T-cell hyporeactivity foreshadows poor COVID-19 outcomes

Hyporeactivity of the T-cell response seems to signal longer virus persistence and poor outcomes in patients with the novel coronavirus disease (COVID-19), a recent study has found.

Fifty-five COVID-19 patients were enrolled in the study, of whom 30 needed mechanical ventilation and 25 did not. In the former subgroup, 23 survived and seven died. Forty-two healthy controls were also enrolled in parallel.

Using heparinized whole blood samples and polyclonally activated T cells, the researchers assessed T cell activation in the participants, described not only as cytokine release but also by their downstream effects on different cells, including basophils, neutrophils, and monocytes.

In healthy controls, T cell activation led to a strong downregulation of CD131 (to 13 percent), a receptor of interleukin-3 (IL-3) often expressed by basophils and used as a marker for their activation. Concomitantly, in response to T cell activation, CD14+ monocytes showed a marked upregulation in their IL-3 receptor molecule, CD123 (to 1,225 percent).

In COVID-19 patients, such responses were attenuated. Those on ventilation, for example, showed only weak CD131 suppression on basophils (to 77 percent) and a similarly muted upregulation of CD123 (to 345 percent). The magnitude of responses in nonventilated patients lay in between the ventilated patients and healthy controls.

Notably, using multiple blood samples collected over a prolonged period of time, the researchers could track the changes in T-cell hyporeactivity in relation to disease course. Samples from two ventilated patients with fatal outcomes showed persistent hyporeactivity lasting for up to 14 days, while those who were eventually weaned off ventilation showed improving reactivity patterns.

“[O]ur data suggest that approaches to overcome T-cell hyporeactivity combined with concepts to specifically suppress hyperinflammation induced by innate immune cells, particularly monocytes/macrophages, could be promising immunotherapy for critically ill COVID-19 patients,” the researchers said.