A Short Series of Case Reports of COVID-19 in Immunocompromised Patients.

Immunocompromised individuals are at risk of prolonged SARS-CoV-2 infection due to weaker immunity, co-morbidities, and lowered vaccine effectiveness, which may evolve highly mutated variants of SARS-CoV-2. Nonetheless, limited data are available on the immune responses elicited by SARS-CoV-2 infection, reinfections, and vaccinations with emerging variants in immunocompromised patients. We analyzed clinical samples that were opportunistically collected from eight immunocompromised individuals for mutations in SARS-CoV-2 genomes, neutralizing antibody (NAb) titers against different SARS-CoV-2 variants, and the identification of immunoreactive epitopes using a high-throughput coronavirus peptide array. The viral genome analysis revealed two SARS-CoV-2 variants (20A from a deceased patient and an Alpha variant from a recovered patient) with an eight amino-acid (aa) deletion within the N-terminal domain (NTD) of the surface glycoprotein. A higher NAb titer was present against the prototypic USA/WA1/2020 strain in vaccinated immunocompromised patients. NAb titer was absent against the Omicron variant and the cultured virus of the 20A variant with eight aa deletions in non-vaccinated patients. Our data suggest that fatal SARS-CoV-2 infections may occur in immunocompromised individuals even with high titers of NAb post-vaccination. Moreover, persistent SARS-CoV-2 infection may lead to the emergence of newer variants with additional mutations favoring the survival and fitness of the pathogen that include deletions in NAb binding sites in the SARS-CoV-2 surface glycoprotein.

Immunoreactive peptide maps of SARS-CoV-2.

Serodiagnosis of SARS-CoV-2 infection is impeded by immunological cross-reactivity among the human coronaviruses (HCoVs): SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, 229E, HKU1, and NL63. Here we report the identification of humoral immune responses to SARS-CoV-2 peptides that may enable discrimination between exposure to SARS-CoV-2 and other HCoVs. We used a high-density peptide microarray and plasma samples collected at two time points from 50 subjects with SARS-CoV-2 infection confirmed by qPCR, samples collected in 2004-2005 from 11 subjects with IgG antibodies to SARS-CoV-1, 11 subjects with IgG antibodies to other seasonal human coronaviruses (HCoV), and 10 healthy human subjects. Through statistical modeling with linear regression and multidimensional scaling we identified specific peptides that were reassembled to identify 29 linear SARS-CoV-2 epitopes that were immunoreactive with plasma from individuals who had asymptomatic, mild or severe SARS-CoV-2 infections. Larger studies will be required to determine whether these peptides may be useful in serodiagnostics.