Our Single cell based COVID-19 study, highlights a dysregulated antigen presentation, CD40-CD40LG deficiency-mediated heightened immune/inflammatory/stress and antiviral response in the COVID-19 positive and recovered individuals, faster cellular transition in the COVID-19 patients, and COVID-19 disease biomarkers such as FOS, CD45, and CD74. These findings may further assist in understanding the complexity of immune response heterogeneity that possibly can serve to delineate treatment strategies for SARS-CoV-2 infection. This evidence concerns the gene CD74 and COVID-19.