A moth to a flame? Fulfilling connectedness needs through romantic relationships protects conspiracy theorists against COVID-19 misinformation

Conspiracy theorists' unpopular opinions likely make them more apprehensive about interactions with others, frustrating their need to belong. Therefore, they may be susceptible to believing misinformation because evidence that others share their beliefs provides "social proof” that they can expect interactions with others to be positive and rewarding. The present research examined whether alternatively fulfilling the need for social connection through romantic relationships could protect conspiracy theorists against COVID-19 misinformation. In a 3-week daily diary study (N = 555), experimental participants implicitly learned to associate their romantic partners with positive experiences (by repeatedly pairing their partner with highly positive and approachable stimuli, McNulty et al., 2017). We then assessed how much participants trusted individuals they might normally distrust, as a manipulation check, and how much participants tuned their daily personal beliefs and behavior to match the U.S. public's daily susceptibility to COVID-19 misinformation. Participants high on conspiratorial thinking trusted fellow community members more in the experimental than control condition. Participants high on conspiratorial thinking in the experimental condition were also less likely to treat the U.S. public's greater daily susceptibility to COVID-19 misinformation as proof that they could discount the virus. The present findings suggest that rewarding romantic connections might be leveraged to limit conspiracy theorists' susceptibility to believing public skepticism about COVID-19. © 2023 The Authors

Sensitizing the Behavioral-Immune System: The Power of Social Pain

People who believe they are invulnerable to infectious diseases often fail to protect themselves against the disease threats that others pose to them. The current paper hypothesizes that social pain-the experience of feeling interpersonally hurt or rejected-can sensitize the behavioral-immune system by giving people added reason to see others as worthy of protecting themselves against. We obtained four daily diary samples involving 2,794 participants who reported how hurt/rejected they felt by those they knew, how personally concerned they were about the spread of illness/COVID-19, and how vigilantly they engaged in self-protective behaviors to safeguard their health each day. An integrative data analysis revealed robust evidence that people who believed they were invulnerable to infectious disease engaged in more concerted efforts to protect themselves against the greater daily risk of contracting COVID-19 when being in acute social pain gave them added reason to see others as harmful to them.

Trust as a daily defense against collective disease threats

Although the isolated threat of disease often motivates people to avoid others, people need the help and cooperation of others to protect themselves against pandemic disease threats. Therefore, the fear of contracting a highly contagious virus like COVID-19 should motivate people to believe that they can in fact count on the help and cooperation of others for protection. Trusting in others provides the basis to anticipate their cooperation. Therefore, we expected a greater daily threat of contracting COVID-19 to motivate people to trust more in others, providing needed assurance that others would keep them safe from harm. We obtained 4 daily diary samples involving 2794 participants who provided in excess of 18,000 daily observations within the first three months of the COVID-19 pandemic. Each day, we tracked (1) disease threat, captured daily by personal concerns about COVID-19 and infection totals in the nearest most populous city, and (2) trust in others, captured daily by expressions of trust in intimates, collective caregivers (e.g., President, Congress), and strangers. Participants in two samples completed 2-month follow-ups. Integrative analyses of the daily diaries revealed that people trusted more in intimates and collective caregivers on days they had greater (vs. less) reason to be concerned about COVID-19. Further integrative analyses of the follow-up data revealed that participants who were initially more likely to trust in others on days when COVID-19 cases in nearby communities spread more rapidly later reported greater confidence that others would keep them safe from harm. That is, they evidenced greater physical, interpersonal, and collective security in social connection than participants who were initially less likely to defensively trust in others on such occasions. The present findings suggest that ecological threats may dynamically motivate people to trust others more than they otherwise would, providing optimism that collectively-faced crises may motivate social cooperation when it is most needed. © 2022

Novel recombinant measles virus vaccine prevents measles virus disease in rhesus macaques

