The coronavirus may shut down the immune system’s vital classrooms

The coronavirus may shut down the immune system’s vital classrooms Autopsies suggest germinal centers, where antibody responses are honed, don’t develop in severe COVID-19 Science | AAAS

At the top of the long list of uncertainties about COVID-19 is whether people who recover will develop durable immune responses to the coronavirus that causes it. A research team that has autopsied people who died from COVID-19 has now discovered they lack so-called germinal centers, classrooms in the spleen and lymph nodes in which immune cells learn to mount a long-lasting antibody response to a pathogen. Although the finding may not apply to people who have mild or asymptomatic coronavirus infections, it may help explain COVID-19 progression in the sickest cases and provide important insights to vaccine developers.

The study, led by immunologist Shiv Pillai of the Ragon Institute of MGH, MIT and Harvard and published last week in Cell, may take on increased importance as a report out yesterday provided the first compelling evidence that a person can become reinfected with SARS-CoV-2, suggesting antibody protection could be fleeting in some people.

Pillai and co-workers analyzed the spleen and the thoracic lymph nodes, which drain immune cells from the lungs, of 11 people who died from COVID-19, comparing the tissues with those of six age-matched people who died from other causes. When all goes well, these sites gather antibodymaking B cells into newly formed germinal centers, distinctive microstructures where these cells mature and refine their antibody response to the virus. But germinal centers did not form in the thoracic lymph nodes and spleens of the autopsied COVID-19 patients, the researchers reported. “This is kind of shocking that they don’t, but they don’t,” Pillai says.

The work confirms a smaller study of autopsied COVID-19 patients reported online on 7 August in Current Medical Science by Duan Ya-Qi of the Huazhong University of Science and Technology and colleagues. “These two independent studies establish a profound lack of [antibody] responses in the deceased population of COVID-19 patients,” says Yang Xiang-Ping, a senior author of that paper.

Smita Iyer, an immunologist at the University of California, Davis, who published a preprint that describes germinal center formation in monkeys infected with SARV-CoV-2, says Pillai and colleagues have made “an important addition to the field,” noting that “clearly the immune system didn’t do what it was supposed to do.” But Iyer cautions that the data from her monkey studies, which may more closely mirror asymptomatic or mild disease in humans as the monkeys never develop severe disease, did not find an absence of germinal centers. “The immune response to SARS-CoV-2 is extremely heterogenous,” she says. ...