Immunocompromised patients and COVID infections: who is at risk?

Early in the pandemic, clinicians noticed that some immunocompromised patients had persistent SARS-CoV-2 infections, some lasting weeks or even months.

That has raised concerns that one of those cases could be behind an emerging virus variant that has benefited from a prolonged battle against the immune system.

A prospective study, “Shedding and evolution of SARS-CoV-2 in immunocompromised patients during the omicron period: a multicenter prospective analysis,” published in the journal Lancet microbe provides more clarity on which patient populations are at higher risk of prolonged infections – and suggests that this fear is likely unwarranted.

The study, led by Adam Lauring, MD, Ph.D., of Michigan Medicine’s Division of Infectious Diseases, is part of the larger IVY Network study sponsored by the CDC and led by Vanderbilt University.

The collaborative team followed 150 immunocompromised patients with COVID infections across five US health systems in 2022.

Each patient was studied and tested using nasal swabs collected from the start of SARS-CoV-2 infection until they were negative.

“We specifically looked at those who were at risk of prolonged infection, so they never cleared the virus,” Lauring said.

Immunocompromised conditions

Study participants suffered from a diverse set of immunocompromised conditions, ranging from people with B-cell cancers or receiving anti-B-cell therapy; solid organ or stem cell transplant recipients; people living with AIDS; and those with non-B cell cancers and autoimmune or autoinflammatory diseases.

The team found that only 25% of patients tested positive using the gold standard highly sensitive PCR test for 21 days or more after illness onset.

Only 8% tested positive for live virus for 21 days or more. The median time to last positive test was nine days.

“Unlike many reported cases, we found that very few people suffered from prolonged infection,” Lauring said.

Specifically, people with AIDS and those with B-cell cancers, such as certain leukemias and lymphomas, were more likely to have prolonged infections than patients with autoimmune diseases or non-B-cell cancers. And of the 59 enrolled patients who underwent solid organ transplant with T-cell immunosuppression, only one had an infection lasting more than 56 days.

Prolonged infection also appears to coincide with certain immunosuppressive treatments.

Importance of antibodies

Patients receiving treatment with rituximab or CAR-T therapy, which targets B cells, were more likely to suffer longer-lasting infections, highlighting the importance of antibodies (produced by B cells) for immunity .

Importantly, the team also notes that mutations within the subset of patients who had prolonged infections rarely, if ever, matched those of variants circulating within the broader global community.

“A lot of the success of a virus is its ability to evade immunity,” Lauring said.

“However, immunity is heterogeneous: what might lead a virus to evade the immune system in an immunocompromised patient versus patients at the population level is different.”

An overview of who is most at risk

As global immunity evolves due to vaccination and infection, monitoring this particular patient population for new variants may not be practical, he explained.

The study provides much-needed information about which immunocompromised patients are at greatest risk, Lauring says. He hopes the study will also lead to a refocusing of efforts to develop better therapies for these patients.