The Vaccine "Kills" Fetal Blood Stem Cells Study
The Vaccine "Kills" Fetal Blood Stem Cells Study
A bombshell, but hopefully not as-bad-as-it-looks finding for babies born from Covid-vaccinated mothers.
A new study finds that both asymptomatic infection with SARS-CoV-2 and Covid vaccination, but especially the latter, appear to deplete the blood stem cell reservoir of fetuses and newborns.
Key takeaways:
Umbilical cord blood (essentially a snapshot of the newborn’s blood at time of birth) usually provides a rich sample of the HSPCs which later spawn all other immune and blood cell types (after birth, they tend to hide in bone marrow or peripheral tissues). Assays exist to measure how robust the “spawning into other cell types” potency of these cells is by immersing them in signals. In the Covid-vaccinated, HSPCs were so depleted that the authors couldn’t even perform the assays. As a general rule, “breaks the assay” is a sign of a truly aberrant result.
Earlier-in-pregnancy injections resulted in greater depletion of neonate HSPCs, which suggests that “jabs,” indeed, are being “bad” here. I speculate that sustained high maternal inflammation is dysregulating innate immune programming in the fetus and possibly impeding liver development.
The implications may be somewhat mundane — such as higher rates of later allergy or autoimmune disease, as has been found for children of obese mothers (another chronic inflammatory condition). Or, you know, these babies could all have VAIDS, neural dysfunction, and early cardiac arrest (see background section at bottom).
The authors didn’t find any spike protein in the samples. So at least there’s that (of course, maternal antibodies would likely have masked any spike protein anyway).
The paper:
This paper was already highlighted by the blogger “The Naked Emperor” yesterday, which is the source of the “killing” imagery. My comments will thus focus on context; the background biology and uncertainty regarding these results and their implications.
I’ll adhere to my normal format of presenting the set up and results before the background; but since HSPCs are an obscure subject the reader may want to scroll down to the bottom sections first.
The Set-Up
Women giving birth to normal-term, normal-weight babies with vaginal delivery between March and December 2021 were recruited to have umbilical cord blood donated for study.
So, all cord blood samplings are upon birth, collected at a single hospital in a more or less Delta-predominant era, with premature or underweight births excluded, which is as far as the study goes for “matching” unvaccinated and vaccinated mothers. So it does not rule out demographic differences especially regarding obesity (supplemental details of the study groups are not yet online), but I am pretty satisfied that we should expect a healthy vaccinee bias to mitigate, rather than drive the observed effects of injection.
Mothers with a prior recorded infection with SARS-CoV-2 were for whatever reason excluded; but several of the donors were nonetheless positive for antibodies to either spike or N protein. Unvaccinated mothers with either type of antibody, and Covid-vaccinated mothers with N antibodies, were considered to be previously asymptomatically infected (though, this doesn’t actually exclude unreported symptomatic infections). Unvaccinated mothers with no antibodies were classified as negative. It will all make sense in the figure below.
Results:
i. SARS-CoV-2 infection and Covid vaccination seem to deplete or impede development of fetal blood mononuclear and stem cells
(Again, scroll to the bottom sections for a background on HSPCs, discussion of implications, etc.)
As a quick note, there is little way to distinguish MNC and HSPC depletion from sequestration. For now I am taking the results at face value; the Background section offers a finer discussion of these results.
ii. Time from injection magnifies HSPC depletion, implying either sustained or time-dependent developmental interference.
iii. HSPCs for presumed infected and Covid vaccinated more prone to apoptosis.
A sample of donors from each group where compared for levels of Annexin in flow cytometry, with the percent of HSPC cells that also were positive for Annexin, implying they are undergoing or have already undergone apoptosis, presented below. Results for N-protein-negative (presumed uninfected) Covid vaccinated were not obtained. For the antibody-positive unvaccinated, all but two outlier donors seem normal; for the vaccinated, it is difficult to parse between outlier or trend due to the small sample size.
Gene expression analysis was performed to determine what was driving apoptosis (ELISA was negative for circulating cytokines); I don’t find the results impressive.
iv. HSPCs could not even be culture-assayed in the Covid vaccinated
Due to the poor recovery of CD34+ [HSPC] cells from the vaccinated donor group after thawing cryopreserved stocks, these [standard umbilical cord blood HSPC] assays were only performed with [non-vaccinated] negative and non-vaccinated N-/S+ donor groups’ CD34+ cells.
