Patients with hematologic cancers such as leukemia who are hospitalized with COVID-19 are more likely to die than are those with solid cancers who contract the infection and go to the hospital, according to an analysis posted as a preprint to In Review on February 2. The researchers suggest that compromised immune responses could lead to these poor outcomes in blood cancer patients with acute COVID-19, as they found that a depletion of CD8+ T cells was associated with the highest mortality among all the participants.

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“If you think about it, it makes sense. Patients with leukemia by definition have a cancer of the immune system,” says Mikkael Sekeres, the chief of hematology at the University of Miami’s Sylvester Cancer Center who was not involved in the study. Corrupted bone marrow produces abnormal white blood cells, which is why people with leukemia are more susceptible to infection in the first place, adds Sekeres, who belongs to an American Society of Hematology research group gathering ongoing data about clinical outcomes of blood cancer patients with COVID-19.

Since early on in the pandemic, multiple studies have found that cancer patients with COVID-19 have higher mortality rates than patients without cancer, especially if the cancer is in their blood. The reason is unclear. “Maybe inadequate immune responses are part of the problem,” says Santosha Vardhana, an oncologist at Memorial Sloan Kettering Cancer Center and an author of the study.

Vardhana and colleagues wanted to learn which immune profiles correlate with a higher risk of death in cancer patients with COVID-19, and if blood cancer patients were more likely than others to have the riskiest of those profiles. They compared the mortality rates and immune profiles of blood and solid cancer patients with COVID-19 at Sloan Kettering in New York and the University of Pennsylvania in Philadelphia.

They saw elevated mortality rates among hospitalized patients with blood cancer and COVID-19 compared to those with other cancers, as in the earlier studies. Among 45 blood cancer patients with COVID-19 at Sloan Kettering, for example, almost half died in the hospital compared to 20% of 39 people with solid cancer.

In a group of COVID-19 patients at Penn, more than half with blood cancer (12 of 22) died within 30 days of leaving the hospital. This was true for one-third (26 of 78) of those with solid cancer.

The immune profiles of these two groups might explain the difference, Vardhana says. Compared to COVID-19 patients with solid cancer, those with blood cancer had elevated levels of inflammatory markers that suggested a heightened immune response to the virus.

“Even when [blood cancer patients] have cleared the virus, they then seem to still have a lingering effect of COVID, so it looks more like a chronic infection,” says Sheeba Irshad, an oncologist at King’s College London who has also profiled the immune responses of cancer patients to COVID-19 but was not involved in this study. Irshad says that solid cancer patients with COVID-19 generally mount an immune response like that of people without cancer, whereas the immune profiles of blood cancer patients are distinctive.

A detailed analysis of the lymphocytes of 45 COVID-19 patients, conducted at Penn, supports Irshad’s claim. Just like those without cancer, most solid cancer patients had a balanced complement of B cells, CD4+ T cells, and CD8+ T cells—all of which are critical for adaptive immunity to a virus. In contrast, those with blood cancer showed less B cell and CD4+ T immune cell production, indicating compromised immunity.

At Sloan Kettering, blood cancer patients with few B cells frequently died in the hospital. Solid cancer patients, on the other hand, found it easier to maintain their B cell counts and usually lived as long as they had enough CD8+ T cells. Patients who faced significant CD8+ T cell depletion, across all cancer types, died in the hospital 71 percent of the time even when their B cell responses were adequate.

Vardhana notes that some chemotherapies suppress T cells, making it an open question whether COVID-19 itself or a cancer patient’s chemotherapy contributes more to T cell depletion. He says he hopes to tackle this question in future research.

Implications for COVID-19 vaccines for cancer patients

This study arrives as COVID-19 vaccination programs are ramping up in the United States, prompting the American Association for Cancer Research’s COVID-19 and Cancer Task Force to call for cancer patients to receive priority vaccine access because having cancer is a risk factor for developing severe COVID-19. While this aligns with recommendations from the US Centers for Disease Control and Prevention, there is little direct evidence of the interaction between the vaccine and cancer because many people with cancer were excluded from vaccine trials.

Vardhana argues that vaccination could be helpful for many cancer patients, though, given that both currently approved vaccines in the US generate a robust CD8+ T cell response.

“Based on the fact that we have some data to suggest that a T cell response is important and helpful, it’s reasonable to get [the vaccine],” Vardhana says. Irshad is more cautious, arguing that more evidence of the specific benefits of vaccines for cancer patients is needed. Her recommendation is that everyone who cares for someone with cancer—family members and health care workers—be vaccinated so that there is some degree of protection around that person.

E. Bange et al. CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer. In Review, doi:10.21203/rs.3.rs-162289/v1, 2021.