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Research Article
Luisa Imberti
ASST Spedali Civili di Brescia: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2075-8391
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Coronavirus Disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.
Methods: Demographic, clinical and laboratory data were collected in 1,000 COVID-19 patients (367 females and 633 males), 500 hospitalized in the first wave and 500 in the second one, at the ASST Spedali Civili of Brescia from March to December 2020. Statistical analyses have been employed to compare data obtained in females and males, taking into account their age, and during the first and second COVID-19 waves.
Results: The mean age at the time of hospitalization was similar in females and males but was significantly higher for both in the second wave; the time elapsed from symptoms onset to hospital admission did not differ between sexes in the two waves and no correlation was observed between delayed hospital admission and length of hospitalization. The number of multi-symptomatic males was higher than that of females and patients with a higher number of comorbidities were more frequently admitted to intensive care unit (ICU) and more frequently died. Older males remained in ICU longer than females and showed a longer disease duration, mainly the first wave. The highest levels of white blood cells, neutrophils, C-reactive protein and fibrinogen were significantly higher in males and in the first, and along with higher levels of D-dimer, ferritin, lactate dehydrogenase and procalcitonin which were preferentially documented in patients requiring ICU or died. While the ICU death rate was higher in males, the overall death rate did not differ between the sexes; however, the deceased women were older.
Conclusions: These data indicate that once patients were hospitalized, the risk of dying was similar between females and males. Therefore, future studies should aim at understanding the reasons why, for a given number of SARS-CoV-2 infection, less females develop the disease requiring hospitalization.
Keywords
COVID-19, sex-related differences, pandemic wave(s), Intensive care unit (ICU), SARS-CoV-2
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryTable1.xlsx
Supplementary Table 1.xls Symptoms reported by COVID-19 patients at the hospital admission. Row numbers (percentages) and statistical significance, indicated as effect size (Chi square) and P value, are reported. Grey boxes indicate higher values for females rather than males, while bold numbers indicate higher values for males rather than females; the underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The three columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. aThe mean number (standard deviation) of COVID-19-related symptoms is reported and statistical significance is indicated as effect size (t test) and P value. The normal distribution of this variable was tested using the Kolmogorov-Smirnov test (d=0.058 and d=0.17 for Age and Total number of symptoms, respectively, meaning data normally distributed).
- SupplementaryTable2.xlsx
Supplementary Table 2.xls Comorbidities affecting hospitalized COVID-19 patients. Row numbers (percentages) and statistical significance, indicated as effect size (Chi square) and P value, are reported. Grey boxes indicate the higher values in the first wave, while bold numbers indicate the higher values in the second wave; the underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The three columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. aThe number of comorbidities is reported as mean (standard deviation) and the statistical significance is indicated as effect size (t test) and P value. The normal distribution of this variable was tested using the Kolmogorov-Smirnov test. COPD: chronic obstructive pulmonary disease, HIV: human immunodeficiency virus
- SupplementaryTable3.xlsx
Supplementary Table 3.xls Complications occurring to COVID-19 patients during hospitalization. Row numbers (percentages) and statistical significance, indicated as effect size (Chi square) and P value, are reported. The underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The three columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. aThe mean number (standard deviation) of complications is reported; statistical significance is indicated by effect size (t test) and P value. The normal distribution of this variable was tested using the Kolmogorov-Smirnov test. bLaboratory findings not specifically associated with systemic inflammation and infections.
- SupplementaryTable4.xlsx
Supplementary Table 4.xls Laboratory parameters of female and male COVID-19 patients who were hospitalized during the first and second pandemic waves. Grey boxes indicate higher values for females rather than males, while bold numbers indicate higher values for males rather than females; the underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. Statistical significance is reported as effect size (F; ANOVA) and P value. ALT: alanine aminotransferase, AST: aspartate aminotransferase, CRP: high-sensitivity C-reactive protein, LDH: lactate dehydrogenase, WBC: white blood cells
- SupplementaryTable5.xlsx
Supplementary Table 5.xls Laboratory parameters of patients who were admitted to ICU and who recovered or deceased. Statistical significance is reported as effect size (t test) and P value. Grey boxes indicate higher values for patients who were not admitted to ICU (No ICU) rather than those who required ICU, while bold numbers indicate higher values for patients admitted to ICU rather than those who did not require ICU; the underlined numbers indicate the higher values observed in patients who survived (Alive), while those in italic indicate the higher values observed in deceased patients. ALT: alanine aminotransferase, AST: aspartate aminotransferase, CRP: high-sensitivity C-reactive protein, ICU: intensive care unit, LDH: lactate dehydrogenase, WBC: white blood cells.
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View the published article at Biology of Sex Differences.
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See the published version of this preprint at Biology of Sex Differences.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Luisa Imberti
ASST Spedali Civili di Brescia: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2075-8391
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Biology of Sex Differences.
