Recent research found that patients with cancer and COVID-19 are susceptible to long-term infection, particularly if they have hematologic cancers or metastatic disease. Patients with prolonged COVID-19 had immune system alterations, such as lymphopenia and T-cell exhaustion, and metabolic abnormalities that may have impaired their ability to fight the virus.

Recent research has revealed that patients with cancer are susceptible to long-term COVID-19 infections, particularly if they have hematologic cancers or metastatic disease. The findings, presented at the American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer, held February 3–5, suggest that patients with long-term infections may have immune system alterations and metabolic abnormalities that impair their ability to fight the virus.

Early research from China reported higher COVID-19 mortality among patients with cancer. More recent studies suggest that certain patients with cancer are more vulnerable—for example, those with hematologic malignancies.

To investigate further, Laurence Zitvogel, MD, PhD, of Gustave Roussy Institute in Villejuif, France, and colleagues analyzed blood samples and nasal swabs from 971 people with COVID-19 in France and Canada, 521 of whom had cancer. They discovered that COVID-19 infections lasted longer in patients with cancer. Among participants from Gustave Roussy, for instance, viral RNA was detected for a median of 40 days in patients with cancer, versus 21 days in cancer-free controls.

Patients with hematologic or metastatic cancers were more likely to have prolonged viral shedding than were those with solid or localized tumors. Additionally, prolonged viral shedding was prevalent in patients with a high viral load at diagnosis, and it typically led to more severe disease.

Patients with long-term shedding shared several characteristics indicative of impaired immunity. Compared with patients who cleared the virus relatively quickly, they harbored more exhausted CD8+ T cells and had an increased likelihood of virally induced lymphopenia. About 40% of patients with a high viral load and lymphopenia died within 50 days, compared with around 10% of patients with a low viral load and more lymphocytes.

The scientists also detected metabolic abnormalities in cells from patients with lymphopenia. For example, the polyamine pathway, which helps control lymphocyte activation, was disrupted, and bile salts, which perform immune-regulating functions, were reduced. In addition, patients with a high viral load and lymphopenia had more intestinal bacteria in their blood, which could promote lymphocyte death.

According to Zitvogel, the findings suggest that SARS-CoV-2 sparks a vicious cycle. In patients with metastatic or hematologic cancers or existing lymphopenia, the virus may further reduce lymphocyte numbers by inducing T-cell exhaustion, liberating bacteria from the intestines, and altering immune cell metabolism. As a result, patients may be unable to clear the virus for an extended period. The findings support viral-load testing in patients with cancer and COVID-19, Zitvogel said. If patients have a high viral load, they should receive antiviral therapies, such as monoclonal antibodies, or treatments that boost lymphocyte numbers.

The work also raises that possibility that prolonged viral shedding could contribute to the continued transmission of the virus because patients with cancer may remain infectious. Moreover, other research has found that people with long-term infections can generate new viral variants that may be better at evading the immune system, and may make vaccines less effective.

The research “goes some way to explaining why some patients have worse outcomes” when they have COVID-19, said Samra Turajlic, MBBS, PhD, of the Francis Crick Institute in London, UK, who wasn't involved in the work. Now, scientists need to determine whether the effect differs based on cancer type and treatment, as well as risk factors such as age and comorbidities, she said.

The possibility that patients with cancer and COVID-19 could contribute to the emergence of new viral variants is worrying, said Jeremy Warner, MD, of Vanderbilt University in Nashville, TN, who wasn't connected to the research. He added that the findings could lead to changes in therapy for patients with cancer to make them less vulnerable to severe COVID-19: “If a patient has lymphopenia, you might worry about giving them treatments,” such as steroids. –Mitch Leslie