Evaluating the utility of a two-assay serological algorithm for hepatitis C screening in a low prevalence population.

INTRODUCTION: Screening for hepatitis C virus (HCV) is performed by testing for anti-HCV antibodies, which may yield false-positive results leading to additional testing and other downstream consequences for the patient. We report our experience in a low prevalence population (<0.05%) using a two-assay algorithm aimed at testing specimens with borderline or weak positive anti-HCV reactivity in the screening assay by a second anti-HCV assay prior to confirming positive anti-HCV results with RT-PCR. MATERIALS AND METHODS: Retrospective analysis of 58,908 plasma samples was obtained over a 5-year period. Samples were initially tested using the Elecsys Anti-HCV II assay (Roche Diagnostics), with borderline or weakly positive results (defined in our algorithm as a Roche cutoff index of 0.9-19.99) reflexively analyzed using the Architect Anti-HCV assay (Abbott Diagnostics). The Abbott anti-HCV results dictated the final anti-HCV interpretation for reflexed samples. RESULTS: Our testing algorithm resulted in 180 samples requiring second-line testing, with final anti-HCV results interpreted as 9% positive, 87% negative, and 4% indeterminate. The positive predictive value (PPV) of a weakly positive Roche result was 12%, which was significantly lower than the PPV using our two-assay approach (65%). CONCLUSIONS: The incorporation of a two-assay serological testing algorithm in a low prevalence population provides a cost-effective method of improving the PPV of HCV screening in specimens with borderline or weakly positive anti-HCV results.

Propofol-induced interference with activated partial thromboplastin time-based monitoring of therapeutic heparin anticoagulation.

PURPOSE: The activated partial thromboplastin time (aPTT) is a coagulation assay commonly utilized for monitoring therapeutic heparin anticoagulation. aPTT methods based on optical detection are vulnerable to spectral interference from hemolysis, icterus, lipemia, and other substances. Intravenous lipid emulsions of primarily 20% have been shown to interfere with multiple clinical laboratory assays, including those measuring aPTT by optical methods, but there is limited data on propofol's effect. The primary objective of this study was to determine the rate of interference of propofol with aPTT measurements in patients receiving both propofol and intravenous heparin. METHODS: A retrospective observational cohort study of intensive care unit patients who received concomitant propofol and heparin infusions (N = 38 patients) and whose heparin therapy was monitored by aPTT (N = 531 aPTTs) was conducted. Review of the electronic medical record was completed to obtain relevant clinical and laboratory data, while the laboratory information system was queried for analytical interference with the aPTT assay. RESULTS: A total of 109 aPTTs (21%) spanning 21 patients (55%) had documented aPTT interference. All 21 patients had at least one aPTT requiring ultracentrifugation prior to reporting, and 12 aPTTs from 4 patients were unreportable due to interference. Patients with and without aPTT interference received similar doses of propofol. None of the cases of aPTT interference were caused by hemolysis or hyperbilirubinemia. CONCLUSION: A potential medication-assay interaction was observed in approximately half of patients who received concomitant propofol and heparin infusions and had aPTT measured for anticoagulation management. Sample ultracentrifugation removes the optical interference in most cases but significantly prolongs aPTT reporting and delays appropriate adjustments to heparin dosing.

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

Data on the frequency and causes of icteric interference in clinical chemistry laboratory tests.