Version 1
Posted 07 Jun, 2021
No community comments so far
Editorial decision: Minor Revision
On 04 Jun, 2021
Reviewer #2 agreed
On 21 May, 2021
Reviews received
Received 20 May, 2021
Reviewer #1 agreed
On 19 May, 2021
Reviewers invited
Invitations sent on 19 May, 2021
First submitted
On 19 May, 2021
Editor assigned
On 18 May, 2021
Submission checks complete
On 18 May, 2021
Editor invited
On 18 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Biology of Sex Differences.
Background: Coronavirus Disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.
Methods: Demographic, clinical and laboratory data were collected in 1,000 COVID-19 patients (367 females and 633 males), 500 hospitalized in the first wave and 500 in the second one, at the ASST Spedali Civili of Brescia from March to December 2020. Statistical analyses have been employed to compare data obtained in females and males, taking into account their age, and during the first and second COVID-19 waves.
Results: The mean age at the time of hospitalization was similar in females and males but was significantly higher for both in the second wave; the time elapsed from symptoms onset to hospital admission did not differ between sexes in the two waves and no correlation was observed between delayed hospital admission and length of hospitalization. The number of multi-symptomatic males was higher than that of females and patients with a higher number of comorbidities were more frequently admitted to intensive care unit (ICU) and more frequently died. Older males remained in ICU longer than females and showed a longer disease duration, mainly the first wave. The highest levels of white blood cells, neutrophils, C-reactive protein and fibrinogen were significantly higher in males and in the first, and along with higher levels of D-dimer, ferritin, lactate dehydrogenase and procalcitonin which were preferentially documented in patients requiring ICU or died. While the ICU death rate was higher in males, the overall death rate did not differ between the sexes; however, the deceased women were older.
Conclusions: These data indicate that once patients were hospitalized, the risk of dying was similar between females and males. Therefore, future studies should aim at understanding the reasons why, for a given number of SARS-CoV-2 infection, less females develop the disease requiring hospitalization.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryTable1.xlsx
Supplementary Table 1.xls Symptoms reported by COVID-19 patients at the hospital admission. Row numbers (percentages) and statistical significance, indicated as effect size (Chi square) and P value, are reported. Grey boxes indicate higher values for females rather than males, while bold numbers indicate higher values for males rather than females; the underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The three columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. aThe mean number (standard deviation) of COVID-19-related symptoms is reported and statistical significance is indicated as effect size (t test) and P value. The normal distribution of this variable was tested using the Kolmogorov-Smirnov test (d=0.058 and d=0.17 for Age and Total number of symptoms, respectively, meaning data normally distributed).
- SupplementaryTable2.xlsx
Supplementary Table 2.xls Comorbidities affecting hospitalized COVID-19 patients. Row numbers (percentages) and statistical significance, indicated as effect size (Chi square) and P value, are reported. Grey boxes indicate the higher values in the first wave, while bold numbers indicate the higher values in the second wave; the underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The three columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. aThe number of comorbidities is reported as mean (standard deviation) and the statistical significance is indicated as effect size (t test) and P value. The normal distribution of this variable was tested using the Kolmogorov-Smirnov test. COPD: chronic obstructive pulmonary disease, HIV: human immunodeficiency virus
- SupplementaryTable3.xlsx
Supplementary Table 3.xls Complications occurring to COVID-19 patients during hospitalization. Row numbers (percentages) and statistical significance, indicated as effect size (Chi square) and P value, are reported. The underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The three columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. aThe mean number (standard deviation) of complications is reported; statistical significance is indicated by effect size (t test) and P value. The normal distribution of this variable was tested using the Kolmogorov-Smirnov test. bLaboratory findings not specifically associated with systemic inflammation and infections.
- SupplementaryTable4.xlsx
Supplementary Table 4.xls Laboratory parameters of female and male COVID-19 patients who were hospitalized during the first and second pandemic waves. Grey boxes indicate higher values for females rather than males, while bold numbers indicate higher values for males rather than females; the underlined numbers indicate the higher values observed in the first wave, while those in italic indicate the higher values observed in the second wave. The columns at the right-hand side report the results of logistic regressions using Sex and Wave as predictors and Age as covariate of no interest. Statistical significance is reported as effect size (F; ANOVA) and P value. ALT: alanine aminotransferase, AST: aspartate aminotransferase, CRP: high-sensitivity C-reactive protein, LDH: lactate dehydrogenase, WBC: white blood cells
- SupplementaryTable5.xlsx
Supplementary Table 5.xls Laboratory parameters of patients who were admitted to ICU and who recovered or deceased. Statistical significance is reported as effect size (t test) and P value. Grey boxes indicate higher values for patients who were not admitted to ICU (No ICU) rather than those who required ICU, while bold numbers indicate higher values for patients admitted to ICU rather than those who did not require ICU; the underlined numbers indicate the higher values observed in patients who survived (Alive), while those in italic indicate the higher values observed in deceased patients. ALT: alanine aminotransferase, AST: aspartate aminotransferase, CRP: high-sensitivity C-reactive protein, ICU: intensive care unit, LDH: lactate dehydrogenase, WBC: white blood cells.
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