By Al-Zuabi, H; Kamel, MI; El-Shazly, MK; Al-Kandari, W; Mandani, G; Hamadah, G; Nasser, AH (2022).

Greener Journal of Medical Sciences

Vol. 12(2), pp. 161-171, 2022

ISSN: 2276-7797

Copyright ©2022, the copyright of this article is retained by the author(s)

https://gjournals.org/GJMS

 

 

 

 

 

Gender differences among hospitalized COVID-19 patients.

 

 

Homoud Al-Zuabi1, Mohamed I Kamel2, Medhat K El-Shazly3, Wafaa Al-Kandari4, Ghaidaa Mandani5, Ghazlan Hamadah6, Ahmed H Nasser7

 

 

1 MRCGP, Consultant Family Medicine, Head of Chronic Diseases Clinic Team, Head of the Department of Non-communicable Disease, MOH, Kuwait.

2 MD, Consultant of Public Health, Department of Occupational Medicine, Ministry of Health, Kuwait & Professor of Community Medicine, Faculty of Medicine, Alexandria University, Egypt.

3 MD, Consultant of Public Health, Department of Planning, MOH, Kuwait & Professor of Health Statistics, Medical Research Institute, Alexandria University, Egypt.

4 MRCGP, Consultant Family Medicine, Member of Chronic Diseases Clinic Team, Head of Jaber Hospital Quarantine Center and Director of School Health Administration, MOH, Kuwait.

5 MRCGP, Family Medicine Senior Specialist, Jaber Hospital Quarantine & School Health Administration MOH, Kuwait.

6 Kuwait Board (AGD), RCSI Dublin (AGD). Advanced General Dentist Specialist, Jaber Hospital Quarantine & PHC, Kuwait.

7.General Nursing Diploma, Registered Nurse, Farwaniya Hospital, MOH, Kuwait.

 

 

Correspondence to:

 

Prof. Dr. Medhat Shazly

Department Medical Statistics,

Medical Research Institute,

Alexandria University, Egypt

Tel: + 965 24620622    

Mobile: + 965 739 3758

E-mail: medshaz@ yahoo. com

 

 

 

 

 

ARTICLE INFO

ABSTRACT

 

Article No.: 102522087

Type: Research

Full Text: PDF, HTML, PHP, EPUB

 

Background: A growing body of evidence indicates gender difference in the severity of COVID-19.

Objectives: The aim of the present study is to highlight gender difference regarding symptoms, laboratory investigations, complications, and outcome parameters of COVID-19 in admitted cases during the first wave of the disease.

Methods: A cross sectional retrospective descriptive epidemiological approach was carried out using electronic patients’ records review.

Results: One thousand and one hundred fifty males (77.6%) and 332 females (22.4%) cases for COVOD-19 were subjected to the final analysis. The proportions of general body ache, loss of smell and sore throat were significantly higher among females (13.9%, 2.7% and 15.7%) than males (9.9%, 0.3% and 11.0%), whereas shortness of breath was significantly higher in males than females. A significantly higher proportion of women were more likely to suffer from low ferritin level than men, whereas men were more likely to suffer from a low lymphocytic count. Also, a higher proportion of males suffered from high levels of creatinine than females. No significant difference between males and females regarding COVID-19 complications except for respiratory complications that were more significantly encountered among males than females.  Not only more males (11.9%) tended to use oxygen therapy than females (7.2%) but they used it through nasal masks (54% compared with 29.2%) and at a higher flow rate (26.3% compared with 8.3% at a flow rate more than 10 L/min). A higher percentage of male cases then females required to be admitted to the ICU significantly (p < 0.001) as 9.7% of males needed care in the intensive care units (ICU) compared with only 3.3% of females.

Conclusions: There is a difference of COVID-19 presentation, severity, and hospitalization, between men and women. Overall, this renders males to be at a higher risk for severe forms of the COVID-19 disease especially with regard to respiratory complications.

 

 

Accepted:  27/10/2022

Published: 05/11/2022

 

*Corresponding Author

Prof. Dr. Medhat Shazly

E-mail: medshaz@ yahoo. com

Phone: + 965 24620622

 

Keywords: gender-difference, admitted cases, Covid-19.

