Five years in, and it finally FEELS close.
o7
strange face that nose is wearing
Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines
https://www.nature.com/articles/s41421-021-00329-3
Abstract
Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8 T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.
Discussion
This is a comprehensive investigation of the pathophysiological changes, including detailed immunological alterations in people after COVID-19 vaccination. Results indicated that vaccination, in addition to stimulating the generation of neutralizing antibodies, also influenced various health indicators including those related to diabetes, renal dysfunction, cholesterol metabolism, coagulation problems, electrolyte imbalance, in a way as if the volunteers experienced an infection. scRNA-seq of PBMCs from volunteers before and after vaccination revealed dramatic changes in immune cell gene expression, not only echoing some of the clinical laboratory measures but also suggestive of increased NF-κB-related inflammatory responses, which turned out to be mainly taking place in classical monocytes. Vaccination also increased classical monocyte contents. Moreover, the gene set positively contributing to MVS scores, also known to be associated with severe symptom development, was highly expressed in monocytes. Type I interferon (IFN-α/β) responses, supposedly beneficial against COVID-19, were downregulated after vaccination. In addition, the negative MVS genes were highly expressed in lymphocytes (T, B, and NK cells), yet showed reduced expression after vaccination. Together, these data suggested that after vaccination, at least by day 28, other than generation of neutralizing antibodies, people’s immune systems, including those of lymphocytes and monocytes, were perhaps in a more vulnerable state.
cont.
Interestingly, our preliminary data demonstrated that if we pre-incubated RBD of SARS-CoV-2 with the PBMCs (from volunteers before and after vaccination) and then treated the cells with IFN-α/β, type I interferon responses were actually enhanced in PBMCs after vaccination, suggesting that perhaps vaccination, while reduced a person’s general antiviral ability, enhanced adaptive immune function specifically towards SARS-CoV-2 (Supplementary Fig. S4a). On the other hand, comparing PBMCs before vaccination, pre-treatment of SARS-CoV-2 S-RBD appeared to reduce type I interferon responses (P < 0.05, IRF2, IRF7, STAT2) (Supplementary Fig. S4b), suggesting 1st time exposure of the viral peptide would actually cause a reduction in type I interferon responses in PBMC. These in vitro data nicely supported the scRNA-seq results.
It is worth mentioning that one individual in cohort A who was on antibiotics, happened to not having reduced gene expression linked to type I interferon responses, and this individual also had the highest neutralizing antibody titer within the cohort. We further calculated Pearson’s Correlation Coefficient between neutralizing antibody titers and inflammatory responses measured by averaged gene expression of genes associated with TNFα Signaling via NF-κB and interferon-α (type I interferon) responses. The results were 0.32 and 0.39 with P > 0.05 (Supplementary Fig. S4c), respectively, suggesting immune response changes and adaptive immune protection of the vaccine do not appear to be highly correlated. Whether antibiotics may influence vaccine efficacy remains to be determined. It is also rather interesting that while cohorts A and B had different anti-SARS-CoV-2 antibody production profiles, their PBMCs scRNA-seq results were drastically similar, including their B-cell scRNA-seq data (Supplementary Fig. S5a–c). It should be noted that after vaccination, the majority of responsive B cells, particularly those producing mature anti-COVID-19 antibodies (IgG) including memory B cells, should be primarily located in peripheral lymphatic tissues such as lymph nodes and the spleen, while only a few mature B cells would exist in the circulation. Therefore, the B-cell population in PBMCs preparations may not reflect the whole spectrum of humoral immunity.
cont.
The analyses presented in this study, particularly, scRNA-seq of PBMCs had not been performed for previous vaccine evaluations, whether the changes in immune system function-related genes were COVID-19-specific or could be generally applied to other vaccines or other types of COVID-19 vaccines remained to be determined. However, these types of detailed analyses should be overall beneficial to vaccine development and applications. Our study postulates that it is imperative to consider the potential long-term impact of vaccination to certain medical conditions34 or to general human health.
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homo sapiens =/= ‘Homoborgenesis’
from this bred
https://8kun.top/qresearch/res/17803188.html
>If Pfizer was named after an Italian family instead of a German…
akin to "a coincidence that must never be spoken of…" -DC