Survivors from a wide range of cancers are more likely than people in the general population to be hospitalised or die from seasonal influenza even several years after their cancer diagnosis, according to a London School of Hygiene & Tropical Medicine analysis in EClinicalMedicine. Given that flu and COVID-19 are both epidemic respiratory viruses with broadly similar risk factors, the findings suggest that cancer survivors are also likely to be at raised risk of severe COVID-19 outcomes.
Given that flu and COVID-19 are both epidemic respiratory viruses with broadly similar risk factors, the findings suggest that cancer survivors are also likely to be at raised risk of severe COVID-19 outcomes. With over two million cancer survivors in the UK, the researchers say their results highlight that this group may need to be prioritised for vaccination against both diseases.
In the first large study of its kind looking at this issue, researchers from the London School of Hygiene & Tropical Medicine (LSHTM), analysed medical records from 1990 to 2014 of more than 630,000 people in the UK, including over 100,000 survivors of a range of cancers.
Comparing the rates of influenza hospitalisation and death between cancer survivors and the cancer-free population, the researchers found that the risk of these outcomes was more than 9 times higher in survivors from lymphomas, leukaemia, and multiple myeloma, compared to those with no prior cancer. Crucially, this raised risk persisted for at least 10 years after cancer diagnosis. Despite the risks being raised compared to the general population, the absolute risks of developing severe flu were still relatively low, with about 1 in 1000 survivors of these types of cancer hospitalised with flu each year.
Survivors from other types of cancer also had more than double the risk of severe influenza outcomes for up to five years from diagnosis.
These findings persisted even after accounting for other suspected risk factors such as old age, smoking, socioeconomic status, body mass index and other illnesses.
The researchers also found that cancer survivors were more likely to have other diseases that are associated with increased risk of severe COVID-19 outcomes, such as heart disease, diabetes, respiratory disease and kidney disease.
According to Gov.uk, to date 199,881 patients have been admitted to hospital in the UK with COVID-19, and there have been 63,873 COVID-19 recorded deaths. Age is by far the most important factor determining the absolute risk of developing severe COVID-19, with some studies estimating around 20% of individuals aged over 80 years old require hospitalisation, compared with less than 1% of people aged under 30.
Current guidance on who should be considered vulnerable to COVID-19 is largely based on policies developed for previous epidemic respiratory viruses like influenza. In such guidance, cancer survivors with no recent immunosuppressing treatment are not considered high-risk. However, findings from this new study — combined with other recent UK data showing that cancer survivors had a raised risk of dying from COVID-19- suggests that cancer survivors should be included as a vulnerable group for COVID-19 and influenza management policies.
Helena Carreira, one of the lead authors of the study and Research Fellow at LSHTM, said: "We knew that people with cancer are at high risk of severe outcomes from these epidemic viruses soon after diagnosis, but we found that this increased risk also continues for several years after diagnosis. This means that vaccination and other preventative strategies are important considerations for the much broader population of longer-term cancer survivors."
Professor Krishnan Bhaskaran, senior author of the study and Professor of Statistical Epidemiology at LSHTM, said: "These findings have an immediate relevance as we enter the winter period: we have a flu vaccine available, and the likelihood of a COVID-19 vaccine in the near future. Understanding how vaccination should be prioritised to protect the most vulnerable will be crucial over the next few months."
The authors acknowledge limitations of their study, including that it is not certain that risk factors for severe influenza will have the same associations with COVID-19; and a lack of data on cancer treatments that patients had received.
The research was part of the BEYOND Cancer programme investigating the long-term health of cancer survivors. The study was funded by the Wellcome Trust and the Royal Society.
Prevalence of COVID-19-related risk factors and risk of severe influenza outcomes in cancer survivors: A matched cohort study using linked English electronic health records data
Helena Carreira, Helen Strongman, Maria Peppa, Helen I McDonald, Isabel dos-Santos-Silva, Susannah Stanway, Liam Smeeth, Krishnan Bhaskaran.
EClinicalMedicine, 30 November 2020
People with active cancer are recognised as at risk of COVID-19 complications, but it is unclear whether the much larger population of cancer survivors is at elevated risk. We aimed to address this by comparing cancer survivors and cancer-free controls for (i) prevalence of comorbidities considered risk factors for COVID-19; and (ii) risk of severe influenza, as a marker of susceptibility to severe outcomes from epidemic respiratory viruses.
We included survivors (≥1 year) of the 20 most common cancers, and age, sex and general practice-matched cancer-free controls, derived from English primary care data linked to cancer registrations, hospital admissions and death registrations. Comorbidity prevalences were calculated 1 and 5 years from cancer diagnosis. Risk of hospitalisation or death due to influenza was compared using Cox models adjusted for baseline demographics and comorbidities.
108,215 cancer survivors and 523,541 cancer-free controls were included. Cancer survivors had more diabetes, asthma, other respiratory, cardiac, neurological, renal, and liver diseases, and less obesity, compared with controls, but there was variation by cancer site. There were 205 influenza hospitalisations/deaths, with cancer survivors at higher risk than controls (adjusted HR 2.78, 95% CI 2.04–3.80). Haematological cancer survivors had large elevated risks persisting for >10 years (HR overall 15.17, 7.84–29.35; HR >10 years from cancer diagnosis 10.06, 2.47–40.93). Survivors of other cancers had evidence of raised risk up to 5 years from cancer diagnosis only (HR >5 years 2.22, 1.31–3.74).
Risks of severe COVID-19 outcomes are likely to be elevated in cancer survivors. This should be taken into account in policies targeted at clinical risk groups, and vaccination for both influenza, and, when available, COVID-19, should be encouraged in cancer survivors.
Few data are available to date on how COVID-19 affects cancer survivors. We searched PubMed with the keywords “influenza cancer survivors” to identify studies that compared severe influenza outcomes in cancer survivors and in a control group. No study was identified.
Added value of this study
In this matched cohort study of routinely collected electronic health records, we demonstrated raised risks of influenza hospitalisation or mortality in survivors from haematological malignancies for >10 years after diagnosis, and in survivors from solid cancers up to 5 years after diagnosis.
Implications of all the available evidence
Cancer survivorship appears to be an important risk factor for severe influenza outcomes, suggesting that cancer survivors may also be at raised risk of poor COVID-19 outcomes. This should be taken into account in public health policies targeted at protecting clinical risk groups. Influenza vaccination should be encouraged in this group, and may need to be extended to a wider population of medium- to long-term cancer survivors than currently recommended.
Full text in EClinicalMedicine (Open Access)