If that sounds weird, well, as far as I can tell, it is. The whole reason umbilical cord blood can be evaluated for HSBCs is that it is usually enriched in them; and the cell culture assays used to evaluate cord blood HSBC differentiation potential (hematopoiesis) are not meant to just fail.
v. Culture and humanized mice assays did not reveal anything concerning for the unvaccinated, presumed infected donor group.
Despite the difference in collected cord blood HSPC levels, the unvaccinated, presumed-infected donor HSPCs produced similar responses in a cell culture assay: This means they seem to still function at generating blood and immune cells (again, worrying that the Covid-vaccinated group could not even be measured by this assay).
When HSPCs were injected into immune-deficient mice which express humanized cytokines, there were some differences in the “choices” post-infection HSPCs made in response to these immune signals, with greater expansion of T Cells and reduced expansion of Natural Killer cells (Fig. 4B). This might not be abnormal in the context of innate immune reprogramming after a respiratory infection in pregnancy.
Overall, the assay results were encouraging for the presumed infected group. It might be more helpful to have seen results that included reported (presumably more symptomatic or severe) infections; but that was not the goal of this study design.
vi. No spike protein in umbilical cord blood (hopefully)
The authors checked for spike protein and report that all donors were negative. This is relieving. It should be noted, however, that anti-spike antibodies can mask circulating spike or S1 as long as said antibodies outnumber the antigen, as was confirmed by Röltgen, et al.
Background 1: The Surprisingly Mysterious World of Blood Cells
Blood and immune cells, perhaps more than any other cell type in our bodies, behave like a colony of independent organisms tending to the body as ants do to their hive. Unlike ants who may have one queen, the “queen ants” of our blood cells are the elusive, only recently-discovered hematopoietic (blood-cell-turning-into-capable) stem cells (or stem progenitor cells). These persist and self-renew throughout life, and spawn hematopoietic progenitor cells which gradually specialize along two major branches.
The entire process of specialization is akin to a single cell cycling through different hats (receptors which are detected in the lab by specialized antibodies) and different immune functions; but also potentially dividing further into clonal and descendent cells with identical or complementary functions. Given that this entire process has to be sorted out by taking blood cells out of the body and interrupting whatever progress they were making on their path, it’s amazing we’ve figured out anything about this system at all.
Two other funny points are that some “worker ants” appear early in embryogenesis independent of the appearance of the HSPC “queen ants,” and that all of these different “worker ant” rolls have different recycling rates. Red blood cells require constant refreshment (if recovering from recent depletion, blood will contain a lot of red blood cells that still haven’t discarded their nucleus, as these are fresh arrivals); lung resident macrophages that originate from the yolk sac of the embryo will be partially replaced by HSPC-derived monocytes after immune challenges; yolk-derived, nervous-system-resident macrophages (microglia) take up their stations for life.
It is an understatement to say that humans have essentially no understanding of what specific impacts result from insult to the HSPC “queen ant” reservoir. On the one hand, the implicit exponential nature of the queen-to-worker pipeline may mean that a reduction in HSPCs does not reduce the capacity to kick out required immune and blood cells in quantity; on the other, it may likewise be the case that “queen ant” redundancy enriches “worker ant” flexibility, coordination, and homeostasis downstream; and it is almost certain that detrimental effects will only magnify in old age, as immunosenescence kicks in. So, while a study in 2016 found that near-elimination of the HSPC pool in mice had little effect on how blood and immune cells differentiated (hematopoiesis), such short-term resiliency possibly comes at the cost of long-term endurance.
Humans live longer than mice (fingers crossed). At the same time, recent work suggests that HSPCs in humans may expand after birth, implying better prospects for recovery of the normal pool.
Collateral damage: Beyond the immune system
Likewise, it is difficult to speculate how depletion of the HPSC pool either reflects or effects harms to the even more primordial yolk-derived macrophages. If the “queen ants” are stressed during fetal development, it is not unreasonable to imagine that these independent, occasionally lifelong “worker ants” are stressed as well, with potential effects not only on immune function but neural and cardiac function and health.
HSPC dysregulation could further upset the rolling homeostasis between yolk-derived macrophages and HSPC-monocyte “recruits,” with numerous tissue and organ diseases being characterized by an excess of the latter.
