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Background Multiinflammatory syndrome in children (MIS-C) is a novel and rare inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2 infection in school-age children. Reports in the past year have suggested a multisystem pathophysiology characterized by hyperinflammation, gastrointestinal distress, and cardiovascular complications. Clinical laboratory investigations, including routine blood testing for inflammatory (e.g., C-reactive protein, ferritin) and cardiac (e.g., troponin, brain natriuretic peptides) markers have provided insight into potential drivers of disease pathogenesis, highlighting the role of the laboratory in the differential diagnosis of patients presenting with similar conditions (e.g., Kawasaki disease, macrophage activating syndrome). Content While few studies have applied high-dimensional immune profiling to further characterize underlying MIS-C pathophysiology, much remains unknown regarding predisposing risk factors, etiology, and long-term impact of disease onset. The extent of autoimmune involvement is also unclear. In the current review, we summarize and critically evaluate available literature on potential pathogenic mechanisms underlying MIS-C onset and discuss the current and anticipated value of various laboratory testing paradigms in MIS-C diagnosis and monitoring. Summary From initial reports, it is clear that MIS-C has unique inflammatory signatures involving both adaptive and innate systems. Certain cytokines, inflammatory markers, and cardiac markers assist in the differentiation of MIS-C from other hyperinflammatory conditions. However, there are still major gaps in our understanding of MIS-C pathogenesis, including T cell, B cell, and innate response. It is essential that researchers not only continue to decipher initial pathogenesis but also monitor long-term health outcomes, particularly given observed presence of circulating autoantibodies with unknown impact.

Background COVID-19, the disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) can present with symptoms ranging from none to severe. Thrombotic events occur in a significant number of patients with COVID-19, especially in critically ill patients. This apparent novel form of coagulopathy is termed COVID-19 associated coagulopathy and endothelial derived von Willebrand factor (vWF) may play an important role in its pathogenesis. Content vWF is a multimeric glycoprotein molecule that is involved in inflammation, primary and secondary hemostasis. Studies have shown that patients with COVID-19 have significantly elevated levels of vWF antigen and activity, likely contributing to an increased risk of thrombosis seen in CAC. The high levels of both vWF antigen and activity have been clinically correlated with worse outcomes. Furthermore, the severity of a COVID-19 infection appears to reduce molecules that regulate vWF level and activity such as ADAMT-13 and high density lipoproteins (HDL). Finally, studies have suggested that patients with blood group O (a blood group with lower than baseline levels of vWF) have a lower risk of infection and disease severity compared to other blood groups; however, more studies are needed to elucidate the role of vWF Summary CAC is a significant contributor to morbidity and mortality. Endothelial dysfunction with the release of pro-thrombotic factors, such as vWF, needs further examination as a possible important component in the pathogenesis CAC.

Background An evolving COVID-19 testing landscape and issues with test supply allocation, especially in the current pandemic, has made it challenging for ordering providers. We audited orders of the Xpert® Xpress SARS-CoV-2 PCR with reverse transcription (RT–PCR) platform—the fastest of several other testing modalities available—to illuminate these challenges utilizing a multidisciplinary laboratory professional team consisting of a pathology resident and microbiology laboratory director. Methods Retrospective review of the first 5 hundred Xpert Xpress SARS-CoV-2 RT–PCR test orders from a 2-week period to determine test appropriateness based on the following indications: emergency surgery, emergent obstetric procedures, initial behavioral health admission, and later including discharge to skilled care facilities and pediatric admissions. Our hypothesis was that a significant proportion of orders for this testing platform were inappropriate. Results On review, a significant proportion of orders were incorrect, with 69.8% (n = 349, P Conclusions Significant, pervasive inappropriate ordering practices were identified at this center. A laboratory professional team can be key to identifying problems in testing and play a significant role in combating inappropriate test utilization.

