SARS-CoV-2 Foam Cells: The 2025 Study on Lung Scarring and Clots

This guide walks through a 2025 Nature Microbiology paper on lung macrophages in SARS-CoV-2 infection. It covers what the researchers did, what they found, how it lines up with clotting studies we've already explained, and what the paper itself says it can't answer.

What did the 2025 foam cell study find?

The paper is Battaglia, Post, Yao and colleagues, SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation, with Angela Wahl and J. Victor Garcia as corresponding authors. It was published online in August 2025.

Its main findings, in the models tested:

• SARS-CoV-2 infection increased macrophage numbers in lung tissue
• many macrophages became foam cells, enlarged and filled with lipid droplets
• foam cells expressed pro-fibrotic and pro-thrombotic genes
• infected lung tissue developed fibrin thrombi and fibrosis markers that persisted after viral clearance
• the antiviral EIDD-2801, started early, prevented the macrophage and foam cell increase in mice

Start with the vocabulary

What is a macrophage?

Macrophages are immune cells that swallow infected cells and debris. The paper studied two groups in the lung: interstitial macrophages in the tissue and enlarged macrophages in the air spaces. In mice with a human immune system, macrophages could come from the lung tissue itself or from monocytes in the blood.

What is a foam cell?

The paper defines foam cells as enlarged macrophages that contain lipid droplets. In infected lung tissue they averaged about 326 square micrometers, against about 39 for interstitial macrophages, and almost 90% stained for the lipid-droplet marker adipophilin. Foam cells are also found in atherosclerotic plaques.

What are fibrosis and thrombi?

The paper measured fibrosis with two markers: collagen and smooth muscle actin (SMA). A thrombus is a clot. The thrombi here were fibrin clots in lung tissue, including one shown blocking a blood vessel, not the circulating fibrin amyloid microclots studied in Long COVID blood.

How did the researchers test it?

Most of the work used humanized mice, mice implanted with human lung tissue that SARS-CoV-2 can infect. The paper reports these results:

The team also infected the lung-only mice with SARS-CoV-1, MERS and two bat coronaviruses (SHC014 and WIV1). All four left macrophage numbers significantly lower than in uninfected tissue. Only SARS-CoV-2 raised them.

Why would foam cells matter for clots and scarring?

In uninfected tissue, foam cells already expressed more genes for extracellular matrix organization and collagen synthesis than interstitial macrophages. During SARS-CoV-2 infection, foam cells expressed more genes for platelet activation and aggregation, which the authors note contribute to thrombus formation.

The tissue findings matched. Thrombi appeared in infected lung tissue but not in uninfected controls, and collagen and SMA were higher at days 14 and 28 after infection. The authors call foam cells "potential drivers" of COVID-19 clotting and propose that infection-induced foam cells help blood clots form.

They also name a limitation: they had no information on foam cells in circulation, and clotting after infection isn't limited to the lungs.

Did the damage outlast the virus?

In the BLT-L mice, which have a human immune system, it did. Infectious virus dropped by about tenfold at day 6, and none was detected in any lung implant at day 14. The authors note that the average time to clear the virus in humans is about 8 days.

Day 14 was also when macrophage numbers were highest. Fibrin thrombi were present at days 6 and 14, collagen and SMA were raised at day 14, and several inflammatory genes were still elevated. The authors write that even people without severe COVID-19 symptoms "could incur lasting and potentially permanent lung damage."

The paper measured infectious virus, not viral RNA or protein. For what's known about testing for lingering spike protein, see spike protein persistence testing.

Could an early antiviral prevent it?

In mice, early treatment did. The team reused lung tissue from their 2021 Nature study, where EIDD-2801 was given by mouth every 12 hours, starting 12 hours before infection or 24 or 48 hours after.

• Starting 12 hours before or 24 hours after infection kept macrophage numbers at uninfected levels.
• Starting at 48 hours lowered macrophage numbers, but they stayed above uninfected levels.
• Starting at 24 or 48 hours kept foam cell numbers at uninfected levels.
• Treated mice had less collagen and SMA than untreated infected mice.

The authors say this indicates the macrophage changes are a direct result of viral infection of lung tissue. They add that it still needs to be determined whether starting EIDD-2801 at symptom onset would prevent or delay fibrosis and thrombosis.

Next step

Want more COVID research explained without the jargon?

Explore our library of plain-English guides to clotting, immune and Long COVID research.

See the at-home test

How does this fit with other COVID clotting research?

Several studies we've covered also link SARS-CoV-2 infection to clotting:

The Englert and Thierry studies are about neutrophils and the traps they release (NETs). Our NETs and microclots explainer describes this as immunothrombosis: the immune and clotting systems acting together. The foam cell paper doesn't use that term, and it doesn't study neutrophils.

It also didn't measure microclots or amyloid fibrin. That research, from Kell, Pretorius and colleagues (2022), is covered in our pillar on amyloid microclots and Long COVID.

What the study did not prove

The study didn't:

• include anyone with Long COVID or measure Long COVID symptoms
• measure circulating microclots, amyloid fibrin or D-dimer
• look for foam cells in the blood
• show directly that foam cells form the thrombi (the authors call them potential drivers)
• test EIDD-2801 started at symptom onset

The human evidence is small. The three COVID-19 lungs came from people aged 40, 77 and 91, and the four comparison lungs from donors aged 17 to 27. The authors say direct comparison with their models isn't possible because the length of infection in the human samples is unknown, and the macaques weren't age matched.

What does this mean if you have Long COVID?

The paper didn't study Long COVID. The authors suggest unresolved macrophage build-up and foam cell formation could potentially contribute to it, which would need studies in people to confirm.

If you want to know what blood tests can and can't show, our Long COVID blood test guide covers why routine panels often look normal, and the amyloid fibrin test guide explains Thioflavin T staining for fibrin amyloid microclots. Our at-home amyloid test uses that method on a dried blood sample. It doesn't measure lung tissue or virus, and it isn't a diagnosis.

The bottom line

In human lung tissue in mice, and in macaques, SARS-CoV-2 raised lung macrophage numbers and turned many into foam cells. In the mice, those foam cells carried pro-fibrotic and pro-thrombotic genes. Thrombi and fibrosis markers persisted after infectious virus was cleared, and early EIDD-2801 prevented the macrophage and foam cell rise in mice.

The authors propose that foam cells help drive clotting and lung damage in COVID-19. The study doesn't test that in people with Long COVID.

This article is educational and doesn't diagnose illness or recommend treatment.