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 14, Number 1, January 2022, pages 45-52

A Retrospective Cross-Sectional Study of Severe Breakthrough SARS-CoV-2 Infection in the General Population Requiring Hospitalization Within a Single Health System

**Table 1.** Baseline Characteristics of Patients With Breakthrough SARS-CoV-2 Infections
	All (n = 78)	Partially vaccinated (n = 39)	Fully vaccinated (n = 39)	P value
^aIf developed any time during the hospitalization. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SD: standard deviations; CAD: coronary artery disease; CKD: chronic kidney disease; ESRD: end-stage renal disease; HD: hemodialysis; COPD: chronic obstructive pulmonary disease; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; HR: heart rate; RR: respiratory rate; SPO₂: oxygen saturation; NC: nasal cannula; HFNC: high-flow nasal cannula; NIV: noninvasive mechanical ventilation; MV: invasive mechanical ventilation; WBC: white blood cell; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; PaO₂/FiO₂: ratio of partial pressure of oxygen to fractional inspired oxygen; ECMO: extra corporeal membrane oxygenation; ICU: intensive care unit; LOS: length of stay.
Age (years), mean (SD)	71.78 (12.99)	70.12 (11.35)	73.43 (14.41)	0.26
Sex (female), n (%)	42 (53.85)	19 (48.72)	23 (58.97)	0.82
Race, n (%)				0.51
White	47 (60.26)	21 (53.85)	26 (66.67)
Black	26 (33.33)	15 (38.46)	11 (28.21)
Other	5 (6.41)	3 (7.69)	2 (5.13)
Comorbidities, n (%)
CAD	24 (30.77)	10 (25.64)	14 (35.90)	0.32
CKD stage 3 - 5	30 (38.46)	12 (30.77)	18 (46.15)	0.16
ESRD on HD	3 (3.85)	1 (2.56)	2 (5.13)	0.55
Malignancy	22 (28.21)	12 (30.77)	10 (25.64)	0.61
COPD	21 (26.92)	13 (33.33)	8 (20.51)	0.20
Diabetes mellitus	38 (48.72)	19 (48.72)	19 (48.72)	0.99
Immunocompromised status	14 (17.95)	8 (20.51)	6 (15.38)	0.55
BMI, mean (SD)	31.80 (8.79)	30.83 (7.71)	32.77 (9.75)	0.33
Symptoms in ED, n (%)				0.03
Cough	4 (5.13)	3 (7.69)	1 (2.56)
Fever	3 (3.85)	3 (7.69)	0.00
Shortness of breath	41 (52.56)	22 (56.41)	19 (48.72)
Chest pain	2 (2.56)	0.00	2 (5.13)
Diarrhea	1 (1.28)	0.00	1 (2.56)
Weakness	12 (15.38)	8 (20.51)	4 (10.26)
Others	15 (19.23)	3 (7.69)	12 (30.77)
Symptom onset post-vaccination (days), mean (SD)	6.89 (6.24)	8.20 (6.60)	5.58 (5.65)	0.06
Symptom onset greater than 2 weeks post-vaccination (days), n (%)	8 (10.26)	6 (15.38)	2 (5.13)	0.21
Vitals in ED, mean (SD)
SBP (mm Hg)	134.98 (28.54)	133.38 (31.74)	136.58 (25.25)	0.62
DBP (mm Hg)	75.51 (16.61)	75.82 (16.84)	75.20 (16.60)	0.87
MAP (mm Hg)	89.96 (16.20)	89.25 (14.71)	90.66 (17.73)	0.70