The presence of elevated levels of bilirubin (icterus) in serum or plasma specimens has the potential to interfere with clinical chemistry and other laboratory assays. Along with hemolysis and lipemia, icterus represents one of the most common endogenous interferences with laboratory tests. There are two common mechanisms by which icterus can cause assay interference. The first common mechanism is spectral interference due to absorption at wavelengths used in assays by bilirubin and/or bilirubin breakdown products. The second common mechanism involves chemical reaction of bilirubin with the reagents used in some enzymatic assays. Most automated clinical chemistry platforms can perform rapid estimates of indices for hemolysis, icterus, and lipemia (HIL), typically by measuring absorbance at wavelengths impacted by these interferences. The data in this article provides results from a detailed 12-month retrospective review of icteric indices and the impact on 114 clinical chemistry assays at an academic medical center in the United States. The data include 414,502 specimens from 94,081 unique patients (51,851 females; 42,230 males), with a total of 2,791,591 discrete clinical chemistry assays performed on the specimens. Detailed chart review was performed for all patients who had one or more specimens with an icteric index of 40 or higher ('severe icterus'), including determination of the medical diagnoses likely causing icterus and the mortality of these patients within 1 and 3 years following laboratory testing. Data for all specimens include patient location at time of testing (emergency department, inpatient unit, or outpatient site), sex, age, HIL indices, specific clinical chemistry assays performed, and number of times specimens had icteric indices exceeding the icteric index threshold in the package inserts for the clinical chemistry assays performed. The dataset reported is related to the research entitled "Frequency of Icteric Interference in Clinical Chemistry Laboratory Tests and Causes of Severe Icterus" [S. Mainali, A.E. Merrill, M.D. Krasowski, Frequency of icteric interference in clinical chemistry laboratory tests and causes of severe icterus, Pract. Lab. Med. (2021) 27: e00259].

SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors.

Vaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to measure patient antibody levels before and after transfusion with COVID-19 Convalescent Plasma (CCP) and compare the antibody levels following transfusion of CCP from vaccinated and nonvaccinated donors. Plasma samples before and after transfusion were obtained from 25 recipients of CCP and COVID-19 antibody levels measured. Factors that effect changes in antibody levels were examined. In the 21 patients who received CCP from nonvaccinated donors, modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose, calculated by the unit volume multiplied by the donor antibody level. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with reasonable accuracy(R2> 0.90). In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19. If available, CCP from vaccinated donors with very high antibody levels should be used. One unit of CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors.

Small volume retinol binding protein measurement by liquid chromatography-tandem mass spectrometry.

BACKGROUND: The measurement of plasma concentrations of retinol binding protein is a component of nutritional assessment in neonatal intensive care. However, serial testing in newborns is hampered by the limited amount of blood that can be sampled. Limitations are most severe with preterm infants, for whom close monitoring may be most important. METHODS: We developed an assay to quantify retinol binding protein using trypsin digestion and liquid chromatography-tandem mass spectrometry, which requires a serum or plasma volume of 5 µl. Additionally, we validated the method according to current recommendations and performed comparison with a standard nephelometry platform in clinical use. RESULTS: The assay demonstrated linearity from below 1 mg/dL (0.48 µM) to more than 20 mg/dL (9.7 µM), and an imprecision of 11.8% at 0.43 mg/dL (0.21 µM). The distribution of results observed with the new method was different when compared with nephelometry. CONCLUSION: Liquid chromatography-tandem mass spectrometry facilitated testing a smaller sample volume, thereby increasing the ability to monitor key nutritional markers in premature infants. The differences in results compared with a commercially-available nephelometric assay revealed questionable results for lower concentrations by immunoassay.

Prevalence of maternal obesity at delivery and association with maternal and neonatal outcomes.

INTRODUCTION: Maternal obesity has been linked to adverse outcomes for mothers and their offspring, including, but not limited to gestational hypertension (gHTN), gestational diabetes (GDM), pre-eclampsia, fetal macrosomia, and emergency cesarean section. Recent investigations have also shown that obesity, as defined by a body mass index (BMI) ≥ 30, especially severe obesity (BMI ≥ 40), is a risk factor for both hospitalization and death from COVID-19. OBJECTIVES: The objective of this study is to determine the prevalence and association of maternal obesity at delivery with adverse antenatal, intrapartum, and neonatal outcomes in a cohort of consecutive delivering patients at a tertiary care center in Iowa from May to September 2020. A secondary objective is to determine if maternal obesity has any relationship to past or current COVID-19 infection status at the time of delivery. This is a secondary analysis of a prospective cohort study to analyze obstetric outcomes among COVID-19 infected and uninfected patients. METHODS: We conducted a prospective cohort study using demographic and clinical data obtained from the electronic medical record. Excess plasma was collected from routine blood samples obtained at delivery admission to determine the seroprevalence of COVID-19 antibody using the DiaSorin and Roche antibody assays. Frequency variables were each calculated separately, and a comparison of maternal and neonatal outcomes was conducted using the generalized linear mixed modeling (GLMM) framework to account for varying distributions (normal and binary). RESULTS: 1001 women delivered during the study period and 89.7% met criteria for being overweight or obese; 17.9% met criteria for severe obesity. Women with obesity had 49.8% lower odds of possessing private insurance, and women with severe obesity were less than half as likely to plan to breastfeed at the time of discharge. Women with obesity of any kind had a significantly increased odds of GDM and gHTN, and an increased risk of an infant with macrosomia, hypoglycemia, and NICU admission. No significant association was found between BMI and COVID-19 infection or disease severity. CONCLUSION: This study provides insight into obstetric complications facing women with obesity, especially those with severe obesity. This report serves to highlight potential challenges, such as insurance status and labor complications, that impact women of high BMI to a greater degree when compared to their normal-weight counterparts.

