Furthermore, the negative association of PMN IL-1β levels (after ex vivo stimulation with IFN and nigericin) with disease severity (WHO ordinal scale, Fig 6A) and patient neutrophil counts (Fig 6A and 6C) supports the exhaustion hypothesis, wherein PMNs from severe COVID-19 patients may be less responsive to stimuli due to prior in vivo activation. Here, IFNA1 is linked to COVID-19.