HR (beats/min)	93.37 (22.45)	92.53 (21.45)	94.20 (23.65)	0.74
RR (breaths/min)	21.43 (5.63)	21.17 (5.78)	21.69 (5.53)	0.69
SPO₂ (%)	93.43 (7.48)	92.79 (9.10)	94.07 (5.44)	0.45
Oxygen supplementation in ED, n (%)				0.23
NC	48 (61.54)	28 (71.79)	20 (51.28)
HFNC	1 (1.28)	0.00	1 (2.56)
NIV	4 (5.13)	2 (5.13)	2 (5.13)
MV	0.00	0.00	0.00
None	25 (32.05)	9 (23.08)	16 (41.03)
Labs in ED, mean (SD)
Hemoglobin (12 - 16 g/dL)	12.31 (2.15)	12.64 (1.87)	11.97 (2.38)	0.17
WBC (4.5 - 12.5 × 10³/µL)	8.22 (4.16)	8.44 (3.89)	8.01 (4.45)	0.64
Platelets (150 - 450 × 10³/µL)	206.07 (96.52)	216.71 (98.11)	195.43 (94.97)	0.33
Blood urea nitrogen (136 - 145 mmol/L)	26.29 (19.43)	26.87 (20.87)	25.71 (18.13)	0.79
Creatinine (0.55 - 1.30 mg/dL)	1.58 (1.83)	1.63 (2.31)	1.53 (1.22)	0.81
AST (35 - 37 U/L)	41.85 (32.80)	44.02 (36.21)	39.69 (29.31)	0.56
ALT (12 - 78 U/L)	33.48 (25.87)	37.15 (32.22)	29.82 (17.05)	0.21
Albumin (3.5 - 5.5 g/dL)	2.93 (0.16)	2.90 (0.45)	2.96 (0.48)	0.58
INR (0.99 - 1.1)	1.17 (0.69)	1.21 (0.92)	1.14 (0.35)	0.65
D-dimer (0.19 - 0.50 mg/L)	3.19 (6.52)	3.27 (7.42)	3.12 (5.57)	0.91
At rest^a, n (%)				0.006
RR > 30 (beats/min)	1 (1.28)	0.00	1 (2.56)
HR > 125 (beats/min)	4 (5.13)	2 (5.13)	2 (5.13)
SPO₂ < 93%	41 (52.56)	27 (69.23)	14 (35.90)
PaO₂/FiO₂ < 300 (mm Hg)	9 (11.54)	0.00	9 (23.08)
None	23 (29.49)	10 (25.64)	13 (33.33)
Oxygen supplementation^a, n (%)				0.94
HFNC	7 (8.97)	4 (10.26)	3 (7.69)
NIV	9 (11.54)	4 (10.26)	5 (12.82)
MV	9 (11.54)	5 (12.82)	4 (10.26)
ECMO	0.00	0.00	0.00
None	53 (67.95)	26 (66.67)	27 (69.23)
Shock^a, n (%)				0.45
SBP < 90 (mm Hg)	5 (6.41)	1 (2.56)	4 (10.26)
DBP < 60 (mm Hg)	7 (8.97)	4 (10.26)	3 (7.69)
Vasopressor use	6 (7.69)	4 (10.26)	2 (5.13)
None	60 (76.92)	30 (76.92)	30 (76.92)
Clinical deterioration^a, n (%)				0.17
Renal	17 (21.79)	6 (15.38)	11 (28.21)
Neurological	18 (23.08)	12 (30.77)	6 (15.38)
Hepatic	0.00	0.00	0.00
None	43 (55.13)	21 (53.85)	22 (56.41)
ICU admission^a, n (%)	13 (16.67)	9 (23.08)	4 (10.26)	0.21
Death^a, n (%)	13 (16.67)	5 (12.82)	8 (20.51)	0.36
ICU LOS (days), mean (SD)	1.21 (3.30)	1.43 (3.36)	0.99 (3.26)	0.55
LOS (days), mean (SD)	7.19 (6.75)	7.97 (7.50)	6.41 (5.91)	0.26
Infection by months, n (%)				<0.001
January	12 (15.38)	12 (30.77)	0.00
February	19 (24.36)	16 (41.03)	3 (7.69)
March	7 (8.97)	4 (10.26)	3 (7.69)
April	3 (3.85)	2 (5.13)	1 (2.56)
May	6 (7.69)	0.00	6 (15.38)
June	4 (5.13)	1 (2.56)	3 (7.69)
July	13 (16.67)	1 (2.56)	12 (30.77)
August	14 (17.95)	3 (7.69)	11 (28.21)
Vaccine type, n (%)				0.07
Pfizer-BioNTech	75 (96.15)	36 (92.31)	39 (100)
Moderna	3 (3.85)	3 (7.69)	0.00

