Gender Differences in Patients With COVID-19: Focus on Severity and Mortality.
Journal: 2020/May - Frontiers in Public Health
ISSN: 2296-2565
Abstract:
Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.
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Front Public Health 8: 152

Gender Differences in Patients With COVID-19: Focus on Severity and Mortality

Patients and Data Sources

Cases Series of COVID-19

The case series analysis covers 43 patients with COVID-19 who were treated at Wuhan Union Hospital by the medical team of Beijing Tongren Hospital from January 29, 2020 to February 15, 2020.

Public Data Set of COVID-19

The public data set covers the first 37 cases of patients who died from COVID-19 and 1,019-cases of COVID-19 survivors from the public data set from the Chinese Public Health Science Data Center.

Cases Series of SARS

This study also included data of 524 SARS patients, including 139 deaths from 29 hospitals in early 2003. These patients were hospitalized in Beijing between 25 March and 22 May 2003.

Diagnosis and clinical classification criteria and treatment plan (trial version 5) of COVID-19 was launched by the National Health Committee of the People's Republic of China (http://www.nhc.gov.cn/). The clinical classification of severity is as follows: (1) Mild, only mild symptoms, imaging shows no pneumonia; (2) Moderate, with fever, respiratory tract symptoms, and imaging shows pneumonia; (3) Severe, meet any of the following signs: (a) respiratory distress, respiratory rate ≥ 30 beats / min; (b) in the resting state, finger oxygen saturation ≤ 93%) arterial blood oxygen partial pressure (PaO2/oxygen concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa); (4) Critical, one of the following conditions: (a) respiratory failure occurs and requires mechanical ventilation, (b) Shock occurs, (c) ICU admission is required for combined organ failure.

The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University.

Cases Series of COVID-19

The case series analysis covers 43 patients with COVID-19 who were treated at Wuhan Union Hospital by the medical team of Beijing Tongren Hospital from January 29, 2020 to February 15, 2020.

Public Data Set of COVID-19

The public data set covers the first 37 cases of patients who died from COVID-19 and 1,019-cases of COVID-19 survivors from the public data set from the Chinese Public Health Science Data Center.

Cases Series of SARS

This study also included data of 524 SARS patients, including 139 deaths from 29 hospitals in early 2003. These patients were hospitalized in Beijing between 25 March and 22 May 2003.

Diagnosis and clinical classification criteria and treatment plan (trial version 5) of COVID-19 was launched by the National Health Committee of the People's Republic of China (http://www.nhc.gov.cn/). The clinical classification of severity is as follows: (1) Mild, only mild symptoms, imaging shows no pneumonia; (2) Moderate, with fever, respiratory tract symptoms, and imaging shows pneumonia; (3) Severe, meet any of the following signs: (a) respiratory distress, respiratory rate ≥ 30 beats / min; (b) in the resting state, finger oxygen saturation ≤ 93%) arterial blood oxygen partial pressure (PaO2/oxygen concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa); (4) Critical, one of the following conditions: (a) respiratory failure occurs and requires mechanical ventilation, (b) Shock occurs, (c) ICU admission is required for combined organ failure.

The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University.

Statistical Analysis

Data were expressed as mean ± SD, median [interquartile range (IQR)], or percentages, as appropriate. To compare the differences between the two groups, mean values and percentages were used between the two groups by the Student t-test, Mann-Whitney U-test, or chi-square (χ) test. Kaplan–Meier survival curves and the log-rank test was used for testing the survival rates between males and females. Statistical analyses were performed using the SAS software (version 9.4). P < 0.05 (two-tailed) was considered to be statistically significant.

Case Series of Covid-19

The demographic and clinical characteristics are shown in Table 1. The median age was 62 years (IQR, 51 to 70). Fever (95.3%) and cough (65.1%) were the most common symptoms, while diarrhea (16.3) was not common. 37.2% of patients had at least one underlying disorder (i.e., hypertension, diabetes, cardiovascular diseases, and chronic lung diseases). There is no significant difference in median age between male and female groups, but the maximum of the range of IQR is lower in male (66 years in men vs. 73 years in women). Symptoms and comorbidities were comparable between men and women. As expected, men had a higher level of hemoglobin. However, male patients also had elevated serum creatinine, white blood cells, and neutrophils. Among the 43-case series, 13 (30.2%) were diagnosed with Mild or Moderate pneumonia, while 14 (32.6%) and 16 (37.2%) were diagnosed with Severe and Critical pneumonia, respectively. Chi-square (χ) test for trend indicated that men's cases of COVID-19 tended to be more serious than women's (P = 0.035), according to the clinical classification of severity (Figure 1).

