Adverse events following the first, second and third doses of a COVID-19 vaccine in hemodialysis patients

Figures & data

Table 1. Characteristics of the study participants.

Characteristics	n = 438
Age (years)	64 ± 12
Female, n (%)	170 (39)
Vintage (years)	6.0 ± 5.9
Body height (cm)	162 ± 8
Body weight (kg)	63 ± 13
Body mass index (kg/m^2)	24 ± 4
Diabetes mellitus, n (%)	202 (50)
Hypertension, n (%)	242 (59)
Immunosuppressant, n (%)	9 (2)
Dialysis access, n	438
Arteriovenous fistula, n (%)	348 (79)
Arteriovenous graft, n (%)	60 (14)
Permcath, n (%)	30 (7)
First vaccine type, n	438
ChAdOx1, n (%)	434 (99)
mRNA-1273, n (%)	4 (1)
Second vaccine type, n	408
ChAdOx1, n (%)	402 (99)
mRNA-1273, n (%)	6 (1)
Prime-boost regimen, n	408
Homologous (ChAdOx1/ChAdOx1)	402 (99)
Homologous (mRNA-1273/mRNA-1273)	2 (1)
Heterologous (ChAdOx1/mRNA-1273)	4 (1)
Third vaccine type, n	367
mRNA-1273, n (%)	356 (97)
BNT162b2, n (%)	6 (2)
MVC-COV1901, n (%)	4 (1)
ChAdOx1, n (%)	1 (0.3)
Kt/V (Daugirdas)	1.52 ± 0.21
Albumin (g/dL)	3.9 ± 0.4
Hemoglobin (g/dL)	11.3 ± 1.4
Ferritin (ng/mL)	371 (240, 522)
Intact parathyroid hormone (pg/mL)	192 (84, 436)

Abbreviations. ChAdOx1: Oxford/AstraZeneca ChAdOx1 nCoV-19; mRNA-1273: Moderna mRNA-1273 SARS-CoV-2; BNT162b2: BioNTech/Pfizer BNT162b2; MVC-COV1901: Medigen MVC-COV1901.

Figure 1. The frequency of reported adverse events within 7 days of the first, second, and third doses of a COVID-19 vaccine among the study participants. Notably, 99% of the participants received the ChAdOx1 vaccine as their first and second doses, and the mRNA-1273 vaccine accounted for 97% of their third doses. The adverse events are presented in descending order of the first COVID-19 vaccine.

Table 2. Comparison of the frequency of adverse events following COVID-19 vaccination among the three doses.

