Immunity debt vs post covid immune deficiency (PCID).
Not an immunology expert, but here are 25 papers/articles that collectively argue for PCID.
Immunity debt is a made up term that reflects poor science.
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1/ *May 1 2020, Title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)
” T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted.” pubmed.ncbi.nlm.nih.gov/32425950/
2/ July 2020, Title: AIDS and COVID-19 are two diseases separated by a common lymphocytopenia
”reduction in B-cells found in both diseases & more severe reduction in the total amount of T-cells in COVID-19 vs AIDS” @jeffgilchrist researchgate.net/publication/34…
3/ September 28 2020, Title: SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes
”SARS-CoV-2 spike binds to CD4 and mediates entry of SARSCoV-2 in T cells, then assembles viral factories, impairs cell function and may cause cell death.
”medrxiv.org/content/10.110…
4/ Sept 28 2020, Title: Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation
Superantigens in SARS2 in terms of MIS-C in children, possible role in cytokine storm in adults doi.org/10.1073/pnas.2…
5/ *Nov 17 2020, Title: Immune suppression in the early stage of COVID-19 disease
”We uncovered changes in the protein landscape that revealed immunosuppression and impaired tight junctions in COVID-19 patients in the early stage of infection.” nature.com/articles/s4146…
6/ Dec 20 2020, Title: Akt-Fas to Quell Aberrant T Cell Differentiation and Apoptosis in Covid19
” depict SARS-Cov-2 as a lympho-manipulative pathogen; it distorts T cell function, numbers, and death, and creates a dysfunctional immune response” ncbi.nlm.nih.gov/pmc/articles/P…
7/ Mar 11 2021, Title, HLA class I–associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children.
This paper discusses superantigens in terms of MIS-C in children. doi.org/10.1172/JCI146….
8/ May 25 2021, Title, Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.
Superantigens in terms of MIS-C in children. Focusses on SARSCov2 in the GI tract of children promoting superantigen in MIS-C doi.org/10.1172/JCI149…
9/ Sept 22 2021, Title: SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
10/ Oct 1 2021, Title: Uncertainty around the Long-Term Implications of COVID-19
”perspective on some long-term risks of mutational escape, viral persistence, reinfection, immune dysregulation and neurological and multi-system complications (Long COVID).” mdpi.com/2076-0817/10/1…
11/ Nov 16 2021, Title: PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response
’PD-1 blockade restores T cell function after covid-induced exhaustion’ insight.jci.org/articles/view/…
12/ Jan 22 2022, Title: Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection
Important paper showing immune function was not restored even at 8 months. nature.com/articles/s4159…
13/ Mar 3 2022,Title: Understanding the Effects of Age and T-Cell Differentiation on COVID-19 Severity: Implicating a Fas/FasL-mediated Feed-Forward Controller of T-Cell Differentiation. Mechanism for superantigen deterioration of immune response in COV19 frontiersin.org/articles/10.33…
14/ Mar 10 2022, Title: The immunology and immunopathology of COVID-19
Cautious overview. 1 mention of t cell lowering in long covid. science.org/doi/10.1126/sc…
15/ Apr 11 2022, Superantigens and SARS-CoV-2
”proteins that hyper-stimulate T cells via the crosslinking of T cell receptors (TCR) with MHC Class II molecules” mdpi.com/2076-0817/11/4….
