Sex bias in COVID-19-associatedIllness severity and mortality in cancer patients: Asystematic review and meta-analysis

ABSTRACT

Importance There is strong evidence that COVID-19 is associated with higher morbidity and mortality in malescompared to females in the general population. However, whether the same sex bias exists in the cancer patientpopulation is unknown. Several published studies have examined this question, but the results are inconclusive andinconsistent and the association remains unclear. Objective: To evaluate the sex differences in the risk of severe illness and mortality attributable to COVID-19 in thecancer patient population. Data Sources Published articles that evaluated clinical outcomes associated with severe illness or deathattributable to COVID-19 in the cancer patient population from inception to June 1, 2020, were identified bysearching PubMed and EMBASE, as well as the ASCO 2020 Virtual Annual Conference, ESMO conferences heldfrom January 2020 to June 1, 2020, and the preprint databases medRxiv and bioRxiv. Study Selection Prospective or retrospective analyses, studies published in English, providing clinical outcomesdata with sex differences in the cancer patient population. Data Extraction and Synthesis: Author, date of publication, country, type of studies, median and range of age, cancer types included in the studies, definitions of clinical outcomes, and the odds ratios (OR) for severe illness ordeath attributable to COVID-19 were retrieved. Where OR data were not available, raw data were used to calculatethe OR in a univariate analysis model and included in the meta-analysis. Main Outcome(s) and Measure(s) The primary outcome of interest was OR of (1) severe illness, (2) death, and(3) composite outcome of severe illness and death attributable to COVID-19 in males versus females. Results: Overall, 2,764 patients (9 studies) were analyzed in retrospective study settings. Of the included studies, two studies were multinational whereas the rest were conducted in China (4), France (1), United Kingdom (1), andUnited States (1). Median ages were similar across studies (range 62-70). Three studies reported outcomes fordeath and six studies reported outcomes for severe illness. Of the seven studies, all but one defined severe illnessas illness requiring ICU admission or leading to death and attributable to COVID-19. Pooled ORs for the compositeoutcome was 1.68 (95% CI, 1.27-2.24), death was 1.98 (95% CI, 1.21-3.26), and severe illness was 1.48 (95% CI,1.05-2.10), all disfavoring males. Random effects model was used with the Dersimonian-Laird Model throughoutanalyses and significant heterogeneity was subsequently confirmed (I2, 48.1%;tau2, 0.0816). No significantbetween-study bias was detected per Begg's funnel plot. Conclusions and Relevance The male sex was associated with higher risk of severe illness, death, and thecomposite outcome of both attributable to COVID-19. This finding has implications in informing the clinical prognosisand decision making regarding oncologic patients.