 

 

 

 

 


Introduction:

 

Coronavirus disease (COVID-19) was first described in China in December 2019 as a severe form of acute respiratory syndrome, and since then has spread worldwide to be announced by the World Health Organization (WHO) in July 2020 as an out-of-control global pandemic. By May 2021, the number of confirmed infections reached over 169 million with more than 3.5 million deaths reported to the WHO.(1) COVID-19 virus is one of the seven coronaviruses that cause infections in humans, it became an epidemic in a brief period and had a considerable impact on a global scale.(2) Whenever a new infectious disease emerges, knowledge regarding clinical features, diagnostic tools and treatment options is critical.(3) A growing body of evidence indicates gender difference in the clinical outcomes of COVID-19.(4, 5)

Men are consistently over-represented in COVID-19 severe outcomes, including higher fatality rates. There is a difference in the perceived symptoms between males and females where evidence suggested that female patients significantly experienced fatigue, anosmia, headache, sore throat, and nasal obstruction more than male patients. However, male patients significantly experienced other symptoms as cough and fever. (6) Apart from chronic medical conditions and old age (>65years), male gender was associated with more severe forms of the disease. Although the number of recorded confirmed cases is similar in males and females, however the mortality rate tends to be higher in males. (7) The severity of COVID-19, as measured by hospitalisation, admission to intensive care units, intubation for mechanical ventilation, and death, has consistently been 1.5 to 2 times greater for men than for women around the world.(8-10)

These differences are likely due to gender-specific behaviors, genetic and hormonal factors, and sex differences in biological pathways related to COVID-19 infection. Several social, behavioral, and comorbid factors are implicated in the generally worse outcomes in men compared with women. (11)

Essential for the success of clinical care is awareness by clinicians that the diseases they are treating, are characterised by differences between women and men in epidemiology, pathophysiology, clinical manifestations, psychological effects, progression, and response to treatment. (12) It is important to identify the degree to which COVID-19 affects males and females differently to understand the disease consequences and explore the prognostic factors for individualized assessment. (11)

This study aimed at exploring gender difference perceived symptoms, laboratory investigations, complications, and outcome parameters of COVID-19 in admitted cases during the first wave of the disease.

 

 

Subjects and methods

 

Setting:

 

This study was conducted in Jaber Al-Ahmed hospital. The time interval of the study was set as four months from April to July 2021.

 

Study design:

 

A cross sectional retrospective descriptive epidemiological approach was carried out using electronic patients’ records review, aiming at highlighting gender difference among hospitalized COVID-19 patients in Jaber hospital in Kuwait regarding personal characteristics, presenting manifestations, investigations, vital signs on admission, associated chronic diseases, COVID-19 complications, and outcome parameters.

 

Sampling:

 

A time sample (four months) was set for this study starting from February to May 2019. All admitted cases during this period were included in the study. This period was chosen as during that time all positive cases for COVID-19 (both Kuwaiti and non-Kuwaiti) across all health governorates were referred to this hospital. After this period, only Kuwaiti patients were admitted to this hospital.

 

Research tools:

 

A pre-designed structured questionnaire was designated for data collections. It included the following domains:

-      Personal characteristics as age, gender, nationality, Smoking, weight, and height.

-      Associated co-morbid conditions mainly hypertension, cardiovascular and respiratory diseases, diabetes, dyslipidemia, and endocrine insufficiency.

-      Presenting symptoms mainly general, respiratory and gastrointestinal symptoms.

-      Investigations and vital signs on admission as systolic blood pressure (SBP) (mmHg), diastolic blood pressure (DBP) (mmHg), heart rate (PPM), respiratory rate (BPM), blood oxygen saturation (SpO2) (%), D-Dimer (ng/mL), CRP (mg/L), LDH (IU/L), troponin (ng/L), ferritin (ng/mL), lymphocytic count, serum creatinine (µmol/L), blood sugar (mmol/L), glycated Hb (HbA1c) (mmol/mol).