Utilization of anti-factor Xa levels to guide reversal of oral factor Xa inhibitors in the emergency department.

PURPOSE: Oral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti-factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures. METHODS: A retrospective review of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020, was completed. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal. RESULTS: Thirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients. CONCLUSION: This study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents.

Frequency of icteric interference in clinical chemistry laboratory tests and causes of severe icterus.

OBJECTIVES: The aims of this study were to identify the causes of severe icterus in an academic medical center patient population and to assess the impact of icterus on clinical chemistry testing using assay package insert thresholds. DESIGN: and Methods: In this retrospective study at an academic medical center core clinical laboratory, icteric, hemolysis, and lipemia indices were available for all serum and plasma chemistry specimens analyzed on Roche Diagnostics cobas 8000 analyzers over a 12-month period, encompassing 414,502 specimens from 94,081 unique patients (51,851 females; 42,230 males) including children, inpatient, outpatient, and emergency department patients. Extensive chart review was done for all 57 patients (4 pediatric, 53 adult; 534 total specimens) who had one or more samples with an icteric index of 40 or higher (defined as severe icterus). RESULTS: Specimen icteric index exceeded package insert icteric index thresholds in 0.14% of clinical chemistry assays, with the highest number of instances for creatinine (1358 samples, 0.6% of total tests), total protein (1194 samples, 2.2%), and ammonia (161 samples, 3.9%). The 57 patients with an icteric index of 40 or higher accounted for 49.7% of all instances where the icteric index exceeded the specific assay package insert limit. The most common etiologies of this group of 57 patients were alcohol-related liver disease (34 patients), biliary tract disease (7 patients), and neoplasms (6 patients). CONCLUSIONS: Approximately half of all instances where specimen icteric index exceeded assay package insert thresholds occurred in a small cohort of patients with severe liver/biliary tract disease.

Use of Middleware Data to Dissect and Optimize Hematology Autoverification.

BACKGROUND: Hematology analysis comprises some of the highest volume tests run in clinical laboratories. Autoverification of hematology results using computer-based rules reduces turnaround time for many specimens, while strategically targeting specimen review by technologist or pathologist. METHODS: Autoverification rules had been developed over a decade at an 800-bed tertiary/quarternary care academic medical central laboratory serving both adult and pediatric populations. In the process of migrating to newer hematology instruments, we analyzed the rates of the autoverification rules/flags most commonly associated with triggering manual review. We were particularly interested in rules that on their own often led to manual review in the absence of other flags. Prior to the study, autoverification rates were 87.8% (out of 16,073 orders) for complete blood count (CBC) if ordered as a panel and 85.8% (out of 1,940 orders) for CBC components ordered individually (not as the panel). RESULTS: Detailed analysis of rules/flags that frequently triggered indicated that the immature granulocyte (IG) flag (an instrument parameter) and rules that reflexed platelet by impedance method (PLT-I) to platelet by fluorescent method (PLT-F) represented the two biggest opportunities to increase autoverification. The IG flag threshold had previously been validated at 2%, a setting that resulted in this flag alone preventing autoverification in 6.0% of all samples. The IG flag threshold was raised to 5% after detailed chart review; this was also the instrument vendor's default recommendation for the newer hematology analyzers. Analysis also supported switching to PLT-F for all platelet analysis. Autoverification rates increased to 93.5% (out of 91,692 orders) for CBC as a panel and 89.8% (out of 11,982 orders) for individual components after changes in rules and laboratory practice. CONCLUSIONS: Detailed analysis of autoverification of hematology testing at an academic medical center clinical laboratory that had been using a set of autoverification rules for over a decade revealed opportunities to optimize the parameters. The data analysis was challenging and time-consuming, highlighting opportunities for improvement in software tools that allow for more rapid and routine evaluation of autoverification parameters.

