Interesting post I found just now and wondered how it might be affected by CLL ..has anyone else seen anything about this?
By O.S.F.
Posted on 08/23/2021 at 12:33
Two studies published at the end of last week establish that two types of predisposition, which mainly affect men and the elderly, promote the development of serious forms
It has been a given since the early days of the Covid-19 pandemic: in the face of this disease, we are not all equal. When some develop only mild symptoms, or go completely asymptomatic, others are severely affected, with sometimes dramatic consequences. Since the emergence of Sars-CoV-2, researchers have been trying to understand these differences. Last week, two new studies confirmed what initial work had established in October 2020: a large proportion of severe forms are explained by a genetic or immunological abnormality.
Deficient protein
Inserm professors Jean-Laurent Casanova and Laurent Abel, who lead a Franco-American team alongside professor-researchers from the University of Paris and doctors from the AP-HP, published at the end of 2020 two studies in the journal Science. In these, they explained that 10 to 15% of severe forms of Covid-19 were due to "a deficiency in the type 1 interferon (IFN 1) pathway".
This protein "usually produced rapidly by the immune system in response to viral infection" has the "primary effect of inhibiting the replication of the virus in infected cells." "According to them, this IFN1 deficiency is caused by two distinct factors: either genetic, for" 3 to 4% of severe forms ", or immunological, in 10 to 11% of cases.
Age, a risk factor
Thursday, August 19, two new studies, published in the journal Science Immunology, completed this work. They conclude that the proportion of severe forms caused by type 1 interferon deficiency actually represents “20 to 25%” of cases. The first study looked at the genetic causes of this deficiency. The authors identified that variants in the TLR7 gene, which plays a major role in the mechanism of IFN 1 production, lead to the development of critical forms.
Men being globally more affected than women, they focused on the analysis of the X chromosome. Through a large case study, thanks to the support of 400 research centers in 38 different countries, they found patients a "loss of function" of this TLR7 gene. This "genetic anomaly" explains "1.3% of severe forms of Covid-19 in men", and it is "more common (1.8%)" in those under 60 years of age.
The other study, concerning immunological factors, concludes that 15 to 20% of severe forms are "caused by the presence - in the blood of patients - of autoantibodies which specifically target IFN1." According to the researchers, “These antibodies block the protective effect of IFN1 on viral replication. The Sars-CoV-2 virus thus enters cells without encountering resistance and replicates in an uncontrolled manner. By analyzing thousands of data, they also found that the presence of these "autoantibodies" increases with age, which is part of the reason why age is a major risk factor for Covid-19.
Written by
RosettaClapp
To view profiles and participate in discussions please or .
X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
The first study indicates that 20% of COVID-19 deaths in people over 70 appear to be due to an autoimmunity to one's own interferon1. But they also list several other rare syndromes (edited to put space between sentences to aid digestion):
"These auto-Abs against type I IFNs were found in about 0.3% of a general population sample of 1,227 subjects collected before the pandemic and aged 20 to 69 years, suggesting that they predated SARS-CoV-2 infection and caused critical COVID-19 rather than being triggered by it (9).
Moreover, production of these antibodies can be genetically driven, and can begin during early childhood, as attested by their presence in almost all patients with autoimmune polyendocrine syndrome type-1 (APS-1) due to germline mutations of AIRE (17–19). APS-1 patients are, indeed, at very high risk of developing severe or critical COVID-19 pneumonia (20, 21).
These auto-Abs are also found in patients with combined immunodeficiency and hypomorphic mutations of RAG1 or RAG2 (22), in men with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and mutations of FOXP3 (23), and in women with incontinentia pigmenti and heterozygous null mutations of X-linked NEMO (9). They are also seen in patients treated with IFN-α or IFN-β (24, 25), in patients with systemic lupus erythematosus (26, 27), thymoma (28), or with myasthenia gravis (29, 30). Finally, they underlie a third of adverse reactions to the 17D live attenuated vaccine against yellow fever virus (YFV), further suggesting that they were present in these patients, as in patients with critical COVID-19, before viral infection (31)."
So I think there are multiple rare conditions that together add up to 20%. Some of them, like combined immunodeficiency (CID), appear to be evident in childhood. Others, like lupus often take years to properly diagnose. The commas in the article make it difficult to parse (a bulleted table would have been much better), but the section beginning "in men with immune dysregulation" and ending with "IPEX syndrome" appears to me to refer to the IPEX syndrome, and not to any immune dysregulation many of us experience:
Immunodysregulation, polyendocrinopathy and enteropathy X-linked
The second study concerns a congenital X-linked recessive TLR7 deficiency that I imagine may not be known to some patients.
The good news is since these are genetic anomalies, they should be evident via genetic tests. The bad news is that if one is an adult, they may not know, or may not present with obvious symptoms that lead to such testing.
Even so, it's good to see the genomic testing is being done by researchers to find out why some 70 years olds have an easy time of COVID, and other succumb.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Good news on vaccine efficacy for the 80%
Research needed for vaxx/CLL
Covid Vaccination ✈️🚢🚇🚠🚘
COVID - Infectious or Not
New Dana Farber Research 