Background: Measles-Mumps-Rubella (MMR) is an effective live-virus vaccine against measles virus (MeV). However, use of MMR is limited by its inability to boost MeV immunity, lack of immunogenicity in infants, and contraindication in pregnant and immunocompromised persons. Methods: We evaluated a novel recombinant dimeric MeV hemagglutinin protein vaccine (rMeV) in a rhesus macaque model. Sixteen macaques were primed at day 0 and boosted at day 42 by experimental group: 1) MMR x2;2) rMeV x2;3) MMR prime/rMeV boost;4) control;n=4. Macaques were challenged intratracheally with Bilthoven strain wild type MeV 8 months later. Blood, bone marrow (BM), and lymph node (LN) samples were collected over 3–28 days after challenge. Replication-competent MeV was measured in peripheral blood mononuclear cells (PBMC), BM cells, and LN cells by infectious assay;MeV RNA in PBMC and BM cells was determined by quantitative reverse transcriptase polymerase chain reaction. Plasma was evaluated for MeV-specific IgG and plaque reduction neutralization titer (PRNT). Results: Six months after vaccination, mean PRNT was 2,432 in rMeV x2 (standard deviation (SD) 3,840), 3,584 in MMR-prime/rMeV boost (SD 3,072) and 5,120 in MMR x2 groups (SD 3,547). Upon infectious challenge, macaques who received any MeV-containing vaccine developed no clinical signs of measles and had no detectable infectious virus in PBMC, BM cells, or LN cells. All unvaccinated macaques had virus in PBMC that peaked at day 7 (mean 3,162 TCID50/mL, SD 4.1) and resolved by day 14 post challenge, and one macaque developed an extensive rash. Macaques who received any MeV-containing vaccine had no detectable MeV RNA in PBMC or BM cells, whereas all unvaccinated macaques had detectable MeV RNA that peaked at day 7 (1.6e5 copies, SD 10.5) in PBMC. In all experimental groups, MeV-specific IgG titers increased after MeV challenge. Conclusion: Macaques who received rMeV and/or MMR were protected from rash, viremia, and detection of MeV RNA in PBMC and BM cells, unlike unvaccinated macaques. These data suggest that rMeV vaccine generates protective immune responses against measles and may be a novel candidate for future measles vaccine strategies. Study of cellular responses after rMeV vaccination and MeV challenge is warranted. Disclosures: Jessica Rubens, MD, Mevox: Grant/Research Support Guillaume Stewart-Jones, PhD, Moderna: Inventor of SARS-CoV-2 vaccine sequences;Moderna: Stocks/Bonds Michael Watson, MD, MEVOX Ltd: Board Member;MEVOX Ltd: Ownership Interest;MEVOX Ltd: Stocks/Bonds Barney S. Graham, MD, PhD, BSG: BSG is an inventor on patents for the stabilization of the RSV F protein (WO2014160463A1, Prefusion RSV F proteins and their use).;National Institutes of Health: Inventor on patents for RSV vaccines;National Institutes of Health: inventor on patents for measles and other paramyxovirus vaccines Diane Griffin, MD PhD, Gilead: Grant/Research Support;GlaxoSmithKline: Advisor/Consultant;GreenLight Biosciences: Advisor/Consultant;Merck: Advisor/Consultant;MeVox: Grant/Research Support;Takeda Pharmaceuticals: Advisor/Consultant.

Sensitizing the Behavioral-Immune System: The Power of Social Pain

People who believe they are invulnerable to infectious diseases often fail to protect themselves against the disease threats that others pose to them. The current paper hypothesizes that social pain—the experience of feeling interpersonally hurt or rejected—can sensitize the behavioral-immune system by giving people added reason to see others as worthy of protecting themselves against. We obtained four daily diary samples involving 2,794 participants who reported how hurt/rejected they felt by those they knew, how personally concerned they were about the spread of illness/COVID-19, and how vigilantly they engaged in self-protective behaviors to safeguard their health each day. An integrative data analysis revealed robust evidence that people who believed they were invulnerable to infectious disease engaged in more concerted efforts to protect themselves against the greater daily risk of contracting COVID-19 when being in acute social pain gave them added reason to see others as harmful to them. © The Author(s) 2022.