Proteomics, Lipidomics, Metabolomics, and 16S DNA Sequencing of Dental Plaque From Patients With Diabetes and Periodontal Disease.

Oral microbiome influences human health, specifically prediabetes and type 2 diabetes (Pre-DM/DM) and periodontal diseases (PDs), through complex microbial interactions. To explore these relations, we performed 16S rDNA sequencing, metabolomics, lipidomics, and proteomics analyses on supragingival dental plaque collected from individuals with Pre-DM/DM (n = 39), Pre-DM/DM and PD (n = 37), PD alone (n = 11), or neither (n = 10). We identified on average 2790 operational taxonomic units and 2025 microbial and host proteins per sample and quantified 110 metabolites and 415 lipids. Plaque samples from Pre-DM/DM patients contained higher abundance of Fusobacterium and Tannerella than plaques from metabolically healthy patients. Phosphatidylcholines, plasmenyl phosphatidylcholines, ceramides containing non-OH fatty acids, and host proteins related to actin filament rearrangement were elevated in plaques from PD versus non-PD samples. Cross-omic correlation analysis enabled the detection of a strong association between Lautropia and monomethyl phosphatidylethanolamine (PE-NMe), which is striking because synthesis of PE-NMe is uncommon in oral bacteria. Lipidomics analysis of in vitro cultures of Lautropia mirabilis confirmed the synthesis of PE-NMe by the bacteria. This comprehensive analysis revealed a novel microbial metabolic pathway and significant associations of host-derived proteins with PD.

The effect of the Covid-19 shutdown on glycemic testing and control.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels. METHODS: HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal. RESULTS: HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p < 0.0005). CONCLUSION: HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results.

Experience With Pretravel Testing for SARS-CoV-2 at an Academic Medical Center.

International travel has been a significant factor in the coronavirus disease 2019 pandemic. Many countries and airlines have implemented travel restrictions to limit the spread of the causative agent, severe acute respiratory syndrome coronavirus-2. A common requirement has been a negative reverse-transcriptase polymerase chain reaction performed by a clinical laboratory within 48 to 72 hours of departure. A more recent travel mandate for severe acute respiratory syndrome coronavirus-2 immunoglobulin M serology testing was instituted by the Chinese government on October 29, 2020. Pretravel testing for severe acute respiratory syndrome coronavirus-2 raises complications in terms of cost, turnaround time, and follow-up of positive results. In this report, we describe the experience of a multidisciplinary collaboration to develop a workflow for pretravel severe acute respiratory syndrome coronavirus-2 reverse-transcriptase polymerase chain reaction and immunoglobulin M serology testing at an academic medical center. The workflow primarily involved self-payment by patients and preferred retrieval of results by the patient through the electronic health record patient portal (Epic MyChart). A total of 556 unique patients underwent pretravel reverse-transcriptase polymerase chain reaction testing, with 13 (2.4%) having one or more positive results, a rate similar to that for reverse-transcriptase polymerase chain reaction testing performed for other protocol-driven asymptomatic screening (eg, inpatient admissions, preprocedural) at our medical center. For 5 of 13 reverse-transcriptase polymerase chain reaction positive samples, the traveler had clinical history, prior reverse-transcriptase polymerase chain reaction positive, and high cycle thresholds values on pretravel testing consistent with remote infection and minimal transmission risk. Severe acute respiratory syndrome coronavirus-2 immunoglobulin M was performed on only 24 patients but resulted in 2 likely false positives. Overall, our experience at an academic medical center shows the challenge with pretravel severe acute respiratory syndrome coronavirus-2 testing.

Practical Considerations for Implementation of SARS-CoV-2 Serological Testing in the Clinical Laboratory: Experience at an Academic Medical Center.

