Immunoglobulin A as a key immunological molecular signature of post-COVID-19 conditions, 2023, Graziele Fonseca de Sousa et al

[Mij]

Abstract
COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC).

We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account gender, vaccination, hospitalization and age. Fatigue and myalgia were the most common symptoms and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant for the development of PCC.

Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA.

Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.

https://www.medrxiv.org/content/10.1101/2023.05.11.23289866v1

 

[Hutan]

Brazilian research

When I read the abstract, I sigh at seeing post-covid conditions being lumped altogether. I don't think that is helpful trying to understand what is going on. And so, I'm not sure that any finding from people with diverse conditions, as here, will be useful. To be fair, this study does try to find subgroups.

I think we have seen a range of antibody levels in people with Lond Covid, I'm not sure that we have seen a clear picture of something notable happening in overall levels. I don't know what IgA antibodies/immunoblobulins are.

Here's a googled definition, but we probably need to know more than this:

Immunoglobulin A (IgA) is an antibody blood protein that’s part of your immune system. Your body makes IgA and other type of antibodies to help fight off sickness. Having an IgA deficiency means that you have low levels of or no IgA in your blood.

IgA is found in mucous membranes, mainly in the respiratory and digestive tracts. It is also found saliva, tears, and breastmilk. A deficiency seems to play a part in asthma and allergies. Researchers have also linked IgA deficiency to autoimmune health problems. These are health problems that cause your body’s immune system to attack your body by mistake.

The paper suggests that other papers have found increased production of IgA in Post-Covid Condition.

The sample sounds to be of all of the patients attending a post-Covid clinic who agreed to participate (151/255). Incidence of fatigue was 80%, myalgia 80%. 'Hypoprosexia' (72%) was new to me - 'a difficulty concentrating' - hopefully not a term that catches on due to its potential for confusion.

While all the patients were IgG positive for SARS-CoV-2, only a portion of them were IgA positive, in contrast to IgM, for which all the patients were negative, indicating that they were not in the acute phase of COVID-19 and were post-COVID-19 patients.

IgA levels showed a significant difference between the nPCC and PCC groups, indicating an increase in the plasma levels of SARS-CoV-2 IgA in PCC patients (0.639 ± 0.028 OD) (Fig. 4B).

Here's the comparison between IgA in controls and the PCC people:

 

[Hutan]

Cruz et al. (2023) (37) reported higher levels of IgA against the N and S viral proteins in PCC patients, especially in those with severe acute disease. Now, in this work, we observed that PCC patients were positive for IgA, indicating that this immunological factor could be a key feature for understanding the mechanisms underlying PCC.

However, unlike Cruz et al. (2023) (37), the present work showed a different scenario in which IgA production was not only observed in the severely acute patients. Hospitalized PCC patients were IgA positive, although non-hospitalized patients were also positive, indicating that hospitalization or disease severity was not the main factor influencing IgA production in PCC patients. The physiological causes of IgA positivity require further investigation, but possibilities include exacerbated inflammation, genetic predisposition, dysregulation of system homeostasis, and age (33,36-40).

 

[Hutan]

Biochemistry, Immunoglobulin A
This paper gives some background on IgA.

Immunoglobulin A (IgA), one of the five primary immunoglobulins, plays a pivotal role in mucosal homeostasis in the gastrointestinal, respiratory, and genitourinary tracts, functioning as the dominant antibody of immunity in this role.[1] It is the second most abundant immunoglobulin type found in the body and, consequently, has a crucial role in protection against antigens.[2] IgA production is greater than all other immunoglobulin subtypes, necessary for the many roles it plays systemically.

From Wikipedia:

IgA has two subclasses (IgA1 and IgA2) and can be produced as a monomeric as well as a dimeric form. The IgA dimeric form is the most prevalent and is also called secretory IgA (sIgA). sIgA is the main immunoglobulin found in mucous secretions, including tears, saliva, sweat, colostrum and secretions from the genitourinary tract, gastrointestinal tract, prostate and respiratory epithelium. It is also found in small amounts in blood.

That latter sentence then begs the question - how important are levels of IgA in blood? Perhaps what needs to be looked at is levels of IgA in the places where it is mostly found?

 

[Jonathan Edwards]

That latter sentence then begs the question - how important are levels of IgA in blood? Perhaps what needs to be looked at is levels of IgA in the places where it is mostly found?

IgA is puzzling in that very low levels in blood (serum IgA deficiency) are common and don't seem to matter much at least in developed countries. The assumption tends to be that the main function is to protect mucous membrane barriers using the secreted dimer.

The problem with looking at level in tissue microenvironment, though, is that concentrations will be confounded by all sorts of irrelevant factors - essentially because one is not studying a steady state fluid phase. The density of IgA plasma cells within a certain distance from mucous surface might be more relevant.

I think measuring blood IgA is fair enough because a difference in levels of the sort reported would indicate at least some sort of change in IgA production or dimerisation (which effects compartmentalisation). To me it seems like an interesting and plausible finding.

It may be worth remembering that a very significant proportion of our plasma cells and antibody production occurs in gut mucosa. Gut is absolutely stuffed with lymphocytes and plasma cells, unsurprisingly perhaps, since it is our main interface with foreign chemicals. Gut trouble makes people feel ill pretty reliably. So maybe post-Covid symptoms have something to do with prolonged production of unhelpful IgA - or at least some persistent signal that has IgA production in gut as a spin off.

 

[wastwater]

I suspect I may have an IGA deficiency as someone in my rare eye genes group mentioned this as being a cause for under reactive to bacteria In Younger years that’s grown out of and then over reactive after viral illness
https://www.southtees.nhs.uk/services/pathology/tests/immunoglobulins-igg-iga-igm/
IgA deficiency is the commonest of the primary disorders. The incidence is 1 in 500 of the population but 30% are symptom free.