-      COVID-19 complications as respiratory, infection, and others complications

-           Outcome parameters as oxygen therapy, duration of hospital stay, admission to the ICU, need of intensive ventilation and outcome on discharge

 

Normal blood oxygen level is defined as 95-100% when measured with a pulse oximeter. (13) Normal level of serum ferritin is considered as 20 to 250 ng/mL for adult males, and 10 to 120 ng/mL for adult females 18 to 39 years and 12 to 263 ng/mL for females 40 years and older. (14, 15) A normal level of serum creatinine is defined as 61.9 to 114.9 µmol/L for men and 53 to 97.2 µmol/L for women. (16)

All the necessary approvals for carrying out the research were obtained. The Ethical Committee of the Kuwaiti Ministry of Health approved the research. The permission of the Deputy Ministry of Health in Kuwait as well as head of Jaber hospital were obtained. The researchers were trained on skills required to carry this research efficiently in terms of how to review patient’s medical record for abstracting the rquired data and to enter these data into the pre designed file. A pilot study was carried out on 20 cases.

 

Data management:

 

The data collected was logged in the google form directly. Daily revision of the completed data was routinely carried out. After completing data collection through google forms, this data was red on an Excel sheet that was in turn changed into an SPSS file (Statistical Package for Social Science, version 22) for the analysis.

Data cleaning was performed through checking possible mistakes by a serried range, minimum and maximum values as well as frequency distribution and cross tabulations to ensure that all questions had valid codes and values.

Categorical variables are presented as frequencies (number and percentages) and continuous variables as means (with SDs) or medians (with interquartile ranges [IQRs]). Simple descriptive statistics were used. Comparison between groups were performed using Chi square or Fisher’ Exact tests for categorical data and student t-test or Wilcoxon rank sum test for qualitative variables.

 

 

Results

 

Reviewing the medical records of the cases admitted to the selected hospital during the defined period resulted in inclusion of 1482 positive cases for COVID-19. One thousand and one hundred fifty males (77.6%) and 332 females (22.4%) were subjected to the final analysis.

Table 1 describes the gender differences regarding personal characteristics of the included patients. The mean age of females (44.1±14.6) was insignificantly higher than that of males (43.0±14.6) (t = 1.82, P=0.07). Cases in the age group ≥ 60 years represented 18.7% of females and 11.6% of males. There was a significant difference between male and female cases regarding nationality (χ2 = 194.0, P<0.001). Just less than half of male cases were Indian (46.0%) while 48.5% of female cases were Kuwaiti, whereas the least proportion were noticed in Bengali both in males (10.1%) and females (3.3%). The least governorates that presented in both males and females were Al-Jahra and Mubarak Al-Kabeer, while 31.6% of male cases were residents of Farwaniya and 27.1% of female cases were from Hawalli (χ2 = 25.76, P<0.001). The BMI was significantly higher in females (29±6.3) than males (27.0±4.8), (t = 3.81, P<0.001). Smoking was rarely reported in both males and females, in spite being significantly more presented in males than females.


 

 

Table (1): Personal characteristics of male and female hospitalized COVID-19 patients

Variable

Males

(n=1150)

Females

(n=332)

Test of significance

( p )

No.

%

No.

%

Age (years)

 

 

 

 

 

<30

165

14.3

51

15.4

 

30-39

351

30.5

96

28.9

 

40-49

299

26.0

65

19.6

 

50-59

202

17.6

58

17.5

 

≥60

133

11.6

62

18.7

 

Mean ± SD

43.0 ± 12.7

44.5±14.6

t = 1.82

Min - Max

19 – 94

19 – 85

P = 0.07

Nationality:

 

 

 

 

 

Kuwaiti

197

17.1

161

48.5

Ӽ2=193.99

Indian

529

46.0

60

18.1

p<0.001

Egyptian

133

11.6

17

5.1

 

Bengali

116

10.1

11

3.3

 

Others

175

15.2

83

25.0

 

Governorate

 

 

 

 

 

Capital

283

25.1

74

22.5

Ӽ2=25.76

Hawalli

205

18.2

89

27.1

p<0.001

Farwaniyah

356

31.6

84

25.5

 

