardiac function deteriorated alongside intracellular SARS-CoV-2 reactivation in cardiomyocytes and disrupted vascular network formation.

This study demonstrates that SARS-CoV-2 persistently infects the heart opportunistically causing cardiac dysfunction triggered by detrimental stimuli such as ischemia, potentially predicting a post COVID-19 era heart failure pandemic.

Graphical abstract

 

I don’t have any expertise to judge such work, but I feel like a lot goes missing when you’re studying a persistent infection in-vitro without evidence of it existing in-vivo. After all the persistency is supposed to be taken care of by complex immune systemic mechanisms which could probably be lacking in such a model.

As such to me it could make sense to try to understand whether what you’re observing is a real-world phenomena or simply an effect of your in-vitro model. That’s hard to do within an in-vitro model, but one could at least also use different common viruses to see if these also display these same persistent effects. From this one could deduce if these are indeed effects of SARS-COV-2 or if these are just general effects caused by many viruses or by insufficient modelling.

After all if these models were indeed accurate then the prediction of a post COVID-19 era heart failure pandemic should be backed by data and I don’t think it is. So if you would see that many viruses would display such a behaviour then the model would ultimately be incorrect since we would have otherwise experienced multiple heart failure pandemics by these other viruses.

As such I think the main takeaway from such a study could only be that “These results indicate that mild infection can cause persistent SARS-CoV-2 infection of cardiac tissue without causing functional impairment.” (and IMO "can" should be "could").