Identifying the Next Mutation of Concern - Exploiting Genomics for Tracking Sars-Cov-2 Mutations and Their Biological Impact in Canada

Intro: Viruses, including SARS-CoV-2, which causes COVID-19, are constantly changing. These genetic changes (aka mutations) occur over time and can lead to the emergence of new variants that may have different characteristics. After the first SARS-CoV-2 genome was published in early 2020, scientists all over the world soon realized the immediate need to obtain as much genetic information from as many strains as possible. However, understanding the functional significance of the mutations harbored by a variant is important to assess its impact on transmissibility, disease severity, immune escape, and the effectiveness of vaccines and therapeutics. Method(s): Here in Canada, we have developed an interactive framework for visualizing and reporting mutations in SARS-CoV-2 variants. This framework is composed of three stand-alone yet connected components;an interactive visualization (COVID-MVP), a manually curated functional annotation database (pokay), and a genomic analysis workflow (nf-ncov-voc). Finding(s): COVID-MVP provides (i) an interactive heatmap to visualize and compare mutations in SARS-CoV-2 lineages classified across different VOCs, VOIs, and VUMs;(ii) mutation profiles including the type, impact, and contextual information;(iii) annotation of biological impacts for mutations where functional data is available in the literature;(iv) summarized information for each variant and/or lineage in the form of a surveillance report;and (v) the ability to upload raw genomic sequence(s) for rapid processing and annotating for real-time classification. Discussion(s): This comprehensive comparison allows microbiologists and public health practitioners to better predict how the mutations in emerging variants will impact factors such as infection severity, vaccine resistance, hospitalization rates, etc. Conclusion(s): This framework is cloud-compatible & standalone, which makes it easier to integrate into other genomic surveillance tools as well. COVID-MVP is integrated into the Canadian VirusSeq data portal (https://virusseqdataportal.ca) - a national data hub for SARS-COV-2 genomic data. COVID-MVP is also used by the CanCOGeN and CoVaRR networks in national COVID-19 genomic surveillance.Copyright © 2023

Hiv Viral Load Suppression and Racial Disparities during the Covid-19 Pandemic in Nyc

Background: Antiretroviral therapy is highly effective in achieving HIV viral load suppression (VLS) but requires sustained engagement in care. The COVID-19 pandemic disrupted medical care, and its impact on engagement in HIV care and VLS remains unclear. Health information exchanges (HIEs) enable examination of patient care across multiple health systems. We sought to leverage HIE data to examine the effect of pandemic-related disruptions in HIV care on VLS and to explore racial/ethnic disparities in VLS. Method(s): We performed a retrospective observational study of people living with HIV (PLWH) using de-identified data from Healthix, an HIE encompassing >20 million patients and 8,000 healthcare facilities in the greater New York City (NYC) region, between 1/1/2018 and 7/14/2022. We identified PLWH based on HIV viral load (VL) tests and HIV diagnosis codes (ICD and SNOMED). We established two cohorts: PLWH engaged in care in 2020 with >=1 VL test in 2019, 2020, and 2021(Group A) and PLWH not engaged in care in 2020 with >=1 VL test in 2019 and 2021 but 0 VL tests in 2020 (Group B). HIV VLS outcomes were categorized as suppressed (< 200 copies/mL) or not suppressed ( >200 copies/mL) using the last VL in 2019, first VL in 2021, and last recorded VL. We compared proportions using X2-tests and fit a group-stratified logistic regression to examine the effect of race/ethnicity on VLS. Result(s): We identified 711,358 VL tests representing 81,122 patients at 249 facilities. Of these patients, 36,199 met our definition of PLWH. Of those, 12,448 met the inclusion criteria for Group A, and 3,377 met the inclusion criteria for Group B. In 2019, Group B had a lower VLS proportion than Group A (85.9% vs 88.1%, X2 = 12.3, p< 0.0001). In 2021, this gap increased;the proportion of VLS was 80.7% in Group B and 88.0% in Group A (X2 = 121.8, p< 0.00001). Most recently, VLS in Group B had increased to 85.6%, but the inter-group gap in VLS had grown from 2.2% to 4.4%. Within both groups, Black and Hispanic patients had lower odds of VLS than white patients. This disparity was greatest in Group B when they reengaged in care in 2021, with 72.0% of Black patients (OR 0.30, 95% CI 0.22-0.42), and 79.1% of Hispanic patients (OR 0.45, 95% CI 0.31-0.63), compared to 89.5% of white patients achieving VLS. Conclusion(s): VLS remained high among PLWH who stayed engaged in care in 2020, dropped among PLWH who disengaged in care, and was lower in minoritized groups even after controlling for engagement in care.

Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Why Does It Feel Different? Provider Moral Distress in Removing Unwanted Aggressive Intervention for Conscious Patients (TH123B)

Outcomes: 1. Illustrate increased moral distress associated with removing unwanted aggressive interventions for conscious patients compared to unconscious patients. 2. Demonstrate the importance of the interdisciplinary team in supporting providers experiencing moral distress. When providing end-of-life care, removing unwanted aggressive intervention is more challenging in a conscious patient. If the intent to provide comfort and reduce suffering is the same, why does it feel different when the patient is conscious? This case examines the moral distress experienced by the palliative care team who assisted a conscious patient with Duchenne muscular dystrophy achieve his goal of liberation from the ventilator. A 41-year-old male with Duchenne muscular dystrophy and prior COVID-19 infection presented with respiratory failure. The patient had COVID-19 infection in April 2022 and was ventilator dependent since then. The palliative care team was consulted for goals of care discussion. After extensive discussion with the patient and his family, the patient decided to be disconnected from the ventilator and wanted a peaceful passing because long-term ventilatory support was no longer acceptable to him. He was afraid of being aware of struggling to breathe and requested to be asleep throughout this process. Specifically, he said he wanted "to close my eyes and see [my family] on the other side." When the patient was comfortable and asleep as he and his family desired, he was disconnected from the ventilator and died peacefully with his family around him. During this process, the palliative care team's intent was clear: follow the patient's wishes and provide comfort. Ethically, there is no difference in removing unwanted aggressive interventions between conscious and unconscious patients, but the team experienced significantly more distress in this case. After the patient's death, the interdisciplinary team provided support to help the palliative care team work through the distress experienced.Copyright © 2023