Ahmadi

187

16.6

47

14.3

 

Jahra

50

4.4

8

2.4

 

Mubarak Alkabeer

46

4.1

27

8.2

 

BMI:*

 

 

 

 

 

Under-weight

4

1.0

2

1.5

 

Normal

143

34.8

32

24.6

 

Over-weight

183

44.5

44

33.8

 

Obese

56

13.6

32

24.6

 

Severe obese

25

6.1

20

15.4

 

Mean ± SD

27.00 ± 4.78

29.00 ± 6.32

t = 3.81

Min - Max

16.18 – 59.86

18.42 – 52.62

p < 0.001

Smoking:**

 

 

 

 

 

No

300

83.8

131

95.6

Ӽ2=12.30

Yes

58

16.2

6

4.4

p<0.001

*: missing 739 males and 202 females

**: missing 792 males and 195 females

 

 

 


Table 2 shows the frequency of chronic diseases among the studied patients. The proportions of diabetes mellitus, respiratory diseases and hypothyroidism were significantly higher in female than male cases (χ2 = 10.01, P=0.002), (χ2 = 24.19, P<0.001) and (χ2 = 28.80, P<0.001) respectively. As shown in table 3, higher proportion of females (13.9%) complained from general body ache than males (9.9%) significantly (χ2 = 4.16, P=0.04). Also, the proportions of loss of smell and sore throat were higher among females (2.7% and 15.7%) than males (0.3% and 11.0%) significantly (P< 0.001 and P = 0.02 respectively). Shortness of breath was significantly higher in males than females (11.3% versus 7.2%, P = 0.03).

 


 

 

Table (2): Frequency of chronic diseases among male and female hospitalized COVID-19 patients

Chronic diseases

Males

(n=1150)

Females

(n=332)

Test of significance

( p )

 

No.

%

No.

%

 

Hypertension:

204

17.7

71

21.4

Ӽ2=2.27 (P=0.15)

Cardiovascular

59

5.1

14

4.2

Ӽ2=0.46 (P=0.57)

Dyslipidemia

25

2.2

7

2.1

Ӽ2=0.01 (P=0.94)

Diabetes mellitus

172

15.0

74

22.3

Ӽ2=10.01 (p=0.002)

Respiratory diseases

31

2.7

29

8.7

Ӽ2=24.19 (p<0.001)

Renal diseases

22

1.9

10

3.0

Ӽ2=1.47 (P=0.23)

Hypothyroidism

10

0.9

18

5.4

Ӽ2=28.80 (p<0.001)

Immune suppression

2

0.2

2

0.6

Fisher’s Exact (P=0.22)

Organ transplant

2

0.2

2

0.6

Fisher’s Exact (P=0.22)

Others:

43

3.7

34

10.2

Ӽ2=22.11 (p<0.001)

 

 

Table (3): Frequency of presenting manifestations of male and female hospitalized COVID-19 patients

Manifestations

Males

(n=1150)

Females

(n=332)

Test of significance

( p )

 

No.

%

No.

%

 

General

 

 

 

 

 

Fever

324

28.2

80

24.1

Ӽ2=2.16 (P=0.14)

Headache

43

3.7

16

4.8

Ӽ2=0.79 (P=0.28)

Body aches

114

9.9

4.6

13.9

Ӽ2=4.16 (p=0.04)

Fatigue

16

1.4

7

2.1

Ӽ2=0.87 (p=0.35)

Respiratory

 

 

 

 

 

Cough

372

32.3

122

36.7

Ӽ2=2.24 (p=0.13)

Blocked nose

9

0.8

2

0.6

Fisher’s Exact (P=1.00)

Loss of smell

4

0.3

9

2.7

Fisher’s Exact (P<0.001)

Sore throat

127

11.0

52

15.7

Ӽ2=5.18 (p=0.02)

Chest pain

9

0.8

0

0.0

Fisher’s Exact (P=0.22)

Shortness of breath

130

11.3

24

7.2

Ӽ2=4.60 (p=0.03)

