In this study, disease severity (mortality and ICU) were analyzed in patients with cancer affected with COVID-19. This is considered to be the first umbrella review to assess this relationship by identifying the primary studies of previously published meta-analyses analyzed worldwide. The current meta-meta-analysis summarizes the information from over 300 primary studies and 10 meta-analyses (mortality) and adds to the strength of the findings of the separate studies. In addition, information about ICU admission was reported in 5 systematic reviews and meta-analyses.
It is a known fact that the COVID-19 pandemic affects individuals with chronic diseases, especially cancer, more than other people [16, 32, 33]. Clinical outcomes were much worse, particularly in patients with cancer affected by COVID-19. In a meta-analysis, which included a total of 81 studies (19 for mortality) and 61532 participants, conducted by Khoury et al. [17], a significant increase in mortality was reported in patients with cancer affected by COVID-19 (RR = 2.12, 95% CI: 1.71–2.62, p < 0.001, I2 = 84.4%). They also reported an increased mortality in patients with hematological (RR = 1.42, 95% CI: 1.31–1.54, p < 0.001, I2 = 6.8%) and lung cancers (RR = 1.68, 95% CI: 1.45–1.94, p < 0.001, I2 = 32.9%) compared to patients with other cancers. In the systematic review and meta-analysis conducted by Arayici et al. [16], which included 709908 participants and 58 primary studies, it was revealed that both mortality (RR = 2.26, 95% CI: 1.94–2.62, p < 0.001, I2 = 96.0%) and ICU admission (RR = 1.45, 95% CI: 1.28–1.64, p < 0.001, I2 = 87.0%) considerably increased in SARS-CoV-2 infected cancer patients. They also reported that the incidence of cancer (%8, 95% CI: 8–9%) is higher than the worldwide incidence of cancer (approximately 0.2%) [16]. Similarly, in another meta-analysis including 22166 cancer groups and 143814 control groups, it was reported that mortality increased 2.54 (95% CI: 1.47–4.42, p < 0.001) times and ICU admission increased 2.18 (95% CI: 0.78–6.04, p < 0.001) times in cancer patients suffering from COVID-19 [21]. In other systematic reviews and meta-analyses reporting mortality and/or ICU-related risks in SARS-CoV-2 infected cancer patients, increased mortality and intensive care admissions were reported in cancer patients compared to the control group [18, 19, 20, 22, 23, 24, 25].
Data from ten studies [16–25] for mortality and five eligible studies for ICU admission [16, 18, 19, 21, 24] were analyzed by meta-meta analysis in this research. The current umbrella review and meta-meta-analysis concluded that disease severity is worse in patients with cancer affected by COVID-19. In the analyses, it was determined that mortality (OR = 2.02, %95 CI: 1.74–2.35, p < 0.001) (Fig. 2) and ICU admission (OR = 1.84, %95 CI: 1.44–2.34, p < 0.001) (Fig. 4) significantly increased in cancer patients suffering from COVID-19. Sensitivity analyses -each study is excluded from the analysis separately- were performed to confirm the robustness of the analysis results. No significant changes were observed in the sensitivity analyses. Egger's linear regression test, schematic illustrations of funnel plots, and Begg and Mazlumdar's rank correlation test were applied to evaluate publication bias. No significant publication bias was found in the test results and funnel plots (Supplemental Fig. S1 and Supplemental Fig. S3) (Mortality: Eggers’s test: intercept = 0.88, t = 0.87, p = 0.464; Begg test = 0.27, p = 0.788, ICU: Eggers’s test: Intercept = 1.94, t = 1.34, p = 0.273; Begg test = 0.98, p = 0.327).
Limitations and strengths
The strengths of the current umbrella review and meta-meta analysis include the inclusion of multiple systematic reviews and meta-analyses; a reassessment of analyses with increased strength; and, importantly, raising the level of evidence. In addition, since it gathers meta-analyses with a high level of evidence under one umbrella, it will make it easier for researchers working on the severity of COVID-19 on cancer patients to review these studies. The limitations include: primary studies included in meta-analyses may have differences in patient selection and treatment regimens; there may be a potential bias in the selection of non-hospitalized patients, particularly for mortality; the effect of treatments received by cancer patients could not be evaluated; The COVID-19 pandemic has been managed differently in each country, which may lead to a variation in the results of primary studies particularly susceptibility to COVID-19. In addition to all these, the same samples and studies may have been included in some meta-analyses. However, since primary studies were combined into different studies and a new result was reported, each meta-analysis was considered as a new study.