In sum, any stressor that depletes or prevents development of the fetal HSPC pool may also do the same to the yolk-derived macrophage pool that cares for the nervous and cardiac systems, or impair the later homeostasis between yolk-derived and HSPC-derived macrophages later in life. The potential impact on health and body function therefore extends far beyond circulation and immunity; it is functionally “everything.”
On the other hand, HSPC depletion might not be that bad…
Background 2: What is Known About HSPC Depletion
Unsurprisingly, given that research on HSPCs and really the entire blood and immune cell ecosystem (hematopoiesis) is still in early days, it’s very hard to attach this new study’s results to any precedent or baseline. I offer the reader two potential insights.
Maternal inflammation may impair liver-associated HSPC development.
The “queen ants” of HSPCs do not migrate to the bone marrow until just before and after birth; hence their normal high level in umbilical cord blood. Before then, they appear to either reside or originate in the liver and spleen. In a study comparing mice born to mothers given a high fat diet vs. a normal diet, maternal obesity and high fat diets restricted HSPC expansion as well as liver development, implying a relationship between the two.
Since the Lipid Nanoparticle vehicle used for the mRNA-based Covid vaccines turns out to be highly inflammatory in mice, with observed fetal innate immune reprogramming, HSPC depletion following double-injection could simply be a result of the Covid vaccines prompting a sustained inflammatory state.
Comparison: Effects of maternal obesity on child health.
Generically, however, high inflammation potentially has adverse effects that expand beyond immune reprogramming. Given that inflammation is tightly regulated during pregnancy, disruptions from either infection or mRNA transfection can interrupt the normally pathways of development:
The above image is from a paper discussing impacts of maternal obesity, often a chronic inflammatory condition, on fetal development and childhood health; indeed, long-term outcomes from Covid-vaccine-induced maternal inflammation might closely resemble those observed with maternal obesity. This includes higher rates of illness in childhood including potentially immune-mediated ailments like asthma or inflammation-associated cardiovascular disease.
One study did, indeed, find that maternal obesity results in reduced cord blood mononuclear cells, which may include HSPCs (it's not clear to me how they would be excluded); but HSPCs were not measured separately.
Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood.
These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring.
Since I am not aware of any studies investigating differences specifically in cord blood HSPC levels by maternal obesity status or other chronic immune conditions, we can call these prior observations the “baseline” for the expected long-term outcomes for the children in today’s study: Higher overall rates of certain ailments, but nothing on the scale of a disaster.
The key word there, of course, being “baseline.”
If you derived value from this post, please drop a few coins in your fact-barista’s tip jar.
Estep, BK. et al. “Skewed Fate and Hematopoiesis of CD34+ HSPCs in Umbilical Cord Blood Amid the COVID-19 Pandemic.” Cell. Online pre-proof.
Röltgen, K. et al. “Immune imprinting, breadth of variant recognition and germinal center response in human SARS-CoV-2 infection and vaccination.” Cell. 2022 Mar 17;185(6):1025-1040.e14.
The authors affirm that their negatives for spike after Day 1 weren't reliable since Day 28 samples could mask Day 1 samples or a certain concentration of added spike (Fig 7 KL)
Schoedel, KB. et al. (2016.) “The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis.” Blood. 2016 Nov 10;128(19):2285-2296.
Lee-Six, H. et al. (2018.) “Population dynamics of normal human blood inferred from somatic mutations.” Nature. 2018 Sep; 561(7724): 473–478.
Park, MD. Silvin, A. Ginhoux, F. Merad, M. “Macrophages in health and disease.” Cell. 2022 Nov 10;185(23):4259-4279.
Kamimae-Lanning, AN. et al. (2015.) “Maternal high-fat diet and obesity compromise fetal hematopoiesis.” Mol Metab. 2015 Jan; 4(1): 25–38.
Denizli, M Capitano, ML. Kua, KL. “Maternal obesity and the impact of associated early-life inflammation on long-term health of offspring.” Front Cell Infect Microbiol. 2022; 12: 940937.
Wilson, RM. et al. (2015.) “Maternal Obesity alters immune cell frequencies and responses in umbilical cord blood samples.” Pediatr Allergy Immunol. 2015 Jun; 26(4): 344–351.
Wow
Wish every mom would read this
Great article! Linking to you https://igorchudov.substack.com/p/is-rsv-more-severe-in-covid-vaccinated