key: cord-0711530-j6bw32sr authors: El‐Qushayri, Amr Ehab; Benmelouka, Amira Yasmine; Dahy, Abdullah; Hashan, Mohammad Rashidul title: COVID‐19 outcomes in paediatric cancer: A large scale pooled meta‐analysis of 984 cancer patients date: 2022-03-05 journal: Rev Med Virol DOI: 10.1002/rmv.2344 sha: e32d9279bd19142c237fa130223c0d845478d097 doc_id: 711530 cord_uid: j6bw32sr We aimed to study the outcomes of COVID‐19 in paediatric cancer patients. On 26 October 2021, we did a systematic search for relevant articles in seven electronic databases followed by manual search. We included cancer patients aged ≤18 years. Event rates and the 95% confidence interval (95%CI) were used to report the results. We included 21 papers after screening of 2759 records. The pooled rates of hospitalisation, intensive care unit (ICU) admission and mortality were 44% (95%CI: 30–59), 14% (95%CI: 9–21) and 9% (95%CI: 6–12), respectively. Moreover, subgroup analysis revealed that high income countries had better COVID‐19 outcomes compared to upper middle income countries and lower middle income countries in terms of hospitalisation 30% (95%CI: 17–46), 60% (95%CI: 29–84) and 47% (95%CI: 36–58), ICU admission 7% (95%CI: 1–32), 13% (95%CI: 7–23) and 18% (95%CI: 6–41), and mortality 3% (95%CI: 2–5), 12% (95%CI: 8–18) and 13% (95%CI: 8–20), in order. In general, absence of specific pharmacologic intervention to prevent infection with the scarcity of vaccination coverage data among paediatric groups and its impact, high priority caution is required to avoid SARS‐CoV‐2 infection among paediatric cancer patients. Furthermore, our results highlight the importance of promoting care facilities for this vulnerable population in low and middle income regions to ensure quality care among cancer patients during pandemic crisis. COVID-19 disease incidence is higher in children with cancer than in the general paediatric population. 7 These patients are subjected to an increased likelihood of being infected subsequently progressing to higher risk of morbidity and mortality. Additionally, oncologic treatment and follow-up mandate frequent visits, increased duration of exposure to hospitals and health care providers in an immune-depleted highly susceptible cancer patients may further enhance the risk of infection. 8 However, researchers also revealed that decreased inflammatory response among blood cancer patients might provide protection from severe COVID-19 morbidity. 9 ,10 Yet, few data are available regarding the true impact of COVID-19 on paediatric cancer patients and the emerging evidence is limited to case reports, case series and small cohorts mostly from developed countries. Several society recommendations and review articles have been released to guide clinicians to manage cancer patients affected with SARS-CoV-2. [11] [12] [13] [14] All authorities attempted to provide circumstantial evidence to guide the management of paediatric cancer patients during rapidly evolving nature of COVID-19 pandemic with new waves of infections and variant of concerns. A systematic review from the early phase of pandemic reported 4% mortality risk (95%CI 1-9) after pooling the data from nearly 100 paediatric cancer patients. 15 With the limited availability of data arising from immense heterogeneity in sources, the authors acknowledged that the estimate is subjected to undermine the impact of COVID-19 risk in paediatric cancer patients. Another study reported higher survival rate of paediatric cancer patients from COVID-19 and sub-group analysis comparing haematological cancer and solid tumours did not reveal significant differences. 16 Although the review authors included data mostly from developed countries with small study size and follow up duration to report complete outcomes during analysis. After searching in seven databases, all results were exported to EndNote Version 8 software and all duplicated records were removed, and then exported the results into Microsoft Excel sheet. At least two authors scanned all the records against the selection criteria and discrepancies were resolved by discussion on two successive stages: one through title and abstract screening and the other through full text screening. A data extraction template was built by the most experienced member and included the characteristics of each study (Reference ID, type of cancer, diagnostic method of COVID-19, male prevalence, sample size, study design and age; Table 1 ) and COVID-19 outcomes (hospitalisation, ICU admission and mortality). At least two authors did the extraction from each included paper. In both steps of screening and extraction, one author was incorporated to check the results of each step for preventing any error that can develop results bias and conclusion accordingly. We rated the quality of evidence using the National Institutes of Health quality assessment tool. 18 The net results of the quality of each paper were reported using the same score reported in earlier published systematic reviews. 