Background The ability to rapidly detect severe accurate respiratory syndrome coronavirus virus-2 (SARS-CoV-2) and influenza virus infection is vital for patient care due to overlap in clinical symptoms. Roche’s cobas® Liat® SARS-CoV-2 & Influenza A/B Nucleic Acid Test used on the cobas Liat was granted approval under the Food and Drug’s Emergency Use Authorization for nasopharyngeal (NP) and nasal swabs collected in viral/universal transport medium (VTM/UTM). However, there is a critical need for media that inactivates the virus, especially when specimens are collected in decentralized settings. This study aimed to investigate the use of PrimeStore Molecular Transport Medium® (PS-MTM®), designed to inactivate/kill and stabilize RNA/DNA for ambient transport and preprocessing of collected samples. Methods A limit of detection (LOD) using serially diluted SARS-CoV-2 RNA in PS-MTM and routine UTM was established using standard quantitative PCR (qPCR). Additionally, a clinical panel of NP and oral swabs collected in PS-MTM during the 2020 coronavirus disease 2019 pandemic were evaluated on the cobas Liat and compared to “gold standard” qPCR on an ABI-7500 instrument. Results SARS-CoV-2 RNA LOD using standard qPCR was equivalent on the cobas Liat instrument. cobas Liat detection from oral/NP swabs in PS-MTM media exhibited equivalent positive percent agreement (100%) and negative percent agreement (96.4%). Conclusion PS-MTM and the Roche cobas Liat are compatible and complimentary devices for respiratory specimen collection and rapid disease detection, respectively. PS-MTM is equivalent to standard VTM/UTM with the added benefit of safe, noninfectious sample processing for near-patient testing.

BackgroundSARS-CoV-2 serologic assays are becoming increasingly available and may serve as a diagnostic aid in a multitude of settings relating to past infection status. However, there is limited literature detailing the longitudinal performance of EUA-cleared serologic assays in US populations, particularly in cohorts with a remote history of PCR-confirmed SARS-CoV-2 infection (e.g., >2 months).MethodsWe evaluated the diagnostic sensitivities and specificities of the Elecsys® Anti-SARS-CoV-2 (anti-N) and Elecsys Anti-SARS-CoV-2 S (anti-S1-RBD) assays, using 174 residual clinical samples up to 267 days post-PCR diagnosis of SARS-CoV-2 infection (n = 154) and a subset of samples obtained prior to the COVID-19 pandemic as negative controls (n = 20).ResultsThe calculated diagnostic sensitivities for the anti-N and anti-S1-RBD assays were 89% and 93%, respectively. Of the 154 samples in the SARS-CoV-2-positive cohort, there were 6 discrepant results between the anti-N and anti-S1-RBD assays, 5 of which were specimens collected ≥200 days post-PCR positivity and only had detectable levels of anti-S1-RBD antibodies. When only considering specimens collected ≥100 days post-PCR positivity (n = 41), the sensitivities for the anti-N and anti-S1-RBD assays were 85% and 98%, respectively.ConclusionsThe anti-S1-RBD assay demonstrated superior sensitivity at time points more remote to the PCR detection date, with 6 more specimens from the SARS-CoV-2-positive cohort detected, 5 of which were collected more than 200 days post-PCR positivity. While analytical differences and reagent lot-to-lot variability are possible, this may indicate that, in some instances, anti-S1-RBD antibodies may persist longer in vivo and may be a better target for detecting remote SARS-CoV-2 infection.

Background Widespread testing of SARS-CoV-2 has resulted in shortages of collection devices and transport media. We evaluated the stability of flocked swabs inoculated with SARS-CoV-2-containing specimen incubated dry (i.e., without transport medium) at room temperature. Methods A pool of SARS-CoV-2 positive specimen was used to inoculate flocked swabs. Five swabs were placed immediately into universal transport media (UTM) following inoculation, and tested immediately (day 0). Fifteen of the swabs were placed into sterile 15-mL conical tubes and incubated at room temperature for 1, 2, or 7 days. Following incubation, swabs were hydrated in separate vials of UTM and tested. This protocol was repeated for viral transport media (VTM) and saline. As a comparison, a series of swabs was prepared and tested in parallel, but stored in the corresponding liquid transport media (UTM, VTM, or saline) and incubated at room temperature. Testing was performed at 1, 2, and 7 days postinoculation in duplicate. All molecular testing was performed using the Roche cobas SARS-CoV-2 assay. Results All dry swabs tested on days 1, 2, and 7 provided results that were within 2 cycle thresholds (CTs) of the average CT values for swabs hydrated in the same media and tested on day 0. There was no statistical difference in CT values between swabs incubated in liquid media versus dry swabs incubated at room temperature prior to hydration in liquid media. Conclusions The utilization of “dry swabs” may simplify specimen collection, negate the need for liquid transport media, and mitigate safety risks while preserving the accuracy of testing.