Tropospheric and Surface Nitrogen Dioxide Changes in the Greater Toronto Area during the First Two Years of the COVID‐19 Pandemic

We present tropospheric nitrogen dioxide (NO2) changes observed by the Canadian Pandora measurement program in the Greater Toronto Area (GTA), Canada, and compare the results with surface NO2 concentrations measured via in situ instruments to assess the local emission changes during the first two years of the COVID‐19 pandemic. In the City of Toronto, the first lock-down period started on 15 March 2020, and continued until 24 June 2020. ECMWF Reanalysis v5 (ERA‐5) wind information was used to facilitate the data analysis and reveal detailed local emission changes from different areas of the City of Toronto. Evaluating seven years of Pandora observations, a clear NO2 reduction was found, especially from the more polluted downtown Toronto and airport areas (e.g., declined by 35% to 40% in 2020 compared to the 5‐year mean value from these areas) during the first two years of the pandemic. Compared to the sharp decline in NO2 emissions in 2020, the atmospheric NO2 levels in 2021 started to recover, but are still below the mean values in pre-pandemic time. For some sites, the pre‐pandemic NO2 local morning rush hour peak has still not returned in 2021, indicating a change in local traffic and commuter patterns. The long‐term (12 years) surface air quality record shows a statistically significant decline in NO2 with and without April to September 2020 observations (trend of −4.1%/yr and −3.9%/yr, respectively). Even considering this long‐term negative trend in NO2, the observed NO2 reduction (from both Pandora and in situ) in the early stage of the pandemic is still statistically significant. By implementing the new wind‐based validation method, the high‐resolution satellite instrument (TROPOMI) can also capture the local NO2 emission pattern changes to a good level of agreement with the ground‐based observations. The bias between ground‐based and satellite observations during the pandemic was found to have a positive shift (5–12%) than the bias during the pre‐pandemic period. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

The relationship between symptoms and functional physiological outcomes in survivors of severe COVID-19 pneumonia

P136 Table 1Results of correlation analysis Correlation analysis 4MGS 1STSreps SpO2% desaturation Results r p-value r p-value r p-value Pre-COVID mMRC dyspnoea score 0(0–1) -0.267** <0.001 -0.285** <0.001 -0.108 0.094 Post-COVID mMRC dyspnoea score 1(0–2) -0.442** <0.001 -0.457** <0.001 -0.143* 0.025 NRS breathlessness 3(0–5) -0.287** <0.001 -0.406** <0.001 -0.490 0.445 NRS fatigue 3(0–5) -0.315** <0.001 -0.379** <0.001 -0.190* 0.003 NRS cough 0(0–2) -0.660 0.292 -0.153* 0.017 0.083 0.194 NRS pain 1(0–4) -0.278** <0.001 -0.346** <0.001 -0.188* 0.003 NRS sleep difficulty 2(0–5) -0.246** <0.001 -0.386** <0.001 -0.122 0.057 Data are presented as median (interquartile range) or frequency (proportion%;95% confidence interval). SpO2% desaturation = SpO2% desaturation from baseline during 1 minute sit to stand test;1STSreps = repetitions per minute during 1 minute sit to stand test;4MGS = 4 metre gait speed;mMRC = modified Medical Research Council;NRS = 0 – 10 numerical rating scale;r = Spearman correlation coefficient. *indicates statistical significance at 0.05 level. **indicates statistical significance at 0.001 level.ConclusionRespiratory symptoms were not strong predictors of 4-metre gait speed and 1-minute sit-to-stand test performance. These data highlight the importance of face-to-face testing to objectively assess functional limitation in patients recovering from severe COVID pneumonia.

