J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 16, Number 5, May 2024, pages 208-219

Updated Bivalent COVID-19 Vaccines Reduce Risk of Hospitalization and Severe Outcomes in Adults: An Observational Cohort Study

Figure 1. Flow figure of inclusion and exclusion criteria. Flow figure of encounters screened for eligibility, encounters excluded from the study, and vaccination categorization.

Figure 2. Probability differences in composite outcomes and hospital admission by vaccination status, adjusted for baseline risk factors. Predictions are based on logistic regression models. Unadjusted model does not control for any covariate, adjusted age/Elix controls for age and Elixhauser comorbidity index and fully adjusted further controls for sex, race pre-existing end-stage renal disease and if the patient was immunocompromised. Error bars represent 95% confidence intervals. Point estimates represent the difference in marginal effects of vaccination status on (a) composite outcome with boosted being the reference and (b) probability of hospital admission with boosted being the reference.

**Table 1.** Demographics, Comorbidities, Initial Vital Signs, In-Hospital Therapies, and Outcomes of All Patients
Variables^a	All	Unvaccinated	Vaccinated	Boosted	Bivalent boosted	P value
^aFor continuous variables, medians (interquartile ranges (IQRs)) and means (standard deviation (SD)) were presented. For categorical variables, frequencies (percentage) were presented. ICU: intensive care unit.
N	21,439	9,630 (44.9%)	9,223 (43.0%)	2,180 (10.2%)	406 (1.9%)
Demographics
Age, years
Mean	48.8 (26.6)	37.8 (26.5)	58.9 (21.3)	66.2 (18.7)	72.3 (14.3)	< 0.001
Median	52 (29, 71)	35 (17, 59)	62 (43, 76)	70 (56, 80)	73 (65, 82)
Sex
Female	12,777 (59.6)	5,762 (59.8)	5,562 (60.3)	1,248 (57.2)	205 (50.5)	< 0.001
Male	8,662 (40.4)	3,868 (40.2)	3,661 (39.7)	932 (42.8)	201 (49.5)
Race
Black or African American	7,034 (32.8)	3,927 (40.8)	2,533 (27.5)	498 (22.8)	76 (18.7)	< 0.001
White or Caucasian	13,109 (61.1)	5,182 (53.8)	6,063 (65.7)	1,553 (71.2)	311 (76.6)
Other	1,296 (6.0)	521 (5.4)	627 (6.8)	129 (5.9)	19 (4.7)
Body mass index, kg/m²
Mean	29.5 (8.4)	29.4 (8.9)	29.8 (8.1)	29.0 (7.4)	29.0 (8.3)	< 0.001
Median	28.2 (23.6, 34)	28.1 (23.1, 34.1)	28.4 (24.1, 34.1)	27.6 (23.7, 33.1)	27.5 (23.5, 3.5)
Comorbidities
Immunocompromised	2,749 (12.8)	917 (9.5)	1,365 (14.8)	404 (18.5)	63 (15.5)	< 0.001