As serologic assays for SARS-CoV-2 become more widely utilized, it is important to understand their performance characteristics and correlation with neutralizing antibodies. We evaluated 3 commonly used SARS-CoV-2 IgG assays (Abbott, DiaSorin, and EUROIMMUN) for clinical sensitivity, specificity, and correlation with neutralizing antibodies, and then compared antibody kinetics during the acute phase of infection.Three panels of samples were tested on every assay. Sensitivity was assessed using a panel of 35 specimens serially collected from 7 patients with RT-PCR-confirmed COVID-19. Specificity was determined using 100 sera samples collected in 2018 from healthy individuals prior to the outbreak. Analytical specificity was determined using a panel of 37 samples from individuals with respiratory illnesses other than COVID-19.Clinical sensitivity was 91.43% (95% CI 76.94-98.20%) for Abbott, and 88.57% (95% CI 73.26-96.80%) for both DiaSorin and EUROIMMUN. Clinical specificity was 99.00% (95% CI 94.55-99.97%) for Abbott and DiaSorin and 94.00% (95% CI 87.40-97.77%) for EUROIMMUN. The IgG assays demonstrated good qualitative agreement (minimum of 94%) and good correlation between the quantitative result for each combination of assays (r2 ≥ 0.90). The neutralizing antibody response did not necessarily follow the same temporal kinetics as the IgG response and did not necessarily correlate with IgG values.The 3 IgG antibody assays demonstrated comparable performance characteristics. Importantly, a qualitative positive IgG result obtained with any of the assays was associated with the presence of neutralizing antibodies; however, neutralizing antibody concentrations did not correlate well with signal to cutoff ratios.

Background Numerous serology assays are available for detection of SARS-CoV-2 antibodies but are limited in that only 1 or 2 target antigen(s) can be tested at a time. Here, we describe a novel multiplex assay that simultaneously detects and quantifies IgG antibodies to SARS-CoV-2 antigens, spike (S), nucleocapsid (N), receptor-binding domain (RBD), and N-terminal domain (NTD) in a single well. Methods Sensitivity was determined using samples (n = 124) from confirmed SARS-CoV-2 RT-PCR positive individuals. Prepandemic (n = 100) and non-COVID respiratory infection positive samples (n = 100) were used to evaluate specificity. Samples were analyzed using COVID-19 IgG multiplex serology assay from Meso Scale Discovery (MSD) and using commercial platforms from Abbott, EUROIMMUN, and Siemens. Results At >14 days post-PCR, MSD assay displayed >98.0% sensitivity [S 100% (95% CI 98.0%–100.0%); N 98.0% (95% CI 97.2%–98.9%); RBD 94.1% (95% CI 92.6%–95.6%); NTD 98.0% (95% CI, 97.2%–98.9%)] and 99% specificity (95% CI 99.3%–99.7%) for antibodies to all 4 antigens. Parallel assessment of antibodies to more than 1 antigen improved the sensitivity to 100% (95% CI 98.0%–100.0%) while maintaining 98% (95% CI 97.6%–98.4%) specificity regardless of the combinations used. When AU/mL concentrations of IgG antibodies from the MSD assay were compared against the corresponding IgG signals acquired from the single target commercial assays, the following correlations were observed: Abbott (vs MSD N, R2 = 0.73), Siemens (vs MSD RBD, R2 = 0.92), and EUROIMMUN (vs MSD S, R2 = 0.82). Conclusion MSD assay offers an accurate and a comprehensive assessment of SARS-CoV-2 antibodies with higher sensitivity and equivalent specificity compared to the commercial IgG serology assays.