Clinical, functional and psychological characteristics of survivors of severe COVID-19 pneumonia: a comparison of outcomes from the first and second waves

P135 Table 1Patient demographics, self-reported scores and functional test results by wave 1st wave 2nd wave p-value Demographics n=167 n=141 Age 59±13 58±12 0.564 Female 60 (35.93;28.94–43.40) 62 (43.97;35.97–52.22) 0.15 BMI (kg/m2) 30.5 (26.6–35.2) 32.1 (28.5–37.9) 0.009 ** BAME 115 (69.7;62.39–76.32) 72 (59.5;50.62–67.94) 0.073 Number of comorbidities 2 (1–3) 2 (1–3) 0.144 Patients Receiving Drugs Dexamethasone 11 (6.63;3.57–11.17) 138 (97.87;94.43–99.40) <0.001 *** Remdesivir 18 (10.84;6.79–16.24) 81 (57.45;49.20–65.39) <0.001 *** Other Immunomodulator 2 (1.20;0.25–3.81) 31 (21.99;15.76–29.35) <0.001 *** Questionnaire Scores n=164 n=132 NRS Breathlessness 2 (0–5) 3 (0–5) 0.153 ≥4 56 (34.78;27.75–42.36) 52 (37.14;29.47–45.34) 0.67 NRS Cough 0 (0–2) 0 (0–3) 0.439 ≥4 17 (10.56;6.52–16.00) 18 (13.64;8.59–20.26) 0.419 NRS Fatigue 3 (0–5) 3 (0–5) 0.867 ≥4 65 (40.63;33.24–48.35) 48 (36.92;28.99–45.43) 0.52 NRS Pain 0 (0–5) 1 (0–3) 0.682 ≥4 44 (27.50;21.03–34.78) 30 (23.08;16.48–30.86) 0.39 NRS Sleep disturbance 2 (0–5) 2 (0–5) 0.558 ≥4 52 (32.50;25.61–40.02) 49 (37.40;29.47–45.89) 0.382 Pre-COVID-19 mMRC 1 (0–2) 1 (1–2) 0.478 Post-COVID-19 mMRC 0 (0–1) 0 (0–1) 0.329 Post-COVID-19 mMRC ≥2 66 (40.99;33.61–48.70) 49 (38.58;30.45–47.23) 0.678 PCFS 2 (0–3) 1 (0–2) 0.055 PCFS ≥2 80 (50.00;42.31–57.69) 51 (42.15;33.62–51.05) 0.191 PHQ-9 ≥10 32 (20.38;14.66–27.19) 29 (23.02;16.33–30.92) 0.592 GAD-7 ≥10 34 (21.38;15.56–28.24) 16 (12.80;7.81- 19.49) 0.059 TSQ ≥6 43 (27.56;21.01–34.94) 27 (22.31;15.60–30.33) 0.319 Functional Tests n=160 n=139 4MGS <0.8 (ms-1) 67 (42.41;34.89–50.19) 47 (35.07;27.38–43.40) 0.201 1STS repetitions 18 (12–23) 17 (12–21) 0.460 <2.5 percentile 96 (60.00;52.29–67.36) 108 (77.70;70.25–84.00) 0.011 * Desaturation ≥4% 52 (34.67;27.40–4 .52) 42 (32.31;24.73–40.67) 0.677 Parametric data are presented as mean ± standard deviation, non-parametric data are presented as median (interquartile range) or frequency (proportion;95% confidence interval). Statistical significance indicated by * (p<0.05), ** (p<0.01), *** (p<0.001). BMI = Body mass index, BAME = Black, Asian or minority ethnic, NRS = Numerical rating scale (0–10), mMRC = modified Medical Research Council for dyspnoea (0–4), PCFS = Post-COVID-19 functional status scale (0–4), PHQ-9 = Patient health questionnaire 9 (0–27), GAD-7 = General Anxiety Disorder-7 scale (0–21), TSQ = Trauma screening questionnaire (0–10), 4MGS = 4-metre gait speed, 1STS = 1-minute sit-to-stand.ConclusionDespite shorter admission duration, and less frequent IMV, the burden of symptoms and functional limitation experienced post-hospitalisation for severe COVID-19 pneumonia was at least as severe during Wave 2 as in Wave 1. Identification of contributing factors and impact on post-COVID rehabilitation outcomes requires further study.

