Post-acute sequelae and adaptive immune responses in people living with HIV recovering from SARS-COV-2 infection, 2022, Peluso, Michael et al

[Mij]

Abstract

Background:
Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).

Methods:
We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n = 39 and n = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T cell responses, as well as differences in the prevalence of PASC.

Results:
Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T cell responses as compared with a well-matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8+ T cells (p = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4+ T cells (p = 0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8+ T cells (0.34-fold effect, p = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, p = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.

Conclusions:
We identified potentially important differences in SARS-CoV-2-specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

https://journals.lww.com/aidsonline...equelae_and_adaptive_immune_responses.73.aspx

 

[Hutan]

University of San Francisco team. It's a shame it isn't open access - I would have thought with the level of public funding for HIV/AIDS research, and in the public good, it could have been.

Based on the abstract:
The odds ratio of 4 for people with HIV getting PASC is interesting, although it would be good to see what the persistent symptoms are. I wonder if anyone has heard or seen anecdotal evidence of Long Covid being more prevalent in people with HIV.

We've seen some studies report inflammatory markers in Long Covid (IL-6 and TNFa have come up quite a bit), but then we have also seen some studies not finding inflammatory markers. It would be good to see a scattergraph of those markers in this study.

Larger and more detailed studies of PASC in PWH are urgently needed.

This is true. Maybe some of the AIDS research budget can be used for this.

@dave30th - perhaps you have some networks to get the message of possibly higher risk of Long Covid in people with HIV out, and to hear if this finding in a small sample seems to be being borne out?

PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8+ T cells (p = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4+ T cells (p = 0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8+ T cells (0.34-fold effect, p = 0.02).

PD-1?

Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.[5]

PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells).[6][7]

 

[Hutan]

PD-1

Programmed Cell Death Protein 1–Positive CD8+ T Cells in Multiple Sclerosis
Exhausted Fighters or Peacekeepers. Jul 2022

In chronic infections and malignancies, exhausted CD8+ T cells prominently express PD-1
In recent years, antibodies against PD-1 and its ligands, PD-L1/L2, have become an important therapy for people having malignancies.
...
The fact that patients with the largest accumulation of these cells in the CSF benefit most from steroid treatment supports the idea that PD-1+ CD8+ T cells play an important role in the inflammatory response in early MS.

It sounds complicated in MS: PD-1 might be present on t-cells in the central nervous system but not in the periphery.


In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signalling 2021 Germain, Levine, Hanson

TIMD3 is highly expressed in T-cells and myeloid dendritic cells, implicating a role in both innate and adaptive immunity, with loss-of-function mutations leading to autoimmune disorders in 20% of patients, resulting from uncontrolled immunological activation [36]. Additionally noted by Dixon et al. [36] is the high expression of TIMD3 in ‘exhausted’ T-cells in cancers and chronic viral infections, although the associated upregulation of the expression of PD-1 (programmed cell death protein 1) was not observed in our patient cohort (p = 0.6 and q = 0.9, Supplementary File 1). Nevertheless, high TIMD3 expression inhibits effector T-cell responses and the infiltration of T lymphocytes in adipose tissues, partially increasing the inflammation around adipose tissues in patients [36].

EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities 2022, Cox et al

Our in vitro studies using ME/CFS serum with elevated activin A levels as well as virus dUTPase–derived conditioned media showed differential induction of a TFH cell–like phenotype characterized by high expression of PD-1, ICOS, and CXCR5 and secretion of IL-21, in an activin A–dependent mechanism. To the best of our knowledge, this is the first study reporting the presence of TFH cell regulators in the serum of ME/CFS patients that are capable of modulating TFH cell differentiation in vitro.

This paper looks to be worth checking out in detail. I've just cut and pasted here - I'm not sure how crucial the ME/CFS serum was or if the studies were done with healthy serum as a control.