Perspective: diagnostic laboratories should urgently develop T cell assays for SARS-CoV-2 infection

Abstract

Introduction: Diagnostic tests play a critical role in the management of Sars-CoV-2, the virus responsible for COVID-19. There are two groups of tests, which are in widespread use to identify patients who have contracted the virus. The commonly used reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test becomes negative once viral shedding ceases by approximately three weeks. Antibody tests directed to viral antigens become positive after the second week of infection. IgG antibody responses to the virus are muted in children, pregnant females and those with mild symptoms. IgA and IgM antibodies rapidly wane although IgG antibodies directed to the receptor-binding domain (RBD) of the spike (S) glycoprotein are more durable. Current data shows variability in the sensitivity of commercial and in-house antibody tests to SARS-CoV-2. Areas covered: The role of T cells in acute illness is uncertain but long-term protection against the virus may rely on memory T cell responses. Measuring memory T cell responses is important for retrospective confirmation of cases, who may have been infected early in the pandemic before reliable RT-qPCR tests were available and whose SARS-CoV-2 antibodies may have become undetectable. Relevant peerreviewed published references from PubMed are included up to 15 March 2021. The reader is advised to seek up-to-date information on specific aspects of COVID-19 which are changing on a daily basis. Expert opinion: After surveying the literature, the authors present the case for urgent development of diagnostic T cell assays for SARS-CoV-2 by accredited laboratories.

Letter to the editor regarding ‘perspective: diagnostic laboratories should urgently develop T cell assays for SARS-CoV-2 infection’

“…These data are consistent with reports showing elevated T-cell responses in symptomatic individuals that can persist months after SARS-CoV-2 infection [ 13 ]. Also, the data align with the proposed clinical value of T-cell testing in patients who may have reduced antibody levels, such as convalescent patients long after infection and individuals with asymptomatic or mild infections [ 1 , 10 ], as well as those who experience long-term complications or inflammatory sequelae, such as multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A) [ 5 , 14 , 15 ]. These observations, as well as other rapidly accumulating data, support the role of T-cell repertoire testing in providing critical insights on the SARS-CoV-2 immune response, which is relevant for evaluating natural as well as vaccine-induced immunity.…”

“…In ‘Perspective: Diagnostic laboratories should urgently develop T-cell assays for SARS-CoV-2 infection,’ Ameratunga and colleagues present the case for urgent development of T-cell assays for diagnosis of past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [ 1 ]. We agree with the authors’ assessment that there is a need for rigorously validated T-cell–based assays and that these assays have clinical utility for identifying past SARS-CoV-2 infection, particularly for patients with borderline or undetectable results using RT-PCR or serology tests.…”

“…We agree with the authors’ assessment that there is a need for rigorously validated T-cell–based assays and that these assays have clinical utility for identifying past SARS-CoV-2 infection, particularly for patients with borderline or undetectable results using RT-PCR or serology tests. T-cell assays may have value for identifying prior SARS-CoV-2 infection in the following groups: convalescent patients with waning antibody titers; individuals with a history of asymptomatic or mild infection who may have a poor or diminished antibody response; patients with unexplained myocarditis, pulmonary fibrosis, thrombotic events, or psychiatric morbidity long after initial infection; individuals who may mount a T-cell response without an antibody response; and patients receiving donor blood products that may contain SARS-CoV-2–specific antibodies [ 1–6 ].…”

“…Although the authors correctly noted a lack of commercially available assays at the time of submission [ 1 ], we would like to report the development and validation of a highly sensitive and standardized T-cell–based assay (T-Detect™ COVID, available from Adaptive Biotechnologies, Seattle, Washington, USA) that received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) on 5 March 2021 for identification of prior SARS-CoV-2 infection from blood samples [ 7 ]. T-Detect COVID relies on next-generation sequencing of the T-cell receptor (TCR) repertoire to identify sequences associated with clonal expansion of SARS-CoV-2–specific T-cells [ 8 ].…”

“…Currently, T-Detect COVID is the only available NGS-based T-cell assay for evaluating past SARS-CoV-2 infection and is offered only in the United States. Similar to the ELISpot and interferon-γ release assays described by Ameratunga and colleagues [ 1 ], the T-Detect COVID assay is designed to provide a binary response indicating evidence of prior SARS-CoV-2 infection. However, unlike functional T-cell assays, supporting quantitative results are not provided with the T-Detect COVID report, and in the absence of this additional information (e.g.…”