19, 20 We conducted the analysis by using the Comprehensive Metaanalysis software version 3. In all outcomes, we reported the results as the pooled prevalence and the associated confidence interval (95%CI). Moreover, we conducted a subgroup analysis for studying the effect of each country income and COVID-19 outcomes in cancer patients. Countries income was categorised into low income countries (LICs), low middle income countries (LMICs), upper middle income countries (UMICs) and high income countries (HICs) that was reported in the World Bank. 21 We used a random effects model in all the analysis due to presence of heterogeneity estimated by a p value of < 0.1 or I 2 > 50. [22] [23] [24] We further assessed publication bias if 10 or more studies were represented in one outcome using the two-tailed Egger's test and publication bias was evident when p value < 0.1. 25 We screened a total of 2759 records after transferring the databases results without duplicates. We further assessed 61 full texts for eligibility which ended up with a total of 21 articles including 14 studies and additional seven studies following manual search procedures 7,26-45 ( Figure 1 , Table 1 ). Two studies were conducted in India, two in Pakistan, two in Brazil, two in Poland, two in Egypt and remaining each one from the following countries: USA, Iran, UK, Colombia, Spain, Peru, Algeria, Greece, Turkey, Mexico and Italy. Diagnosis of COVID-19 was done by reverse transcriptase polymerase chain reaction (RT-PCR) in 14 studies, IgM/IgG and PCR in one study, radiology in one study, radiology and serology in one study and four studies did not report the diagnostic method of COVID-19. Eight, six and seven papers were conducted in LMICs, UMICs and HICs. Thirteen studies reported a pooled prevalence 44% patients underwent hospitalisation due to COVID-19 (95%CI: 30-59; (16), Ewing sarcoma (7), T-lymphoblastic lymphoma (3), osteosarcoma (3), germ cell tumour (2), rhabdomyosarcoma (2), neuroblastoma (1), pineal brain tumour (1), Hodgkin lymphoma (1) Intensive care unit admission was reported by 10 studies with a prevalence of 14% (95%CI: 9-21; Figure 3a ). High income countries had lower ICU admission rate compared to UMICs and LMICs, 7% (95%CI: 1-32), 13% (95%CI: 7-23) and 18% (95%CI: 6-41), respectively ( Figure 3b ). We found evidence of publication bias (p < 0.05; Figure 3c ). Of total 20 studies, the pooled mortality prevalence was 9% (95%CI: 6-12; Figure 4a ). Subgroup analysis demonstrated that mortality was higher in LMICs and UMICs than HICs with the prevalence of 13% (10), renal tumour (8), acute myeloid leukaemia (7), non-Hodgkin lymphoma (4), osteosarcoma (4), retinoblastoma (2), other (7) Fair (6) inflammation observed in adults. 46 This may be related to the precarious nutritional status of children in these countries. 34 Sociocultural behaviours of people living in these regions and lack of adequate hygiene maintenance may also contribute to infection risk in paediatric cancer patients. 35 Moreover, the inequalities in country income may also have an impact on patients' access to health care facilities, especially during the lockdown period, which possibly explain the higher mortality in MICs in our results. 35 Furthermore, the delay in COVID-19 diagnosis is a significant predictor of COVID-19 severity that reflects in turn for COVID-19 adverse outcomes. 53 In the cohort study of Moreover, we did not find any paper that discussed the outcomes of COVID-19 in cancer patients in LICs which indicates a necessity for more data for finding the survival outcome from this group of patients. In front of the absence of specific treatments and the lack of data on vaccine, caution should be taken to avoid COVID-19 infection among paediatric cancer patients. Hospitals in LICs and MICs should improve their services and management protocols to mitigate the burden of SARS-CoV-2 infection in paediatric cancer patients. None. The authors received no funding for this study. None. Amr Ehab El-Qushayri was responsible for the idea and the study design. All authors shared in the data extraction. Amr Ehab El-Qushayri analysed the data and interpreted it. All authors shared in the writing of the full text and approval of final version before submission. The data that supports the findings of this study are available from the corresponding author upon reasonable request. EL-QUSHAYRI ET AL. 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