Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase.

WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms1-5. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a region of the helicase domain subject to interdomain movement during DNA unwinding. VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), but not in microsatellite-stable, cells. The compound was well tolerated in mice and led to robust tumour regression in multiple MSI-H colorectal cancer cell lines and patient-derived xenograft models. Our work shows an allosteric approach for inhibition of WRN function that circumvents competition from an endogenous ATP cofactor in cancer cells, and designates VVD-133214 as a promising drug candidate for patients with MSI-H cancers.

Hospice and palliative care utilization in 16 004 232 medicare claims: comparing trauma to surgical and medical inpatients.

Background: Hospice and palliative care (PC) utilization is increasing in geriatric inpatients, but limited research exists comparing rates among trauma, surgical and medical specialties. The goal of this study was to determine whether there are differences among these three groups in rates of hospice and PC utilization. Methods: Patients from Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files for 2016-2020 aged ≥65 years were analyzed. Patients with a National Trauma Data Standard-qualifying ICD-10 injury code with abbreviated injury score ≥2 were classified as 'trauma'; the rest as 'surgical' or 'medical' using CMS MS-DRG definitions. Patients were classified as having PC if they had an ICD-10 diagnosis code for PC (Z51.5) and as hospice discharge (HD) if their hospital disposition was 'hospice' (home or inpatient). Use proportions for specialties were compared by group and by subgroups with increasing risk of poor outcome. Results: There were 16M hospitalizations from 1024 hospitals (9.3% trauma, 26.3% surgical and 64.4% medical) with 53.7% women, 84.5% white and 38.7% >80 years. Overall, 6.2% received PC and 4.1% a HD. Both rates were higher in trauma patients (HD: 3.6%, PC: 6.3%) versus surgical patients (HD: 1.5%, PC: 3.0%), but lower than in medical patients (HD: 5.2%, PC: 7.5%). PC rates increased in higher risk patient subgroups and were highest for inpatient HD. Conclusions: In this large study of Medicare patients, HD and PC rates varied significantly among specialties. Trauma patients had higher HD and PC utilization rates than surgical, but lower than medical. The presence of comorbidities, frailty and/or severe traumatic brain injury (in addition to advanced age) may be valuable criteria in selection of trauma patients for hospice and PC services. Further studies are needed to inform the most efficient use of hospice and PC resources, with particular focus on both timing and selection of subgroups most likely to benefit from these valuable yet limited resources. Level of evidence: Level III, therapeutic/care management.

Would you be surprised? Prospective multicenter study of the Surprise Question as a screening tool to predict mortality in trauma patients.

BACKGROUND: The Surprise Question (SQ) ("Would I be surprised if the patient died within the next year?") is a validated tool used to identify patients with limited life expectancy. Because it may have potential to expedite palliative care interventions per American College of Surgeons Trauma Quality Improvement Program Palliative Care Best Practices Guidelines, we sought to determine if trauma team members could use the SQ to accurately predict 1-year mortality in trauma patients. METHODS: A multicenter, prospective, cohort study collected data (August 2020 to February 2021) on trauma team members' responses to the SQ at 24 hours from admission. One-year mortality was obtained via social security death index records. Positive/negative predictive values and accuracy were calculated overall, by provider role and by patient age. RESULTS: Ten Level I/II centers enrolled 1,172 patients (87.9% blunt). The median age was 57 years (interquartile range, 36-74 years), and the median Injury Severity Score was 10 (interquartile range, 5-14 years). Overall 1-year mortality was 13.3%. Positive predictive value was low (30.5%) regardless of role. Mortality prediction minimally improved as age increased (positive predictive value highest between 65 and 74 years old, 34.5%) but consistently trended to overprediction of death, even in younger patients. CONCLUSION: Trauma team members' ability to forecast 1-year mortality using the SQ at 24 hours appears limited perhaps because of overestimation of injury effects, preinjury conditions, and/or team bias. This has implications for the Trauma Quality Improvement Program Guidelines and suggests that more research is needed to determine the optimal time to screen trauma patients with the SQ. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Implementing Guidelines for NICU Parent Presence: Effects on Parent and Infant Stress.

