Covid & The Immune System

The multitude of cellular types can be expected to behave differently when receiving invading pathogens such as mammalian viruses. The nature-dictated causes for such intrinsic cellular diversity become the criteria for the emergence of specific virus-receptor interactions on that particular host cellular surface, in order to accommodate contact with various other living entities whether desirable to the host or not. At present, we are presented with an example of two contrasting behaviours wherein the well-known HIV-1 and the more recently emergent SARS-CoV-2 cause adverse consequences to the differentiation and functions of progenitor stem cells. These include the two different downstream multipotent CD34+ hematopoietic (HSPC) and CD133+ endothelial (ESPC) stem-progenitor cells of their common pluripotent hemangioblast precursors. The two viruses target the respective endothelial and hematopoietic stem-progenitor cells to thrive upon the relevant host cellular surrounded stromal microenvironments by adopting reciprocally-driven mechanistic routes, which incidentally cause pathogenesis either directly of ESPC (SARS-CoV-2), or indirectly of HSPC (HIV-1). HIV-1 utilizes the CD4+ T-lymphocyte receptor thereby advancing pathogenesis indirectly to the CD34+ HSPC. SARS-CoV-2 directly targets the CD133+ ESPC via ACE2 receptor causing cytokine storms of the CD4+ T-lymphocytes. In this manner, these two viruses cause and extend their damage to the other cellular sub/types coexisti...

We’re in our *3rd* post-lockdown viral respiratory season and admissions for viral resp illness+pneumonia are 6 standard deviations above the historical average. I do not understand how so many reasonable people haven’t figured out that the “immunity debt” scapegoat is disinfo.🧵 https://t.co/6JHLSqp1Cl— Dr. Lisa Iannattone (@lisa_iannattone) December 2, 2023

Increasing evidence suggests immune dysregulation in individuals recovering from SARS- CoV-2 infection. We have undertaken an integrated analysis of immune responses at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 individuals recovering from mild, moderate, severe, or critical COVID-19. Anti-Spike and anti-RBD IgG responses were largely stable up to 24wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper and regulatory T cells) in COVID-19 convalescents compared to healthy controls, which were most strongly evident at 12 and 16wpi. RNA sequencing suggested ongoing immune and metabolic dysregulation in convalescents months after infection. Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was financially supported by grants from The Hospital Research Foundation, Flinders Foundation, The Womens and Childrens Hospital Foundation, and the Flinders University College of Medicine and Public Health COVID-19 grant scheme. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study participants were recruited via the Central Adelaide Health Network (CALHN). The study was performed in accordance with the ethical principles consistent with the latest version of the Declaration of Helsinki (version Fortaleza 2013), Good Clinical Practice (GCP) and according to the National Health and Medical Research Council (NHMRC) Guidelines for Research published in the National Statement on the Ethical Conduct in Human Research (2007; updated 2018). The protocol was approved CALHN Human Research Ethics Committee, Adelaide, Australia (Approval No. 13050) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes RNA-Seq data have been deposited in the Gene Expression Omnibus (GEO) under accession GSE169687. Count tables, metadata, and R code for all analyses (serology, flow cytometry and RNA-Seq) have been uploaded to the Lynn Laboratory BitBucket (https://bitbucket.org/lynnlab/covid-sa).

Lymphocytopenia - Etiology, pathophysiology, symptoms, signs, diagnosis & prognosis from the Merck Manuals - Medical Professional Version.

Innate immune cells remain altered for at least a year after infection.

Epigenetics and clinical observations referring to Betacoronavirus lead to the conjecture that Sarvecovirus may have the ability to infect lymphocytes…

A leading doctor unpacks how Covid rewires genes and disrupts our immune systems. He says, "We’re immunocompromised."

What is going on with our immune cells after COVID-19 infection?This thread will explore some of the impacts of COVID infection on our immune system even after people are recovered including:- Missing naive T-cells- Exhausted T-cells- Loss of B-cell maturation

The immune system responds more strongly to the strain of a virus that it first met, weakening response to other strains. Can this ‘imprinting’ be overcome?

COVID-19 reduces the numbers and functional competence of certain types of immune cells in the blood, say researchers. This could affect responses to secondary infections.

A recent paper published in the journal Nature describes how SARS-CoV-2 infection induces a serious medical condition called lymphopenia by directly attacking and killing our immune T cells.

Researchers found that Covid-19 infects and kills T cells, especially in severe cases.

