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Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal (GI) tract. Fecal calprotectin (fCAL) is a noninvasive laboratory test used in the diagnosis and monitoring of IBDs such as Crohn's disease and ulcerative colitis. The fCAL send-out test that our facility has been offering so far uses an ELISA-based method. In the current study, we sought to validate the performance of a Buhlmann fCAL turbo assay in an automated Abbott Alinity C analyzer (AFCAL) in our core laboratory. Five-day imprecision studies showed good performance for both within-run (5.3%) and between-day (2.5%) measurements. The reportable range was verified as 30–20,000 µg/g. Deming regression and Bland–Altman analysis indicated a strong correlation of r = 0.99 with a low, acceptable bias of 1.8% for AFCAL relative to the predicate Buhlmann fCAL ELISA results. AFCAL's clinical performance was determined retrospectively in 62 patients with ICD codes for IBD. Overall, the implementation of AFCAL in our routine clinical testing has improved our turnaround time, reduced the cost per test, and significantly increased our clinician satisfaction. [ABSTRACT FROM AUTHOR]

The presence of a certain group of auto-antibodies (AAbs) is known to correlate with the severity of COVID-19. It is, however, unknown if such AAbs are prevalent and impact COVID-19-related outcomes in lung transplant recipients (LTRs) who are immunosuppressed. We performed a retrospective study of LTRs with COVID-19 and analyzed samples before and after COVID-19 for IgG AAbs. AAbs analysis was carried out using autoimmune and coronavirus microarray and the resulting cross-sectional differences in Ab-scores and clinical variables were analyzed using Fischer's Exact test for categorical variables and a paired t-test for continuous variables. Linear regression was used to analyze the differences in Ab-scores and COVID-19 severity. LTRs with non-severe [NS gp (n = 10)], and severe [S gp (n = 8)] COVID-19 disease were included. Ferritin and acute respiratory failure were higher in the S group (p = 0.03; p < 0.0001). Among the AAbs analyzed, interferon-related AAbs (IFN-alpha2, IFN-beta, IFN lamba, IFN-epsilon), eight interleukin-related AAbs, and several tissue-related AAbs were also found to be changed significantly from pre- to post-COVID-19 (p < 0.05). IFN-lambda (p = 0.03) and IL-22 (p = 0.002) were significantly associated with COVID-19 severity and remained significant in linear regression analysis while controlling for other variables. AAbs are common in LTRs, and certain groups of antibodies are particularly enhanced in LTRs with severe COVID-19. Preliminary observations of this study need to be confirmed by a larger sample size. [ABSTRACT FROM AUTHOR]

Background: Lung-transplant (LT) recipients are at high risk for COVID-19 due to immunosuppression and respiratory tropism of SARS-CoV-2. The information on the effect of COVID-19 mRNA vaccines to elicit immunogenic responses after a two-dose (2D) regimen in LT recipients is sparse. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines' 2D regimen on anti-spike responses in immunocompromised LT recipients. Methods: We utilized serum samples from LT recipients vaccinated for SARS-CoV-2 with 2D of either the Pfizer-BioNTech or Moderna vaccines and 2D-vaccinated naïve (non-transplanted and non-exposed to COVID-19) group. Antibody responses were assessed using the FDA-approved SARS-CoV-2 anti-nucleocapsid protein IgG assay (IgGNC), the SARS-CoV-2 anti-spike protein IgM assay (IgMSP), and the SARS-CoV-2 anti-spike protein IgG II assay (IgGSP). CD4+ T-cell activity was assessed as a marker of immune competence using the ImmuKnow® assay. Results: About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated a positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited a significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6–7.5 AU/mL) compared to non-transplanted, uninfected naïve subjects (14,209 AU/mL, 95% CI: 11,261–18,836 AU/mL; p < 0.0001). In LT patients, the Moderna-evoked seropositivity trend was higher than Pfizer. Conclusion: 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with a higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation. [ABSTRACT FROM AUTHOR]

An accurate creatinine (Cr) estimate is pivotal for the assessment of renal function. Both patient- and practice-spawned factors palliate the test accuracy of serum creatinine (sCr) and can erratically represent actual kidney function. This study evaluated the caregivers' awareness of enzymatic serum creatinine (E-sCr) assay interfering in dopamine/dobutamine (DD)-infused patient samples and the frequency of such interference in a critical care setting. We conducted an sCr awareness survey among UT Southwestern physicians, nurses, and pharmacists. We then performed a cross-sectional E-sCr comparison against the kinetic Jaffe method using the DD-infused patient samples collected from central venous catheters (CVC), peripherally inserted central catheter (PICC) lines, and the peripheral vein (PV). We retrospectively compared the longitudinal E-sCr results of the CVC/PICC draws with the corresponding blood urea nitrogen (BUN) levels. The survey results show a significant lack of awareness among caregivers about the negative interference of DD infusions on E-sCr. Cross-sectional E-sCr assessment relative to the Jaffe method displayed a negative interference in 12% of CVC/PICC line samples (7/57 DD-infused patients) compared to none in the PV draws. A longitudinal assessment of E-sCr, BUN, and potassium (K) levels from CVC/PICC line samples further confirmed a spurious decrease for E-sCr in about 12/50 (24%) patients who did not show a concurrent BUN or K decrease. The results suggest that a direct PV sampling accompanied by clinical laboratory-directed proactive discussion/activities can foster awareness among caregivers and eschew the false E-sCr estimates in DD-infused patients. [ABSTRACT FROM AUTHOR]

