Immunogenic SARS-CoV-2 S and N Protein Peptide and Cytokine Combinations as Biomarkers for Early Prediction of Fatal COVID-19

Abstract

Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk.

Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination

“…It indicates that vaccination by inactivated vaccines elicits a moderate cytokine response. For instance, IL‐18, IL‐6, and IL‐10, which have been corroborated to play a role in fatal COVID‐19 37,38 showed lower serum expression in the vaccinated group. On the other side, the appropriate expression of some cytokines in the infected individuals can inform the optimization of inactivated vaccines, as cytokines have the potential used as the adjuvant.…”

Immunized mice naturally process in silico-derived peptides from the nucleocapsid of SARS-CoV-2

“…1 ). Peptides in the RNA-binding domain are reactive during the early recovery of COVID-19, whereas CTD peptides are more reactive during late recovery [ 26 ]. These findings indicate that Npep2 can be used as a biomarker to identify severe cases and prevent complications.…”

Respuesta inmunitaria al SARS-CoV-2 previa a la vacunación en personal de salud de Alto Paraná, Paraguay, un estudio seroepidemiológico

“…El personal de salud es considerado una población de alto riesgo por encontrarse en la primera línea de acción en los diferentes niveles de atención sanitaria, además de la posibilidad de convertirse en diseminadores de infecciones dentro y fuera del ámbito hospitalario, por lo que su estudio es fundamental para evaluar la eficiencia de las medidas de protección adoptadas, y así, contribuir a evitar el colapso del sistema de sanitario 10,11 . En septiembre del 2020 la Organización Panamericana de la Salud informaba del gran número de personal de salud que había sido afectado, refiriéndose a la pandemia como una situación sin precedentes que había golpeado fuertemente a este sector 12 .…”