Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19

What does this publication say and mean?

First of all: there is always a lot of data, and it is understandable the public want to know: public health is very important. But, not every scientific detail needs to be flagged up; it is often not helpful nor informative.

The basic finding in this manuscript is that a type of white blood cells, monocytes, that move to where an inflammation is and contribute to immune response by interacting with other cells and cleaning up debris, change focus DURING infection. This is how it is supposed to be!

Important as well, found in the methods section; "Samples were collected from March 2020 to February 2021 and none of the participants had received a COVID-19 vaccine." So, no prior immunity! Monocytes float in the blood, are generated in the bone marrow, and largely mind their own business. Till they get recruited to a site of inflammation. At that site they get activated; you expect to see this during a SARS-CoV-2 infection, and indeed the authors report this.

Activation for monocytes is needed so they change function: also normal. The function moves from detecting pathogens and responding to them in the very initial phase, to helping clear up the debris, damage and to repair the tissues.
​(source picture Monocyte recruitment during infection and inflammation)

When activated, monocytes can differentiate into other cell types: macrophage or dendritic-like cells and have different functions. Hence; comparing monocytes from healthy, not infected people, with monocytes from infected people; there will be lots of differences! This is a given.

Monocytes change from their initial function to sample their environment and helping to stimulate other cells. This you can detect because they have less molecules that, for example, stimulate T cells (HLA, CD80, CD86, etc). And NO, that is not "dysregulation": that is normal and quite subtle! Just a little less.

And, if you use those previously activated monocytes and compare them with not already activated monocytes, then they are less good in helping T cells. BUT: if you have another infection, you will recruit NEW monocytes and you will be absolutely fine stimulating T cells!

The authors found, interestingly, that the monocytes from patients with acute COVID-19, show a pro-thrombotic phenotype characterized by increased expression of pathways involved in immunothrombosis and increased capacity to form cell aggregates with platelets.

A pro-thrombotic transcriptional programme, which was functionally tested, and shown to hold true;

But, is this something to be worried about? An important question is of this is COVID-19 specific. That was not tested at all, and can not be concluded. And yes, thrombosis may be a more general pathway as result of an infection and subsequent response.

See for example: Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models

The conclusion is thus not that SARS-CoV-2 causes immune damage, dysregulation or tolerance, it is also not that it always causes blood cloths, although that is a risk with many things, including infections, and can be prevented with vaccination.

Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19

To wrap up. Acute COVID-19:
- results in monocyte recruitment, activation, differentiation
- this, as expected, makes those monocytes less responsive to new stimuli
- and those monocytes promote clotting, which may not be COVID-19-specific
- new monocytes are constantly made and will be ready for a new infection and behave as you would expect: protecting you from severe disease

And that is all.