Men Report Worse Respiratory, Inflammatory Status with SARS-CoV-2 than Women

Johns Hopkins data suggest men are being hospitalized more frequently with infection, and are facing more severe outcomes.

Women with SARS-CoV-2 infection are less likely to be admitted to the hospital than men, and instances when they are admitted, they present with lower mean parameters of respiratory and inflammatory burden driven by COVID-19, according to new research.

In data presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2021 virtual sessions this week, a team of Johns Hopkins University investigators reported discernable differences in severe COVID-19 among men and women, and at varied ages.

The findings could indicate the means by which clinicians may be able to monitor suspected SARS-CoV-2 and an individual’s risk to severe disease progression.

As author Eileen P. Scully, MD, PhD, said in her presentation, early pandemic data suggested a bias in male mortality risk. Up until February 2021, males have comprised less than half (49%) of all SARS-CoV-2 diagnoses, but have comprised 57% of all deaths, based on data from 132 countries.

Whether this is due fully or partially to factors including sex-differentiated care-seeking tendencies, health status, illness presentation, comorbidities, or treatment responses is still not understood at 12 months of the pandemic.

“The mechanisms for this effect have not yet been defined, and may potentially offer therapeutic targets for intervention,” Scully said.

Scully and colleagues assessed data from the Johns Hopkins Medicine (JHM) five hospital system for SARS-CoV-2 test positivity and admission rates from March – October 2020. They used the JHM COVID-19 registry, JH-CROWN, to extract detailed patient-level data, which was analyzed for male-female differences through descriptive statistics.

From the observed 213,175 tests, 57% were conducted in females; they reported a similar SARS-CoV-2 positivity rate (8.2%) as males (8.9%). However, males were more likely to become hospitalized after SARS-CoV-2 confirmation (33% vs 28%).

Among the 2608 hospitalized patients with SARS-CoV-2, more males reported fever; females more frequently reported headaches, loss of smell, and vomiting (P <.05).

Regarding respiratory metrics, females had more favorable profiles on average, with lower respiratory rates and greater SpO2:FiO2 ratios than men (P <.001).

Females reported lower IL-6, ferritin, CRP, higher absolute lymphocyte count, and lower neutrophil:lymphocyte ratios in females at admission and peak lab values.

Comorbidity burden, per Charlson scores, were similar across genders, but specifically different: females had greater rates of obesity and asthma (P <.001). Heart disease (P = .06), complicated hypertension (P <.01), chronic kidney disease, smoking, and alcohol use (P <.001) were all greater among males.

Medication prescribed to combat SARS-CoV-2 was similarly frequent among men and women, though tocilizumab was prescribed more frequently to men.

Overall, men had a greater incidence of severe disease and death outcomes across all observed age groups (36%) than women (36%; P <.001). The gender outcome difference was most significant among patients in the age 18-49 years group, where it was more than two-fold for men (25% vs 11%; P <.001).

Despite greater rates of obesity and asthma among hospitalized SARS-CoV-2 patients, females were less frequently hospitalized due to the virus than men, and had less frequent severe outcomes, and presented with less severe respiratory and inflammatory parameters.

The findings highlight features of severe SARS-CoV-2 risk differences among men and women, and provide guidance closer to individualized risk reduction.

Despite an excess of obesity, females had a lower severity of respiratory parameters and lower inflammatory markers on presentation and had a lower frequency of severe outcomes from SARS-CoV-2 infection. Sex and age interactions with severe disease highlight critical risk features unique to males and females.

“Taken together, these data suggest that sex differences in the inflammatory response to SARS-CoV-2 infection and subsequent clinical presentations are the mediators of the differences we see in outcomes of males and females, and suggest that we should focus attention on the immune response after we encounter this virus.”