Association of Antineoplastic Therapy With Decreased SARS-CoV-2 Infection Rates in Patients With Cancer

Question Will patients with cancer treated with antineoplastic compounds associated with lower angiotensin-converting enzyme 2 (ACE2) expression exhibit lower SARS-CoV-2 infection rates? Findings In an in silico analysis of the Library of Integrated Network-Based Cellular Signatures database, 91 compounds were associated with gene downregulation of the ACE2 entry receptor for SARS-CoV-2, including mTOR/PI3K inhibitors and antimetabolites. Patients who received a potential ACE2-lowering antineoplastic exhibited a statistically significantly reduced SARS-CoV-2 positivity rate of 7.0% compared with 12.9% in patients who received other antineoplastic therapies. Meaning Potential ACE2-lowering antineoplastics, including mTOR/PI3K inhibitors and antimetabolites, may exhibit clinical anti-SARS-CoV-2 activity. Importance Novel therapies for SARS-CoV-2 infection are urgently needed. Antineoplastic compounds that target cellular machinery used by SARS-CoV-2 for entry and replication, including angiotensin-converting enzyme 2 (ACE2), may disrupt SARS-CoV-2 activity. Objectives To determine whether patients with cancer treated with potential ACE2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates. Design, Setting, and Participants We used the Library of Integrated Network-Based Cellular Signatures database to identify antineoplastic compounds associated with decreased ACE2 gene expression across cell lines. We then evaluated a retrospective cohort of 1701 patients who were undergoing antineoplastic therapy at Memorial Sloan Kettering Cancer Center in New York, New York, during the COVID-19 pandemic to determine if treatment with an ACE2-lowering antineoplastic was associated with a decreased odds ratio (OR) of SARS-CoV-2 infection. Patients included in the analysis underwent active treatment for cancer and received a SARS-CoV-2 test between March 10 and May 28, 2020. Main Outcome and Measure The association between potential ACE2-lowering antineoplastic treatment and a positive SARS-CoV-2 test. Results In the cohort of 1701 patients, SARS-CoV-2 infection rates were determined for 949 (55.8%) female and 752 (44.2%) male patients (mean [SD] age, 63.1 [13.1] years) with diverse cancers receiving antineoplastic therapy. In silico analysis of gene expression signatures after drug treatment identified 91 compounds associated with downregulation of ACE2 across cell lines. Of the total cohort, 215 (12.6%) patients were treated with 8 of these compounds, including 3 mTOR/PI3K inhibitors and 2 antimetabolites. In a multivariable analysis of patients who received an ACE2-lowering antineoplastic adjusting for confounders, 15 of 215 (7.0%) patients had a positive SARS-CoV-2 test compared with 191 of 1486 (12.9%) patients who received other antineoplastic therapies (OR, 0.53; 95% CI, 0.29-0.88). Findings were confirmed in additional sensitivity analyses including cancer type, steroid use, and a propensity-matched subcohort. Gemcitabine treatment was associated with reduced SARS-CoV-2 infection (OR, 0.42; 95% CI, 0.17-0.87). Conclusions and Relevance In this cohort study, in silico analysis of drug-associated gene expression signatures identified potential ACE2-lowering antineoplastic compounds, including mTOR/PI3K inhibitors and antimetabolites. Patients who received these compounds exhibited statistically significantly lower rates of SARS-CoV-2 infection compared with patients given other antineoplastics. Further evaluation of the biological and clinical anti-SARS-CoV-2 properties of identified antineoplastic compounds is warranted. This cohort study seeks to determine whether patients with cancer treated with potential angiotensin-converting enzyme 2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates.

Automated summary

Patients with cancer treated with potential ACE2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates. These antineoplastic compounds may have clinical significance in combating SARS-CoV-2.