Hyeyoung Lee , M.D., Ji Hyeong Ryu , B.S., Hye-Sun Park , M.S., Ki Hyun Park , M.S., Hyunjoo Bae , B.S., Sojeong Yun , B.S., Ae-Ran Choi , B.S., Sung-Yeon Cho , M.D., Chulmin Park , Ph.D., Dong-Gun Lee , M.D., Jihyang Lim , M.D., Jehoon Lee , M.D., Seungok Lee , M.D., Soyoung Shin , M.D., Haeil Park , M.D., and Eun-Jee Oh , M.D.. Ann Lab Med 2019;39:566-71. https://doi.org/10.3343/alm.2019.39.6.566

Sojeong Yun, B.S., Ji Hyeong Ryu, M.S., Joo Hee Jang, B.S., Hyunjoo Bae, M.S., Seung-Hyo Yoo, M.T., Ae-Ran Choi, M.T., Sung Jin Jo, M.D., Jihyang Lim, M.D., Jehoon Lee, M.D., Hyejin Ryu, M.D., Sung-Yeon Cho, M.D., Dong-Gun Lee, M.D., Jongmin Lee, M.D., Seok Chan Kim, M.D., Yeon-Joon Park, M.D., Hyeyoung Lee, M.D., and Eun-Jee Oh, M.D.. Ann Lab Med 2021;41:577-87. https://doi.org/10.3343/alm.2021.41.6.577

Quantitative SARS-CoV-2 antibody assays against the spike (S) protein are useful for monitoring immune response after infection or vaccination. We compared the results of three chemiluminescent immunoassays (CLIAs) (Abbott, Roche, Siemens) and a surrogate virus neutralization test (sVNT, GenScript) using 191 sequential samples from 32 COVID-19 patients. All assays detected >90% of samples collected 14 days after symptom onset (Abbott 97.4%, Roche 96.2%, Siemens 92.3%, and GenScript 96.2%), and overall agreement among the four assays was 91.1% to 96.3%. When we assessed time-course antibody levels, the Abbott and Siemens assays showed higher levels in patients with severe disease (p < 0.05). Antibody levels from the three CLIAs were correlated (r = 0.763–0.885). However, Passing–Bablok regression analysis showed significant proportional differences between assays and converting results to binding antibody units (BAU)/mL still showed substantial bias. CLIAs had good performance in predicting sVNT positivity (Area Under the Curve (AUC), 0.959–0.987), with Abbott having the highest AUC value (p < 0.05). SARS-CoV-2 S protein antibody levels as assessed by the CLIAs were not interchangeable, but showed reliable performance for predicting sVNT results. Further standardization and harmonization of immunoassays might be helpful in monitoring immune status after COVID-19 infection or vaccination.

Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (n = 23), non-reactivation (n = 24) versus CMV disease (n = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells’ maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4⁺ T cell expression decreased significantly compared with that in the BXM group. However, CD4⁺CD161⁺ and CD4⁺CD25⁺CD127low T cell expression levels increased significantly. In the CD8⁺ T cell subset, a decrease in CD8⁺CD28nullCD57⁺ and CD8⁺CCR7⁺ T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4⁺CD161⁺ and CD4⁺CD25⁺CD127low T cells and an early decrease in CD8⁺CD28nullCD57⁺ and CD8⁺CCR7⁺ T cells, some of which are associated with acute rejection.

Even though vaccines protected many from infection, not all were protected, and vaccinated individuals displayed a wide range of clinical outcomes, from complete protection against infection to multiple breakthrough infections. This study aimed to identify baseline differences following identical ChAdOx1/ChAdOx1/BNT162b2 in infection-free and breakthrough-infected individuals to find molecular signatures linked to enhanced SARS-CoV-2 protection. Samples from a previous longitudinal study were analyzed, classifying subjects as ‘Protected’ or ‘Infected’ based on infection status over two years. SARS-CoV-2–specific immunological assays and single-cell RNA sequencing evaluated baseline differences. Although humoral response measurements showed no significant difference, enhanced cellular responses via enzyme-linked immunospot assays were observed in the Protected group. Differentially expressed genes and pathway analysis of T/NK subsets showed the Infected group had reduced inflammation and interferon responses. The Infected group also displayed downregulated interaction with CD4+ T cells. B subset analysis revealed more memory B cells in the Infected group, accompanied by downregulation of immune regulatory genes and upregulation of the small ubiquitin-related modifier pathway. Our findings revealed differential molecular signatures in the baseline immune subsets of vaccinated individuals with prolonged protection and breakthrough infection. Reduced immune regulation and altered cell interactions may contribute to breakthrough infection, providing insights for future vaccine development and targeted protective strategies.