key: cord-0975783-jo7i2855
authors: Hodder, Angus; Williams, Lindsey; Chu, Jan; Bamford, Alasdair; Rodrigues, Charlene; Gilmour, Kimberley; Awuah, Arnold; Tahami, Fariba; Dalton, Caroline; McGarrity, Orlagh; Vora, Ajay
title: SARS-CoV-2–specific T-cell responses to recurrent COVID-19 pneumonitis in a patient with post-CART B-cell aplasia
date: 2022-01-12
journal: Blood Adv
DOI: 10.1182/bloodadvances.2021006626
sha: 76d71c269738ca51baab509d7577bae7f7f29ed2
doc_id: 975783
cord_uid: jo7i2855

nan

! Figure!1! Assay!used!to!assess!patient's!T4cell!response! ! Figure 1 The role of T cells in the pathogenesis of acute coronavirus disease-19 (COVID-19) and the subsequent establishment of short and long-term immune response to the natural infection and to vaccination is under intense investigation [1] [2] [3] . It is generally agreed that a coordinated humoral and cellular immune response plays a key role in protection from disease [4] [5] [6] [7] . In this context we read with interest the study by Dhakal et al 8 As he had no measurable SARS-CoV-2 specific anti-spike antibody in serum, we investigated whether he had mounted a T cell response to the virus. Separated peripheral blood mononuclear cells from the patient were isolated from lithium heparin blood, and then put through an assay as shown in Figure 1 . They were cultured for 72 hours in the presence of media alone, or with the addition of PHA as a positive control, or in the presence of peptides to SARS-CoV-2 spike, nucleocapsid and membrane proteins. This was followed by pulsing with tritiated thymidine and incorporation of tritium into proliferating cells measured by scintillation counting. Patient's results were the mean of duplicates; proliferation to spike antigen was 7857 counts per minute (cpm), to membrane antigen was 5876 cpm, and to nucleocapsid antigen was 7119 cpm. The mean proliferative response in 4 healthcare workers, post symptomatic SARS-CoV-2 PCR positive infection were 4906 cpm to spike antigen, 7260 cpm to membrane antigen and 5551 cpm to nucleocapsid antigen. As such we evidenced that he had proliferative responses to spike, nucleocapsid and membrane proteins in the assay that are comparable to those of healthy controls with no known immunological dysfunction. The batch of immunoglobulin infusion he was receiving for replacement therapy tested negative for SARS-CoV-2 spike and nucleocapsid specific antibody.

To our knowledge, this is the first report of a CAR-T patient clearing SARS-CoV-2 despite ongoing severe B-cell aplasia and lack of a humoral response. We did not have samples to test T cell responses at earlier time points so it is possible that viral clearance may have been in part achieved by the anti-viral drugs he received for the last episode of pneumonitis 10 . However, the presence of strong T cell responses to all 3 viral proteins in the in vitro assay coinciding with in vivo viral clearance provides strong circumstantial evidence that cell mediated immunity, alongside innate immunity, was the primary mechanism for viral control. As such, antibody testing does not provide a complete measure of immunity to SARS-CoV-2 infection (and, by extrapolation, vaccination) in patients incapable of mounting a humoral response. Studies in this context must include T cell responses to determine the presence or absence of immunity. Good proliferative response to spike, nucleocapsid and membrane proteins.

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