SARS-CoV-2 viral remnants and implications for inflammation and post-acute infection sequelae

At present, we do not understand precisely how the SARS-CoV-2 coronavirus induces a spectrum of immune responses in different infected hosts, including severe inflammation in some, or how post-acute infection sequelae come about. In this review, we consider a conceptual framework whereby the virus itself is a reservoir of peptide motifs with pro-inflammatory activity. These motifs can potentially be liberated by highly variable proteolytic processing by the host. We focus on the ability of viral peptide motifs that can mimic innate immune peptides (more commonly known as ‘antimicrobial peptides’ (AMPs)). AMPs (and their ‘xenoAMP’ mimics) are not themselves pathogen-associated molecular patterns (PAMPs) that activate innate immunity via recognition by host pattern recognition receptors (PRRs) but can strongly amplify PRR activation via promoting multivalent PAMP presentation.