Immuno-proteomic profiling reveals aberrant immune cell regulation in [airways in post-COVID-19 respiratory disease], 2022, Vijayakumar et al

[Kalliope]

Immunity: Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease by Bavithra Vijayakumar et al


Highlights

• Post-COVID-19 airways, but not blood, show immune and proteomic changes
• Different post-COVID-19 lung abnormalities relate to distinct immunological features
• Increased BAL cytotoxic T cells are linked to epithelial damage and airway disease
• BAL myeloid and B cell numbers correlate with the degree of lung CT abnormality

Summary
Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.

 

[Kalliope]

The study is from January 2022, but Medscape had an article about it two days ago:
Dampening Immune response May Resolve Post-COVID Breathlessness

Quote:
Persistent breathlessness is reported by more than 50% of patients recovering from COVID-19. Now researchers have suggested that this may be due to long-lasting immune activity in the airways, raising the possibility of finding ways to overcome the problem.

 

[Jonathan Edwards]

This sounds like nonsense to me. The only thing that will happen to immune cells in the airways is that they will be coughed up as phlegm. There is no 'immune regulation' in what is in effect an inflammatory garbage space outside the body.

There might be too many cells in the lung parenchyma feeding this garbage pipe and it might be useful to reduce the number but I cannot see them as having much to do with 'regulation'.

 

[Hutan]

I imagined it a bit like going through people's rubbish can tell you something about how they live, looking at the easy-to-get bronchoaveolar lavage could tell you something about what was going on in the lung tissue. Although they do talk about T cells (and other immune cells) in the airways:

Our post-COVID-19 data support the concept that sustained activation of CD8 Trm cells in the airways long after recovery from acute disease contributes to the ongoing damage to the respiratory epithelium, resulting in airway disease.

The mechanism underlying increased Trm cells in the airways is unclear, although several studies have reported virus-specific CD8 T cells in lung tissue up to a year post-infection

persistent antigens have been observed months after other respiratory infections such as IAV (Kim et al., 2010), and SARS-CoV-2 antigen depots could drive ongoing cytotoxic activity and maintenance of CD8 Trm cells.
Second, the persistence of lung-resident Trm cells is reliant on the availability of local T cell survival signals such as IL-7 (Szabo et al., 2019) and the CXCR3 ligands (Slütter et al., 2013). Indeed, IL-7 and the CXCR3 ligands are part of the protein network that is maintained in the post-COVID-19 airway.

As is often the case, this paper doesn't have good controls. Rather than a comparison between healthy people and people with post-Covid breathing issues, what we really want to see is a comparison between people with post-Covid breathing issues and people post-Covid without lingering symptoms. I guess changes over time in the post-Covid people with breathing issues is somewhat helpful.

Points I thought were interesting in the paper:

The severity of the acute illness didn't predict the 3 to 6 month 'airway phenotype' (note that all patients were hospitalised so the scale is only from moderate to very severe). And CT scans weren't good predictors of reduced lung function.

The authors seem convinced that there is ongoing lung epithelial cell death, after the Covid-19 infection is over.

The airway proteome was also distinct from that observed in healthy individuals, with elevation in proteins associated with ongoing cell death, loss of barrier integrity and immune cell recruitment. None of these airway abnormalities were reflected in the proteome or immune cells of the matched peripheral blood.

This relates to what we have often said - testing peripheral blood ad nauseum for clues as to what is going on in ME/CFS isn't going to be productive if the issue is in specific tissues.

The proteins that were most significantly differentially abundant between post-COVID-19 and controls were thyroxine-binding globulin (SERPINA7), dipeptidyl peptidase 4 (DPP4), plasma serine protease inhibitor (SERPINA5), kallikrein-related peptidase-6 (KLK6), lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1), amphiregulin (AREG), factor 3 (F3), Fms-related tyrosine kinase 3 ligand (FLT3LG), glutaminyl-peptide cyclotransferase (QPCT), metalloproteinase-3 (MMP3), and Proto-oncogene tyrosine-protein kinase Src (SRC)
....Pathway annotation of the 22 upregulated proteins using STRING-db highlighted “leucocyte activation,” “regulation of cell death,” “response to injury,” and “response to wounding”

They grouped the proteins they found in the airway fluid into two - ones associated with epithelial injury and repair, and others associated with other roles. One was the complement component C1q receptor (CD93).

Of course, from an ME/CFS point of view, it would have been good to know if airway proteomes differed according to whether people also had other lingering symptoms. There's no mention of that in the paper.