Background Anti–SARS-CoV-2 serological responses may have a vital role in controlling the spread of the disease. However, the comparative performance of automated serological assays has not been determined in susceptible patients with significant comorbidities. Methods In this study, we used large numbers of samples from patients who were negative (n = 2030) or positive (n = 112) for COVID-19 to compare the performance of 4 serological assay platforms: Siemens Healthineers Atellica IM Analyzer, Siemens Healthineers Dimension EXL Systems, Abbott ARCHITECT, and Roche cobas. Results All 4 serology assay platforms exhibited comparable negative percentage of agreement with negative COVID-19 status ranging from 99.2% to 99.7% and positive percentage of agreement from 84.8% to 87.5% with positive real-time reverse transcriptase PCR results. Of the 2142 total samples, only 38 samples (1.8%) yielded discordant results on one or more platforms. However, only 1.1% (23/2030) of results from the COVID-19–negative cohort were discordant. whereas discordance was 10-fold higher for the COVID-19–positive cohort, at 11.3% (15/112). Of the total 38 discordant results, 34 were discordant on only one platform. Conclusions Serology assay performance was comparable across the 4 platforms assessed in a large population of patients who were COVID-19 negative with relevant comorbidities. The pattern of discordance shows that samples were discordant on a single assay platform, and the discordance rate was 10-fold higher in the population that was COVID-19 positive.

Background Saliva has garnered great interest as an alternative specimen type for molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data are limited on the relative performance of different molecular methods using saliva specimens and the relative sensitivity of saliva to nasopharyngeal (NP) swabs. Methods To address the gap in knowledge, we enrolled symptomatic healthcare personnel (n = 250) from Barnes-Jewish Hospital/Washington University Medical Center and patients presenting to the Emergency Department with clinical symptoms compatible with coronavirus disease 2019 (COVID-19; n = 292). We collected paired saliva specimens and NP swabs. The Lyra SARS-CoV-2 assay (Quidel) was evaluated on paired saliva and NP samples. Subsequently we compared the Simplexa COVID-19 Direct Kit (Diasorin) and a modified SalivaDirect (Yale) assay on a subset of positive and negative saliva specimens. Results The positive percent agreement (PPA) between saliva and NP samples using the Lyra SARS-CoV-2 assay was 63.2%. Saliva samples had higher SARS-CoV-2 cycle threshold values compared to NP swabs (P Conclusion These data demonstrate molecular assays have variability in performance for detection of SARS-CoV-2 in saliva.

Background The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patient samples is of critical importance in the management of patients and monitoring transmission in the population. However, data on the analytical performance characteristics for detection of SARS-CoV-2 in clinical specimens between individual targets within the same platform, and among different analytical platforms, are limited. Methods Here we evaluated the performance of 6 different sample-to-answer SARS-CoV-2 detection methods—Roche cobas 6800, Cepheid GeneXpert, Diasorin Simplexa, Luminex Aries emergency use authorization (EUA), Luminex Aries research use only (RUO), and bioMérieux BioFire—in clinical specimens with a range of viral loads. Results The positive percentage agreement between the Roche cobas 6800 and GeneXpert was 100%, Diasorin 95%, Aries EUA 74%, Aries RUO 83%, and BioFire 97%. Notably, in samples with cycle threshold (Ct) values below 30 for the E gene on the Roche cobas 6800 platform, we found 100% positive agreement among all platforms. Given these results, we examined the distribution of over 10 000 Ct values of all positive specimens from individuals at our institution on the Roche cobas platform. Nearly 60% of specimens from asymptomatic individuals had a PCR Ct value >30 as measured using the cobas 6800 assay E gene. Conclusions Our results demonstrate performance characteristics between different platforms by Ct value and provide data regarding the distribution of viral RNA present in positive specimens.