Pre-existing end-stage renal disease	694 (3.2)	194 (2.0)	358 (3.9)	133 (6.1)	9 (2.2)	< 0.001
Elixhauser weighted score
Mean	3.17 (3.3)	2.2 (2.9)	4.0 (3.5)	4.8 (3.6)	5.1 (3.5)	< 0.001
Median	2 (0,5)	1 (0,3)	3 (1,6)	4 (2,7)	5 (2,8)
Elixhauser, category
0	3,947 (18.4)	2,438 (25.3)	1,284 (13.9)	202 (9.3)	23 (5.7)	< 0.001
1 to 2	6,192 (28.9)	3,192 (33.1)	2,425 (26.3)	481 (22.1)	94 (23.2)
3 to 4	4,279 (20.0)	1,744 (18.1)	1,968 (21.3)	486 (22.3)	81 (20.0)
≥ 5	7,021 (32.7)	2,256 (23.4)	3,546 (38.4)	1,011 (46.4)	208 (51.2)
Initial vital signs
Respiratory rate, breaths per minute
< 30	21,041 (98.2)	9,467 (98.4)	9,042 (98.1)	2,134 (97.9)	398 (98.0)	0.282
≥ 30	381 (1.8)	153 (1.6)	175 (1.9)	45 (2.1)	8 (2.0)
Pulse, beats per minute
< 90	10,451 (48.8)	4,304 (44.7)	4,656 (50.5)	1,237 (56.8)	254 (62.6)	< 0.001
≥ 90	10,976 (51.2)	5,318 (55.3)	4,564 (49.5)	942 (43.2)	152 (37.4)
Systolic blood pressure, mm Hg
< 90	261 (1.2)	87 (0.9)	127 (1.4)	42 (1.9)	5 (1.2)	< 0.001
≥ 90	21,161 (98.8)	9,533 (99.1)	9,090 (98.6)	2,137 (98.1)	401 (98.8)
Temperature, °C
< 36	442 (2.1)	159 (1.7)	229 (2.5)	48 (2.2)	6 (1.5)	< 0.001
36 - 38	19,033 (89.0)	8,502 (88.4)	8,177 (88.9)	1,991 (91.5)	363 (89.6)
> 38	1,921 (9.0)	952 (9.9)	796 (8.7)	137 (6.3)	36 (8.9)
Blood oxygen saturation, %
< 90	588 (2.7)	277 (2.9)	247 (2.7)	56 (2.6)	8 (2.0)	0.582
≥ 90	20,836 (97.3)	9,345 (97.1)	8,970 (97.3)	2,123 (97.4)	398 (98.0)
In-hospital therapies
O₂ therapy	5,618 (26.2)	2,131 (22.1)	2,623 (28.4)	713 (32.7)	151 (37.2)	< 0.001
Nasal cannula/non-rebreather	4,008 (18.7)	1,463 (15.2)	1,922 (20.8)	506 (23.2)	117 (28.8)	< 0.001
High-flow O₂	556 (2.6)	255 (2.6)	231 (2.5)	57 (2.6)	13 (3.2)	0.801
Non-mechanical ventilation	593 (2.8)	211 (2.2)	276 (3.0)	94 (4.3)	12 (3.0)	< 0.001
Vasopressor	598 (2.8)	230 (2.4)	269 (2.9)	84 (3.9)	15 (3.7)	0.001
Primary outcome
Composite severe disease	1,178 (5.5)	477 (5.0)	530 (5.7)	152 (7.0)	19 (4.7)	0.001
ICU-level care	1,015 (4.7)	405 (4.2)	453 (4.9)	139 (6.4)	18 (4.4)	< 0.001
Mechanical ventilation	461 (2.2)	202 (2.1)	194 (2.1)	56 (2.6)	9 (2.2)	0.563
Death	416 (1.9)	178 (1.8)	183 (2.0)	48 (2.2)	7 (1.7)	0.705
Secondary outcomes
Hospital admission	9,390 (43.8)	3,543 (36.8)	4,366 (47.3)	1,246 (57.2)	235 (57.9)	< 0.001
Length of stay, h
Mean	172.1 (170.0)	183.0 (176.2)	167.3 (170.0)	171.2 (164.3)	147.0 (128.7)	< 0.001
Median	122 (72, 212)	127, (76, 233)	121 (71, 200)	121 (71, 216)	101 (64, 171)