Gastrointestinal

 

 

 

 

 

Loss of taste

8

0.7

7

2.1

Fisher’s Exact (P=0.02)

Nausea

13

1.1

7

2.1

Fisher’s Exact (P=0.18)

Vomiting

16

1.4

6

1.8

Fisher’s Exact (P=0.61)

Diarrhea

34

3.0

15

4.5

Ӽ2=1.97 (p=0.16)

Abdominal pain

4

0.3

3

0.9

Fisher’s Exact (P=0.19)

Others

14

1.2

2

0.6

Fisher’s Exact (P=0.55)

 


 

 

Table 4 presents the investigations and vital signs on admission among the studied case. The mean systolic blood pressure was significantly higher in males (127.8±15.9) than in females (124.1±17.2), (p < 0.001). Diastolic blood pressure showed the same pattern. However, no significant difference between both sexes regarding hypertension. Blood oxygen concentration was significantly lower in males than females. The median value of LDH was significantly higher in males than females (243 versus 217, P =0.04). The median level of ferritin in blood was higher in males than females significantly, p <0.001. However, the median value of lymphocytic level was significantly higher in females than males (2.0 versus 1.7, p < 0.001). Significant higher percentage of males presented with high level of blood creatinine (7%) then females (3.9%), p = 0.04.


 

 

Table (4): Investigations and vital signs on admission among male and female hospitalized COVID-19 patients

Investigations and vital signs

Male

Female

Test of significance ( p )

SBP (mmHg)

 

 

 

Number

1150

332

t = 3.60

Min - Max

72 – 230

90 - 190

P < 0.001

Mean + SD

127.8±15.9

124.1±17.2

 

DBP (mmHg)

 

 

 

Number

1150

332

t = 3.20

Min - Max

38 – 120

52 – 115

P =0.001

Mean + SD

79.3±9.2

77.5±8.5

 

Measuring blood pressure:

 

 

 

 

 

Normal

950

826

280

84.3

Ӽ2=0.55

Hypertension

200

17.4

55

15.7

P=0.46

Heart rate (BPM)

 

 

 

Number

1150

332

t = 0.99

Min - Max

47 – 140

58 – 128

P = 0.33

Mean + SD

85.4±12.7

86.2±12.1

 

Respiratory rate (BPM)

 

 

 

Number

1150

332

t = 1.04

Min - Max

12 – 44

18 – 32

P = 0.30

Mean + SD

21.1±2.4

20.9±1.7

 

SpO2 (%)

 

 

 

Number

1150

332

t = 2.32

Min - Max

71 – 100

92 – 100

P = 0.02

Mean + SD

97.4±2.4

97.7±1.4

 

SpO2 (%) level:

 

 

 

 

 

<90

19

1.7

0

0.0

Ӽ2=7.18

90 -

4

4.2

9

2.7

P=0.03

≥95

1083

94.2

323

97.3

 

D Dimer (ng/mL)

 

 

 

Number

216

46

Mann-Whitney U

Median

274

255

P = 0.67

IQR

270

411

 

CRP (mg/L)

 

 

 

Number

843

162

Mann-Whitney U

Median

8

7

P = 10

IQR

37

15.3

 

LDH (IU/L)

 

 

 

Number

191

42

Mann-Whitney U

Median

243

217

P = 0.04

IQR

185.6

124.2

 

Troponin (ng/L)

 

 

 

Number

76

23

Mann-Whitney U

Median

8

6

P = 0.59

IQR

9.8

12.5

 

Ferritin (ng/mL)

 

 

 

Number

144

49

Mann-Whitney U

Median

561

79.8

P < 0.001

IQR

773.0

334.2

 

Ferritin level:

 

 

 

 

 

Normal

142

98.6

32

65.3

Fisher's Exact

Low

2

1.4

17

34.7

P<0.001

Lymphocytic count

 

 

 

Number

1150

332

Mann-Whitney U

Median

1.70

2.00

P < 0.001

IQR

1.20

1.28

 

Creatinine (µmol/L)

 

 

 

Number

1150

332

Mann-Whitney U

Median

79.00

58.16

P < 0.001

IQR

19.00

14.00

 