BACKGROUND: Relationships between parents and infants are essential for mitigating stressors encountered in neonatal intensive care units (NICUs) and are supported by parent presence and engagement. PURPOSE: The purpose of this study was to compare NICU parent and infant outcomes pre- and postimplementation of an intervention aimed at increasing parent presence and engagement in the NICU. This family-centered care intervention consisted of communicating specific guidelines for parent presence. METHODS: Data related to parent presence, skin-to-skin care, and breastfeeding; parental stress; infant outcomes including weight gain, length of stay, feeding status at discharge, and stress; and unit-level outcomes were collected from a convenience sample of 40 NICU families recruited preimplementation and compared with data for 38 NICU families recruited postimplementation of specific guidelines for parent presence. To establish comparability of groups, infants were assigned scores using the Neonatal Medical Index. RESULTS: Parent presence, engagement in skin-to-skin care, and breastfeeding rates were not significantly different between groups. Stress-related outcomes were significantly decreased in NICU mothers, fathers, and infants, and infant feeding outcomes were improved in the postintervention group. CONCLUSIONS: Specific guidelines for parent presence may represent an invitation for parents to engage with their NICU infants and may positively impact parent and infant stress.

Driving Under the Influence of Cannabis: Impact of Combining Toxicology Testing with Field Sobriety Tests.

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers. METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired. RESULTS: There was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo. CONCLUSIONS: Requiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired.

Pathogenesis of annular lesions: Why a ring presentation?

Annular lesions represent a distinct morphology which characterizes many well-known dermatologic conditions. Little is definitively known regarding the pathogenesis of annular lesions, however there a few well-regarded hypotheses. Lesions that clear centrally while enlarging peripherally may result from a local central tissue anergy, or tolerance. The central area in lesions due to dermatophyte infections or subacute cutaneous lupus erythematous may have a central immunity to the antigen that trigged the lesion. The peripheral spread of inflammatory mediators may also contribute to lesions that expand centrifugally. In a highly active immune response, some of the inflammatory mediators may spread to adjacent tissue, which can propagate the inflammatory reaction. The additional hypotheses regarding pathogenesis are disease specific with individual mechanisms having been proposed. This chapter will describe both general and disease specific mechanisms that may contribute to the formation of annular lesions.

Development of surgical palliative care as a field and community building in palliative care: past, present, and future directions.

The professionalization of hospice and palliative medicine has been well documented, as has its associated rise to specialty status. The movement to formalize hospice and palliative medicine in the United States included ten sponsoring boards for initial certification through a practice pathway. Thus, it began with the potential for subspecialty interests, advocacy, and training. This review will examine the emergence of surgical palliative care as a field within hospice and palliative medicine as well as its unique place within the specialty of surgery, where it is sometimes hailed as an inherent, historically present body of knowledge and skill, and just as often, remarked upon as an ahistorical oxymoron. The phases of formation, early adoption, popularization, and normalization will be described and illustrated by the benchmarks of formal education requirements, board eligibility and certification, and professional relationships fostered by medical societies and online communities. Community building in palliative care must acknowledge the diversity of its constituents and the differences in subspecialty identity formation and sources of professional credibility and legitimacy. Metaphors for practitioners of surgical palliative care range from the rarity of the unicorn to the swarm intelligence principles of the beehive. Future directions include facing the questions about the role of specialty training and practice in surgical palliative care compared to renewed emphasis on palliative principles in general surgical training and practice.

Driving Performance and Cannabis Users' Perception of Safety: A Randomized Clinical Trial.