Table 1. Demographics, Comorbidities, Initial Vital Signs, In-Hospital Therapies, and Outcomes of All Patients

Variables^a

All

Unvaccinated

Vaccinated

Boosted

Bivalent boosted

P value

^aFor continuous variables, medians (interquartile ranges (IQRs)) and means (standard deviation (SD)) were presented. For categorical variables, frequencies (percentage) were presented. ICU: intensive care unit.

21,439

9,630 (44.9%)

9,223 (43.0%)

2,180 (10.2%)

406 (1.9%)

Demographics

Age, years

Mean

48.8 (26.6)

37.8 (26.5)

58.9 (21.3)

66.2 (18.7)

72.3 (14.3)

< 0.001

Median

52 (29, 71)

35 (17, 59)

62 (43, 76)

70 (56, 80)

73 (65, 82)

Sex

Female

12,777 (59.6)

5,762 (59.8)

5,562 (60.3)

1,248 (57.2)

205 (50.5)

< 0.001

Male

8,662 (40.4)

3,868 (40.2)

3,661 (39.7)

932 (42.8)

201 (49.5)

Race

Black or African American

7,034 (32.8)

3,927 (40.8)

2,533 (27.5)

498 (22.8)

76 (18.7)

< 0.001

White or Caucasian

13,109 (61.1)

5,182 (53.8)

6,063 (65.7)

1,553 (71.2)

311 (76.6)

Other

1,296 (6.0)

521 (5.4)

627 (6.8)

129 (5.9)

19 (4.7)

Body mass index, kg/m²

Mean

29.5 (8.4)

29.4 (8.9)

29.8 (8.1)

29.0 (7.4)

29.0 (8.3)

< 0.001

Median

28.2 (23.6, 34)

28.1 (23.1, 34.1)

28.4 (24.1, 34.1)

27.6 (23.7, 33.1)

27.5 (23.5, 3.5)

Comorbidities

Immunocompromised

2,749 (12.8)

917 (9.5)

1,365 (14.8)

404 (18.5)

63 (15.5)

< 0.001

Pre-existing end-stage renal disease

694 (3.2)

194 (2.0)

358 (3.9)

133 (6.1)

9 (2.2)

< 0.001

Elixhauser weighted score

Mean

3.17 (3.3)

2.2 (2.9)

4.0 (3.5)

4.8 (3.6)

5.1 (3.5)

< 0.001

Median

2 (0,5)

1 (0,3)

3 (1,6)

4 (2,7)

5 (2,8)

Elixhauser, category

3,947 (18.4)

2,438 (25.3)

1,284 (13.9)

202 (9.3)

23 (5.7)

< 0.001

1 to 2

6,192 (28.9)

3,192 (33.1)

2,425 (26.3)

481 (22.1)

94 (23.2)

3 to 4

4,279 (20.0)

1,744 (18.1)

1,968 (21.3)

486 (22.3)

81 (20.0)

≥ 5

7,021 (32.7)

2,256 (23.4)

3,546 (38.4)

1,011 (46.4)

208 (51.2)

Initial vital signs

Respiratory rate, breaths per minute

< 30

21,041 (98.2)

9,467 (98.4)

9,042 (98.1)

2,134 (97.9)

398 (98.0)

0.282

≥ 30

381 (1.8)

153 (1.6)

175 (1.9)

45 (2.1)

8 (2.0)

Pulse, beats per minute

< 90

10,451 (48.8)

4,304 (44.7)

4,656 (50.5)

1,237 (56.8)

254 (62.6)

< 0.001

≥ 90

10,976 (51.2)

5,318 (55.3)

4,564 (49.5)

942 (43.2)

152 (37.4)

Systolic blood pressure, mm Hg

< 90

261 (1.2)

87 (0.9)

127 (1.4)

42 (1.9)

5 (1.2)

< 0.001

≥ 90

21,161 (98.8)

9,533 (99.1)

9,090 (98.6)

2,137 (98.1)

401 (98.8)

Temperature, °C

< 36

442 (2.1)

159 (1.7)

229 (2.5)

48 (2.2)

6 (1.5)

< 0.001

36 - 38

19,033 (89.0)

8,502 (88.4)

8,177 (88.9)

1,991 (91.5)

363 (89.6)

> 38

1,921 (9.0)

952 (9.9)

796 (8.7)

137 (6.3)

36 (8.9)

Blood oxygen saturation, %

< 90

588 (2.7)

277 (2.9)

247 (2.7)

56 (2.6)

8 (2.0)

0.582

≥ 90

20,836 (97.3)

9,345 (97.1)

8,970 (97.3)

2,123 (97.4)

398 (98.0)

In-hospital therapies

O₂ therapy

5,618 (26.2)

2,131 (22.1)

2,623 (28.4)

713 (32.7)

151 (37.2)

< 0.001

Nasal cannula/non-rebreather

4,008 (18.7)

1,463 (15.2)

1,922 (20.8)

506 (23.2)

117 (28.8)

< 0.001

High-flow O₂

556 (2.6)

255 (2.6)

231 (2.5)

57 (2.6)

13 (3.2)

0.801

Non-mechanical ventilation

593 (2.8)

211 (2.2)

276 (3.0)

94 (4.3)

12 (3.0)

< 0.001

Vasopressor

598 (2.8)

