Experimental Auxora may disrupt immune circuits in COVID-19 pneumonia

Inside intensive-care units, the most useful sample is sometimes taken from the hardest-to-reach place. Researchers studying patients with severe COVID-19 pneumonia on mechanical ventilation collected fluid from their lungs while testing Auxora, an experimental drug that may interrupt the immune circuits behind dangerous inflammation.

The study, published in the Journal of Clinical Investigation, focused on CRAC channels—calcium-release channels that help activate immune cells. Auxora blocks them. In lung samples from the ventilated patients, the researchers found evidence that the drug dampened the exchange between T-cells and macrophages, immune cells implicated in severe pneumonia.

RNA sequencing and other laboratory tests pointed to T-cells as the main target. By reducing signals from these cells, Auxora appeared to limit the activation of inflammatory macrophages. That mechanism builds on observations made during the COVID-19 pandemic, when G. R. Scott Budinger and colleagues linked persistent lung inflammation to interactions between monocyte-derived macrophages and T-cells.

So what changes for patients? Not treatment today, and not every form of pneumonia. This small trial was not designed to measure clinical outcomes, although other studies of Auxora reported a reduction in 30-day mortality among COVID-19 patients. The immediate gain is a clearer way to identify which immune pathway a drug is affecting, potentially helping researchers match immune-targeting treatments to the patients most likely to benefit.

Budinger, chief of Pulmonary and Critical Care at Northwestern’s Feinberg School of Medicine, said the idea could extend to influenza and RSV, but he also stressed the limits: bacterial pneumonia, viral pneumonia and infections caused by different pathogens may trigger different immune responses. Future studies will need deeper molecular profiling of patients before testing which of them should receive such drugs.