Background We launched a retrospective analysis of SARS-CoV-2 antibodies in 192 patients with COVID-19, aiming to depict the kinetic profile of SARS-CoV-2 antibodies and explore the factors related to SARS-CoV-2 antibody expression. Methods Data on 192 confirmed patients with COVID-19 between January and February 2020 was collected from the designated hospital that received patients with COVID-19 in Guangzhou, China. Moreover, a cohort of 130 suspected patients with COVID-19 and 209 healthy people were also enrolled in this study. IgM and IgG antibodies to SARS-CoV-2 were detected by the chemiluminescence immunoassay kits in different groups. Results A total of 192 COVID-19 cases were analyzed, of which had 81.8% anti-SARS-CoV-2 IgM detected and 93.2% anti-SARS-CoV-2 IgG detected, respectively, at the time of sampling. The kinetics of anti-SARS-CoV-2 IgM and IgG showed that, the confirmed cases had anti-SARS-CoV-2 IgM seroconversion occurred 5–10 days after the onset of the symptoms, and then IgM rose rapidly to reach a peak within around 2–3 weeks, maintaining at its peak for 1 week before its decline. While they had anti-SARS-CoV-2 IgG seroconversion simultaneously or sequentially with IgM, reaching its peak within around 3 to 4 weeks and began to decline after the fifth week. Besides, correlation analysis showed that in patients with COVID-19 the level of IgM was related to gender and disease severity (P Conclusion The findings of this study show that anti-SARS-CoV-2 IgM and IgG can be important assisting COVID-19 diagnosis, especially in the early phase of infection. Furthermore, antibody expression in patients with COVID-19 is also correlated with disease severity, age, gender, and virus clearance or continuous replication.

Background. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated. Methods. The ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS-CoV-2 PCR-positive patients, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS-CoV-2 negative patients. Serology results were compared to a cell based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay. Results. The Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received two-doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme Nabs assay correlated with the PSV SARS-CoV-2 ID50 neutralization titers (R2= 0.70), while correlation of the Roche S-antibody assay was weaker (R2= 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received two-doses of the Moderna vaccine (ID50: 597) compared to individuals that received a single dose (ID50: 284). Conclusions. The Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection., Summary: The Roche S (spike protein)-antibody and Diazyme neutralizing-antibodies (NAbs) assays were evaluated for their clinical utility in the detection of SARS-CoV-2 related adaptive immune responses by testing SARS-CoV-2 PCR-confirmed patients, SARS-CoV-2-vaccinated individuals, and SARS-CoV-2-negative individuals. Commercial serology results were compared to results generated using a cell-based SARS-CoV-2 pseudovirus (PSV) NAbs assay and previously validated SARS-CoV-2 commercial serology assays (Roche N (nucleocapsid protein) antibody and Diazyme IgG). We demonstrate that the Roche S-antibody and Diazyme NAbs assays detected adaptive immune response in SARS-CoV-2 vaccinated individuals and the presence of SARS-CoV-2 PSV NAbs. The Roche S-antibody assay had an observed positive percent agreement (PPA) of 100% for individuals who received two doses of the Pfizer or Moderna vaccine. By contrast, the Roche N assay and Diazyme IgG assay did not detect vaccine adaptive immune responses. Our findings also indicate that the Diazyme NAbs assay correlates strongly with the levels of SARS-CoV-2 ID50 neutralization titers using the PSV Nab assay in vaccinated individuals.

Background In North America, both messenger RNA (mRNA) vaccines, Pfizer-BioNTech BNT162b2, and Moderna mRNA-1273, each utilizing a 2-dose regimen, have started to be administered to individuals. Methods We evaluated the quantitative serologic antibody response following administration of either a single dose or both doses of an mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in a cohort of 98 participants (88 healthcare workers [HCW] and 10 solid organ transplant [SOT] recipients). Antibody levels were compared across 3 immunoassays: Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics), SARS-CoV-2 TrimericS IgG (DiaSorin), and SARS-CoV-2 IgG II Quant (Abbott). Results Among HCW, sensitivity ranged from 100% (Roche), 99% (Abbott) and 98% (DiaSorin). The SARS-CoV-2 IgG II Quant and SARS-CoV-2 TrimericS IgG assays showed good agreement with a Pearson correlation coefficient of R = 0.95. Pearson correlation coefficients of R = 0.82 and 0.83 were obtained for Elecsys Anti-SARS-CoV-2 S vs SARS-CoV-2 TrimericS IgG and SARS-CoV-2 IgG II Quant vs Elecsys Anti-SARS-CoV-2 S, respectively. Significant differences in antibody levels between HCW and SOT recipients were observed. A decrease in antibody levels from time of vaccine administration to blood draw was evident. Among those with a second dose, an increase in antibody levels with increased time between administration of the first and second dose was observed. Conclusions The absolute values generated from each of the assay platforms are not interchangeable. Antibody levels differed with increased time between vaccine administration and with increased time between administration of the first and second dose. Further, significant differences in antibody levels between HCW and SOT recipients were observed.

