Mild COVID-19 imprints long-term Inflammation

Today's post is discussing the recent paper "Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages" published in Mucosal Immunology March 2022.

The bottom line-

A new study finds that people who have had a mild Covid-19 infection also experience an increased inflammatory phenomenon in the body for at least five months after being infected with SARS-CoV-2. This appeared to normalise at one year.

What the researchers set out to do

They already knew that severe Covid-19 infection results in Monocyte-derived macrophages (MDM) driving an inflammatory response and they are a major source of eicosanoids in airway inflammation.

Monocyte-derived macrophages

A type of white blood cell called the Monocyte-derived macrophage (or MDM) drives the inflammatory response to SARS-CoV-2 and contributes to cytokine storms seen in severe COVID-19. Severe COVID-19 is associated with profound changes in the myeloid compartment (where white blood cells are made) including increased production of dysfunctional, pro-inflammatory monocytes during the first weeks after SARS-CoV-2 infection.


These are cell signalling molecules. They are involved in physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues.

Long term symptoms of an acute Covid-19 infection - known as PASC and Long Covid - can occur in up to 20% of individuals who have been classified as "mild ". The researchers wanted to see if these people has similar immune dysregulation.

What the researchers did

They studied the profiles in MDM of convalescent SARS-CoV-2-infected individuals with previous mild disease.

What they found out

Increased Eicosanoids I have already discussed but look at these-

Increased Leukotrienes cause tightening of airway muscles and the production of excess mucus and fluid. These chemicals play a key role in allergies, allergic rhinitis, and asthma, also causing a tightening of your airways, making it difficult to breathe.

COVID strangle, anyone?

Increased Prostanoids also regulate the activity of blood platelets both positively and negatively and are involved in vascular homeostasis and hemostasis.

Increased spike protein response

Microclots, anyone?

Increased Chemokines (CCL2) recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by infection.

Persistant inflammation, anyone?

They showed that inflammatory gene expression and eicosanoid profiles as well as altered responsiveness to inflammatory cues are maintained at least 5 months post infection. Pro-inflammatory metabolites were selectively increased in post COVID-19 MDM, suggesting that SARS-CoV-2 infection drives an increase in pro-inflammatory eicosanoids and their metabolites.

Analysis of MDM eicosanoid profiles from donors of the same cohort at 12 months post infection indicated that pro-inflammatory metabolite synthesis of post COVID-19 MDM had largely returned to baseline levels at this time point. This suggested that pro-inflammatory eicosanoid reprogramming in mild COVID-19 is transient, but that it may contribute to an enhanced inflammatory propensity during the first months post SARS-CoV-2 infection.

They suggest further research

Future studies should further decipher upstream receptors and epigenetic pathways that drive the persistent pro-inflammatory macrophage and eicosanoid reprogramming during SARS-CoV-2 infection - basically why does this happen to some and not to others?

The lack of a defined clinical diagnosis of long COVID and poor reporting of long-term symptoms in the studied post COVID-19 cohort, prevented them from establishing a clear link between high MDM pro-inflammatory production and long-term symptoms of SARS-CoV-2 infection. Future studies should investigate eicosanoid reprogramming in a cohort with clinically defined long COVID.

They also raise an interesting point that steroids may not help.

As airway inflammation, including in COVID-19, is commonly treated by steroids, they investigated potential effects of steroids on leukotriene (LT) synthesis by post COVID-19 MDM.

Fluticasone propionate, a commonly used inhaled glucocorticoid, further increased LT synthesis by post COVID-19 at baseline This suggested that steroid treatment may further aggravate the pro-inflammatory eicosanoid reprogramming in post COVID-19 subjects.


Mild COVID-19 imprints a long-term inflammatory eicosanoid- and chemokine memory in monocyte-derived macrophages

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