Molecular techniques, especially reverse transcriptase polymerase chain reaction (RT-PCR), have been the gold standard for the diagnosis of acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Serological tests for SARS-CoV-2 have been widely used for serosurveys, epidemiology, and identification of potential convalescent plasma donors. However, the clinical role of serologic testing is still limited and evolving. In this report, we describe the experience of selecting, validating, and implementing SARS-CoV-2 serologic testing for clinical purposes at an academic medical center in a rural state. Successful implementation involved close collaboration between pathology, infectious diseases, and outpatient clinics. The most common clinician concerns were appropriateness/utility of testing, patient charges/insurance coverage, and assay specificity. In analyzing test utilization, serologic testing in the first month after go-live was almost entirely outpatient and appeared to be strongly driven by patient interest (including health care workers and others in high-risk occupations for exposure to SARS-CoV-2), with little evidence that the results impacted clinical decision-making. Test volumes for serology declined steadily through October 31, 2020, with inpatient ordering assuming a steadily higher percentage of the total. In a 5-month period, SARS-CoV-2 serology test volumes amounted to only 1.3% of that of reverse transcriptase polymerase chain reaction. Unlike reverse transcriptase polymerase chain reaction, supply chain challenges and reagent availability were not major issues for serology testing. We also discuss the most recent challenge of requirements for SARS-CoV-2 testing in international travel protocols. Overall, our experience at an academic medical center shows that SARS-CoV-2 serology testing assumed a limited clinical role.

Continuation of Over-the-Counter Biotin Supplements in the Inpatient Setting: An Unexpected Source of Laboratory Error.

BACKGROUND: Over the past decade, use of high-dose biotin has increased significantly and can lead to erroneous results on some clinical immunoassays. In collaboration with pharmacists at our institution, we discovered that high biotin doses were being administered to inpatients as a continuation of patient-reported home biotin use. METHODS: This retrospective study evaluated high-dose biotin administration in 226 inpatient encounters from 2009 to 2019 and its potential impact on concurrent immunoassay testing. RESULTS: In 96% of cases, biotin was administered in the inpatient setting as a continuation of patient-reported home use. In total, 322 immunoassays capable of biotin interference were performed across 100 inpatient encounters with high-dose biotin administration. Troponin T and TSH were the most commonly performed immunoassays in this cohort. DISCUSSION: Even though less than 5% of all high-dose biotin orders at our institution are placed for inpatients, hospitalized patients are still at risk for mismanagement due to erroneous immunoassay results. Immunoassay testing susceptible to biotin interference was performed in approximately 45% of inpatient encounters with biotin administration. Laboratories utilizing biotin-susceptible, sensitive cardiac troponin assays should be particularly cautious. Pharmacokinetic data for biotin clearance is especially lacking for certain populations likely to be hospitalized, such as those with renal failure. Given that medical conditions requiring high-dose biotin therapy are extremely rare, we recommend restricting biotin dosing during inpatient encounters for all other patients.

Exponential increase in neutralizing and spike specific antibodies following vaccination of COVID-19 convalescent plasma donors.

BACKGROUND: With the recent approval of COVID-19 vaccines, recovered COVID-19 subjects who are vaccinated may be ideal candidates to donate COVID-19 convalescent plasma (CCP). CASE SERIES: Eleven recovered COVID-19 patients were screened to donate CCP. All had molecularly confirmed COVID-19, and all but one were antibody positive by chemiluminescence immunoassay (DiaSorin) prior to vaccination. All were tested again for antibodies 11-21 days after they were vaccinated (Pfizer/Moderna). All showed dramatic increases (~50-fold) in spike-specific antibody levels and had at least a 20-fold increase in the IC50 neutralizing antibody titer based on plaque reduction neutralization testing (PRNT). The spike-specific antibody levels following vaccination were significantly higher than those seen in any non-vaccinated COVID-19 subjects tested to date at our facility. CONCLUSION: Spike-specific and neutralizing antibodies demonstrated dramatic increases following a single vaccination after COVID-19 infection, which significantly exceeded values seen with COVID-19 infection alone. Recovered COVID-19 subjects who are vaccinated may make ideal candidates for CCP donation.

Side-Effects of COVID-19 on Patient Care: An INR Story.

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.