IMPORTANCE: Expanding cannabis medicalization and legalization increases the urgency to understand the factors associated with acute driving impairment. OBJECTIVE: To determine, in a large sample of regular cannabis users, the magnitude and time course of driving impairment produced by smoked cannabis of different Δ9-tetrahydrocannabinol (THC) content, the effects of use history, and concordance between perceived impairment and observed performance. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled parallel randomized clinical trial took place from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California San Diego. Cannabis users were recruited for this study, and analysis took place between April 2020 and September 2021. INTERVENTIONS: Placebo or 5.9% or 13.4% THC cannabis smoked ad libitum. MAIN OUTCOMES AND MEASURES: The primary end point was the Composite Drive Score (CDS), which comprised key driving simulator variables, assessed prior to smoking and at multiple time points postsmoking. Additional measures included self-perceptions of driving impairment and cannabis use history. RESULTS: Of 191 cannabis users, 118 (61.8%) were male, the mean (SD) age was 29.9 (8.3) years, and the mean (SD) days of use in the past month was 16.7 (9.8). Participants were randomized to the placebo group (63 [33.0%]), 5.9% THC (66 [34.6%]), and 13.4% THC (62 [32.5%]). Compared with placebo, the THC group significantly declined on the Composite Drive Score at 30 minutes (Cohen d = 0.59 [95% CI, 0.28-0.90]; P < .001) and 1 hour 30 minutes (Cohen d = 0.55 [95% CI, 0.24-0.86]; P < .001), with borderline differences at 3 hours 30 minutes (Cohen d = 0.29 [95% CI, -0.02 to 0.60]; P = .07) and no differences at 4 hours 30 minutes (Cohen d = -0.03 [95% CI, -0.33 to 0.28]; P = .87). The Composite Drive Score did not differ based on THC content (likelihood ratio χ24 = 3.83; P = .43) or use intensity (quantity × frequency) in the past 6 months (likelihood ratio χ24 = 1.41; P = .49), despite postsmoking blood THC concentrations being higher in those with the highest use intensity. Although there was hesitancy to drive immediately postsmoking, increasing numbers (81 [68.6%]) of participants reported readiness to drive at 1 hour 30 minutes despite performance not improving from initial postsmoking levels. CONCLUSIONS AND RELEVANCE: Smoking cannabis ad libitum by regular users resulted in simulated driving decrements. However, when experienced users control their own intake, driving impairment cannot be inferred based on THC content of the cigarette, behavioral tolerance, or THC blood concentrations. Participants' increasing willingness to drive at 1 hour 30 minutes may indicate a false sense of driving safety. Worse driving performance is evident for several hours postsmoking in many users but appears to resolve by 4 hours 30 minutes in most individuals. Further research is needed on the impact of individual biologic differences, cannabis use history, and administration methods on driving performance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02849587.

Targeted mass spectrometry-based assays enable multiplex quantification of receptor tyrosine kinase, MAP Kinase, and AKT signaling.

SUMMARY: A primary goal of the US National Cancer Institute's Ras initiative at the Frederick National Laboratory for Cancer Research is to develop methods to quantify RAS signaling to facilitate development of novel cancer therapeutics. We use targeted proteomics technologies to develop a community resource consisting of 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. As proof of concept, we quantify the response of melanoma (A375 and SK-MEL-2) and colorectal cancer (HCT-116 and HT-29) cell lines to BRAF inhibition by PLX-4720. These assays replace over 60 Western blots with quantitative mass spectrometry-based assays of high molecular specificity and quantitative precision, showing the value of these methods for pharmacodynamic measurements and mechanism of action studies. Methods, fit-for-purpose validation, and results are publicly available as a resource for the community at assays.cancer.gov. MOTIVATION: A lack of quantitative, multiplexable assays for phosphosignaling limits comprehensive investigation of aberrant signaling in cancer and evaluation of novel treatments. To alleviate this limitation, we sought to develop assays using targeted mass spectrometry for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. The resulting assays provide a resource for replacing over 60 Western blots in examining cancer signaling and tumor biology with high molecular specificity and quantitative rigor.

SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses.

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 4 commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 patients who were SARS-CoV-2 PCR positive, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 patients who were SARS-CoV-2 negative. 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 2 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 median infective dose (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 2 doses of the Moderna vaccine (ID50, 597) compared to individuals who 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.

A Rapid Assay for SARS-CoV-2 Neutralizing Antibodies That Is Insensitive to Antiretroviral Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike pseudotyped virus (PSV) assays are widely used to measure neutralization titers of sera and of isolated neutralizing Abs (nAbs). PSV neutralization assays are safer than live virus neutralization assays and do not require access to biosafety level 3 laboratories. However, many PSV assays are nevertheless somewhat challenging and require at least 2 d to carry out. In this study, we report a rapid (<30 min), sensitive, cell-free, off-the-shelf, and accurate assay for receptor binding domain nAb detection. Our proximity-based luciferase assay takes advantage of the fact that the most potent SARS-CoV-2 nAbs function by blocking the binding between SARS-CoV-2 and angiotensin-converting enzyme 2. The method was validated using isolated nAbs and sera from spike-immunized animals and patients with coronavirus disease 2019. The method was particularly useful in patients with HIV taking antiretroviral therapies that interfere with the conventional PSV assay. The method provides a cost-effective and point-of-care alternative to evaluate the potency and breadth of the predominant SARS-CoV-2 nAbs elicited by infection or vaccines.

Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers.

Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆9-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids' concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by liquid chromatography with tandem mass spectrometry for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent compared to occasional users, whereas there were no significant differences in OF Cmax. Blood THC remained detectable (≥5 ng/mL) at the final sample collection for 14% of individuals who smoked either the 5.9 or 13.4% THC cigarette, whereas 54% had detectable THC in OF when applying the same cutoff. Occasional and frequent cannabis users' profiles were compared, THC was detectable for significantly longer duration in blood and OF from frequent users. Detection rates between frequent and occasional users at multiple per se cutoffs showed larger differences in blood versus OF. Understanding cannabinoid profiles of frequent and occasional users and the subsequent impact on detectability with current drug per se driving limits is important to support forensic interpretations and the development of scientifically supported driving under the influence of cannabis laws.

Dermatologic support for oncology: Quantifying the consultative services received by hospitalized oncology patients.

Hospitalized oncology patients often require multidisciplinary care. Inpatient consultative dermatologists can provide expertise in the management of cutaneous complications that patients with cancer may experience. The goal of this study was to quantify the types of consults received by hospitalized oncology patients to better understand the utilization of dermatology consults in this population. Hospital billing codes were used to identify inpatient oncology patients and the types of consults they received at a single quaternary care hospital center. Between July 1, 2015, and January 31, 2020, 14,175 patients were admitted to an oncology service for more than 24 hours, and 5,243 (37%) of these patients received at least 1 consultation during their hospital admission. These patients received a total of 10,492 consults from 101 different services. Dermatology had the fifth-highest number of consults (n = 623; 5.9%). Among patients receiving consults, 608 (11.6%) received inpatient dermatology consults. Infectious disease was the service with the most consults (n = 1,485; 14.2%) and was also the service most commonly co-consulted with dermatology (n = 262; 42.1%). The inpatient consultative dermatology service is highly utilized among hospitalized oncology patients, suggesting that expertise in dermatologic care is valued by oncology teams.

Long-term Physical and Psychological Outcomes of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

IMPORTANCE: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is known to cause multiple end-organ complications in its acute phase, but less is known about the long-term association with patients' mental health and quality of life. OBJECTIVE: To examine the chronic physical and psychological sequelae affecting patients with SJS/TEN. DESIGN, SETTING, AND PARTICIPANTS: A survey study conducted at 11 academic health centers in the US evaluated 121 adults diagnosed with SJS/TEN by inpatient consultive dermatologists between January 1, 2009, and September 30, 2019. INTERVENTIONS: Patients completed a survey that included the following validated questionnaires: Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Primary Care Post-Traumatic Stress Disorder Screen (PC-PTSD), and the 12-item Short Form Health Survey (SF-12). The survey also included questions created by the study team regarding fear, patient education, and long-term sequelae relevant to SJS/TEN. MAIN OUTCOMES AND MEASURES: Primary outcome measures were the percentage of patients reporting long-term physical sequelae; the percentage of patients with positive results on PHQ-9, GAD-7, and PC-PTSD screening; and the numeric score on the SF-12 (score of 50 defined as average physical and mental well-being). RESULTS: A total of 121 individuals (73 women [60.3%]; mean [SD] age, 52.5 [17.1] years) completed the survey (response rate, 29.2%). The most common long-term physical sequelae reported were cutaneous problems (102 of 121 [84.3%]), ocular problems (72 of 121 [59.5%]), and oral mucosal problems (61 of 120 [50.8%]). A total of 53.3% (64 of 120) of the respondents had results indicating depression on the PHQ-9, 43.3% (52 of 120) showed signs of anxiety on the GAD-7, and 19.5% had results indicating PTSD on the PC-PTSD. The mean (SD) SF-12 Physical Component Summary score was 42.4 (22.8), and the mean Mental Component Summary score was 46.1 (20.9). A total of 28.2% (33 of 117) of the respondents were unable to work, 68.1% (81 of 119) were fearful of taking new medications, and 30.0% (36 of 120) avoided taking prescribed medications for a diagnosed medical condition. CONCLUSIONS AND RELEVANCE: This survey study found that long-term physical sequelae, depression, and anxiety appear to be common in patients with SJS/TEN, with implications for health and well-being. Improved awareness of these complications may assist health professionals in offering medical care, counseling, and support to patients with SJS/TEN.

Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats.

RATIONALE: Cannabidiol (CBD) reduces craving in animal models of alcohol and cocaine use and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal. However, preclinical evaluation of its efficacy is still lacking. OBJECTIVES: The goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence. METHODS: Male and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for 2 weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for 2 weeks, starting 1 week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps received sesame oil injections (double vehicle) or the highest dose of CBD 30 mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded. RESULTS: CBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD. The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30 mg/kg/day) did not alter these results. CONCLUSIONS: This preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine cessation may be beneficial.

SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses.

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.