Several studies have reported a higher susceptibility of men to develop severe respiratory disease following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when compared with women.1 , 2 To explore the implication of hormonal regulation in coronavirus disease-2019 (COVID-19) clinical outcomes, we assessed SARS-CoV-2 infections, hospital admissions, and deaths in women affected by hormone-driven cancers (HDCs) and treated with antiestrogen therapies (AETs).
Out of 51 060 women (median age: 56 years) tested for SARS-CoV-2 infection from 22 February 2020 to 01 April 2020, 2478 had a clinical history of malignancy (4.9%), including 926 breast and 60 ovarian cancers. Women affected by cancers (331/2478) had a significantly higher prevalence of infection versus non-cancer patients (4414/48 582; P < 0.001).
Cancer patients developed more severe conditions and required hospitalization in 49.5% of cases versus 26.5% of women without cancer. During the study follow-up, 19.3% of cancer patients versus 7.3% of non-cancer patients died.
Compared with women without cancer, patients affected by breast cancer had a higher risk of hospitalization (RoH) [age- and comorbidity-adjusted prevalence odds ratio (adjPOR) = 1.98; 90% confidence interval (CI): 1.42-2.76] and death (26.6%; adjPOR = 2.53; 90% CI: 1.71-3.74). The presence of respiratory comorbidities increased the RoH (adjPOR = 7.89; 90% CI: 6.76-9.20) and death (adjPOR = 1.72; 90% CI: 1.35-2.19). A total of 90.6% of SARS-CoV-2-positive cancer patients were affected by comorbidity as compared with 47.8% of non-cancer patients. Cardiovascular disease was the most frequent (39.9% of cancer patients and 28.4% of non-cancer patients) together with respiratory disease (33.2% and 19.1%, respectively).
Four hundred and eighty-three patients affected by HDCs were receiving AETs. The prevalence of comorbidity was even higher among women under AET (94.2%). Specifically, 198 patients were treated with selective estrogen receptor modulators, degraders, or down-regulators (SERMs), of which 16 were under ovarian function suppression therapy (OFST). Three hundred and thirty-four women were under aromatase inhibitors (AIs), of which 16 were also under OFST, and 48 women were under luteinizing hormone-releasing hormone agonists (LAs) (16 were also under OFST).
SARS-CoV-2 positivity was found in 14 women under SERM treatment (7.1%), 44 women under AI (13.2%), and 3 women under LA (6.3%). Hospitalization was required by 51.9% of women under AET, and 19.2% died.
No significant association with SARS-CoV-2 infection, hospitalization, or death emerged among all patients with HDCs receiving AET. However, SARS-CoV-2 infection was significantly lower in women aged ≥50 years (adjPOR = 0.66; 90% CI: 0.48-0.91). Considering separately the three categories of AETs, only patients under SERMs had a lower prevalence of SARS-CoV-2 (adjPOR = 0.42; 90% CI: 0.21-0.83) as compared with patients not receiving any AETs. SARS-CoV-2 positivity was significantly higher in patients under AIs than in those under SERMs (adjPOR = 2.07; 90% CI: 1.02-4.19).
Altogether, our data indicate that female cancer patients have an increased risk of SARS-CoV-2 infection and develop more severe forms of COVID-19, in line with recent findings.3 , 4 Moreover, ablation of estrogens in these patients reduced the prevalence of COVID-19. Therefore, the use of SERMs in the treatment of COVID-19 patients may represent a possibility. These data need to be further validated in a larger cohort and corrected to multiple variables. Moreover, molecular studies are required to elucidate the molecular bases for the protective effect observed in women under SERM treatment.
The study was approved by the Bioethics Committee of the Veneto Region (protocol no. 245343/2020).
Acknowledgments
Funding
This work was supported by the Dipartimento di Scienze del Farmaco-Universita degli Studi di Padova [grant number MONT_SID18_01] to MM and Fondazione per l'Istituto Oncologico di Ricerca (IOR) to AC.
Disclosure
The authors have declared no conflicts of interest.
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