Association between sex and SARS-CoV-2 infection and hospitalisation as a result of COVID-19
Authors: Yochai Adir, Marc Humbert, Walid Saliba
Journal: The Lancet Respiratory Medicine (2021)

We read with interest the Comment by Mario Fernando and colleagues1Fernando M Agusti A Dharmage S Lodge C Are women with asthma at increased risk for severe COVID-19?.Lancet Respir Med. 2021; 9: 125-126Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar entitled "Are women with asthma at increased risk for severe COVID-19?". On the basis of an analysis of published data,2Atkins JL Masoli JA Delgado J et al.Preexisting comorbidities predicting COVID-19 and mortality in the UK Biobank Community Cohort.J Gerontol A Biol Sci Med Sci. 2020; 75: 2224-2230Crossref PubMed Scopus (308) Google Scholar, 3Chhiba KD Patel GB Vu THT et al.Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.J Allergy Clin Immunol. 2020; 146: 307-314Summary Full Text Full Text PDF PubMed Scopus (220) Google Scholar, 4Lovinsky-Desir S Deshpande DR De A et al.Asthma among hospitalized patients with COVID-19 and related outcomes.J Allergy Clin Immunol. 2020; 146: 1027-1034Summary Full Text Full Text PDF PubMed Scopus (109) Google Scholar 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.1Fernando M Agusti A Dharmage S Lodge C Are women with asthma at increased risk for severe COVID-19?.Lancet Respir Med. 2021; 9: 125-126Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar 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,5Asthma AustraliaImpact of COVID-19 on asthma: rapid review for Asthma Australia.https://asthma.org.au/wp-content/uploads/2020/10/COVID-rapid-review_Summarised-report-for-technical-audience-VF-clean_v2.pdfDate: 2020Date accessed: November 18, 2020Google Scholar, 6Beurnier A Jutant E-M Jevnikar M et al.Characteristics and outcomes of asthmatic patients with COVID-19 pneumonia who require hospitalisation.Eur Respir J. 2020; 562001875Crossref PubMed Scopus (94) Google Scholar 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). 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. Are women with asthma at increased risk for severe COVID-19?Although adults with asthma appear to have a reduced risk of severe COVID-19 compared with younger populations,1 women with asthma might represent a somewhat susceptible subgroup for severe COVID-19 requiring hospitalisation.2 A study by Atkins and colleagues established female sex as an independent risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalisation among patients with asthma in the UK.2 This study and three additional studies from Paris, France, Illinois, USA, and New York, NY, USA, report that 37–53% of all individuals hospitalised with SARS-CoV-2 were women. Full-Text PDF