Long-term SARS-CoV-2-specific and cross-reactive cellular immune responses correlate with humoral responses, disease severity, and symptomatology

长期 SARS-CoV-2 特异性和交叉反应细胞免疫反应与体液反应、疾病严重程度和症状相关

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作者:Ida Laurén, Sebastian Havervall, Henry Ng, Martin Lord, Aleksandra Pettke, Nina Greilert-Norin, Lena Gabrielsson, Aikaterini Chourlia, Catarina Amoêdo-Leite, Vijay S Josyula, Mohamed Eltahir, Iliana Kerzeli, August J Falk, Jonathan Hober, Wanda Christ, Anna Wiberg, My Hedhammar, Hanna Tegel, Joachim

Background

Cellular immune memory responses post coronavirus disease 2019 (COVID-19) have been difficult to assess due to the risks of contaminating the immune response readout with memory responses stemming from previous exposure to endemic coronaviruses. The work herein presents a large-scale long-term follow-up study investigating the correlation between symptomology and cellular immune responses four to five months post seroconversion based on a unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific peptide pool that contains no overlapping peptides with endemic human coronaviruses.

Conclusion

Using a large cohort and a SARS-CoV-2-specific peptide pool we were able to substantiate that initial disease severity and symptoms correlate with the magnitude of the SARS-CoV-2-specific memory T cell responses.

Methods

Peptide stimulated memory T cell responses were assessed with dual interferon-gamma (IFNγ) and interleukin (IL)-2 Fluorospot. Serological analyses were performed using a multiplex antigen bead array.

Results

Our work demonstrates that long-term SARS-CoV-2-specific memory T cell responses feature dual IFNγ and IL-2 responses, whereas cross-reactive memory T cell responses primarily generate IFNγ in response to SARS-CoV-2 peptide stimulation. T cell responses correlated to long-term humoral immune responses. Disease severity as well as specific COVID-19 symptoms correlated with the magnitude of the SARS-CoV-2-specific memory T cell response four to five months post seroconversion.

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