Gender differences among hospitalized COVID-19 patients

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By Al-Zuabi, H; Kamel, MI; El-Shazly, MK; Al-Kandari, W; Mandani, G; Hamadah, G; Nasser, AH (2022). Greener Journal of Medical Sciences, 12(1): 161-171.

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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 differences 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

Table 4: continues

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.

CONCLUSION

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.

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