Long-Term Accuracy of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Interferon-γ Release Assay and Its Application in Household Investigation.

BACKGROUND: An immunodiagnostic assay that sensitively detects a cell-mediated immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed for epidemiological investigation and for clinical assessment of T- cell-mediated immune response to vaccines, particularly in the context of emerging variants that might escape antibody responses. METHODS: The performance of a whole blood interferon-gamma (IFN-γ) release assay (IGRA) for the detection of SARS-CoV-2 antigen-specific T cells was evaluated in coronavirus disease 2019 (COVID-19) convalescents tested serially up to 10 months post-infection and in healthy blood donors. SARS-CoV-2 IGRA was applied in contacts of households with index cases. Freshly collected blood in the lithium heparin tube was left unstimulated, stimulated with a SARS-CoV-2 peptide pool, and stimulated with mitogen. RESULTS: The overall sensitivity and specificity of IGRA were 84.5% (153/181; 95% confidence interval [CI]: 79.0-89.0) and 86.6% (123/142; 95% CI: 80.0-91.2), respectively. The sensitivity declined from 100% (16/16; 95% CI: 80.6-100) at 0.5-month post-infection to 79.5% (31/39; 95% CI: 64.4-89.2) at 10 months post-infection (P < .01). The IFN-γ response remained relatively robust at 10 months post-infection (3.8 vs 1.3 IU/mL, respectively). In 14 households, IGRA showed a positivity rate of 100% (12/12) and 65.2% (15/23), and IgG of 50.0% (6/12) and 43.5% (10/23) in index cases and contacts, respectively, exhibiting a difference of + 50% (95% CI: +25.4 to +74.6) and +21.7% (95% CI: +9.23 to +42.3), respectively. Either IGRA or IgG was positive in 100% (12/12) of index cases and 73.9% (17/23) of contacts. CONCLUSIONS: The SARS-CoV-2 IGRA is a useful clinical diagnostic tool for assessing cell-mediated immune response to SARS-CoV-2.

Cellular and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients: An observational cohort study.

BACKGROUND: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response. METHODS: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination. RESULTS: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators (P < 0.001), mycophenolate (P = 0.002), and B cell lymphoma (P = 0.004); those associated with low cellular response rates included S1P receptor modulators (P < 0.001) and mycophenolate (P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination. CONCLUSIONS: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

Interferon-γ Release Assay for Accurate Detection of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Response.

We investigated feasibility and accuracy of an interferon-γ release assay (IGRA) for detection of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whole blood IGRA accurately distinguished between convalescent and uninfected healthy blood donors with a predominantly CD4+ T-cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the coronavirus disease 2019 pandemic.

Interferon-gamma release assay testing to assess COVID-19 vaccination response in a SARS-CoV-2 seronegative patient on rituximab: a case report.

We describe the case of a 44-year-old female patient on rituximab for the treatment of multiple sclerosis with undetectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG specific antibodies 18 days after the second dose of SARS-CoV-2 vaccine. Interferon-gamma release assay testing for SARS-CoV-2 was positive on day 19, demonstrating a robust T cell-mediated response despite the lack of an antibody-mediated response.

SARS-CoV-2 infection and COVID-19 severity in individuals with prior seasonal coronavirus infection.

We show that individuals with documented history of seasonal coronavirus have a similar SARS-CoV-2 infection rate and COVID-19 severity as those with no prior history of seasonal coronavirus. Our findings suggest prior infection with seasonal coronavirus does not provide immunity to subsequent infection with SARS-CoV-2.

High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease.

BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood, also known as RNAemia, has been reported, but its prognostic implications are poorly understood. This study aimed to determine the frequency of SARS-CoV-2 RNA in plasma and its association with coronavirus disease 2019 (COVID-19) clinical severity. METHODS: An analytical cross-sectional study was performed in a single-center tertiary care institution and included consecutive inpatients and outpatients with confirmed COVID-19. The prevalence of SARS CoV-2 RNAemia and the strength of its association with clinical severity variables were examined and included intensive care unit (ICU) admission, invasive mechanical ventilation, and 30-day all-cause mortality. RESULTS: Paired nasopharyngeal and plasma samples were included from 85 patients. The median age was 55 years, and individuals with RNAemia were older than those with undetectable SARS-CoV-2 RNA in plasma (63 vs 50 years; P = .04). Comorbidities were frequent including obesity (37.6%), hypertension (30.6%), and diabetes mellitus (22.4%). RNAemia was detected in 28/85 (32.9%) of patients, including 22/28 (78.6%) who required hospitalization. In models adjusted for age, RNAemia was detected more frequently in individuals who developed severe disease including ICU admission (32.1 vs 14.0%; P = .04) and invasive mechanical ventilation (21.4% vs 3.5%; P = .02). All 4 deaths occurred in individuals with detectable RNAemia. An additional 121 plasma samples from 28 individuals with RNAemia were assessed longitudinally, and RNA was detected for a maximum duration of 10 days. CONCLUSIONS: This study demonstrated a high proportion of SARS-CoV-2 RNAemia, and an association between RNAemia and clinical severity suggesting the potential utility of plasma viral testing as a prognostic indicator for COVID-19.