Association between sex and SARS-CoV-2 infection and hospitalisation as a result of COVID-19.

We read with interest the Comment by Mario Fernando and colleagues entitled “Are women with asthma at increased risk for severe COVID-19?”. On the basis of an analysis of published data,2, 3, 4 the authors suggest that a higher proportion of asthmatic women would be admitted to hospital for COVID-19 than asthmatic men. The authors then speculate that Th1 immunological skewness, a predisposition towards more severe asthma, structural lung parenchymal differences, and hormonal differences might increase the susceptibility of asthmatic women to severe COVID-19, and in turn hospitalisation. However, after carefully reviewing this Comment and the cited studies, we would like to temper the authors' conclusion and report our findings on a large nation-wide database, which do not support this hypothesis.

Briefly, we analysed data from 214 031 asthmatic adult patients (52·2% women) from the Israel Clalit Health Services. As previously reported in other studies,5, 6 the analysis of this database confirmed that age, lower socioeconomic class, and comorbidities, such as diabetes, hypertension, obesity, and ischaemic heart disease, were all independent risk factors for hospitalisation as a result of COVID-19. When compared with asthmatic men, asthmatic women were significantly older, they presented with higher prevalence of comorbidities, such as diabetes and hypertension, and they had higher body-mass index (BMI) (27·34 kg/m2 vs 25·94 kg/m2). Although no significant difference in the cumulative proportion of positive PCR for SARS-CoV-2 between asthmatic women and men was found (4·7% vs 4·5%; p=0·089), the cumulative proportion of hospitalisation was uncommon but slightly higher in women than in men (0·6% vs 0·4%; p<0·001; crude hazard ratio [HR] 1·39, 95% CI 1·23–1·57). However, a multivariable Cox proportional hazard-regression model revealed that female sex was not an independent risk for hospitalisation as a result of COVID-19 after adjusting only for comorbidities found to be more common in women (hypertension, diabetes, and BMI; HR 1·06, 95% CI 0·94–1·21). Similar findings were observed with more extensive adjustment for age, sex, ethnicity, socioeconomic status, smoking, BMI, diabetes, hypertension, and ischaemic heart disease; compared with asthmatic men, asthmatic women had a HR of 1·00 (95% CI 0·96–1·04) for hospitalisation due to COVID-19.

The association between female sex and risk of hospitalisation due to COVID-19 was significantly modified by hypertension, diabetes, and BMI (figure ). Compared with asthmatic men, asthmatic women without comorbid hypertension were at significantly higher risk of hospitalisation. Conversely, asthmatic women with hypertension, diabetes, and obesity were at significantly lower risk of hospitalisation than asthmatic men (figure).

Figure

The effect of sex (asthmatic women vs asthmatic men) on hospital admission due to COVID-19 in subgroups of selected comorbidities

Multivariable HRs adjusted for age, ethnicity, socioeconomic status, smoking, hypertension, diabetes, ischaemic heart disease, and BMI (n=214 031). BMI=body-mass index. HR=hazard ratio.

In summary, women have an apparent higher disease burden of COVID-19 than men overall (leading to significantly higher rates of hospitalisation, health-care costs, mortality, and severity of disease). However, careful analysis of patient characteristics showed that the higher number of hospitalisations seen among asthmatic women was in fact caused by higher prevalence of comorbidities known to be independent risk factors for COVID-19 severity. Furthermore, subgroup analyses suggest that asthmatic women might have a lower risk of hospitalisation due to COVID-19 than men in a setting of hypertension, diabetes, and obesity.

YA reports personal fees from Teva, grants and personal fees from Actelion, personal fees from Bayer, personal fees from GSK, personal fees from KAMADA, personal fees from Novartis, grants and personal fees from AstraZeneca, and personal fees from Sanofi outside the submitted work. MH reports personal fees from Acceleron, grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Merck, personal fees from Novartis, personal fees from AstraZeneca, and personal fees from Sanofi outside the submitted work. WS declares no competing interests.