Altogether, this raised the hypothesis that macrophage clusters in the lung, functionally equivalent to those in the synovium, may govern chronic inflammation or resolution of COVID-19 pneumonitis, and that the hallmark cytokine signature related to these clusters (e.g., SPP1) might be a useful biomarker of prognosis and a therapeutic target during the unpredictable trajectory of COVID-19. Here, SPP1 is linked to COVID-19.