After global vaccination, there was a drastic reduction in COVID-19 severe cases. However, it is important to understand what physiopathological pathways played a role in patients protection during the pandemic’s first months. Much remains to be understood about the disease, but the protective role of antibodies (Ig) is widely accepted in SARS-CoV-2 infection. Ig functions are mainly carried out by receptors that bind to their Fc portion (FcR), and less attention has been dedicated to the cytoplasmic members of this family. In this work, we used single-cell RNA sequencing (scRNAseq) data to discern cell populations present in bronchoalveolar lavage fluid obtained from healthy individuals or patients with mild or severe COVID-19. Then, we evaluated the transcription of neonatal FcR (FcRn, FCGRT gene) and tripartite motif-containing protein 21 (TRIM21) and its downstream signaling components. The TRIM21 pathway is vital for virus infections as it has a dual function, leading opsonized viruses to degradation by proteasomes and the activation of innate inflammatory anti-virus response. Our findings yielded no supporting evidence to endorse the involvement of FcRn in protecting COVID-19 patients. On the other hand, TRIM21 and related members of the via, such as members of the ubiquitin-proteasome system (UPS), were consistently upregulated in innate and adaptive lymphoid and myeloid cells from mild cases. However, despite the transcription of the danger sensors DDX58 and IFIH1, the transcriptional level of inflammatory IL1B and IL18 was generally very low, along with the NLRP3 danger sensor, members of the NF-κB pathway, and TNF. Although there were much higher numbers of cells in the samples from patients with severe symptoms, most cells transcribed near-zero levels of TRIM21. Therefore, our data suggest that TRIM21 may contribute to SARS-CoV-2 protection by reducing the viral load, while not contributing to the inflammatory branch of the pathway and pathogenic cytokine strom.