Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

Shi, H.; Zuo, Y.; Yalavarthi, S.; Gockman, K.; Zuo, M.; Madison, J. A.; Blair, C. N.; Woods, R. J.; Lood, C.; Knight, J. S.; Kanthi, Y.

Severe cases of coronavirus disease 2019 (COVID-19) are regularly complicated by respiratory failure. While it has been suggested that elevated levels of blood neutrophils associate with worsening oxygenation in COVID-19, it is unknown whether neutrophils are drivers of the thrombo-inflammatory storm or simple bystanders. We now report that patients with COVID-19 (n=96) have markedly elevated levels of the neutrophil activation marker S100A8/A9 (calprotectin) in their blood. Calprotectin tracked with other acute phase reactants including C-reactive protein, D-dimer, ferritin, and absolute neutrophil count, but was superior in identifying patients requiring mechanical ventilation. In longitudinal samples, calprotectin rose as oxygenation worsened. When tested on day 1 or 2 of hospitalization (n=52 patients), calprotectin levels were significantly higher in patients who progressed to severe COVID-19 requiring mechanical ventilation (7805 +/- 7585, n=23) as compared to those who remained free of intubation (3123 +/- 2990, p=0.0059). In summary, serum calprotectin levels track closely with current and future COVID-19 severity, strongly implicating neutrophils as active perpetuators of inflammation and respiratory compromise in COVID-19.