Influenza risk in cancer survivors may hint at severe COVID-19 risk

A study from England suggests that cancer survivors, particularly haematological cancer survivors, may have a long-term risk of hospitalization or death from influenza compared with individuals with no history of cancer. The study authors believe these findings may help identify cancer survivors at risk for severe COVID-19 outcomes.

“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,” said co-lead author Helena Carreira, PhD, from the London School of Hygiene & Tropical Medicine (LSHTM), London, UK.

“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,” said the authors. “This should be taken into account in public health policies targeted at protecting clinical risk groups,” they said.

Using data from English primary care, cancer, hospital admission, and death registries between 1990–2015, the researchers included 108,215 adults with ≥1 year survival following incident diagnosis of 20 of the most common site-specific cancers, and age-, sex-, and general practice-matched them with 523,541 cancer-free controls. Median age was 67 years in both groups, and 52.4 and 53.1 percent of the survivor and cancer-free groups, respectively, were female.

Diabetes, asthma, other respiratory diseases, and cardiac, neurological, renal, and liver disease were more common among cancer survivors than controls, while obesity prevalence was lower. However, these differed by cancer site. At 5 years post-diagnosis, 37.3 percent of cancer survivors had ≥2 comorbidities.

Cancer survivors and controls were followed up for a median 4.7 and 6.2 years, respectively, during which time there were 190 hospitalizations and 15 deaths due to influenza.

The risk of hospitalization or death due to influenza was higher among cancer survivors than those with no cancer history (adjusted hazard ratio [adjHR], 2.78, 95 percent confidence interval [CI], 2.04–3.80), with the greatest risk at 1 to <5 years post-diagnosis (adjHR, 4.34). [EClinicalMedicine 2020;doi:10.1016/j.eclinm.2020.100656]

This risk was especially notable in haematological cancer survivors vs controls (adjHR, 15.17, 95 percent CI, 7.84–29.35), with the highest risk at 1 to <5 years since diagnosis (adjHR, 29.56), but remaining elevated at 5 to <10 years and ≥10 years post-cancer diagnosis (adjHRs, 9.56 and 10.06, respectively).

The risk of hospitalization or death due to influenza was about twofold at 1 to <5 years post-cancer diagnosis in non-haematological cancer survivors (adjHR, 2.22), though not evident in the long-term.

There was no apparent variation in risk between the different haematological cancer types (p=0.08) or solid cancer types (p=0.42).

Adjustment for time-updated influenza vaccination status and ever-receipt of pneumococcal vaccination led to comparable findings (HR, 4.06).

 

Change in vaccination recommendations?

“[The results suggest that] vaccination and other preventative strategies are important considerations for the much broader population of longer-term cancer survivors,” said Carreira.

“Influenza vaccination should be encouraged … and may need to be extended to a wider population of medium- to long-term cancer survivors than currently recommended,” the authors said.

 

Potential implications in COVID-19

“A key aspect of managing the impacts of the pandemic is understanding who is vulnerable to experiencing severe outcomes, so that mitigation strategies can be targeted at those most in need,” the authors said.

“UK policy [currently] defines those with active cancers and/or receiving treatments as high-risk for COVID-19 complications [and] the much larger overall population of cancer survivors does not appear in either moderate- or high-risk groupings,” they said. “[T]hese risk groupings become increasingly important as general population social distancing measures are eased and advice becomes more targeted to those at risk,” they continued.

“These findings have an immediate relevance ... we have a flu vaccine available, and the likelihood of a COVID-19 vaccine in the near future,” noted senior author Professor Krishnan Bhaskaran, also from LSHTM. “Understanding how vaccination should be prioritized to protect the most vulnerable will be crucial over the next few months.”

The authors acknowledged that the risk factors driving severe outcomes in influenza may not be the same as those for COVID-19. “[Nonetheless, recent data has suggested] a broad overlap between those at high risk for seasonal influenza and for severe COVID-19 outcomes,” they said.

They were also unable to discern the impact of cancer treatments on risk, and whether patients were still receiving treatment. “Future studies should focus on the risk of severe COVID-19 in cancer survivors [and] explore the role of comorbidities and prior exposure to specific anti-cancer therapies,” they noted.