Background Racial disparities in SARS-CoV-2 prevalence are apparent. Race is a sociocultural construct, necessitating investigation into how sociocultural factors contribute. Methods This cross-sectional study linked laboratory data of adult patients between February 29 and May 15, 2020 with socio-demographics variables from the 2018 American Community Survey (ACS). Medical sites included healthcare organizations in Michigan, New York, North Carolina, California, Florida, Pennsylvania, and Washington. Race was treated as a proxy for racism and not biological essentialism. Laboratory data included patient age, sex, race, ethnicity, test result, test location, and residential ZIP code. ACS data included economic and educational variables contributing to an SES Index, population density, proportion Medicaid, and racial composition for corresponding ZIP code. Associations between race/socioeconomic variables and test results were examined using odds ratios (OR). Results Of 126 452 patients [mean (SD) age 51.9 (18.4) years; 52 747 (41.7%) men; 68 856 (54.5%) White and 27 805 (22.0%) Black], 18 905 (15.0%) tested positive. Of positive tests, 5238 (SD 27.7%) were White and 7223 (SD 38.2%) were Black. Black race increased the odds of a positive test; this finding was consistent across sites [OR 2.11 (95% CI 1.95–2.29)]. When subset by race, higher SES increased the odds of a positive test for White patients [OR 1.10 (95% CI 1.05–1.16)] but decreased the odds for Black patients [OR 0.92 (95% CI 0.86–0.99)]. Black patients, but not White patients, who tested positive overwhelmingly resided in more densely populated areas. Conclusions Black race was associated with SARS-CoV-2 positivity and the relationship between SES and test positivity differed by race, suggesting the impact of socioeconomic status on test positivity is race-specific.

Introduction The ePlex® SARS-CoV-2 emergency use authorization (EUA) test is a cartridge-based assay for the detection of SARS-CoV-2 in nasopharyngeal specimens. Since performance data has been previously published on this platform, the manufacturer has modified the workflow design in order to improve assay performance. Evaluation of the new workflow, which eliminated the sample delivery device (SDD), led to a dramatic improvement of assay performance while saving time and making cartridge loading more convenient. Methods 145 confirmed positive nasopharyngeal swab specimens were used to evaluate the assay analytical sensitivity, accuracy, and overall time-saving for the 2 workflows that is with and without the use of SDD on the ePlex SARS-CoV-2 test. Results Elimination of the SDD step led to a dramatic increase in accuracy and the overall limit of detection when using 145 previously defined and valid SARS-CoV-2 positive specimens with relatively low, medium, and high cycle thresholds (CT). This simple workflow change led to an overall detection from 94/145 (64.8%) to 131/145 (90.3%), with an additional 37 specimens being detected. CT value ranges revealed that 90% of the specimens in the 33 ≤ CT Conclusion The simple workflow modification eliminating the SDD led to an overall improvement in the detection of positive specimens and also simplified workflow and reduced hands-on time.

Background The COVID-19 pandemic has strained clinical microbiology laboratories due to testing supply allocations. As a result, laboratories have had to invest in multiple COVID-19 assays performed on different testing instruments. Comparing the results achieved by testing positive samples between in-use assays can provide insights into which platforms may be interchangeable for testing in times of supply chain emergencies. Methods Nasopharyngeal and nasal swab specimens collected in viral transport media that tested positive on the Xpert® Xpress SARS-CoV-2 assay were tested on the ePlex® SARS-CoV-2 and BD SARS-CoV-2 Reagents for BD Max™ assays. Positive percent agreement was calculated using the Xpert Xpress SARS-CoV-2 assay as the reference method. Results We tested 78 positive swabs, resulting in a positive percentage agreement (PPA) of 92% (CI 84–97%) for the BD SARS-CoV-2 assay and 58% (CI 47–70%) for the ePlex assay. Following development of a new workflow for the ePlex, we detected SARS-CoV-2 in 7 additional samples, resulting in a new PPA of 68% (CI 56–78). Conclusions During times of supply allocation and shortage of the Xpert Xpress SARS-CoV-2 assay, the BD SARS-CoV-2 assay is well suited to test substitutions due to its high PPA.

