Determinants of SARS-CoV-2 outcomes in patients with cancer vs controls without cancer: a multivariable meta-analysis with genomic imputation

Background: SARS-CoV-2 is known to impact patients with cancer adversely. Previous meta-analyses have lacked clarity on the recency of cancer diagnosis, anti-cancer treatment durations, and SARS-CoV-2 specific variants of concern (VOC). This study aimed to compare SARS-CoV-2 multivariable-adjusted clinical outcomes between patients with cancer and those without cancer, identifying key risk factors spanning pre- and post-Omicron periods. Methods: In this systematic review and meta-analysis, we identified from Medline, Embase, Cochrane Central, and the WHO COVID-19 Research Database prospective and retrospective case–control studies and cohort studies published from 1st January 2019 to 22nd November 2024. We included case–control and cohort studies comparing at least 10 patients with active cancer (diagnosed or treated within three years prior to SARS-CoV-2 infection) to controls without cancer using multivariable analyses. Exclusion criteria included lack of clarity about active/inactive status of cancer, lack of a control group without cancer, lack of multivariate analysis comparing outcomes of interest in patients with active cancer vs patients without cancer, case reports or case series, and SARS-CoV-2 diagnosis not confirmed via laboratory testing. Outcomes measured were SARS-CoV-2 infection severity (WHO ordinal scale) and mortality differences by tumour type, treatment, and VOC (using sequencing data from NCBI Genbank and GISAID). A random-effects meta-analysis model was applied. The systematic review was PRISMA compliant and was registered with PROSPERO, CRD420234454524. Findings: Of 35,501 studies initially identified, 30 met eligibility criteria and were included in the meta-analysis, comprising 281,270 patients with cancer and 18,876,411 controls. Using the Agency for Healthcare Research and Quality (AHRQ) risk of bias standards, 21 studies were rated good, one study rated was fair, and eight studies were rated poor. We found higher mortality odds ratios (OR) in patients with cancer infected with SARS-CoV-2: 1·40 (95% CI: 1·12–1·73, I2 = 98·1%) for solid tumours and 2·10 (95% CI: 1·43–3·07, I2 = 97·3%) for haematological malignancies, with the difference in mortality between these groups not reaching statistical significance (Q (1) = 3·32; p = 0·0068). Amongst the solid cancers, thoracic and colorectal were linked to increased odds of mortality (ORs: 2·63 [95% CI: 1·65–4·20, I2 = 98·7%], and 1·65 [95% CI: 1·26–2·15, I2 = 92·7%], respectively). Metastatic cancers (OR: 3·59; 95% CI: 1·07–12·04, I2 = 99·5%) were also linked to greater odds of mortality compared to localised cancers (OR: 1·76; 95% CI: 1·32–2·34, I2 = 96·6%; p = 0·26). No cancer types showed a reduced risk vs controls. Mortality varied significantly among VOCs; Alpha (OR: 4·59; 95% CI: 2·66–7·92, I2: N/A) and Omicron (OR: 2·74; 95% CI: 1·84–4·09, I2 = 90·2%) were more associated with death than the ancestral Wu-1 (OR: 1·43; 95% CI: 1·14–1·80, I2 = 98·2%) and Delta (OR: 1·94; 95% CI: 1·65–2·29, I2:N/A) variants (X2 (4) = 20·4; p = 0·0004). Interpretation: This comprehensive meta-analysis indicates that patients with active cancer with SARS-CoV-2 have a higher risk of mortality and hospitalisation than those without cancer. The risk of death was comparable between active solid and haematological tumours. SARS-CoV-2 severity and mortality risks were higher with thoracic, colorectal, or any metastatic cancers. Additionally, differences were noted in mortality risks across VOCs, diverging from VOC-associated mortality patterns in the general population. However, the strict three-year cutoff used to define active cancer excludes studies that used broader cancer criteria (i.e., any history of cancer), which may limit generalisability. Further limitations include varied definitions of disease severity, retrospective data collection, incomplete vaccination or lineage data, and significant between-study heterogeneity, potentially influencing these findings. Funding: Cancer Research UK; UK Research and Innovation

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality