A landmark paper[1] entitled, “Fibrin drives thrombo-inflammation and neuropathology in COVID-19,” was published in August 2024 that concluded the mechanism of the thrombotic and neurological symptoms following a SARS-CoV-2 infection, often called “long COVID,” is attributable to the binding of fibrin to discrete portions of the spike protein, specifically three N-terminal domains. This paper is a high impact publication with >110,000 views, placing it in the 99th percentile of articles published contemporaneously. Here I examine the regions of the spike protein that bind to fibrin, fibrinogen, or both. The N-terminus of the spike protein contains the three strongest binding peptides and surprisingly, these regions are also the three insertions in the protein sequence that are unique to SARS-CoV-2 and not found in natural sarbecoviruses. All pre-pandemic sarbecoviruses have either a partial deletion in these regions or have protein amino acid substitutions that are non-conserved and therefore would not support fibrin binding. In addition, the three inserts also correspond to regions of the spike protein that have been shown previously to have high sequence homology with the HIV gp120 protein. GP120 is an HIV surface protein that binds to a host cell surface receptor on CD4+ T-cells and facilitates cell entry to begin infections. In comparing the immunological and clinical presentation of HIV and COVID-19 patients, the commonality of D-dimer production, CD4+ lymphopenia, neurotropism, and IL-10 expression strongly suggests that these protein sequence homologies are clinically relevant. A conclusion that the pathophysiology of long COVID is based on the insertion of spike protein motifs with sequence homology that mimic the HIV gp120 protein motif properties, and that these SARS-CoV-2 motifs are not found in the sarbecovirus subgenus strongly suggests that these inserts were design features in the synthetic assembly of SARS-CoV-2. [1] Ryu, J.K., Yan, Z., Montano, M. et al. Fibrin drives thromboinflammation and neuropathology in COVID-19. Nature 633, 905–913 (2024). https://doi.org/10.1038/s41586-024-07873-4