# Improvement on Ferrous Ion Accumulation and Mitochondrial Dysfunction in the COVID-19 Pseudovirus-Infected Cell Model Simulating the Long COVID Status by Nutritional Strategy

## TL;DR

This study explores how nutritional supplements can reduce mitochondrial dysfunction caused by SARS-CoV-2 pseudovirus in a cell model resembling long COVID.

## Contribution

The novel contribution is identifying lactoferrin, Q10, and Echinacea purpurea extract as effective in mitigating ferrous ion accumulation and mitochondrial damage in a long COVID cell model.

## Key findings

- Lactoferrin, Q10, and Echinacea purpurea extract reduced ferrous ion accumulation and ROS in mitochondria.
- Echinacea purpurea extract showed high levels of caffeic acid and improved mitochondrial dysfunction.
- Pseudovirus infection caused ferrous ion and ROS accumulation, leading to mitochondrial dysfunction.

## Abstract

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerged various mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID (LC), lasting up to 12 weeks or even longer. The mechanism has yet to be clarified. COVID-19 pseudovirus is a suitable model to understand the infection of the COVID-19 virus to cells, which is suitable to see the acute change in cells owing to its one-time infection and inactivation. The ACE2-293T cell infected by COVID-19 pseudovirus was used in this study. After the infection and removal of the pseudovirus, high amounts of ferrous ions were accumulated in mitochondria and then released into the cytosol. Reactive oxygen species (ROS) accumulation was formed and caused mitochondrial dysfunction. To evaluate the effect of nutritional strategy on ferrous ion accumulation and mitochondrial dysfunction, lactoferrin, Q10 and Echinacea purpurea extract (EPE) were used in this study. Results showed that lactoferrin, Q10 and EPE could improve mitochondrial dysfunction by reducing the accumulation of ferrous ions and ROS in the mitochondria. HPLC analysis showed that EPE contained rich caffeic acid, and it also showed perfect improvement in mitochondrial dysfunction. In conclusion, cells infected with pseudovirus could increase the accumulation of ferrous ions and ROS in mitochondria and be released into the cytosol after removing pseudovirus, thereby causing mitochondrial dysfunction. Lactoferrin, Q10 and EPE were an effective nutritional strategy to suppress ferrous ion accumulation, ROS formation and advanced mitochondrial dysfunction.