230 (2.4)

269 (2.9)

84 (3.9)

15 (3.7)

0.001

Primary outcome

Composite severe disease

1,178 (5.5)

477 (5.0)

530 (5.7)

152 (7.0)

19 (4.7)

0.001

ICU-level care

1,015 (4.7)

405 (4.2)

453 (4.9)

139 (6.4)

18 (4.4)

< 0.001

Mechanical ventilation

461 (2.2)

202 (2.1)

194 (2.1)

56 (2.6)

9 (2.2)

0.563

Death

416 (1.9)

178 (1.8)

183 (2.0)

48 (2.2)

7 (1.7)

0.705

Secondary outcomes

Hospital admission

9,390 (43.8)

3,543 (36.8)

4,366 (47.3)

1,246 (57.2)

235 (57.9)

< 0.001

Length of stay, h

Mean

172.1 (170.0)

183.0 (176.2)

167.3 (170.0)

171.2 (164.3)

147.0 (128.7)

< 0.001

Median

122 (72, 212)

127, (76, 233)

121 (71, 200)

121 (71, 216)

101 (64, 171)

**Table 2.** Demographics, Comorbidities, Initial Vital Signs, In-Hospital Therapies, and Outcomes of Admitted Patients
Variables^a	All	Unvaccinated	Vaccinated	Boosted	Bivalent boosted	P value
^aFor continuous variables, medians (interquartile ranges (IQRs)) and means (standard deviation (SD)) were presented. For categorical variables, frequencies (percentage) were presented. ICU: intensive care unit.
N	9,390	3,543 (37.7%)	4,366 (46.5%)	1,246 (13.3%)	235 (2.5%)
Demographics
Age, years
Mean	67.9 (17.5)	63.0 (18.9)	70.0 (16.3)	72.7 (15.0)	76.6 (11.8)	< 0.001
Median	71 (58, 81)	65 (50, 78)	72 (61, 82)	74 (65, 84)	78 (69, 85)
Sex
Female	5,101 (54.3)	1,968 (55.5)	2,359 (54.0)	662 (53.1)	112 (47.7)	0.066
Male	4,289 (45.7)	1,575 (44.5)	2,007 (46.0)	584 (46.9)	123 (52.3)
Race
Black or African American	2,325 (24.8)	1,062 (30.0)	965 (22.1)	255 (20.5)	43 (18.3)	< 0.001
White or Caucasian	6,567 (69.9)	2,313 (65.3)	3,147 (72.1)	927 (74.4)	180 (76.6)
Other	498 (5.3)	168 (4.7)	254 (5.8)	64 (5.1)	12 (5.1)
Body mass index, kg/m²
Mean	29.1 (8.4)	29.6 (8.9)	29.0 (8.3)	28.4 (7.3)	28.2 (7.8)	< 0.004
Median	27.5 (23.4, 33.3)	27.9 (23.4, 34)	27.5 (23.4, 33.1)	27.1 (23.3, 32.4)	26.6 (22.9, 32.1)
Comorbidities
Immunocompromised	1,922 (20.5)	608 (17.2)	977 (22.4)	292 (23.4)	45 (19.1)	< 0.001
Pre-existing end-stage renal disease	583 (6.2)	165 (4.7)	299 (6.8)	110 (8.8)	9 (3.8)	< 0.001
Elixhauser weighted score
Mean	5.2 (3.7)	4.4 (3.6)	5.6 (3.6)	5.8 (3.7)	5.9 (3.6)	< 0.001
Median	5 (2,8)	4 (2,7)	5 (3,8)	6 (3,9)	6 (3,9)
Elixhauser, category
0	852 (9.1)	464 (13.1)	296 (6.8)	77 (6.2)	15 (6.4)	< 0.001
1 to 2	1,821 (19.4)	850 (24.0)	751 (17.2)	184 (14.8)	36 (15.3)
3 to 4	1,829 (19.5)	693 (19.6)	849 (19.4)	247 (19.8)	40 (17.0)
≥ 5	4,888 (52.1)	1,536 (43.4)	2,470 (56.6)	738 (59.2)	144 (61.3)
Initial vital signs
Respiratory rate, breaths per minute
< 30	9,037 (96.3)	3,398 (95.9)	4,209 (96.4)	1,203 (96.5)	227 (96.6)	0.648
≥ 30	352 (3.7)	144 (4.1)	157 (3.6)	43 (3.5)	8 (3.4)
Pulse, beats per minute
< 90	4,849 (51.6)	1,649 (46.6)	2,325 (53.3)	727 (58.3)	148 (63.0)	< 0.001
≥ 90	4,540 (48.4)	1,893 (53.4)	2,041 (46.7)	519 (41.7)	87 (37.0)
Systolic blood pressure, mm Hg
< 90	233 (2.5)	69 (1.9)	118 (2.7)	41 (3.3)	5 (2.1)	0.036
≥ 90	9,155 (97.5)	3,473 (98.1)	4,247 (97.3)	1,205 (96.7)	230 (97.9)
Temperature, °C
< 36	283 (3.0)	97 (2.7)	150 (3.4)	31 (2.5)	5 (2.1)	0.016
36 - 38	8,257 (88.0)	3,097 (87.5)	3,833 (87.8)	1,125 (90.3)	202 (86.0)
> 38	847 (9.0)	347 (9.8)	382 (8.8)	90 (7.2)	28 (11.9)
Blood O₂ saturation, %
< 90	554 (5.9)	264 (7.5)	227 (5.2)	55 (4.4)	8 (3.4)	< 0.001
≥ 90	8,835 (94.1)	3,278 (92.5)	4,139 (94.8)	1,191 (95.6)	227 (96.6)
In-hospital therapies
O₂ therapy	5,329 (56.8)	2,016 (56.9)	2,482 (56.8)	691 (55.5)	140 (59.6)	0.645
Nasal cannula/non-rebreather	3,727 (39.7)	1,353 (38.2)	1,784 (40.9)	484 (38.8)	106 (45.1)	0.028
High-flow O₂	556 (5.9)	255 (7.2)	231 (5.3)	57 (4.6)	13 (5.5)	< 0.001
Non-mechanical ventilation	588 (6.3)	207 (5.8)	275 (6.3)	94 (7.5)	12 (5.1)	0.165
Vasopressor	592 (6.3)	228 (6.4)	265 (6.1)	84 (6.7)	15 (6.4)	0.822
Primary outcome
Composite severe disease	1,164 (12.4)	472 (13.3)	521 (11.9)	152 (12.2)	19 (8.1)	0.052
ICU-level care	1,015 (10.8)	405 (11.4)	453 (10.4)	139 (11.2)	18 (7.7)	0.183
Mechanical ventilation	458 (4.9)	201 (5.7)	192 (4.4)	56 (4.5)	9 (3.8)	0.047
Death	404 (4.3)	174 (4.9)	175 (4.0)	48 (3.9)	7 (3.0)	0.126

