International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship
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Curated by eLife
eLife assessment
This study has looked at the 30-day mortality risk from COVID-19 in a large population of unvaccinated patients with and without cancer. Age and cancer were independent risk factors for death. In particular haematological malignancies and lung cancer presented the highest risk. These data add to the body of evidence regarding the risk of COVID-19 in patients with cancer. This manuscript is of broad interest to oncologists, internists, and infectious disease specialists in managing patients with COVID-19 and cancer.
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Abstract
In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries.
Methods:
We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers.
Results:
We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03).
Conclusions:
Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality.
Funding:
National Cancer Institute and National Institutes of Health.
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eLife assessment
This study has looked at the 30-day mortality risk from COVID-19 in a large population of unvaccinated patients with and without cancer. Age and cancer were independent risk factors for death. In particular haematological malignancies and lung cancer presented the highest risk. These data add to the body of evidence regarding the risk of COVID-19 in patients with cancer. This manuscript is of broad interest to oncologists, internists, and infectious disease specialists in managing patients with COVID-19 and cancer.
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Reviewer #1 (Public Review):
The authors present a retrospective study of COVID-19 mortality within 30 days from a positive SARS-CoV-2 PCR in 1115 patients with cancer and 2851 patients without cancer. Patients were recruited from 16 different centres from 8 countries across 5 continents. Patients were recruited between January and November 2020. All patients with a positive SARS-CoV-2 PCR were included. Demographic and clinical data were collected from electronic patient records. The primary outcome was 30-day mortality. Data were retrieved from patient records and there is a significant proportion of missing data.
The authors found that age and the presence of cancer were independent risk factors of 30-day mortality. Remdesivir was associated with reduced mortality. Within cancer patients, those with haematological malignancies and …
Reviewer #1 (Public Review):
The authors present a retrospective study of COVID-19 mortality within 30 days from a positive SARS-CoV-2 PCR in 1115 patients with cancer and 2851 patients without cancer. Patients were recruited from 16 different centres from 8 countries across 5 continents. Patients were recruited between January and November 2020. All patients with a positive SARS-CoV-2 PCR were included. Demographic and clinical data were collected from electronic patient records. The primary outcome was 30-day mortality. Data were retrieved from patient records and there is a significant proportion of missing data.
The authors found that age and the presence of cancer were independent risk factors of 30-day mortality. Remdesivir was associated with reduced mortality. Within cancer patients, those with haematological malignancies and lung cancer had the highest risk. Overall, the findings of this study are in line with previously published results and don't provide major new insights.
Strength:
This is a multicentric study across several countries including over 3000 patients.
Limitations
This is not the first cohort study in cancer patients, several large studies have addressed risk factors of mortality before (for example Kuderer et al., The Lancet, 2020 and Chaves-McGregor et al. JAMA Oncology, 2021).
The authors identify Remdesivir to reduce mortality in cancer patients and those without cancer. The efficacy of Remdesivir has been addressed in large prospective trials, albeit not in cancer patients.
Treatment of patients with COVID-19 likely varied by country but the authors haven't addressed the impact of this.
Given that the recruited patients were all unvaccinated, the results are likely not completely transferable to the current situation. Vaccination and current antivirals and monoclonal antibodies have reduced the risk of severe disease and death. The current omicron variant has different properties compared to earlier strains. In fact, studies have shown that mortality in cancer patients has improved since 2020 (OnCovid Study Group, JAMA Oncology, 2021).
In conclusion, the authors largely confirm findings from other studies that patients with cancer were at an increased risk of death after COVID-19 infection, especially early on in the pandemic.
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Reviewer #2 (Public Review):
The paper entitled "International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship" by Raad et al. is a multi-center, international, matched cohort, with a relatively large sample size. The aim of this work is to determine independent risk factors that impact survival in the setting of "novel treatment modalities" like Remdesivir. It enrolled patients with COVID-19 and cancer and compared them to cancer-negative controls. The authors conclude that cancer increases mortality from COVID-19 and that Remdesivir can reduce all-cause mortality in a subset of patients receiving low-flow oxygen and the results support their conclusions. Overall, this paper adds to the growing body of literature that implicates cancer as a worse …
Reviewer #2 (Public Review):
The paper entitled "International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship" by Raad et al. is a multi-center, international, matched cohort, with a relatively large sample size. The aim of this work is to determine independent risk factors that impact survival in the setting of "novel treatment modalities" like Remdesivir. It enrolled patients with COVID-19 and cancer and compared them to cancer-negative controls. The authors conclude that cancer increases mortality from COVID-19 and that Remdesivir can reduce all-cause mortality in a subset of patients receiving low-flow oxygen and the results support their conclusions. Overall, this paper adds to the growing body of literature that implicates cancer as a worse predictor of survival among patients with COVID-19. The use of a matched cohort makes it unique and strengthens the findings of this study. The potential weaknesses of this study are its retrospective nature and lack of data on the effect of vaccination in this population since the study was conducted prior to the introduction of vaccines.
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