Creatinine level:

 

 

 

 

 

Normal

1070

93.0

319

96.1

Ӽ2=4.05

High

80

7.0

13

3.9

P=0.04

Blood sugar (mmol/L)

 

 

 

Number

1150

332

Mann-Whitney U

Median

5.80

5.60

P = 0.07

IQR

2.29

1.85

 

HbA1c (mmol/mol)

 

 

 

Number

76

16

Mann-Whitney U

Median

9.35

8.45

P = 0.31

IQR

4.40

3.77

 

 

 


As shown in table 5, no significant difference between male and females cases regarding COVID-19 complications except for respiratory complications that were more significantly encountered among males than females as acute respiratory failure (p = 0.01), pneumonia (p = 0.03) and ARDS (p 0.03).


 

 

Table (5): Frequency of complications among male and female hospitalized COVID-19 patients

Complications

Males

(n=1150)

Females

(n=332)

Test of significance

( p )

No.

%

No.

%

Respiratory

 

 

 

 

 

Acute respiratory failure

172

15.0

32

9.6

Ӽ2=6.14 (P=0.01)

Pneumonia

52

4.5

6

1.8

Ӽ2=5.05 (P=0.03)

ARDS

52

4.5

6

1.8

Ӽ2=5.042 (P=0.03)

Infection

 

 

 

 

 

Secondary infection

45

3.9

9

2.7

Ӽ2=1.06 (P=0.30)

Sepsis

29

2.5

7

2.1

Ӽ2=0.19 (P=0.67)

Septic shock

19

1.6

3

0.9

Fisher’s Exact (P=0.60)

Others

 

 

 

 

 

Acute kidney injury

44

3.8

7

2.1

Ӽ2=2.29 (P=0.13)

Cardiac

33

2.9

7

2.1

Ӽ2=0.57 (P=0.45)

Neurological

9

0.8

2

0.6

Fisher’s Exact (P=1.00)

DIVC

7

0.6

1

0.3

Fisher’s Exact (P=0.69)

Acute liver injury

7

0.6

1

0.3

Fisher’s Exact (P=0.69)

MSIS

6

0.5

1

0.3

Fisher’s Exact (P=1.00)

Rhabdomyolysis

6

0.5

2

0.6

Fisher’s Exact (P=1.00)

Miscellaneous

20

1.7

3

0.9

Ӽ2=1.18 (P=0.28))

 


 

 

The outcome parameters of admitted cases were presented in table 6. The proportion of cases who were subjected to oxygen therapy was significantly higher in males than females (11.9% versus 7.2%, p = 0.02). Meanwhile, higher proportion of males (26.3%) than females (8.3%) required O2 flow higher than 10L/min, p <0.001. just above one third of male cases stayed in the hospital for less than 5 days, and only 17.8% stayed ≥ 20 days. Contrary, 21.2% of female cases stayed in the hospital for less than 5 days whereas 27.4% stayed for ≥ 20 days. A difference that was statistically significant (p< 0.001) A higher percentage of male cases (9.7%) than females (3.3%) required to be admitted to the ICU significantly, p < 0.001.


 

 

Table (6): Outcome parameters of male and female hospitalized COVID-19 patients

Outcome

Male

Female

Test of significance

( p (

No.

%

No.

%

Oxygen therapy

 

 

 

 

 

No

1013

88.1

308

92.8

Ӽ2 = 5.84

Yes

137

11.9

24

7.2

P = 0.02

Type of oxygen therapy

 

 

 

 

 

Mask

74

54.0

7

29.2

Ӽ2 = 5.05

Nasal

63

46.0

17

70.8

P = 0.03

O2 (L/min)

 

 

 

 

 

1 – 5

75

54.7

20

83.3

Ӽ2 = 6.95

6 – 10

26

19.0

2

8.3

P = 0.03

> 10

36

26.3

2

8.3

 

Median (IQR)

5 (9)

2 (3)

Mann-Whitney U

P = 0.001

Duration of Hospital stay (days)

 

 

 

 

 

