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. 2022 Oct 6:ciac663. doi: 10.1093/cid/ciac663

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Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Figure 4. — Comparison of CD4⁺ T-cell responses across the groups and longitudinal immune responses of the 2 patients with sampling at acute and rebound time points. Absolute T-cell counts compared across groups (A, B). Lines represent median values and points represent individual results. The 2 longitudinal patients are identified by an open triangle and open diamond. The empty square represents the coronavirus disease 2019 rebound patient who did not receive nirmatrelvir-ritonavir. T-cell subset flow cytometry data not available for longitudinal patient 2 (triangle) at rebound time point. T-cell stimulations were performed with peptide pools corresponding to spike, nucleocapsid, and membrane proteins as listed on the x-axis. Bars represent medians and groups are defined as acute, rebound, and late presentations. Severe acute respiratory syndrome coronavirus 2–specific CD4 T-cell responses are highlighted by memory (C), cytokine-producing (CD154 + IFN-γ+, CD154 + TNF-α+ or CD154 + IL-2+) (D), activated (CD154 + CD69+) (E), or Ag-specific proliferating (Ki-67+) and activated (PD-1+) T cells (F). For phenotyping of Ki-67 + and PD-1+ cells, a threshold of at least 20 events and a 2-fold increase over unstimulated cells was used, and samples were excluded if they did not meet these thresholds (E, F). Serum N Ag and C-reactive protein trends from the 2 longitudinal patients (G, H). T-cell responses and neutralizing antibodies from the acute and rebound presentation for 2 patients with longitudinal samples (I, J). T-cell responses are from S and N stimulations. Ag-specific CD4 T cells defined by (CD154 + CD69+, CD154 + IFN-γ+ and CD154 + TNF-α+), and neutralizing antibodies represented by percent binding inhibition on the sVNT. Abbreviations: Ag, antigen; S, spike; N, nucleocapsid; spec, specific; sVNT, surrogate virus neutralization test.