Journal of Translational Medicine (Dec 2022)

Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors

  • Mallikarjuna R. Gedda,
  • Patrick Danaher,
  • Lipei Shao,
  • Martin Ongkeko,
  • Leonard Chen,
  • Anh Dinh,
  • Mame Thioye Sall,
  • Opal L. Reddy,
  • Christina Bailey,
  • Amy Wahba,
  • Inna Dzekunova,
  • Robert Somerville,
  • Valeria De Giorgi,
  • Ping Jin,
  • Kamille West,
  • Sandhya R. Panch,
  • David F. Stroncek

DOI
https://doi.org/10.1186/s12967-022-03751-7
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 16

Abstract

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Abstract Background SARS-CoV2 can induce a strong host immune response. Many studies have evaluated antibody response following SARS-CoV2 infections. This study investigated the immune response and T cell receptor diversity in people who had recovered from SARS-CoV2 infection (COVID-19). Methods Using the nCounter platform, we compared transcriptomic profiles of 162 COVID-19 convalescent donors (CCD) and 40 healthy donors (HD). 69 of the 162 CCDs had two or more time points sampled. Results After eliminating the effects of demographic factors, we found extensive differential gene expression up to 241 days into the convalescent period. The differentially expressed genes were involved in several pathways, including virus-host interaction, interleukin and JAK-STAT signaling, T-cell co-stimulation, and immune exhaustion. A subset of 21 CCD samples was found to be highly “perturbed,” characterized by overexpression of PLAU, IL1B, NFKB1, PLEK, LCP2, IRF3, MTOR, IL18BP, RACK1, TGFB1, and others. In addition, one of the clusters, P1 (n = 8) CCD samples, showed enhanced TCR diversity in 7 VJ pairs (TRAV9.1_TCRVA_014.1, TRBV6.8_TCRVB_016.1, TRAV7_TCRVA_008.1, TRGV9_ENST00000444775.1, TRAV18_TCRVA_026.1, TRGV4_ENST00000390345.1, TRAV11_TCRVA_017.1). Multiplexed cytokine analysis revealed anomalies in SCF, SCGF-b, and MCP-1 expression in this subset. Conclusions Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed following recovery from COVID-19 infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04360278 Registered April 24, 2020.

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