< 5

434

37.7

70

21.2

Ӽ2 = 36.45

5 – 9

190

16.5

68

20.5

P < 0.001

10 – 14

154

13.4

53

16.0

 

15 – 19

167

14.5

50

15.1

 

≥ 20

205

17.8

91

27.4

 

Median (IQR)

4 (14)

13 (17)

 

ICU admission

 

 

 

 

 

No

1038

90.3

321

96.7

Ӽ2 = 13.98

Yes

112

9.7

11

3.3

P < 0.001

Duration of ICU stay (days)

 

 

 

 

 

1 – 10

50

44.6

5

45.5

Fisher’s Exact

> 10

62

55.4

6

54.5

P = 1.00

Median (IQR)

12 (15)

12 (14)

Mann-Whitney U

P =0.10

Intensive ventilation

 

 

 

 

 

No

35

31.5

4

36.4

Fisher’s Exact

Yes

76

68.5

7

63.6

P = 0.743

Outcome at discharge

 

 

 

 

 

Recovery

1101

95.7

324

97.6

Ӽ2 = 2.39

Death

49

4.3

8

2.4

P = 0.12

 

 

 


Discussion

 

It is important to reveal the extent to which COVID-19 affects both sexes to elucidate the disease outcome and investigate the prognostic factors for individualized assessment. (11) The available literature dealing with the impact of sex on the outcome and severity of COVID-19 have rarely linked this relationship with the preventive and clinical settings. The current study included 1482 hospitalized COVID-19 patients to study clinical, laboratory and outcome differences between males and females. The overall male/female ratio was 3.46 (1150 males/332 females). This high male/female ratio may have multiple explanations. This may reflect the nature of Kuwait as an attracting country of immigrant workers with a higher proportion of males in the middle age groups. Also, several hospital-based studies revealed an androgen-mediated condition that may have a role in the progression of COVID-19 disease. (17, 18)

The most common perceived manifestations by both males and females were cough (33.3%), fever (27.3%), sore throat (12.1%), body aches (10.8%) and shortness of breath (10.4%). Loss of both smell and taste were significantly more commonly prevalent among females (2.7% and 2.1%) than males (0.3% and 0.7%), while shortness of breath was significantly more common among males (11.3%) than females (7.2%). Also, a significantly higher proportion of females (15.7%) suffered from sore throat than males (11.3%). A retrospective study revealed similar results to the current one regarding loss of taste, smell and sore throat. (19) However, other main manifestations such as cough and fever were more common among males while they did not show any significant difference in the current study. Another study conducted in 2020 revealed that loss of smell and headache were more frequent in female (20) while another study revealed that gastrointestinal manifestations including nausea, vomiting and diarrhea were significantly more frequent in women than men. (21) The differences between these studies might be attributed to both the design and setting of the studies as well as the sex ratio where males were more common in the current study. Also, the dominance of gastrointestinal manifestations differed from one wave of the disease to another. (19)

Laboratory investigations provide valuable information about both the clinical status and severity of hospitalized COVID-19 patients. Consistent with other studies, the current research revealed significant differences among multiple laboratory investigations between males and females. (21, 22) A significantly higher proportion of women (34.77%) were more likely to suffer from low ferritin level than men (1.47%). However, men were more likely to suffer from a low lymphocytic count with a median of 1.7 compared with a median of 2.0 for women. Also, a higher proportion of males (7.0%) suffered from high levels of creatinine than females (3.9%). Lymphopenia and low ferritin levels were also demonstrated among males in other studies. (21, 22) Other laboratory findings such as thrombocytopenia, elevated levels of calcitonin, aspartate and alanine transferase, total bilirubin, C-reactive protein and venous lactate were demonstrated among male hospitalized COVID-19 cases. (22) These findings, on hospital admission, may render males more susceptible for a worse outcome than females.