Table 1

Characteristics of a Case series of COVID-19.

Total (n = 43)Male (n = 22)Female (n = 21)P-value
Age, median (range) – year62 (51–70)59 (51–66)63 (52–73)0.734
Symptoms
Fever – n (%)41 (95.3)21 (95.5)20 (95.2)0.490
Diarrhea – n (%)7 (16.3)3 (13.6)4 (19.0)0.946
Cough – n (%)28 (65.1)16 (72.7)12 (57.1)0.452
Comorbidities –n(%)
Hypertension – n (%)10 (23.3)6 (27.3)4 (19.0)0.782
Diabetes history – n (%)5 (11.6)4 (18.2)1 (0.5)0.370
Cardiovascular diseases – n (%)4 (9.3)2 (9.1)2 (10.0)0.634
Chronic lung diseases – n (%)1 (0.2)1 (0.5)0 (0)0.981
From symptom to diagnosis, median (range) – day12 (8–14)12 (7–13)12 (10–14)0.250
Aspartate aminotransferase – IU/l42.4 ± 18.943.0 ± 15.341.7 ± 22.60.872
Alanine aminotransferase – IU/l42.8 ± 19.045.0 ± 18.040.4 ± 19.50.590
Alkaline phosphatase – IU/l53.4 ± 10.652.6 ± 11.954.3 ± 9.00.736
Lactate dehydrogenase – IU/l369.4 ± 132.7414.8 ± 136.2321.8 ± 112.90.064
Serum creatinine – μmol/l75.3±21.190.4±22.259.4±10.90.000
Fasting Blood Glucose – mmol/l7.3 ± 1.87.7 ± 2.06.7 ± 1.50.325
High sensitive C-reactive protein – mg/l52.3 ± 27.858.9 ± 29.245.6 ± 25.30.323
White blood cells – ×10/l6.8±2.27.7±2.35.8±1.50.027
Hemoglobin – g/l128.8 ± 13.6139.0 ± 11.2117.6 ± 8.60.000
Platelets – ×10/l225.2 ± 57.4230.4 ± 54.1219.6 ± 60.00.682
Neutrophils – ×10/l5.4±2.26.4±2.44.3±1.30.019
Lymphocytes – ×10/l1.0 ± 0.40.9 ± 0.31.1 ± 0.40.284

Data are presented as mean ± SD, medians (interquartile ranges, IQR) and no. (%). Bold values mean statistic difference between males and females.

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Object name is fpubh-08-00152-g0001.jpg

Trend data of clinical classification of severity in a Case series of COVID-19. Numbers of cases of men or women in different clinical classes of severity. Chi-square (χ) test for trend indicated that males tend to experience more serious cases of COVID-19 than females according to the clinical classification of severity including Mild+Moderate, Severe, and Critical.

Public Data Set of COVID-19

In the deceased patients, fever (86.5%) and cough (67.6%) were common, while diarrhea was uncommon (18.9%).The median period from symptom onset to death was 13 days (ranging of IQR 11 to 18 days). Of these deceased patients, 64.9% had at least one underlying disorder (i.e., hypertension, diabetes, cardiovascular disease, or chronic obstructive pulmonary disease) (Table 2).

Table 2

Characteristics of a Public data set of COVID-19 and a Cases series of SARS, in 2003.

COVID-19SARS
Deceased (n = 37)Survived (n = 1019)Deceased (n = 139)Survived (n = 385)
Age, median (range) – year70 (65–81)**47 (35–57)57 (45–69)††32 (24–44)
Male – n (%)26 (70.3)*510 (50.0)74 (53.2)163 (42.3)
Symptoms
Fever – n (%)32 (86.5)136 (97.8)379 (98.4)
Diarrhea – n (%)7 (18.9)30 (21.6)26 (6.8)
Cough – n (%)25 (67.6)107 (77.0)185 (48.1)
Comorbidities – n (%)24 (64.9)79 (56.8)††69 (17.9)
Hypertension – n (%)18 (48.6)64 (46.0)††44 (11.4)
Diabetes history – n (%)11(29.7)30 (21.6)††15 (3.9)
Cardiovascular disease – n (%)8 (21.6)40 (28.8)††23 (6.0)
Chronic lung disease – n (%)3 (8.1)5 (3.6)6 (1. 6)
From onset to death, median (range) – day13 (11–18)15 (10–19)

Data are presented as medians (interquartile ranges, IQR) and n (%).

p < 0.05,
p < 0.01, vs. COVID-19 survived patients.
p < 0.05,
p < 0.01, vs. SARS survived patients.