Table 1. Baseline Characteristics of Patients With Breakthrough SARS-CoV-2 Infections

All (n = 78)

Partially vaccinated (n = 39)

Fully vaccinated (n = 39)

P value

^aIf developed any time during the hospitalization. SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SD: standard deviations; CAD: coronary artery disease; CKD: chronic kidney disease; ESRD: end-stage renal disease; HD: hemodialysis; COPD: chronic obstructive pulmonary disease; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; HR: heart rate; RR: respiratory rate; SPO₂: oxygen saturation; NC: nasal cannula; HFNC: high-flow nasal cannula; NIV: noninvasive mechanical ventilation; MV: invasive mechanical ventilation; WBC: white blood cell; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; PaO₂/FiO₂: ratio of partial pressure of oxygen to fractional inspired oxygen; ECMO: extra corporeal membrane oxygenation; ICU: intensive care unit; LOS: length of stay.

Age (years), mean (SD)

71.78 (12.99)

70.12 (11.35)

73.43 (14.41)

0.26

Sex (female), n (%)

42 (53.85)

19 (48.72)

23 (58.97)

0.82

Race, n (%)

0.51

White

47 (60.26)

21 (53.85)

26 (66.67)

Black

26 (33.33)

15 (38.46)

11 (28.21)

Other

5 (6.41)

3 (7.69)

2 (5.13)

Comorbidities, n (%)

CAD

24 (30.77)

10 (25.64)

14 (35.90)

0.32

CKD stage 3 - 5

30 (38.46)

12 (30.77)

18 (46.15)

0.16

ESRD on HD

3 (3.85)

1 (2.56)

2 (5.13)

0.55

Malignancy

22 (28.21)

12 (30.77)

10 (25.64)

0.61

COPD

21 (26.92)

13 (33.33)

8 (20.51)

0.20

Diabetes mellitus

38 (48.72)

19 (48.72)

0.99

Immunocompromised status

14 (17.95)

8 (20.51)

6 (15.38)

0.55

BMI, mean (SD)

31.80 (8.79)

30.83 (7.71)

32.77 (9.75)

0.33

Symptoms in ED, n (%)

0.03

Cough

4 (5.13)

3 (7.69)

1 (2.56)

Fever

3 (3.85)

3 (7.69)

0.00

Shortness of breath

41 (52.56)

22 (56.41)

19 (48.72)

Chest pain

2 (2.56)

0.00

2 (5.13)

Diarrhea

1 (1.28)

0.00

1 (2.56)

Weakness

12 (15.38)

8 (20.51)

4 (10.26)

Others

15 (19.23)

3 (7.69)

12 (30.77)

Symptom onset post-vaccination (days), mean (SD)

6.89 (6.24)

8.20 (6.60)

5.58 (5.65)

0.06

Symptom onset greater than 2 weeks post-vaccination (days), n (%)

8 (10.26)

6 (15.38)

2 (5.13)

0.21

Vitals in ED, mean (SD)

SBP (mm Hg)

134.98 (28.54)

133.38 (31.74)

136.58 (25.25)

0.62

DBP (mm Hg)

75.51 (16.61)

75.82 (16.84)

75.20 (16.60)

0.87

MAP (mm Hg)

89.96 (16.20)

89.25 (14.71)

90.66 (17.73)

0.70

HR (beats/min)

93.37 (22.45)

92.53 (21.45)

94.20 (23.65)

0.74

RR (breaths/min)

21.43 (5.63)

21.17 (5.78)

21.69 (5.53)

0.69

SPO₂ (%)

93.43 (7.48)

92.79 (9.10)

94.07 (5.44)

0.45

Oxygen supplementation in ED, n (%)

0.23

48 (61.54)

28 (71.79)

20 (51.28)

HFNC

1 (1.28)

0.00

1 (2.56)

NIV

4 (5.13)

2 (5.13)

0.00

None

25 (32.05)

9 (23.08)

16 (41.03)

Labs in ED, mean (SD)

Hemoglobin (12 - 16 g/dL)

12.31 (2.15)

12.64 (1.87)

11.97 (2.38)

0.17

WBC (4.5 - 12.5 × 10³/µL)

8.22 (4.16)

8.44 (3.89)

8.01 (4.45)

0.64

Platelets (150 - 450 × 10³/µL)

206.07 (96.52)

216.71 (98.11)

195.43 (94.97)

0.33

Blood urea nitrogen (136 - 145 mmol/L)

26.29 (19.43)

26.87 (20.87)

25.71 (18.13)

0.79

Creatinine (0.55 - 1.30 mg/dL)

1.58 (1.83)

1.63 (2.31)

1.53 (1.22)

0.81

AST (35 - 37 U/L)

41.85 (32.80)

44.02 (36.21)

39.69 (29.31)

0.56

ALT (12 - 78 U/L)

33.48 (25.87)

37.15 (32.22)

29.82 (17.05)

0.21

Albumin (3.5 - 5.5 g/dL)

2.93 (0.16)

2.90 (0.45)

2.96 (0.48)

0.58

INR (0.99 - 1.1)

1.17 (0.69)

1.21 (0.92)

1.14 (0.35)

