August 9, 2022

To: Dr. Samantha Triplett, Pharm.D.

From: Kelsi Brunke, Pharm.D. Candidate 2023
CC: Dr. Genevieve Engle, Pharm.D.
Re: COVID-19 differences between the sexes
___________________________________________________________________________

In response to your request regarding any differences in the prevalence/incidence and

the presentation/severity of COVID-19 between males and females the following
information is provided.

Response and Recommendation:

There is literature that suggests males have an increased incidence of severe health
outcomes than females in regards to COVID-19.1,2,3,4 Males with COVID-19 infection
may have higher rates of hospitalization, more ICU admissions, higher mortality rates,
and an increased need for mechanical ventilation compared to females. The CDC
reports an increased number of deaths due to COVID-19 in males from January 1, 2020
to July 23, 2022 in comparison to females.5

In general, the literature suggests that the incidence of COVID-19 is most prevalent in
the male population. However, the CDC reports a higher incidence of COVID-19 cases
in the female population.6

Analysis and Synthesis:

In a retrospective study by Gomez et al, investigators compared hospitalization rates,
admissions to the ICU, vasopressor use, intubation, and mortality in adult females and
males with confirmed COVID-19 infections.1 The study was conducted from March 1,
2020 to June 21, 2020 and utilized data from the Rush University System for Health in
Illinois to detect sex differences when comparing complications of COVID-19.
Participants were ≥18 years old with confirmed COVID-19 by a PCR test or a
point-of-care rapid test. Participants were characterized by sex and demographics were
collected for patients positive for COVID-19 and those who were hospitalized. The
presentation of COVID-19 was similar between both female and male participants
consisting of cough and shortness of breath. Male participants (n=3808) had a higher
incidence of fever (defined as >38℃), while females (n=4300) had a higher incidence of
diarrhea, vomiting, and myalgia. In this study, more males were admitted to the hospital
(19% vs. 13%, p<0.001), transferred to the ICU (8% vs. 4%, p<0.001), and had a higher
incidence of death (2% vs. 1%, p=0.003) compared to females. Males also required
more intubation (5% vs. 2%, p<0.001) and vasopressor support (4% vs. 2%, p<0.001),
compared to females. Additionally, the incidence of COVID-19 was higher in the male
population, of the total 38,763 patients screened for COVID-19, 22.8% of males and
19.4% of females were positive for COVID-19 infection (p<0.001).

In Nguyen, et al, the demographics of positive COVID-19 infected patients, length of

hospital stay, number of patients requiring mechanical ventilation, and the mortality rate
of hospitalized patients was assessed.2 The study was conducted from March 1, 2020
through November 30, 2022 and utilized the Vizient clinical database to explore the
discharge records of adults with a COVID-19 diagnosis. The study consisted of 161,206
males and 146,804 females. Males had a higher rate of in-hospital mortality (13.8% vs.
10.2%, p<0.001), higher rate of intubation (21.4% vs. 14.6%, p<0.001), and longer
hospital stays (9.5 ± 12.5 days vs. 7.8 ± 9.8 days, p<0.001) compared to females. In
addition, males had higher mortality rates across all age groups compared to females,
with the highest mortality rate in the ≥85 age group (29.4% vs 21.3%, p<0.001).

In Vahidy FS, et al, the incidence of COVID-19 in males vs females and their health
outcomes, including the length of hospital stay, the need for mechanical ventilation, and
in-hospital mortality rates was assessed.3 Researchers utilized the Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE) guidelines and
conducted a cross–sectional analysis utilizing the Houston Methodist COVID-19
Surveillance and Outcomes Registry, including 8 hospitals in the Houston area. The
investigators gathered data from adults who tested between March 6 to August 22,
2020 for COVID-19 via PCR tests and were admitted to any of the 8 hospitals in
Houston during the same time frame. Results indicated that of the 96,473
patients,15.6% tested positive for COVID-19. Males (n=6,629) had a higher rate of
COVID-19 infection (17.0% vs. 14.6%, OR 1.39, 95% CI (1.33 to 1.45) and higher
hospitalization rates (51.1% vs. 48.9%, p<0.001) compared to females (n=8,393). Males
also had a longer hospital stay compared to females (median of 5 days compared to
median of 4 days, respectively, p<0.001). Additionally, male participants required
mechanical ventilation more than the female participants, (19% vs. 14.7% respectively,
p<0.001).

