Effect of cancer on outcome of COVID-19 patients: a systematic review and meta-analysis of studies of unvaccinated patients
- University of Bologna, Italy
Abstract
Background: Since the beginning of the SARS-Cov2 pandemic, cancer patients affected by COVID-19 have been reported to experience poor prognosis; however, a detailed quantification of the effect of cancer on outcome of unvaccinated COVID-19 patients has not been performed.
Methods: To carry out a systematic review of the studies comparing the outcome of unvaccinated COVID-19 patients with and without cancer, a search string was devised which was used to identify relevant publications in PubMed up to December 31, 2020. We selected three outcomes: mortality, access to ICU, and COVID-19 severity or hospitalization. We considered results for all cancers combined as well as for specific cancers. We conducted random-effects meta-analyses of the results, overall and after stratification by region. We also performed sensitivity analyses according to quality score and assessed publication bias.
Results: For all cancer combined, the pooled odds ratio (OR) for mortality was 2.32 (95% confidence interval [CI] 1.82-2.94, I2 for heterogeneity 90.1%, 24 studies), that for ICU admission was 2.39 (95% CI 1.90-3.02, I20.0%, 5 studies), that for disease severity or hospitalization was 2.08 (95% CI 1.60-2.72, I2 92.1%, 15 studies). The pooled mortality OR for hematologic neoplasms was 2.14 (95% CI 1.87-2.44, I2 20.8%,8 studies). Data were insufficient to perform a meta-analysis for other cancers. In the mortality meta-analysis for all cancers, the pooled OR was higher for studies conducted in Asia than studies conducted in Europe or North America. There was no evidence of publication bias.
Conclusions: Our meta-analysis indicates a two-fold increased risk of adverse outcomes (mortality, ICU admission and severity of COVID-19) in unvaccinated COVID-19 patients with cancer compared to COVID-19 patients without cancer. These results should be compared with studies conducted in vaccinated patients; nonetheless, they argue for special effort to prevent SARS-Cov2 infection in patients with cancer.
Funding: No external funding was obtained.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file.Dataset has been deposited on Dryad (doi:10.5061/dryad.00000004q)
-
Data from: Effect of SARS-CoV-2 infection on outcome of cancer patients: A systematic review and meta-analysis of studies of unvaccinated patientsDryad Digital Repository, doi:10.5061/dryad.00000004q.
Article and author information
Author details
Funding
The authors declare that there was no funding for this work.
Ethics
Human subjects: a) All methods were carried out in accordance with relevant guidelines and regulations.b) The study was considered exempt and the informed consent was not deemed necessary given the nature of the study
Copyright
© 2022, Di Felice et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,149
- views
-
- 195
- downloads
-
- 26
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Effect of cancer on outcome of COVID-19 patients: a systematic review and meta-analysis of studies of unvaccinated patients
eLife 11:e74634.
https://doi.org/10.7554/eLife.74634
Further reading
-
- Cancer Biology
- Genetics and Genomics
The expression of eukaryotic genes relies on the precise 3'-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers – particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation – have received less attention. Here, we systematically analysed somatic mutations affecting 3'UTR polyadenylation signals in human cancers using the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. We found a striking enrichment of cancer-specific somatic mutations that disrupt strong and evolutionarily conserved cleavage and polyadenylation signals within tumour suppressor genes. Further bioinformatics and experimental analyses conducted as a part of our study suggest that these mutations have a profound capacity to downregulate the expression of tumour suppressor genes. Thus, this work uncovers a novel class of noncoding somatic mutations with significant potential to drive cancer progression.
-
- Cancer Biology
- Immunology and Inflammation
The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC) prevents tumor control and strategies to restore anti-cancer immunity (i.e. by increasing CD8 T-cell activity) have had limited success. Here, we demonstrate how inducing localized physical damage using ionizing radiation (IR) unmasks the benefit of immunotherapy by increasing tissue-resident natural killer (trNK) cells that support CD8 T activity. Our data confirms that targeting mouse orthotopic PDAC tumors with IR together with CCR5 inhibition and PD1 blockade reduces E-cadherin positive tumor cells by recruiting a hypoactive NKG2D-ve NK population, phenotypically reminiscent of trNK cells, that supports CD8 T-cell involvement. We show an equivalent population in human single-cell RNA sequencing (scRNA-seq) PDAC cohorts that represents immunomodulatory trNK cells that could similarly support CD8 T-cell levels in a cDC1-dependent manner. Importantly, a trNK signature associates with survival in PDAC and other solid malignancies revealing a potential beneficial role for trNK in improving adaptive anti-tumor responses and supporting CCR5 inhibitor (CCR5i)/αPD1 and IR-induced damage as a novel therapeutic approach.