Table 2. Demographics, Comorbidities, Initial Vital Signs, In-Hospital Therapies, and Outcomes of Admitted Patients

Variables^a

All

Unvaccinated

Vaccinated

Boosted

Bivalent boosted

P value

9,390

3,543 (37.7%)

4,366 (46.5%)

1,246 (13.3%)

235 (2.5%)

Demographics

Age, years

Mean

67.9 (17.5)

63.0 (18.9)

70.0 (16.3)

72.7 (15.0)

76.6 (11.8)

< 0.001

Median

71 (58, 81)

65 (50, 78)

72 (61, 82)

74 (65, 84)

78 (69, 85)

Sex

Female

5,101 (54.3)

1,968 (55.5)

2,359 (54.0)

662 (53.1)

112 (47.7)

0.066

Male

4,289 (45.7)

1,575 (44.5)

2,007 (46.0)

584 (46.9)

123 (52.3)

Race

Black or African American

2,325 (24.8)

1,062 (30.0)

965 (22.1)

255 (20.5)

43 (18.3)

< 0.001

White or Caucasian

6,567 (69.9)

2,313 (65.3)

3,147 (72.1)

927 (74.4)

180 (76.6)

Other

498 (5.3)

168 (4.7)

254 (5.8)

64 (5.1)

12 (5.1)

Body mass index, kg/m²

Mean

29.1 (8.4)

29.6 (8.9)

29.0 (8.3)