Results from observational studies revealed that COVID-19 males tended to have a higher risk of both morbidity and mortality impacts. (8, 23, 24) Participants of the current study suffered from multiple complications. The most common ones were the respiratory complications mainly acute respiratory failure (ARF), pneumonia and acute respiratory distress syndrome (ARDS) which all were significantly more frequently encountered among males (15.0%, 4.5%, 4.5% respectively) than females (9.6%, 1.8%, 1.8% respectively). This might be attributed to the higher proportion of smoking among men revealed in this study. Higher smoking rate in males may explain the cause of COVID-19 severity Smoking negatively affects the lung, making the individual susceptible to multiple respiratory system related diseases. Also, smoking was revealed to reduce immunity against viruses causing a high risk of repeated multiple respiratory diseases especially repeated respiratory infections. (25, 26)

This high rate of respiratory complications among males was reflected upon the need to use oxygen therapy as well as its pattern and flow rate. Not only more males (11.9%) tended to use oxygen therapy than females (7.2%) but they used it through nasal masks (54% compared with 29.2%) and at a higher flow rate (26.3% compared with 8.3% at a flow rate more than 10 L/min).

Several studies revealed that more male COVID-19 patients needed admission to the intensive care units. (8, 9, 27, 28) Data from five European countries (France, Italy, Spain, Switzerland, and Germany) highlight this difference, with men 50% more likely to be admitted to ICU than women. (11) The findings of the current study are consistent with these studies, as 9.7% of males needed care in the intensive care units (ICU) compared with only 3.3% of females however. The duration of admission was more or less similar for both sexes. The higher respiratory complications might be behind the high rate of ICU admission among males while the similar duration of care may be attributed to both the pattern and quality of care inside these units. Another factor to be considered is the ratio of males/females of this study (3.46) which reflects a high rate of hospitalization of men than women.

International data from several countries showed a male/female case fatality ratio ranging from 1.6 to 2.8. (29) Data from China, South Korea, Italy, and autopsy findings from Germany have illustrated that males formed 59–75% of COVID-19 deaths. (5, 30 – 32) A large study from the United Kingdom, dealt with more than 17 million COVID-19 patients, identified that males have a 59% increase in risk of death in comparison to females. (31) The current study also revealed a ratio of hospitalized male/female mortality of 1.79 (4.3% compared with 2.4%). However, this difference is not statistically significant. The higher mortality among males of the current study can be attributed to the significantly higher respiratory complications among males. Again, respiratory failure was stated as the main cause of mortality among COVID-19 patients. (33)

In general, sex disparity of COVID-19 mortality can be explained by a both biological (chromosomes, reproductive organs, and related sex hormones) and gender factors (social and cultural behaviors and activities). (11)

Men have higher age-adjusted rates of pre-existing co-morbidities associated with poor COVID-19 prognosis, including hypertension, cardiovascular disease (CVD), and chronic obstructive pulmonary disease (COPD). (9, 24, 28, 34) Even after adjustment for age, the effect of co-morbidities on COVID-19 mortality was greater for men than women. (5) Klein in 2012 reported that after virus infection, females have been observed to mount more robust humoral and adaptive immune responses than males. As a result of heightened immunity to viruses, both the intensity and prevalence of viral infections are often lower for females than males. (7) Other factors that may explain the gender difference in COVID-19 prognosis are the immune suppressive effect of testosterone, the immune enhancing effect of estrogen, (35, 36)

The main limitation of the current study is being hospital based and depending mainly on secondary data (records of hospitalized patients). However, the large number of recruited cases and a selection of the only specialized hospital to deal with COVID-19 cases from all districts of Kuwait can provide both power and advantage for carrying out this study.

 

 

Conclusions

 

This study demonstrates a difference of COVID-19 presentation, severity, and hospitalization, between men and women. Overall, this renders males to be at a higher risk for severe forms of the COVID-19 disease especially with regard to respiratory complications. Hospital physicians should be aware of these differences to guide the diagnosis and subsequent management decisions. These results would help in developing specific and effective management strategies.

 

 

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Cite this Article: Al-Zuabi, H; Kamel, MI; El-Shazly, MK; Al-Kandari, W; Mandani, G; Hamadah, G; Nasser, AH (2022). Gender differences among hospitalized COVID-19 patients. Greener Journal of Medical Sciences, 12(1): 161-171.