Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic

Estep, Benjamin K.; Kuhlmann, Charles J.; Osuka, Satoru; Suryavanshi, Gajendra; Nagaoka-Kamata, Yoshiko; Samuel, Ciearria N.; Blucas, Madison T.; Jepson, Chloe E.; Goepfert, Paul

doi:10.1016/j.isci.2022.105544

Cited by 10 publications

(7 citation statements)

References 76 publications

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“…In our opinion, the results of this study are of interest when considered together with recently published reports demonstrating that the S-protein has an impact on biological functions of hematopoietic cells [28–30]. In particular, Estep et al found that SARS-CoV-2 infection and COVID-19 vaccination dramatically impair the functionalities and survivability of hematopoietic stem progenitor cells (HSPCs) in the umbilical cord blood [30]. Collectively these studies suggest that SARS-CoV-2 S-protein, COVID-19 mRNA vaccines and SARS-CoV-2 infection might have dramatic effects of the hematopoietic compartment.…”

Section: Discussionmentioning

confidence: 60%

“…Relevant to this issue are reported evidences of circulating Spike Protein detected in post-COVID-19 mRNA vaccinated subjects [18][19][20][21][22][23], and several reports outlining that Sprotein affects cellular metabolism and gene expression in a variety of tissue systems [12,[24][25][26][27][28][29], including the hematopoietic system [28,29]. Accordingly, the effects of SARS-CoV-2 infection and/or vaccination on the hematopoietic system should be carefully considered [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

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The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

Zurlo,

Gasparello,

Verona

et al. 2023

Preprint

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The COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, and has been hypothesized to be responsible for damaging cells of several tissues and for some important side effects of RNA-based COVID-19 vaccines. The aim of this study was to verify the effect of the BNT162b2 vaccine on erythroid differentiation of the human K562 cell line, that has been in the past intensively studied as a model system mimicking some steps of erythropoiesis. We found that the BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation of K562 cells. Reverse-transcription-PCR and Western blotting assays demonstrated that suppression of erythroid differentiation was associated with sharp inhibition of the expression of α-globin and γ-globin mRNA accumulation. Inhibition of accumulation of ζ-globin and ε-globin mRNAs was also observed. In addition, we provide in silico studies suggesting a direct interaction between SARS-CoV-2 Spike protein and Hb Portland, that is the major hemoglobin produced by K562 cells. This study thus provides information suggesting the need of great attention on possible alteration of hematopoietic parameters following SARS-CoV-2 infection and/or COVID-19 vaccination.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

Zurlo,

Gasparello,

Verona

et al. 2023

Preprint

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“…In addition, all women in this cohort had a rapid favorable outcome after delivery. Another study found an increased proportion of differentiation towards BFU-E in cord bloods at term obtained from women previously infected and who recovered from SARS-CoV-2 58 . This could indicate that the erythropoiesis induction we observed shortly after the infection may be sustained throughout the pregnancy.…”

Section: Discussionmentioning

confidence: 93%

Enhanced fetal hematopoiesis in response to symptomatic SARS-CoV-2 infection during pregnancy

Alkobtawi,

Ngô,

Chapuis

et al. 2023

Commun Med

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Background Pregnant women and their fetuses are particularly susceptible to respiratory pathogens. How they respond to SARS-CoV-2 infection is still under investigation. Methods We studied the transcriptome and phenotype of umbilical cord blood cells in pregnant women infected or not with SARS-CoV-2. Results Here we show that symptomatic maternal COVID-19 is associated with a transcriptional erythroid cell signature as compared with asymptomatic and uninfected mothers. We observe an expansion of fetal hematopoietic multipotent progenitors skewed towards erythroid differentiation that display increased clonogenicity. There was no difference in inflammatory cytokines levels in the cord blood upon maternal SARS-CoV-2 infection. Interestingly, we show an activation of hypoxia pathway in cord blood cells from symptomatic COVID-19 mothers, suggesting that maternal hypoxia may be triggering this fetal stress hematopoiesis. Conclusions Overall, these results show a fetal hematopoietic response to symptomatic COVID-19 in pregnant mothers in the absence of vertically transmitted SARS-CoV-2 infection which is likely to be a mechanism of fetal adaptation to the maternal infection and reduced oxygen supply.

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“…Очевидно, це пов'язано також із здатністю цього цитокіну опосередковано, через дію на клітини впливати на ремоделювання матриксу. Ряд досліджень вказують на здатність IFN-γ індукувати апоптоз [17,18,19], а також координувати не тільки імунну регуляцію, але й проліферацію клітин. [20].…”

Section: гістологічна характеристикаunclassified

Histological Characteristics of Experimental Wounds of Soft Tissues of the Femur of Rats and the Role of IFN-γ in the Dynamics of their Healing

Іонов¹,

Komisova²

2022

Ukr. ž. med. bìol. sportu

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The purpose of the study was to evaluate the histomorphological changes in samples of the wound canal of the soft tissues of the femur of rats and to study the role of interferon-gamma (IFN-γ) in the dynamics of wound healing. Materials and methods. The study was conducted on 24 Wistar rats. Animals were divided into two groups – intact (6 rats) and experimental (18 rats). Animals of the experimental group were used to simulate wounds. Rats were euthanized on the 10th, 20th, and 40th days (6 animals for each time) after wound simulation. Blood for the study was taken by the method of open cardiac puncture. The levels of INF-γ in the blood serum of animals were determined by enzyme immunoassay. Histological processing of the samples was carried out according to generally accepted methods, the sections were stained with hematoxylin and eosin, as well as picrofuchsin according to Van Gieson. Results and discussion. The work revealed changes in the expression of IFN-γ in the blood serum of animals with wounds: an increase in the levels of IFN-γ on the 10th and 20th days after modeling wounds compared to the levels of rats in the intact group (p<0.05). A decrease in the levels of IFN-γ on the 40th day of the experiment compared to a similar level of this cytokine on the 10th and 20th days after wound simulation was shown (p<0.05). The results of histological studies show signs of the proliferative phase in the form of a significant number of fibroblasts and newly formed vessels, as well as the beginning of the remodeling stage in the form of the organization of collagen fibers in parallel bundles in the wound canals in different areas within 10 days. On the 20th day, the absence of inflammatory cells in the preparations of the damaged areas is noted. Also at the tissue level at this time, signs of the remodeling phase were revealed: a significant decrease in the number of blood vessels and fibroblasts was observed, the connective tissue in the areas acquired a mature appearance in the form of dense layers with single fibrocytes. In the injury zone on the 40th day of the experiment, scars from mature connective tissue were noted. Conclusion. In an experimental study, we showed the morphological and physiological features of the healing of soft tissue injuries in normal rats. The established structural features of wound areas at different stages of healing and the dynamics of IFN-γ release allow us to determine its important role not only in inflammation, but also in the stages of proliferation and remodeling. Determination of the concentration of IFN-γ may be an informative indicator at all stages of repair in the process of healing soft tissue injuries in humans, subjected to further clinical studies

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Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic

Cited by 10 publications

References 76 publications

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

Enhanced fetal hematopoiesis in response to symptomatic SARS-CoV-2 infection during pregnancy

Histological Characteristics of Experimental Wounds of Soft Tissues of the Femur of Rats and the Role of IFN-γ in the Dynamics of their Healing

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