Thread by @JackHadfield14

🔬New study shows SARS-CoV-2 causes direct damage to heart cell mitochondria - even months after recovery - helping potentially explain Long COVID heart symptoms like chest pain, palpitations & fatigue.

Been waiting to have time to read this paper. Let’s break it down. 🧵

Researchers studied 5 people who had COVID-19 weeks or months earlier. They all had new or unusual heart problems, like chest pain, irregular heartbeat, or even cardiac arrest.

Each patient had a heart biopsy (a sample of heart tissue examined under a microscope).

All 5 patients were diagnosed with myocarditis - inflammation and injury in heart muscle.

But interestingly, it wasn’t typical myocarditis with large immune cell infiltration. Inflammation was mild.

The key problem? Structural damage inside the heart muscle cells.

Using electron microscopes, researchers saw that mitochondria - the energy-producing parts of cells - were swollen, full of holes, and missing their inner structure (cristae).

This was found in 40-60% of mitochondria in each patient’s heart cells.

This mitochondrial damage happened even in patients 2-3 months post-COVID, suggesting it can persist long after infection clears.

Loss of cristae means the cell can’t produce enough energy (ATP), which could explain Long COVID symptoms like fatigue and heart issues.

They also found:

- Collagen buildup (fibrosis) in the heart muscle

- Signs of cell aging (lipofuscin pigment)

- Myofibril damage (these are structures needed for heart muscle contraction)

All of this weakens heart function, even without visible scarring on MRI.

One patient - a healthy 30-year-old man - collapsed during exercise due to cardiac arrest. He had no blocked arteries and no heart disease history.

Biopsy revealed severe mitochondrial damage and mild myocarditis. He was 5 weeks post-COVID at the time.

Another patient had chest pain, but normal heart imaging (CMR, echo, ECG). Only the biopsy showed mitochondrial injury and cell damage. This shows subclinical myocarditis is possible even when standard tests look normal.

To confirm if the virus itself could cause this damage, researchers infected mice with Omicron BA.5.2 and BQ.1.

7 days after infection, the mouse heart cells showed the same type of mitochondrial disorganization: swelling, vacuoles, cristae loss.

In infected mice:

- 60-75% of mitochondria were damaged

- No such damage in uninfected control mice

This strongly suggests that SARS-CoV-2 causes mitochondrial injury, even if the heart isn’t directly infected.

They also did 3D electron microscopy to measure mitochondrial damage more accurately.

In 3D, 60-90% of mitochondria were disordered in patient heart tissue - slightly higher than the 2D estimate.

Next, they ran proteomics (protein profiling) on the mouse hearts.

They found big changes in mitochondrial proteins, especially:

- Import machinery (TOM, TIM proteins)

- Energy production (respiratory chain)

- Damage repair and antioxidant proteins

In particular, they found changes in:

- TOM40/TOM20: brings proteins into mitochondria

- TIM13: part of mitochondrial membrane

- Samm50: helps build mitochondrial structure

- ALDH2 and Txnrd2: antioxidants that protect mitochondria

They also saw upregulation of proteins in the oxidative phosphorylation pathway, which mitochondria use to generate energy (ATP).

This might be a compensatory response, as the cell tries to repair damaged mitochondria or make new ones.

Despite this response, core structural damage persisted, including:

- Loss of cristae (internal folds needed for energy production)

- Swelling and vacuolation

- Disorganization of the heart muscle fibers

No SARS-CoV-2 proteins were found in the mouse hearts at day 7. That’s expected - the virus is usually cleared by then in this model.

So mitochondrial injury in this case likely comes from indirect effects: inflammation, immune response, stress - not virus living in the heart.

Bottom line:

✅ SARS-CoV-2 damages mitochondria in heart cells
✅ This can persist for months after recovery
✅ Damage may explain Long COVID symptoms (fatigue, arrhythmia, chest pain)
✅ Biopsy reveals injury even when standard tests are normal

Full paper:

linkinghub.elsevier.com/retrieve/pii/S…