Background: The persisting Coronavirus disease 2019 (COVID-19) pandemic and limited vaccine supply has led to a shift in global health priorities to expand vaccine coverage. Relying on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing alone cannot reveal the infection proportion, which could play a critical role in vaccination prioritization. We evaluated the utility of a combination orthogonal serological testing (COST) algorithm alongside RT-PCR to quantify prevalence with the aim of identifying candidate patient clusters to receive single and/or delayed vaccination. Methods: We utilized 108,505 patients with suspected COVID-19 in a retrospective analysis of SARS-CoV-2 RT-PCR vs. IgG-nucleocapsid (IgGNC) antibody testing coverage in routine practice for the estimation of prevalence. Prospectively, an independent cohort of 21,388 subjects was simultaneously tested by SARS-CoV-2 RT-PCR and IgGNC to determine the prevalence. We used 614 prospective study subjects to assess the utility of COST (IgGNC, IgM-spike (IgMSP), and IgG-spike (IgGSP)) in establishing the infection proportion to identify a single-dose vaccination cohort. Results: Retrospectively, we observed a 6.3% (6871/108,505) positivity for SARS-CoV-2 RT-PCR, and only 2.3% (2533/108,505) of cases had paired IgGNC serology performed. Prospectively, IgGNC serology identified twice the number of COVID-positive cases in relation to RT-PCR alone. COST further increased the number of detected positive cases: IgGNC+ or IgMSP+ (18.0%); IgGNC+ or IgGSP+ (23.5%); IgMSP+ or IgGSP+ (23.8%); and IgGNC+ or IgMSP+ or IgGSP+ (141/584 = 24.1%). Conclusion: COST may be an effective tool for the evaluation of infection proportion and thus could define a cohort for a single dose and/or delayed vaccination. [ABSTRACT FROM AUTHOR]

Background: Patients with hematological malignancies (HM), including multiple myeloma (MM), frequently suffer from immune deficiency-associated infectious complications because of both the disease and the treatment. Alarming results from China and the UK confirm the vulnerability of HM patients to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven coronavirus disease 2019 (COVID-19). Given that the immunoassay interference from the endogenous monoclonal immunoglobulin (M paraprotein) and treatment antibodies continually challenges the MM management, it is critical to evaluate the SARS-CoV-2 serology tests for suspected interference/cross-reactivity. Methods: We compared the degree of interference in three SARS-CoV-2 serology assay platforms in HM patients with and without COVID-19 and on various therapeutic monoclonal antibody (t-mAb) treatments. Further, we confirmed the cross-reactivity in pooled samples from normal and COVID-19 + samples spiked with respective antibodies in vitro. Results: None of the 93 HM patient samples with or without t-MAbs showed cross-reactivity on any of the three serology platforms tested. Conclusions: The tested three serologic assays for SARS-CoV-2 are specific and do not have cross-reactivity with M-components or t-MAbs indicating that they can be used safely in oncology practice and in research exploring the immunologic response to COVID-19 in patients with HM. [ABSTRACT FROM AUTHOR]

Background: Therapeutic humanized IgG1 kappa monoclonal antibody (t-mAb), daratumumab (DARA) is a Food and Drug Administration approved drug for the treatment of relapsed/refractory plasma cell myeloma (PCM). DARA appears on serum protein electrophoresis (SPEP) and on serum immunofixation (sIFE) as an IgG kappa monoclonal immunoglobulin protein (M-protein), complicating the assessment of the patients' response to therapy. A more ominous threat to patient safety can occur with the misinterpretation of the presence of a small t-mAb spike as being the residual product of the patient's neoplastic clone, presented either as oligoclonality or new clonality, which could result in incorrect interpretation of failure to achieve remission. Methods: In this report, we describe a novel and cost-effective technique based on biotinylated recombinant CD38 and streptavidin-coated magnetic beads to capture and remove residual DARA present in PCM patient serum samples. The treated samples are then run like regular samples on SPEP and sIFE. We validated this simple technique in DARA-spiked PCM samples and patient samples on DARA treatment. Results: Our simple capture technique completely extracted DARA in all of the tested serum specimens and allowed the assessment of residual M-protein without DARA interference. The results were reproducible and highly specific for DARA, and did not have any impact on endogenous M-protein migration and quantification by SPEP and sIFE. The cost of this technique is much lower and it can be performed in-house with a very short turnaround time compared to the currently available alternative methods. There is a great need for such reflex technologies to avoid interpretation errors. Conclusions: This method is an effective way to eliminate DARA interference in SPEP and sIFE, and can be easily implemented in any clinical laboratory without any patent restriction. This simple technique can be adopted for other t-mAbs using their respective ligands and will help to reduce additional doses of toxic treatment and further testing in patients on t-mAbs with a false positive M-protein spike. [ABSTRACT FROM AUTHOR]