Circulating inflammatory monocytes/macrophages
A detailed account of the role of inflammatory macrophages in the pathogenesis of SARS-CoV is reported by He et al. (2007). Animal studies have demonstrated extensive recruitment and accumulation of these cells in the lungs, which correlated with the release of TNF-α, IL-1β, and IL-6 and the development of ARDS, reviewed by Gralinski and Baric (2015). Interestingly, depletion of these inflammatory macrophages in animals infected with SARS-CoV was associated with a high recovery rate, thus suggesting their critical role in disease pathogenesis (Channappanavar et al., 2016). Similarly, SARS-CoV infection in animals with STAT1 knockout in alternatively activated macrophages displayed attenuated lung damage and protection from disease (Page et al., 2012). Besides, a large number of clinical studies support an integral role of IMMs in SARS-CoV infected patients (Wong et al., 2004; Tisoncik et al., 2012; Liu et al., 2019). Recent studies from BALF from COVID-19 patients have also demonstrated the critical role of circulating monocyte-derived macrophages in the induction of robust proinflammatory reaction (Liao et al., 2020). Blood cell analysis of 18 COVID-19 patients revealed an activated status of inflammatory macrophages (Zhang D. et al., 2020). In line with these findings, scRNA-seq followed by immune cell profiling of blood cells revealed an increased number of CD14++ monocytes (Wen et al., 2020). Severe and critically ill patients also exhibit macrophage activation syndrome (MAS) in some cases (Giamarellos-Bourboulis et al., 2020). Thus, all the evidence directs towards a critical role of inflammatory macrophages in disease severity during COVID-19 and a potential therapeutic target. Intervention which reduces the impetus to induce MAS like antibodies directed against IL-6 and IL-1β has shown promising clinical outcomes, reviewed by Otsuka and Seino (2020).