Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 disease pandemic. In some patients, the symptoms are mild, and a fraction of SARS-CoV-2-infected individuals develop severe illness with a high fatality rate due to lung damage and acute respiratory distress syndrome.1Innate lymphoid cells (ILCs) are a recently identified type of effector immune cells that rapidly sense environmental stimuli and participate in early immune responses by promptly secreting large amounts of cytokines.2 The ILC2 subpopulation was shown to mediate Type 2 responses and to recruit eosinophils during viral lung infections upon the release of alarmins (e.g., IL-33) by damaged epithelial cells.3,4,5 ILC2s were also shown to participate in the termination of inflammatory responses and tissue repair by amphiregulin secretion. In addition, ILC2s are critical in the early phases of allergic lung inflammation, including that induced by the protease allergen papain.6 Based on the essential function of the papain-like protease PLpro in regulating SARS-CoV-27 (Fig. 1a) and the severe lung damage caused by this virus, we sought to investigate the potential involvement of ILC2s in immune responses to COVID-19.