T-cell exhaustion in COVID-19: what do we know?
SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients
“Patients with COVID-19 may develop abnormal inflammatory response, followed in some cases by severe disease and long-lasting syndromes. We show here that in vitro exposure to SARS-CoV-2 activates the expression of the human endogenous retrovirus (HERV) HERV-W proinflammatory envelope protein (ENV) in peripheral blood mononuclear cells from a subset of healthy donors, in ACE2 receptor and infection-independent manner.”
COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences
COVID hacks our gene switches, worsening infection and sparking long(-term) COVID inflammation.
➡️"There is a growing body of evidence pointing towards the diverse roles of epigenetic alterations in COVID-19 severity." ➡️"The pathogenesis of COVID-19 extends far beyond the initial viral infection, revealing a complex and dynamic interplay between SARS-CoV-2 and the host."
Frontiers | Immune cell communication networks and memory CD8+ T cell signatures sustaining chronic inflammation in COVID-19 and Long COVID
Researchers analyzed 73,000 immune cells from COVID-19 patients.
They found that memory CD8+ T cells stay overactive and exhausted long after infection, keeping the immune system in a low-grade inflammatory state that may drive Long COVID.
In vitro complement activation via nucleocapsid and spike proteins of SARS-CoV-2 in COVID-19 patients
The N protein may play a larger role than spike in severe immune overreactions.
SARS-CoV-2 infection induces ZBP1-dependent PANoptosis in bystander cells | PNAS
SARS-CoV-2 and HIV-1: So Different yet so Alike. Immune Response at the Cellular and Molecular Level
SARS-CoV-2 and HIV-1 both cause CD4⁺ T cell loss, cytokine storms, and immune exhaustion.
Shared mechanisms—like pyroptosis and inhibitory receptor upregulation—suggest overlapping therapeutic targets.
Spike proteins of coronaviruses activate mast cells for degranulation via stimulating Src/PI3K/AKT/Ca2+ intracellular signaling cascade | Journal of Virology
New study shows that SARS-CoV2 Spike Proteins induces Mast Cell Activation and MCAS
Immune dysregulation in long COVID patients uncovered in new study
“The results showed that compared to COVID-19 patients who had fully recovered, long COVID patients showed evidence of immune dysregulation and systemic inflammation, with the distribution of T cells exhibiting global differences indicative of continued immune responses.”
The results showed that compared to COVID-19 patients who had fully recovered, long COVID patients showed evidence of immune dysregulation and systemic inflammation, with the distribution of T cells exhibiting global differences indicative of continued immune responses.
Study: COVID can trigger changes to the immune system that may underlie persistent symptoms | CIDRAP
“Study: COVID can trigger changes to the immune system that may underlie persistent symptoms”
The identification of a SARs-CoV2 S1 protein derived peptide with super-antigen-like stimulatory properties on T-cells
A peptide derived from the SARS-CoV-2 S1 spike protein, named P3, can stimulate a significant portion of human T cells.
This stimulation leads to increased production of inflammatory cytokines and granzyme B.
Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2
“Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2”
Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2
SARS-CoV-2 can trigger an overactive immune response, leading to the release of large amounts of pro-inflammatory cytokines.
“SARS-CoV-2 can trigger an overactive immune response, leading to the release of large amounts of pro-inflammatory cytokines.
This excessive cytokine release can cause widespread inflammation, leading to damage in various organs, including the lungs, heart, and kidneys.”
Severe COVID-19 may lead to long-term innate immune system changes
Severe COVID-19 can cause persistent alterations in the innate immune system, leading to high levels of inflammation even after recovery.
Changes in gene expression in blood-forming stem cells were found, which were passed down to immune cells.
Studies pinpoint immune cells and proteins linked to long COVID
“In the blood of the long COVID patients, the team [at the University of Alberta] found higher levels of various proteins related to systemic inflammation—especially galectin-9 and artemin.. higher levels of galectin-9 in patients are associated with increased inflammation and brain fog.. higher levels of artemin are associated with widespread pain, more severe pain and cognitive impairment.. galectin-9 is shed by stressed neutrophils—the most abundant white blood cells—in long COVID patients. This released galectin-9 can promote chronic inflammation by affecting various immune cells.. long COVID dysregulates the production of red blood cells, which results in an abundance of immature red blood cells in the blood of these patients. Normally, immature red blood cells are present in the bone marrow but not in the blood of healthy people. It is these immature red blood cells in the blood that suppress the immune system and contribute to the elevation of artemin in the plasma of long-COVID patients."