In Sundaram SS, et al, the demographics of positive COVID-19 patients were assessed
to determine if mortality rate, the incidence of acute respiratory distress syndrome
(ARDS) or sepsis, and the use of mechanical ventilation varied between males and
females.4 The study was conducted from December 1, 2019 through November 30,
2020 and utilized data from the Cerner EHR, which included 87 hospitals. Of the
100,902 study population, 50.7% of participants were female. During the study, a total of
8,574 patients died, of which 58.2% were male and 41.3% were female. Additionally,
males were found to have an increased risk of ARDS compared to females (5.08% vs.
3.15% respectively, p<0.00001) and sepsis (18.52% vs. 13.54% respectively,
p<0.00001). As for the requirement of mechanical ventilation, rates were similar
between sexes but the p value suggests there is a statistically significant difference,
males (3.36%) and females (2.94%), p=0.00001.

According to the CDC, from the time period of January 1, 2020 to July 23, 2022, there
have been a total of 4,510,396 male and 4,059,787 female deaths of all ages
associated with COVID-19.5 Males have an increased incidence of mortality associated
with COVID-19 compared to females. Despite the higher mortality rates in men, the
CDC reports that as of August 3, 2022, females have a higher incidence of COVID-19
infections compared to male patients (53.5% vs. 46.5% respectively).6

Therefore, the incidence of COVID-19 infection may not be associated with male or
female sex, as described above. Despite the literature associating higher mortality rates
with males, other confounding factors can be contributing to the mortality rates and that
statement cannot be inferred.

Medline was searched for literature using the following search terms:
● “sex differences” AND (MH “COVID-19”) - 276 results
● “males” AND “females” AND (MH “COVID-19”) - 33,361 results
Thank you for contacting the Christy Houston Foundation Drug Information Center at
the Belmont University College of Pharmacy. Please do not hesitate to contact the Drug
Information Center at 615-460-8382 or druginfo@belmont.edu with any additional
questions.

References:
1. Gomez JM, Du-Fay-de-Lavallaz JM, Fugar S, et al. Sex differences in COVID-19
hospitalization and mortality. J Women’s Health. 2021;30(5):646-653.
doi:10.1089/jwh.2020.8948
2. Nguyen NT, Chinn J, De Ferrante M, Kirby KA, Hohmann SF, Amin A. Male
gender is a predictor of higher mortality in hospitalized adults with COVID-19.
Plos ONE. 2021;16(7):1-6. doi:10.1371/journal.pone.0254066
3. Vahidy FS, Pan AP, Ahnstedt H, et al. Sex differences in susceptibility, severity,
and outcomes of coronavirus disease 2019: cross sectional analysis from a
diverse US metropolitan area. Plos ONE. 2021;16(1):1-14.
doi:10.1371/journal.pone.0245556
4. Sundaram SS, Melquist S, Kalgotra P, et al. Impact of age, sex, race, and
regionality on major clinical outcomes of COVID-19 in hospitalized patients in the
United States. BMC Infect Dis. 2022;22(1):659-669.
doi:10.1186/s12879-022-07611-z
5. Provisional COVID-19 deaths by sex and age. Centers for Disease Control and
Prevention. Updated July 27, 2022. Accessed August 3, 2022.
https://data.cdc.gov/widgets/9bhg-hcku?mobile_redirect=true
6. Demographic trends of COVID-19 cases and deaths in the US reported to CDC.
Centers for Disease Control and Prevention. Updated August 3, 2022. Accessed
August 3, 2022. https://covid.cdc.gov/covid-data-tracker/#demographics