Type of reaction	First dose (n = 431)	Second dose (n = 408)	Third dose (n = 367)	Second vs. first		Third vs. first		Third vs. second
	n (%)	n (%)	n (%)	Odds ratio (95% CI)	p value	Odds ratio (95% CI)	p value	Odds ratio (95% CI)	p value
Any adverse event	340 (79)	202 (50)	308 (84)	0.25 (0.18–0.34)	<0.001	1.42 (0.98–2.05)	0.07	5.77 (4.07–8.18)	<0.001
Any injection site reaction	212 (49)	113 (28)	276 (75)	0.38 (0.28–0.51)	<0.001	3.26 (2.39–4.45)	<0.001	8.63 (6.20–12.00)	<0.001
Redness	26 (6)	29 (7)	74 (20)	1.19 (0.69–2.07)	0.53	3.98 (2.47–6.40)	<0.001	3.33 (2.11–5.27)	<0.001
Itching	15 (3)	8 (2)	35 (10)	0.55 (0.23–1.32)	0.18	2.93 (1.57–5.47)	0.001	5.29 (2.41–11.59)	<0.001
Pain	204 (47)	101 (25)	259 (71)	0.35 (0.26–0.47)	<0.001	2.73 (2.02–3.69)	<0.001	7.79 (5.63–10.78)	<0.001
Ecchymosis	12 (3)	8 (2)	8 (2)	0.70 (0.28–1.73)	0.44	0.78 (0.31–1.93)	0.59	1.11 (0.41–3.00)	0.83
Nodules	20 (5)	13 (3)	44 (12)	0.68 (0.33–1.38)	0.28	2.82 (1.63–4.89)	<0.001	4.16 (2.20–7.89)	<0.001
Any systemic reaction	297 (69)	142 (35)	195 (53)	0.22 (0.17–0.30)	<0.001	0.50 (0.37–0.68)	<0.001	2.23 (1.66–3.01)	<0.001
Fever	131 (30)	17 (4)	46 (13)	0.09 (0.05–0.16)	<0.001	0.31 (0.21–0.46)	<0.001	3.31 (1.86–5.90)	<0.001
Fever (temperature ≥ 38 °C)	46 (11)	6 (1)	24 (7)	0.12 (0.05–0.29)	<0.001	0.58 (0.34–0.98)	0.04	4.80 (1.92–12.00)	<0.001
Mild fever (temperature 37.5 ∼ 37.9 °C)	44 (10)	6 (1)	12 (3)	0.13 (0.06–0.31)	<0.001	0.30 (0.15–0.57)	<0.001	2.27 (0.84–6.12)	0.11
Fever with unknown temperature	41 (10)	5 (1)	10 (3)	0.12 (0.05–0.30)	<0.001	0.26 (0.13–0.54)	<0.001	2.29 (0.77–6.80)	0.14
Any bodily pain	157 (36)	51 (13)	77 (21)	0.23 (0.16–0.33)	<0.001	0.45 (0.33–0.63)	<0.001	1.94 (1.31–2.88)	0.001
Headache	77 (18)	25 (6)	46 (13)	0.29 (0.18–0.47)	<0.001	NA		2.30 (1.37–3.88)	0.002
Myalgia	112 (26)	21 (5)	49 (13)	0.15 (0.09–0.24)	<0.001	0.44 (0.30–0.64)	<0.001	2.96 (1.73–5.07)	<0.001
Arthralgia	46 (11)	16 (4)	31 (8)	0.34 (0.19–0.61)	<0.001	0.77 (0.47–1.25)	0.28	2.26 (1.21–4.23)	0.01
Chest pain	12 (3)	4 (1)	3 (1)	NA		NA		NA
Gastrointestinal reactions	106 (25)	25 (6)	52 (14)	0.20 (0.12–0.31)	<0.001	0.51 (0.35–0.73)	<0.001	2.57 (1.55–4.25)	<0.001
Poor appetite	78 (18)	12 (3)	36 (10)	0.14 (0.07–0.25)	<0.001	0.49 (0.32–0.76)	<0.001	3.64 (1.86–7.12)	<0.001
Nausea	39 (9)	10 (2)	17 (5)	0.25 (0.12–0.50)	<0.001	0.48 (0.27–0.88)	0.02	1.97 (0.88–4.38)	0.10
Vomiting	12 (3)	8 (2)	11 (3)	0.70 (0.28–1.73)	0.44	1.08 (0.47–2.49)	0.85	1.55 (0.62–3.92)	0.35
Diarrhea	21 (5)	3 (1)	12 (3)	0.14 (0.04–0.49)	<0.001	0.66 (0.32–1.36)	0.26	4.58 (1.28–16.44)	0.02
Skin reactions (noninjection site)	10 (2)	5 (1)	4 (1)	NA		NA		NA
Rash	2 (0.5)	2 (0.5)	2 (0.5)	NA		NA		NA
Redness (mucosa)	0 (0)	1 (0.2)	0 (0)	NA		NA		NA
Itching	9 (2)	5 (1)	3 (1)	NA		NA		NA
Other reactions	221 (51)	103 (25)	153 (42)	0.31 (0.23–0.42)	<0.001	0.68 (0.51–0.91)	0.01	2.20 (1.61–3.01)	<0.001
Chills	44 (10)	13 (3)	56 (15)	0.29 (0.15–0.54)	<0.001	1.59 (1.04–2.44)	0.03	5.55 (2.97–10.36)	<0.001
Fatigue	208 (48)	89 (22)	118 (32)	0.28 (0.21–0.39)	<0.001	0.50 (0.37–0.67)	<0.001	1.76 (1.27–2.45)	0.001
Sleepiness	116 (27)	56 (14)	76 (21)	0.43 (0.30–0.61)	<0.001	0.71 (0.51–0.99)	0.05	1.67 (1.14–2.45)	0.01
Shortness of breath	5 (1)	2 (0.5)	4 (1)	NA		NA		NA
Chest tightness	14 (3)	4 (1)	9 (2)	0.30 (0.10–0.91)	0.03	0.75 (0.32–1.76)	0.51	2.54 (0.78–8.35)	0.12
Dizziness	58 (13)	20 (5)	23 (6)	NA		NA		NA
Anaphylactic reaction	1 (0.2)	0 (0)	0 (0)	NA		NA		NA
Daily activity was affected	19 (4)	6 (1)	10 (3)	0.32 (0.13–0.82)	0.02	0.60 (0.27–1.31)	0.20	1.86 (0.67–5.19)	0.24
Sought medical attention (e.g., visiting clinics)	4 (1)	2 (0.5)	7 (2)	NA				NA
Required medications	118 (27)	30 (7)	67 (18)	0.19 (0.13–0.30)	<0.001	0.58 (0.41–0.83)	<0.001	3.00 (1.88–4.80)	<0.001
Acetaminophen	104 (24)	26 (6)	64 (17)	0.20 (0.12–0.32)	<0.001	0.66 (0.46–0.94)	0.02	3.31 (2.02–5.41)	<0.001
Required intravenous medication	7 (2)	1 (0.3)	2 (0.5)	NA		NA		NA

Note. 99% of the participants received the ChAdOx1 vaccine as their first and second doses, and the mRNA-1273 vaccine accounted for 97% of their third doses.

