Altered transcriptomic immune responses of maintenance hemodialysis patients to the COVID-19 mRNA vaccine
- Department of Medicine, University of Illinois at Chicago, United States
- Department of Bioengineering, University of Illinois at Chicago, United States
- Department of Microbiology and Immunology, University of Illinois at Chicago, United States
- Department of Medicine, Stanford University, United States
- Department of Medicine, University of Colorado Denver, United States
- Department of Biological Sciences, University of Illinois at Chicago, United States
Figures
Figure 1 with 3 supplements
Results of differential gene expression and blood transcription module (BTM) analysis.
(A) Differentially expressed genes (DEGs) increased after second vaccination dose compared to first, and at early time points compared to day 7 (D7). DEGs are shown for maintenance hemodialysis (HD) …
Figure 1—figure supplement 1
Differentially expressed genes (DEGs) increased after second vaccination dose compared to first, and at day 1 (D1, for healthy controls [HC]) and day 2 (D2, for maintenance hemodialysis [HD] compared to day 7 [D7]).
DEGs are shown for HC and HD regardless of SARS-CoV-2 history. Red color indicates upregulated DEGs and blue color indicates downregulated DEGs. The DESeq2 R package was used to identify genes that …
Figure 1—figure supplement 2
Hemodialysis (HD) patients without prior SARS-CoV-2 infection show increased myeloid activity at V1D7 and decreased metabolic activity at V2D7 compared to controls (HC).
The most differentially enriched blood transcription modules (BTMs) between HC and HD with no prior infection with SARS-CoV-2 are shown (p<0.05, FDR-adjusted) at V1D7 and at 1 wk after second …
Figure 1—figure supplement 3
Hemodialysis (HD) patients with prior SARS-CoV-2 infection show increased expression of innate and adaptive immune blood transcription modules (BTMs) post-vaccination.
The most significantly enriched BTMs are shown (up to six) for day 2 (D2) and day 7 (D7) after each vaccination dose (V1, V2) in HD with prior infection with SARS-CoV-2 (p<0.05, FDR-adjusted). …
Figure 2
Antibodies significantly increasedin both healthy control (HC) and maintenance hemodialysis (HD) groups 1 wk after the second vaccination dose (p<0.001) and 6 mo after initial vaccination (p<0.001) with the BNT162b2 mRNA COVID-19 vaccine.
(A) Anti-spike IgG levels in HC and HD subjects with and without prior SARS-CoV-2 history before vaccination (V1D0), 1 wk after second vaccination dose (V2D7), and 6 mo after initial vaccination …
Figure 3
Increased expression of multiple blood transcription modules (BTMs) at V2D2 is predictive of higher anti-spike IgG at V2D7.
Of 30 enriched BTMs at V2D2, increased expression of 18 BTMs is predictive of increased anti-spike IgG at V2D7 (p<0.05, FDR-corrected), controlling for SARS-CoV-2 history. Predictive pathways …
Figure 4
Baseline ferritin level and post-V1 white blood cell count (WBC) are clinical predictors of post-V2 antibody responses in maintenance hemodialysis (HD) patients.
(A) Ferritin levels associated with lowest all-cause mortality predict the development of higher anti-spike IgG after vaccination at V2D7 (p<0.01) and M6 (not shown, p<0.05) in maintenance HD …
Tables
Table 1
Demographic and clinical data for maintenance hemodialysis and control subjects.
| Hemodialysis | Control | p-value | |
|---|---|---|---|
| Total # of subjects | 20 | 20 | |
| Gender | |||
| Male | 11 | 10 | 1.0 |
| Female | 9 | 10 | 1.0 |
| Age (mean (sd)) | 54 (12) | 54 (13) | 0.98 |
| Race/ethnicity | |||
| Black/African American | 10 | 3 | 0.041 |
| Asian/Pacific Islander | 1 | 2 | 1.0 |
| White/Caucasian | 2 | 8 | 0.067 |
| Hispanic/Latinx | 7 | 6 | 1.0 |
| Other | 0 | 1 | 1.0 |
| BMI, kg/m2 (mean (sd)) | 27.8 (5.1) | 28.7 (6.4) | 0.61 |
| Medical history | |||
| Diabetes | 11 | 1 | 0.0012 |
| Hypertension | 18 | 4 | <0.001 |
| Other CV disease* | 9 | 0 | 0.0012 |
| Dyslipidemia | 10 | 0 | <0.001 |
| Autoimmune disease† | 3 | 0 | 0.23 |
| Immunosuppression‡ | 1 | 0 | 1.0 |
| Active malignancy§ | 1 | 0 | 1.0 |
| Positive COVID-19 history | 8 | 5 | 0.5 |
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*
Includes coronary artery disease (CAD), congestive heart failure (CHF), atrial fibrillation (AF), peripheral vascular disease (PVD), and cerebral vascular accent (CVA).
-
†
Includes systemic lupus erythematosus (SLE), immune thrombocytopenic purpura (ITP), and microscopic polyangiitis (MPA).
-
‡
Hydroxychloroquine.
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§
Defined as malignancy requiring treatment in the last 6 mo; one patient with papillary thyroid cancer requiring thyroidectomy, no systemic treatment required.
Table 2
Baseline clinical lab values for maintenance hemodialysis (HD) patients.
| Normal range | Mean (SD) | |
|---|---|---|
| Kidney/HD status | ||
| Urea reduction ratio | - | 0.74 (0.052) |
| Months on HD | - | 46 (44) |
| Iron | ||
| Ferritin (ng/ml) | 10–259 | 838 (550) * |
| % Transferrin saturation | 25–50 | 38 (13) |
| Albumin | 3.4–5 | 4.1 (0.40) |
| CBC | ||
| White blood cells (k/ul) | 3.9–12 | 6.0 (2.1) |
| Hgb (g/dl) | 13.2–18 | 10.5 (1.5) * |
| Lymphocytes (k/ul) | 1.3–4.2 | 1.5 (0.7) |
| Neutrophils (k/ul) | 1.3–7.5 | 3.7 (1.5) |
| Monocytes (k/ul) | 0.4–1 | 0.5 (0.2) |
| Eosinophils (k/ul) | 0.2–0.5 | 0.2 (0.2) |
-
*
Indicates value outside of normal range.
Additional files
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Supplementary file 1
Significantly enriched blood transcription modules at day 1 in healthy controls (HC) following the first vaccination dose (V1D1).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp1-v1.csv
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Supplementary file 2
Significantly enriched blood transcription modules at day 7 in healthy controls (HC) following the first vaccination dose (V1D7).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp2-v1.csv
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Supplementary file 3
Significantly enriched blood transcription modules at day 1 in healthy controls (HC) following the second vaccination dose (V2D1).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp3-v1.csv
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Supplementary file 4
Significantly enriched blood transcription modules at day 7 in healthy controls (HC) following the second vaccination dose (V2D7).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp4-v1.csv
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Supplementary file 5
Significantly enriched blood transcription modules at day 2 in hemodialysis subjects (HD) following the first vaccination dose (V1D2).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp5-v1.csv
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Supplementary file 6
Significantly enriched blood transcription modules at day 7 in hemodialysis subjects (HD) following the first vaccination dose (V1D7).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp6-v1.csv
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Supplementary file 7
Significantly enriched blood transcription modules at day 2 in hemodialysis subjects (HD) following the second vaccination dose (V2D2).
- https://cdn.elifesciences.org/articles/83641/elife-83641-supp7-v1.csv
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MDAR checklist
- https://cdn.elifesciences.org/articles/83641/elife-83641-mdarchecklist1-v1.docx