Background Guidelines from the CDC and the IDSA suggest the use of serologic testing to support the diagnosis of COVID-19 in individuals with high clinical suspicion that repeatedly test negative by diagnostic methods. Given that variability in specimen type, collection technique, and time from symptoms all reduce the sensitivity of molecular methods for SARS-CoV-2. The routine use of serology to diagnose and manage patients with symptoms concerning COVID-19 is tempting, despite limited studies in the literature supporting this approach. Here, we assessed the utility of serology testing for diagnosing SARs-CoV-2 in symptomatic, PCR-negative patients. Methods Remnant EDTA plasma specimens were obtained from 393 patients with clinical suspicion for COVID-19 and a negative SARs-COV-2 RNA test by the nasopharyngeal swab. The specimens were analyzed for SARs-CoV-2 IgG on an Abbott Architect i2000 (Abbott diagnostic). Patient information and symptoms adjudication were obtained from patient electronic health records. Results 14 of 393 patients were positive for antibodies to SARS-CoV-2 (seropositivity rate of 3.6%), 6 of which were from patients with previous RT-PCR-confirmed COVID-19 infection. Among patients without previously diagnosed COVID-19, the seropositivity rate in symptomatic patients was 1.2% (2/171), in patients with altered mental status was 4.3% (2/46), and in asymptomatic patients with no known previous COVID-19 diagnoses was 2.6% (4/170). The seropositivity rate among symptomatic patients presenting ≥ 14 days after symptom onset was 0% (0/67), 7-13 days was 5% (1/20), and for patients < 7 days, was 2.1% (1/47). Among the 4 patients with AMS that were serologically positive, 2 were previously diagnosed by PCR. Conclusion There is a low diagnostic utility of SARS-COV-2 serological testing for identifying novel cases of acute SARS-CoV-2 infections in the ED after a negative PCR test.

Background Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results. Methods INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January–June 2019, period 1) and a portion of the COVID-19 pandemic period (January–June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts. Results Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients. Conclusion The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays have emerged as a response to the global pandemic, warranting studies evaluating their clinical performance. This study investigated 7 commercially available SARS-CoV-2 serological assays in samples from noninfected individuals and hospitalized patients. Methods SARS-CoV-2 qualitative serological assays by Abbott (IgG), Beckman (IgG), DiaSorin (IgG), EUROIMMUN (IgG and IgA), Roche and Bio-Rad (Total) were evaluated using specimens collected pre-December 2019 (n = 393), from nucleic acid amplification testing (NAAT) negative patients (n = 40), and from 53 patients with COVID-19 by NAAT collected 3–21 days post-onset of symptoms (POS) (N = 83). Negative agreement (NA), positive agreement (PA), and positive and negative predictive values (PPV and NPV) at prevalences of 5% and 10% were calculated. Results The overall %NA; 95% CI in the negative samples were: Roche 99.8%; 99.3–100.2, Beckman 99.8%; 98.7–100.0, Abbott and Bio-Rad 99.3%; 98.0–99.9, DiaSorin 98.4; 97.2–99.6, EUROIMMUN IgG 97.5%; 95.5–98.7, and EUROIMMUN IgA 79.7%; 75.9–83.5), accounting for positive/equivocal results as false positives. The %PA; 95% CI in samples collected 14+ days POS (n = 24) were: Bio-Rad 83.3%; 68.4–98.2, Abbott and Roche 79.2%; 62.9–95.4, EUROIMMUN IgA 70.8%; 52.6–89.0, Beckman 58.3%; 38.6–78.1, DiaSorin 54.2; 34.2–74.1, and EUROIMMUN IgG 50.0%; 30.0–70.0, accounting for negative/equivocal results as false negatives. NPVs ranged from 97.4%–98.9% and 94.7%–97.7% for prevalences 5% and 10%, respectively. PPVs ranged from 15.5%–94.8% and 27.9%–97.4% for prevalences 5% and 10%, respectively. Conclusion The Roche and Beckman assays resulted in fewer false positives, followed by the Bio-Rad and Abbott assays. While the Bio-Rad assay demonstrated higher antibody detection in COVID-19-positive patients, PA claims cannot be established with a high level of confidence in our sample population.