Development and validation of a novel patient-reported outcomes (PRO) measure for symptom burden in patients with cancer and COVID-19 infection

Background: The symptom burden experienced by patients with cancer who contract the COVID-19 (C19) infection remains to be fully understood. To accurately assess this symptom burden, we developed a valid, reliable patient-reported outcome (PRO) measure of C19 symptoms combined with a known measure of cancer symptom burden. Methods: Within the institutional initiative on COVID-19 and cancer named Data- Driven Determinants for COVID-19 Oncology Discovery Effort (D3CODE), patients with cancer and PCR-positive C19 tests were invited to participate in this longitudinal study after providing consent. Pts completed the EQ-5D-5L and the 13 symptom severity and 6 interference items of the core MD Anderson Symptom Inventory (MDASI) plus 14 COVID-specific symptom items generated from literature and expert review. Items were measured on a 0-10 scale, 0 = none to 10 = worst imaginable symptom or interference. Demographic and disease information was collected. Psychometric procedures determined validity and reliability of the MDASI-COVID. Results: 600 pts enrolled, mean age 56.5y (range 20 to 91y). 59% female, 80% white. 78% solid tumors, 19% heme cancers. 12.5% required hospitalization for C19. Median number of days between positive C19 test and PRO completion was 17 days. Mean overall health rating on EQ-5D-5L was 78.3 (SD 19.6), best being 100. Highest mean (M) severity symptoms on the MDASI-COVID were fatigue (M 3.45, SD 2.17), drowsiness (M 2.50, SD 2.89), sleep disturbance (M 2.44, SD 2.99), malaise (M 2.37, SD 3.05), and distress (M 2.27, SD 2.90). Most severe (≥ 7) symptoms) reported were fatigue (21.3% of pts), change in taste (14.8%), change in smell (14.4%), malaise (14.3%), sleep disturbance (14.3%), and drowsiness (14%). Internal consistency (Cronbach α) of the 27 symptom items was 0.957, of the 6 interference items was 0.937. Mean severity of the 27 symptom items was significantly correlated with overall EQ-5D-5L health rating (correlation = -0.45, P < 0.0005), demonstrating concurrent validity. Mean symptom severity and interference showed known-group validity between patients who required C19 hospitalization (symptom M 2.32, SD 2.09;interference M 3.29, SD 3.02) and those who did not (symptom M 1.69, SD 1.85;interference M 2.20, SD 2.64) (symptom P 0.007;interference P 0.004). Conclusions: We have validated a novel PRO, the MDASI-COVID, to quantify the combined symptom burden in patients with cancer and COVID-19. This measure allows longitudinal evaluation of COVID-19 on cancer symptom burden and provide clinicians with an accurate tool for ongoing symptom assessment and management. Longitudinal analysis on long-term symptoms related to COVID-19 and cancer are ongoing.

COVID-19 Infection Control Measures in Long-Term Care Facility, Pennsylvania, USA

Residents of long-term care facilities are at risk for coronavirus disease. We report a surveillance exercise at such a facility in Pennsylvania, USA. After introduction of a testing strategy and other measures, this facility had a 17-fold lower coronavirus disease case rate than neighboring facilities.

Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 Sera.

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glycoprotein (VSVΔG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n > 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week.IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We therefore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.

