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In Reply We thank Dekker, Peng et al, Maitland et al, and Robinson et al for their interest and insightful comments on our article.1 These authors raised salient points on confounders, such as older age and cigarette smoking, on the higher incidence of coronavirus disease 2019 (COVID-19) in our cohort of patients with cancer. Additionally, Maitland et al and Robinson et al queried our secondary observation that older patients with lung cancer represented a particularly susceptible subgroup. We will attempt to respond to these points.
In our article, we had acknowledged that age is a confounder of our findings because most solid cancers tend to occur in older patients. Compounding this conundrum, a study of 32 583 COVID-19 cases in Wuhan, China, from December 8, 2019, to March 8, 2020, revealed a positive association between the daily rate of cases and age (relative risk of 2.33 for patients aged 60-79 years compared with those aged 20-39 years).2 To resolve this, one would need to perform an age-standardized comparison of incidence of COVID-19 cases between patients with cancer and patients without cancer.
Nonetheless, in an age-matched case-control study, Dai and colleagues3 observed that patients with cancer were more susceptible to in-hospital infection compared with patients without cancer (19.04% vs 1.49%). The increased risk of infection is likely multifactorial. As raised by Dekker and Peng et al, cigarette smoking and repeat visitation to the hospital are potential risk factors for severe acute respiratory syndrome coronavirus 2 infection. The association of cigarette smoking would be difficult to ascertain without information on the number of pack-years and current cigarette smoking status; moreover, the dose dependency of ACE2 upregulation by cigarette smoking is unclear. Regarding the latter, it is widely recognized that repeated hospital visits for chemotherapy and radiotherapy pose a heightened risk of virus transmission to patients with cancer. Guidelines on contingency planning to adapt cancer treatment and infection control protocols have thus been proposed.4
We also wholly agree with Maitland et al that the association of older patients with lung cancer and COVID-19 is at best suggestive and requires validation in larger cohorts. While we found that patients with non–small cell lung cancer older than 60 years had a higher incidence of COVID-19 than those younger than 60 years, this difference was not statistically significant (4.3% vs 1.8%; P = .45 using Fisher exact test).1
Finally, Robinson et al raised valid comments on ascertainment and misclassification bias. The former is unlikely, because computed tomography (CT) of the chest was part of the diagnostic workup for COVID-19 in Wuhan during the outbreak, and the patients in our study only underwent a CT because of COVID-19–like symptoms. Nonetheless, we acknowledged that other types of viral pneumonia could manifest similar CT changes. However, such misclassification errors would have systematically affected both the study cohort and community cases, and thus it may be reasonable to still expect a higher relative risk of COVID-19 in patients with cancer than patients without cancer.
Regardless, there is now conclusive evidence highlighting that patients with cancer with COVID-19 fare significantly worse than patients without cancer.3,5 The main message of our study is therefore consistent with the widespread advocacy among the oncology community that cancer centers must enforce robust infection control and avoid immunosuppressive anticancer therapies in this vulnerable group of patients during this pandemic.
Corresponding Author: Melvin L. K. Chua, MBBS, PhD, Division of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore 169610 (email@example.com).
Published Online: July 2, 2020. doi:10.1001/jamaoncol.2020.2589
Conflict of Interest Disclosures: None reported.
Funding/Support: Dr Chua is supported by a National Medical Research Council Clinician-scientist award (NMRC/CSA/0027/2018). Dr Xie is supported by Health Commission of Hubei Province Scientific Research Project (WJ2019H002), Health Commission of Hubei Province Medical Leading Talent Project, Fundamental Research Funds for the Central Universities (2042018kf1037, 2042019kf0329), Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University (TFJC2018005), and Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund (znpy2017049, znpy2018070).
Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.
Additional Information: Drs Chua, Yu, and Xie contributed equally to this work.
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Chua MLK, Yu J, Xie C. Risk of COVID-19 in Patients With Cancer—Reply. JAMA Oncol. 2020;6(9):1472–1473. doi:10.1001/jamaoncol.2020.2589
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