The deceased patients were significantly older [median (IQR), 70.3 (65–81) years] and had a higher percentage of ≥65 years (83.8%), in comparison to those who survived [47 (35–57) years old and 13.2% ≥65 years]. COVID-19 was diagnosed at all ages. There were 30 (2.9%) pediatric patients (<14 years) in the group of patients who survived. None of the 37 deceased cases were pediatric patients (Table 2 and Figure 2A). Ages were comparable between men and women in both patients who deceased and survived (Figure 2B). Of the 37 deceased patients, 70.3% were men and 29.7% were woman. The number of men was 2.4 times that of women in the deceased patients. While men and women had the same susceptibility, men were more prone to dying (χ test, P = 0.016) (Figure 2C).

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Object name is fpubh-08-00152-g0002.jpg

Role of age and gender in morbidity and mortality in a Public data set of COVID-19. (A) The whole spectrum of age in patients who died from and survived COVID. (B) Comparation of age between males and females in both patients who died from and survived COVID. (C) Gender distribution in both patients who died from and survived COVID.

Cases Series of SARS, in 2003

Between March 25 and May 22, 2003, a total of 524 SARS patients, including 139 deaths, in the Beijing area were reported from 29 hospitals enrolled in our analysis. Fever (98.4%) and cough (76.9%) were the most common symptoms, while diarrhea (6.7%) was not common. 57.0% of the patients had at least one of the concomitant diseases including hypertension, diabetes, cardiovascular diseases, and chronic lung diseases. The mean duration from self-reported symptoms to death was 15 (IQR: 10–19) days. Table 2 summarizes the clinical and biochemical characteristics of all SARS patients. The median age of the deceased patients was much higher than that of the patients who survived (57 vs. 32, P < 0.001). The rate of the concomitant diseases in the deceased patients was also higher than that of the patients who survived (57.0% vs. 17.9%, P < 0.001). While the deceased patients were significantly older than the patients who survived (Figure 3A), ages were comparable between men and women in both patients who deceased and survived with SARS (Figure 3B). The proportion of men was higher in the deceased group (53.2%) than in the group who survived (42.3%) (χ test, P = 0.027) (Figure 3C). Survival analysis showed that men had a significantly higher mortality rate than women (31.2 vs. 22.6%) in this hospital-based cohort (hazard ratio [95% CI] 1.47 [1.05–2.06], P = 0.026) (Figure 3D).

An external file that holds a picture, illustration, etc.
Object name is fpubh-08-00152-g0003.jpg

Role of age and gender in morbidity and mortality in a Cases series of SARS, in 2003. (A) The whole spectrum of age in patients who died from and survived SARS. (B) Comparation of age between males and females in both patients who died from and survived SARS. (C) Gender distribution in both patients who died from and survived SARS. (D) Survival analysis comparing mortality rates between male and female patients with SARS.

Department of Respiratory and Critical Care Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Department of Internal Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Department of Critical Care Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Department of Otolaryngology and Head Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Department of Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Edited by: Zisis Kozlakidis, International Agency for Research on Cancer (IARC), France
Reviewed by: Javier Carbajo-Lozoya, Technical University of Munich, Germany; Yunchang Shao, China National GeneBank (BGI), China
*Correspondence: Jin-Kui Yang nc.ude.umcc@gnaykj
Shi Liu moc.qq@6929105541
This article was submitted to Infectious Diseases - Surveillance, Prevention and Treatment, a section of the journal Frontiers in Public Health
Edited by: Zisis Kozlakidis, International Agency for Research on Cancer (IARC), France
Reviewed by: Javier Carbajo-Lozoya, Technical University of Munich, Germany; Yunchang Shao, China National GeneBank (BGI), China
Received 2020 Mar 23; Accepted 2020 Apr 9.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS.

Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003.

Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015).

Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

Keywords: SARS-CoV-2, COVID-19, SARS, morbidity, mortality, gender, male, female
Abstract

Acknowledgments

We thank all patients involved in the study. This manuscript has been released as a pre-print at https://www.medrxiv.org/content/10.1101/2020.02.23.20026864v2 (14).

Acknowledgments

Footnotes

Funding. This study was funded by the National Key R&amp;D Program of China (2017YFC0909600), High-level Talent Training Foundation of Beijing Health System (2014–3-011), and Beijing Talent Training Foundation (No. 2009D003003000002).

Footnotes

References

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