Abbreviations. NA, not available due to nonconverged or unstable results.

Table 3. Comparison of adverse events which resolved ≤2 days among the study participants who had the adverse events following COVID-19 vaccination.

Type of reaction	First dose	Second dose	Third dose	Second vs. first		Third vs. first		Third vs. second
	n/total (%)	n/total (%)	n/total (%)	Odds ratio (95% CI)	p value	Odds ratio (95% CI)	p value	Odds ratio (95% CI)	p value
Any injection site reaction	164/212 (77)	72/113 (64)	157/276 (57)	0.51 (0.31–0.84)	0.01	0.41 (0.27–0.61)	<0.001	0.80 (0.51–1.26)	0.34
Fever	125/131 (95)	17/17 (100)	39/46 (85)	NA		0.49 (0.12–2.01)	0.31	NA
Any bodily pain	117/157 (75)	38/51 (75)	55/77 (71)	0.68 (0.31–1.51)	0.34	0.52 (0.27–1.00)	0.05	0.76 (0.33–1.73)	0.50
Gastrointestinal reactions	82/106 (77)	19/25 (76)	39/52 (75)	NA		NA		1.02 (0.08–13.66)	0.98
Skin reactions (noninjection site)	10/10 (100)	2/5 (40)	0/4 (0)	NA		NA		NA
Other reactions	192/221 (87)	84/103 (82)	117/153 (76)	NA		NA		NA
Required medications	107/118 (91)	26/30 (87)	59/67 (88)	NA		NA		NA

Note. 99% of the participants received the ChAdOx1 vaccine as their first and second doses, and the mRNA-1273 vaccine accounted for 97% of their third doses.

Abbreviations. NA, not available due to nonconverged or unstable results.

Table 4. Variables associated with the adverse events following three doses of the COVID-19 vaccination.

	Any adverse event			Any injection site reaction			Any systemic reaction
Variables	Odds ratio	95% CI	p value	Odds ratio	95% CI	p value	Odds ratio	95% CI	p value
Age (every increase of 10 years)	0.67	0.57 − 0.79	<0.001	0.66	0.57 − 0.77	<0.001	0.66	0.57 − 0.76	<0.001
Female sex (male as reference)	2.82	1.90 − 4.18	<0.001	2.04	1.43 − 2.91	<0.001	2.32	1.64 − 3.30	<0.001
AVF (AVG as reference)	1.73	1.05 − 2.84	0.03	1.86	1.15 − 3.01	0.01	1.33	0.84 − 2.11	0.23
mRNA-1273 (ChAdOx1 as reference)	10.5	0.77 − 144.6	0.08	15.6	1.63 − 148.4	0.02	4.86	0.79 − 29.86	0.09
Kt/V (Daugirdas) (every increase of 0.1)	0.96	0.88 − 1.05	0.40	1.02	0.94 − 1.11	0.64	0.92	0.85 − 1.00	0.05
BMI (every increase of 1 kg/m^2)	1.00	0.96 − 1.05	0.89	1.02	0.98 − 1.07	0.31	0.99	0.95 − 1.03	0.57
Diabetes (no diabetes as reference)	1.15	0.81 − 1.63	0.44	0.75	0.54 − 1.05	0.09	1.21	0.88 − 1.67	0.24
Hypertension (no hypertension as reference)	1.11	0.79 − 1.57	0.55	1.10	0.80 − 1.52	0.56	1.12	0.82 − 1.53	0.48
Albumin (every increase of 1 g/dL)	0.80	0.45 − 1.40	0.43	0.78	0.46 − 1.31	0.34	0.75	0.45 − 1.25	0.27
Hemoglobin (every increase of 1 g/dL)	0.93	0.81 − 1.06	0.26	0.94	0.83 − 1.07	0.35	1.00	0.89 − 1.13	0.97
Ferritin (every increase of 100 ng/mL)	0.95	0.89 − 1.01	0.50	0.95	0.89 − 1.01	0.07	0.99	0.93 − 1.04	0.64
Intact PTH (every increase of 100 pg/dL)	0.99	0.95 − 1.03	0.08	0.97	0.93 − 1.01	0.11	1.01	0.98 − 1.05	0.46

Note. All of the above variables were adjusted in the multivariate analyses.

Abbreviations. AVF: arteriovenous fistula; AVG: arteriovenous graft; ChAdOx1: ChAdOx1 nCoV-19 [AstraZeneca]; mRNA-1273: mRNA-1273 SARS-CoV-2 [Moderna]: BMI: body mass index; CI: confidence intervals; DM: diabetes mellitus; HTN: hypertension; PTH: parathyroid hormone.

Data availability statement

Individual-level deidentified participant data will be made available upon request by emailing the corresponding author. The data will be available for 3 years after publication.