0.65

D-dimer (0.19 - 0.50 mg/L)

3.19 (6.52)

3.27 (7.42)

3.12 (5.57)

0.91

At rest^a, n (%)

0.006

RR > 30 (beats/min)

1 (1.28)

0.00

1 (2.56)

HR > 125 (beats/min)

4 (5.13)

2 (5.13)

SPO₂ < 93%

41 (52.56)

27 (69.23)

14 (35.90)

PaO₂/FiO₂ < 300 (mm Hg)

9 (11.54)

0.00

9 (23.08)

None

23 (29.49)

10 (25.64)

13 (33.33)

Oxygen supplementation^a, n (%)

0.94

HFNC

7 (8.97)

4 (10.26)

3 (7.69)

NIV

9 (11.54)

4 (10.26)

5 (12.82)

9 (11.54)

5 (12.82)

4 (10.26)

ECMO

0.00

None

53 (67.95)

26 (66.67)

27 (69.23)

Shock^a, n (%)

0.45

SBP < 90 (mm Hg)

5 (6.41)

1 (2.56)

4 (10.26)

DBP < 60 (mm Hg)

7 (8.97)

4 (10.26)

3 (7.69)

Vasopressor use

6 (7.69)

4 (10.26)

2 (5.13)

None

60 (76.92)

30 (76.92)

Clinical deterioration^a, n (%)

0.17

Renal

17 (21.79)

6 (15.38)

11 (28.21)

Neurological

18 (23.08)

12 (30.77)

6 (15.38)

Hepatic

0.00

None

43 (55.13)

21 (53.85)

22 (56.41)

ICU admission^a, n (%)

13 (16.67)

9 (23.08)

4 (10.26)

0.21

Death^a, n (%)

13 (16.67)

5 (12.82)

8 (20.51)

0.36

ICU LOS (days), mean (SD)

1.21 (3.30)

1.43 (3.36)

0.99 (3.26)

0.55

LOS (days), mean (SD)

7.19 (6.75)

7.97 (7.50)

6.41 (5.91)

0.26

Infection by months, n (%)

<0.001

January

12 (15.38)

12 (30.77)

0.00

February

19 (24.36)

16 (41.03)

3 (7.69)

March

7 (8.97)

4 (10.26)

3 (7.69)

April

3 (3.85)

2 (5.13)

1 (2.56)

May

6 (7.69)

0.00

6 (15.38)

June

4 (5.13)

1 (2.56)

3 (7.69)

July

13 (16.67)

1 (2.56)

12 (30.77)

August

14 (17.95)

3 (7.69)

11 (28.21)

Vaccine type, n (%)

0.07

Pfizer-BioNTech

75 (96.15)

36 (92.31)

39 (100)

Moderna

3 (3.85)

3 (7.69)

0.00

**Table 2.** Logistic Regression (LR) Model-2 Exploring Factors Associated With Severe Breakthrough SARS-CoV-2 Infection
	aOR	95% CI	P value
Area under the receiver operating curve (AUC) for the LR model 0.813, 95% CI: 0.71 - 0.91 (LR model controlled for: fully vs. partially vaccinated status, sex, SPO₂, COPD and immunocompromised status). aOR: adjusted odds ratio; CI: confidence interval; SPO₂: oxygen saturation; COPD: chronic obstructive pulmonary disease.
Fully vaccination status (vs. partially)	2.42	0.71 - 8.28	0.15
Sex (male)	4.03	1.21 - 13.40	0.023
SPO₂ (%)	0.80	0.68 - 0.94	0.009
COPD	0.24	0.05 - 27.01	0.063
Immunocompromised status	6.32	1.48 - 26.18	0.013

Table 2. Logistic Regression (LR) Model-2 Exploring Factors Associated With Severe Breakthrough SARS-CoV-2 Infection

aOR

95% CI

P value

Area under the receiver operating curve (AUC) for the LR model 0.813, 95% CI: 0.71 - 0.91 (LR model controlled for: fully vs. partially vaccinated status, sex, SPO₂, COPD and immunocompromised status). aOR: adjusted odds ratio; CI: confidence interval; SPO₂: oxygen saturation; COPD: chronic obstructive pulmonary disease.

Fully vaccination status (vs. partially)

2.42

0.71 - 8.28

0.15

Sex (male)

4.03

1.21 - 13.40

0.023

SPO₂ (%)

0.80

0.68 - 0.94

0.009

COPD

0.24

0.05 - 27.01

0.063

Immunocompromised status

6.32

1.48 - 26.18

0.013