16/ April 8 2022, Title: SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired 2 T cell development
”SARS-CoV-2 associated thymic atrophy from impaired T cell developmental pathway, also explains dysreg T cell function in COV19” biorxiv.org/content/10.110…
18/ May 14 2022, Title: T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19
”persistent T-cell activation to 12 m after inf & a subgroup of severe COV19 pats with low CD8+ T-cell counts & dysregulated immune” onlinelibrary.wiley.com/doi/10.1111/al…
19/ May 20 2022, Title: SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly
”highlight a new strategy of immune evasion by SARS-CoV-2” biorxiv.org/content/10.110…
20/ Aug 2022, Title: Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases
” SARS-CoV-2 antigen persistence in infected tissues serves as a basis for postacute COVID-19.” ncbi.nlm.nih.gov/pmc/articles/P…
21/ Aug 10 2022, Title: Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women
”CD8+ 67 68 cytotoxic T cells were compromised in recovered patients vs healthy 69 pregnant women” biorxiv.org/content/10.110…
22/ Aug 10 2022, Title: Distinguishing features of Long COVID identified through immune profiling
“provides a basis for future investigations into the immunological underpinnings driving the genesis of Long COVID.” medrxiv.org/content/10.110…
23/ Oct 1 2022, Title: Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome
Findings suggest an unexpected mechanism of abnormal immune downmodulation that is normalized by leronlimab academic.oup.com/cid/article/75…
24/ Oct 19 2022, Title: Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis
” ORF6 as a key SARS-CoV-2 innate immune antagonist” biorxiv.org/content/10.110…
25/ Oct 24 2022, Title: In Cleveland and beyond researchers begin to unravel the mystery of long COVID-19
Covid similar in some ways to AIDS cleveland.com/news/2022/10/i…
And this.
May 7 2021, Title: Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health
"persistent T cell abnormalities in convalescent COV19 patients more than three months after initial infection" frontiersin.org/articles/10.33…
A lot of people want to call it Covid acquired immune deficiency (CAID) and I agree or Covid acquired immune deficiency syndrome (C-AIDS). I agree.
Also, Jan 22 2022, Title: T cell apoptosis characterizes severe Covid-19 disease
”compatible with a model in which T-cell apoptosis accounts for T lymphopenia with severe COV19.” nature.com/articles/s4141…
Long Covid Delphi study preprint just out. 179 panelists. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society. Aims to give recommendations to physcians and researchers. papers.ssrn.com/sol3/papers.cf…
Note: needs some correction (I asked) as left off a full name and to add the SI w names of panel members.
Methods: A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID located in 28 countries across the world.
1/4 Now that I have had time to read through this, it is a solid study of attenuated immune response (CD8+ T cells) after infection focussing on mRNA vaccine-induced immunity & adding to the now large body of evidence that as authors state, (see tweet 2) cell.com/action/showPdf…
2/4 "This suggests that SARS-CoV-2 virus infection may cause long-term damage to the patients’ immune system well after viral clearance."
3/4 There are some limitations, but this study adds, among other things, to the body of evidence showing that most immunologists, at least those studying Covid, in fact argue immune dysregulation - at least for some time.
Body of evidence here. whn.global/scientific/cov…
Has been some discussion on two plots about hazard ratios from reinfections.
This one is from tabulated data in the Aly paper put into a plot. It is NOT 'made up' any more than any real plot of scientific data.
This one was a hypothetical plot not based on specific scientific data. It is NOT real.
This latter plot and the data are described in some detail here.
The concerted attack on the solid science of immune dysregulation seems to indicate the only meeting was not in Davos. Was there a minimisers convention?
Strawmaning 'child immunity' and then discussing general immune dysregulation as in the Munro article is nonsense. We have few studies in children, so we really do not know. But, we know in adults and should take care of children while we wait to find out.
2/20 A few persistent individuals chose 1 or 2 references or say many are for severe disease and try to use strawman arguments to argue immune deficiency is not persisting after covid. The evidence seems against them. I do say in the tweet ‘most are severe, but some are mild.’
3/20 Although I long ago published immune-related papers (PNAS and Trends in Immunology) on catecholamines in lymphocytes, I am not an immune expert. But, I am a scientist qualified to read the current papers.
Most immunologists seem to agree covid harms the immune system. Some are resistant and did not like my original thread of papers. Here I begin 36 more refs that show/imply immune damage. Many studies are for severe covid, but some mild.
Original thread:
1/ August 13, 2020
Good overview. “The systemic COVID-19 syndrome is usually accompanied by mild lymphopaenia*, neutrophilia*, fever, thrombocytopenia*, hyperferritinaemia*," etc immunology.org/sites/default/…
2/ September 28, 2020
“COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines).” nature.com/articles/s4159…