28.4 (7.3)

28.2 (7.8)

< 0.004

Median

27.5 (23.4, 33.3)

27.9 (23.4, 34)

27.5 (23.4, 33.1)

27.1 (23.3, 32.4)

26.6 (22.9, 32.1)

Comorbidities

Immunocompromised

1,922 (20.5)

608 (17.2)

977 (22.4)

292 (23.4)

45 (19.1)

< 0.001

Pre-existing end-stage renal disease

583 (6.2)

165 (4.7)

299 (6.8)

110 (8.8)

9 (3.8)

< 0.001

Elixhauser weighted score

Mean

5.2 (3.7)

4.4 (3.6)

5.6 (3.6)

5.8 (3.7)

5.9 (3.6)

< 0.001

Median

5 (2,8)

4 (2,7)

5 (3,8)

6 (3,9)

Elixhauser, category

852 (9.1)

464 (13.1)

296 (6.8)

77 (6.2)

15 (6.4)

< 0.001

1 to 2

1,821 (19.4)

850 (24.0)

751 (17.2)

184 (14.8)

36 (15.3)

3 to 4

1,829 (19.5)

693 (19.6)

849 (19.4)

247 (19.8)

40 (17.0)

≥ 5

4,888 (52.1)

1,536 (43.4)

2,470 (56.6)

738 (59.2)

144 (61.3)

Initial vital signs

Respiratory rate, breaths per minute

< 30

9,037 (96.3)

3,398 (95.9)

4,209 (96.4)

1,203 (96.5)

227 (96.6)

0.648

≥ 30

352 (3.7)

144 (4.1)

157 (3.6)

43 (3.5)

8 (3.4)

Pulse, beats per minute

< 90

4,849 (51.6)

1,649 (46.6)

2,325 (53.3)

727 (58.3)

148 (63.0)

< 0.001

≥ 90

4,540 (48.4)

1,893 (53.4)

2,041 (46.7)

519 (41.7)

87 (37.0)

Systolic blood pressure, mm Hg

< 90

233 (2.5)

69 (1.9)

118 (2.7)

41 (3.3)

5 (2.1)

0.036

≥ 90

9,155 (97.5)

3,473 (98.1)

4,247 (97.3)

1,205 (96.7)

230 (97.9)

Temperature, °C

< 36

283 (3.0)

97 (2.7)

150 (3.4)

31 (2.5)

5 (2.1)

0.016

36 - 38

8,257 (88.0)

3,097 (87.5)

3,833 (87.8)

1,125 (90.3)

202 (86.0)

> 38

847 (9.0)

347 (9.8)

382 (8.8)

90 (7.2)

28 (11.9)

Blood O₂ saturation, %

< 90

554 (5.9)

264 (7.5)

227 (5.2)

55 (4.4)

8 (3.4)

< 0.001

≥ 90

8,835 (94.1)

3,278 (92.5)

4,139 (94.8)

1,191 (95.6)

227 (96.6)

In-hospital therapies

O₂ therapy

5,329 (56.8)

2,016 (56.9)

2,482 (56.8)

691 (55.5)

140 (59.6)

0.645

Nasal cannula/non-rebreather

3,727 (39.7)

1,353 (38.2)

1,784 (40.9)

484 (38.8)

106 (45.1)

0.028

High-flow O₂

556 (5.9)

255 (7.2)

231 (5.3)

57 (4.6)

13 (5.5)

< 0.001

Non-mechanical ventilation

588 (6.3)

207 (5.8)

275 (6.3)

94 (7.5)

12 (5.1)

0.165

Vasopressor

592 (6.3)

228 (6.4)

265 (6.1)

84 (6.7)

15 (6.4)

0.822

Primary outcome

Composite severe disease

1,164 (12.4)

472 (13.3)

521 (11.9)

152 (12.2)

19 (8.1)

0.052

ICU-level care

1,015 (10.8)

405 (11.4)

453 (10.4)

139 (11.2)

18 (7.7)

0.183

Mechanical ventilation

458 (4.9)

201 (5.7)

192 (4.4)

56 (4.5)

9 (3.8)

0.047

Death

404 (4.3)

174 (4.9)

175 (4.0)

48 (3.9)

7 (3.0)

0.126