Researchers confirm that Covid-19 specifically infects and kills T cells, making it a dangerous virus.

Researchers found that Covid-19 causes "long-lasting depletion and functional impairment" of immune cells that "may have consequences for susceptibility to secondary infections."

Researchers found that Covid-19 reduces your number of dendritic cells, which they describe as "a catastrophe for the immune system" that lasts "for several months after SARS-CoV 2 infection." Abnormal dendritic cell counts can persist for 7 months or longer. These cells are important in fighting off other pathogens, including RSV.

Researchers found that individuals with long COVID have persistent activation of the innate and adaptive immune system at 8 months after infection. Long Covid patients show lower levels of T and B cells, making them more vulnerarable to other types of infections.

Researchers found that Covid-19 can overstimulate the immune system and cause T Cells to basically burn out.

Researchers found a reduced immune response in recovered Covid-19 patients, in particular a reduction in CD4 "helper" T cells, and memory B cells. They found that Covid-19 in general leads to extended stress and exhaustion of your immune system that persists after recovery.

Researchers found that Covid-19 patients show long-term damage to several types of immune cells, including memory CD4 T cells, B cells, leukocytes, and monocytes. Overall, Covid-19 can exhaust your immune system for a year or longer.

Researchers found that Covid can disable Cytotoxic T lymphocytes, which play a critical role in your immune system's ability to right off viruses and bacteria, as well as tumors. They say, "this mechanism could contribute to the failure of the immune system to control SARS-CoV-2 infection.

Researchers found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism. In short, Covid-19 impairs your ability to fight off infections. Even recovered patients showed a lower percentage of memory B cells compared to healthy patients.

Researchers found that in moderate and severe cases of Covid-19, the virus can trigger a switch in white blood cells from "innate immune functions to pro-thrombotic phenotype." Basically, Covid can provoke your immune system to cause blood clots. As Wes Ely says, "Very scary stuff if you want a body & brain to get blood, food & oxygen."

Although very different, in terms of their genomic organization, their enzymatic proteins, and their structural proteins, HIV and SARS-CoV-2 have an extraordinary evolutionary potential in common. Faced with various selection pressures that may be generated by treatments or immune responses, these RNA viruses demonstrate very high adaptive capacities, which result in the continuous emergence of variants and quasi-species. In this retrospective analysis of viral proteins, ensuring the adhesion of these viruses to the plasma membrane of host cells, we highlight many common points that suggest the convergent mechanisms of evolution. HIV and SARS-CoV-2 first recognize a lipid raft microdomain that acts as a landing strip for viral particles on the host cell surface. In the case of mucosal cells, which are the primary targets of both viruses, these microdomains are enriched in anionic glycolipids (gangliosides) forming a global electronegative field. Both viruses use lipid rafts to surf on the cell surface in search of a protein receptor able to trigger the fusion process. This implies that viral envelope proteins are both geometrically and electrically compatible to the biomolecules they select to invade host cells. In the present study, we identify the surface electrostatic potential as a critical parameter controlling the convergent evolution dynamics of HIV-1 and SARS-CoV-2 surface envelope proteins, and we discuss the impact of this parameter on the phenotypic properties of both viruses. The virological data accumulated since the emergence of HIV in the early 1980s should help us to face present and future virus pandemics.

Researchers found significant differences in multiple innate types of immune cells in Long Covid patients, including natural killer cells and various types of T Cells. The differences lasted for at least 6 months. Long Covid patients often show signs of immune system disruption and dysregulation.

Researchers found a significant reduction in T Cell counts in Covid-19 patients, even in "mild" cases. This study was pre-vaccine, but still very concerning given antibody evasion of new variants. Most viruses don't deplete T Cells.

Researchers found persistent over-activation, depletion, and exhaustion of several types of immune cells. Patients 60 years also demonstrated reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days.

Researchers discuss how SARS-CoV-2 contains at least one unique superantigen-like motif not found in any other SARS or endemic coronaviruses. Superantigens are potent antigens that can send the immune system into overdrive. They urge caution in the context of reinfection and waning immunity, and they express alarm about risks taken by governments whose policies enable widespread transmission of an airborne, potential superantigenic pathogen. Finally, they call for more clearly defined vaccination and public health policies to protect against the consequences of repeat exposure.

Researchers found that although T cell counts eventually recover, mild and moderate cases still show abnormal T cell activation after recovery.

Researchers review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. They discuss emerging understandings of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2.

Emerging evidence on severe complications