HUMAN PRE-IMPLANTATION EMBRYOS ARE PERMISSIVE TO SARS-COV-2 ENTRY

Objective: To determine whether human pre-implantation embryos have the potential to be infected by SARS-CoV-2, the virus responsible for COVID-19. Design: Assessment of expression levels of SARS-CoV-2 entry mediators in human embryo biopsies by RNAseq analysis, and infection of cultured embryos with SARS-CoV-2 Spike glycoprotein pseudotyped reporter virions expressing green fluorescent protein (GFP). Materials and Methods: Trophectoderm biopsies from blastocyst-stage embryos (n=24) were processed for RNAseq using a commercial kit and sequenced;results were analyzed for expression of factors implicated in SARS-CoV-2 cellular entry. For viral infection experiments, blastocyst-stage embryos (n=94) were hatched from zonas mechanically, and infected by spinoculation with GFP-reporter virions pseudotyped with the SARS-CoV-2 Spike glycoprotein (required for SARS-CoV-2 entry). Embryos were subsequently monitored for fluorescence at 24-48 hours post-infection. Various control conditions were used as specified in the ‘results’ section. A mixed population of euploid, aneuploid, and untested embryos used in the study were from IVF treatment, donated to research by signed informed consent. The project was approved by an Institutional Review Board. Results: Cells collected from blastocyst-stage embryos robustly expressed the canonical SARS-CoV-2 entry receptor ACE2 and the putative activator protease TMPRSS2, in addition to other reported entry factors. Embryos exposed to reporter virions pseudotyped with SARS-CoV-2 Spike glycoprotein displayed robust GFP signal, often in numerous cells with cytoplasmic localization. Specificity was confirmed by the absences of fluorescence in embryos treated with virions lacking the Spike glycoprotein (“bald” virus), or when embryos were spinoculated with media alone in the absence of virus. Embryos exposed to Spike glycoprotein-positive reporter virus in the presence of neutralizing anti Spike- or anti-ACE2-blocking antibodies exhibited negligible GFP signal, while control monoclonal IgG antibody-treated embryos maintained GFP expression. These results implicated the canonical Spike-ACE2 axis in the viral entry. Lastly, embryos exposed to reporter virions pseudotyped with Spike glycoprotein of SARS-CoV-1 (which also enters cells via ACE2) displayed GFP fluorescence, while embryos exposed to reporter viruses pseudotyped with Spike glycoprotein of MERS (which utilizes Dipeptidyl Peptidase IV (DPP4) instead of ACE2) resulted in no fluorescence. Conclusions: Our results indicate that cells present in pre-implantation embryos are permissive to the canonical Spike-ACE2 viral entry mechanism utilized by SARS-CoV-2. These results encourage further investigation into the potential of SARS-CoV-2 infection in human embryos and may have wider implications in natural conception and ART practice.

Quantifying absolute neutralization titers against SARS-CoV-2 by a standardized virus neutralization assay allows for cross-cohort comparisons of COVID-19 sera (preprint)

The global COVID-19 pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the SARS-CoV-2 spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous BSL3 conditions which limits high throughput screening of patient and vaccine sera. Myriad BSL-2 compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making inter-group comparisons difficult. To address these limitations, we developed a standardized VNA using VSVAG-based CoV-2-S pseudotyped particles (CoV2pp) that can be robustly produced at scale and generate accurate neutralizing titers within 18 hours post-infection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S ELISA and live virus neutralizations in confirmed convalescent patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n>120). Our data show that absolute (abs) IC50, IC80, and IC90 values can be legitimately compared across diverse cohorts, highlight the substantial but consistent variability in neutralization potency across these cohorts, and support the use of absIC80 as a more meaningful metric for assessing the neutralization potency of vaccine or convalescent sera. Lastly, we used our CoV2pp in a screen to identify ultra-permissive 293T clones that stably express ACE2 or ACE2+TMPRSS2. When used in combination with our CoV2pp, we can now produce CoV2pp sufficient for 150,000 standardized VNA/week. ImportanceVaccines and antibody-based therapeutics like convalescent plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) is an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We therefore developed a standardized replication-defective pseudotyped particle system that mimics entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.