Background While it is presumed that immunosuppressed patients, such as solid organ transplant recipients on immunosuppression, are at greater risk from SARS-CoV-2 infection than the general population, the antibody response to infection in this patient population has not been studied. Methods In this report, we follow the anti-SARS-CoV-2 antibody levels in patients with COVID-19 who are undergoing exogenous immunosuppression. Specifically, we studied the antibody response of 3 solid organ transplant recipient patients, 3 patients who take daily inhaled fluticasone, and a patient on etanercept and daily inhaled fluticasone, and compared them to 5 patients not on exogenous immunosuppression. Results We found that the solid organ transplant patients on full immunosuppression are at risk of having a delayed antibody response and poor outcome. We did not find evidence that inhaled steroids or etanercept predispose patients to delayed immune response to SARS-CoV-2. Conclusion The data presented here suggest that solid organ transplant recipients may be good candidates for early targeted intervention against SARS-CoV-2.

Background The need for rapid point-of-care (POC) diagnostics is now becoming more evident due to the increasing need for timely results and improvement in healthcare service. With the recent COVID-19 pandemic outbreak, POC has become critical in managing the spread of disease. Applicable diagnostics should be readily deployable, easy to use, portable, and accurate so that they fit mobile laboratories, pop-up treatment centers, field hospitals, secluded wards within hospitals, or remote regions, and can be operated by staff with minimal training. Complete blood count (CBC), however, has not been available at the POC in a simple-to-use device until recently. The HemoScreen, which was recently cleared by the FDA for POC use, is a miniature, easy-to-use instrument that uses disposable cartridges and may fill this gap. Content The HemoScreen’s analysis method, in contrast to standard laboratory analyzers, is based on machine vision (image-based analysis) and artificial intelligence (AI). We discuss the different methods currently used and compare their results to the vision-based one. The HemoScreen is found to correlate well to laser and impedance-based methods while emphasis is given to mean cell volume (MCV), mean cell hemoglobin (MCH), and platelets (PLT) that demonstrate better correlation when the vision-based method is compared to itself due to the essential differences between the underlying technologies. Summary The HemoScreen analyzer demonstrates lab equivalent performance, tested at different clinical settings and sample characteristics, and might outperform standard techniques in the presence of certain interferences. This new approach to hematology testing has great potential to improve quality of care in a variety of settings.

Background Patient surges beyond hospital capacity during the initial phase of the COVID-19 pandemic emphasized a need for clinical laboratories to prepare test processes to support future patient care. The objective of this study was to determine if current instrumentation in local hospital laboratories can accommodate the anticipated workload from COVID-19 infected patients in hospitals and a proposed field hospital in addition to testing for non-infected patients. Methods Simulation models predicted instrument throughput and turn-around-time for chemistry, ion-selective-electrode, and immunoassay tests using vendor-developed software with different workload scenarios. The expanded workload included tests from anticipated COVID patients in 2 local hospitals and a proposed field hospital with a COVID-specific test menu in addition to the pre-pandemic workload. Results Instrumentation throughput and turn-around time at each site was predicted. With additional COVID-patient beds in each hospital, the maximum throughput was approached with no impact on turnaround time. Addition of the field hospital workload led to significantly increased test turnaround times at each site. Conclusions Simulation models depicted the analytic capacity and turn-around times for laboratory tests at each site and identified the laboratory best suited for field hospital laboratory support during the pandemic.

The COVID-19 pandemic has made a devastating impact on global health and continues to challenge healthcare infrastructure and delivery. The clinical laboratories were no exception as they are responsible for diagnostic testing that dictates many clinical, infection control, and public health decisions. Information technology and laboratory management tools are critical assets for maintaining and adapting operations in response to crises. When utilized effectively, they promote the integration between the clinical laboratory specialties (e.g., chemistry, hematology, microbiology, and molecular pathology). During the COVID-19 pandemic, our systems and processes were strained due to high testing volumes, demand for rapid turnaround times, supply chain constraints, and constantly evolving testing algorithms and result interpretations as our knowledge of the virus and of diagnostics increased over time. In this report, we describe those challenges and subsequent adaptations made by each clinical laboratory section. We hope these details help to provide potential solutions and approaches for other hospitals facing COVID-19 surges or other future pandemics.