A phase 1b study of blinatumomab with the anti-programmed cell death (PD)-1 antibody AMG 404 in adults with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL)

Background: Preclinical data indicate that anti-PD-1 agents can facilitate activity of bispecific T-cell engager (BiTE) molecules. Here we assess the combination of the anti-CD19 BiTE molecule blinatumomab with the anti-PD-1 antibody AMG 404 in adults with R/R ALL (NCT04524455). Methods: Eligible adults with R/R ALL (Ph+ disease included) received 2-5 treatment cycles. Each cycle was 42 days, consisting of 4 weeks of cIV blinatumomab and a 2-week treatment-free interval as per label. In Cohort 1, AMG 404 was dosed IV at 240 mg every 4 weeks (Q4W);first dose was Day (D) 11 of Cycle (C) 1. Primary endpoints were dose-limiting toxicities (DLTs) and other adverse events (AEs). Results: As of 20 Dec 2021, patients (pts) from Cohort 1 (n=8) had median age of 57 (range: 24-73) y, 6/ 8 male, 6/8 Caucasian, 1 with extramedullary disease (duodenum), 2 with prior blinatumomab, and a median of 5 (2-15) prior treatment lines. Two pts remain on study and 2 completed the study;4 pts discontinued the study due to death (n=3) or consent withdrawn (n=1). No DLTs were reported for the 3 evaluable pts. Of the 5 pts not evaluable for DLTs, in C1, 4 had disease progression and 1 an unrelated fatal pneumonia. Treatment-related grade (Gr) ≥3 and/or serious AEs in all 8 pts included cytokine release syndrome (CRS) (1 pt Gr 2, 1 pt Gr 1 and 3), Gr 3 increases in ALT and AST, Gr 3 fever, Gr 3-4 neutropenia, Gr 4 neutropenia/Gr 3-4 thrombocytopenia (same pt), Gr 2 sensorimotor polyneuropathy, Gr 3 hypertension, Gr 3 encephalopathy, and in 1 pt Gr 3-4 decreases in white blood cells, lymphocytes, and neutrophils. One pt developed Gr 3 SARS-COV-2 pneumonia on C2D25, resolving without clinical sequelae. C3 start was delayed by 12 days but protocol treatment resumed uneventfully. All 3 DLT-evaluable pts had a complete response (CR) or CR with partial hematologic recovery (CRh), 2/3 without measurable residual disease (MRD), within 2 cycles;the 3rd pt had an MRD response at the end of C3. Preliminary pharmacokinetic results for the combination of blinatumomab and AMG 404 demonstrated that their exposures were consistent with those observed for each as monotherapy and did not indicate any drug-drug interactions. To date, all samples tested for anti-blinatumomab antibodies have been negative. Conclusions: In this ongoing phase 1b study, the combination of blinatumomab with AMG 404 was tolerated with a manageable safety profile. No DLTs were reported. Enrollment continues in Cohort 2 in which AMG 404 is dosed Q4W at 480 mg starting on C1D1, 48 hours prior to blinatumomab.

eP455: Fetal ultrasound presentation and neonatal diagnosis of Freeman-Sheldon syndrome in son of previously undiagnosed adult male

Background: Freeman-Sheldon syndrome [distal arthrogryposis type 2A (OMIM #193700), DA2A, Freeman-Burian syndrome] is a rare autosomal dominant multiple pterygium syndrome caused by alterations in MYH3. The phenotypic features, particularly of the face, are distinct and easily recognizable, and the diagnosis can be confirmed with molecular gene analysis. Fetal ultrasound imaging may provide important diagnostic clues to facilitate the diagnostic process. Informed consent and parental permission were provided by the parents. Case presentation: The infant’s mother presented for a Maternal Fetal Medicine genetic counseling telehealth appointment (due to COVID-19 pandemic restrictions) as a G7P2132, 32-year old female who had insulin-dependent diabetes and thrombocytosis. Her partner was a 24-year old male with a history of hearing loss, a V-shaped palate, and a lower lip cleft. Gestational age was 14 4/7 weeks and the indications were: increased nuchal translucency, paternal complex medical history, maternal G6PD heterozygote, and recurrent pregnancy loss. During the genetic counseling session, the following were addressed: 1) Maternal heterozygote status for G6PD indicated that if the fetus was male, there was a 50% chance he would be affected with G6PD-deficiency;2) Increased nuchal translucency on fetal ultrasound (US) with measurement at 98th percentile is associated with an increased risk of chromosomal abnormalities, microdeletion/duplications, and Noonan syndrome. The patient reportedly had low risk cell-free DNA but results were not available to the counselor at the time of consult. The option for additional genetic screening and diagnostic testing was declined;3) Three first trimester pregnancy losses with the father of this baby (FOB) were addressed, and parents deferred chromosome analyses at the time;4) Mother shared FOB’s complex history of bilateral sensorineural hearing loss, V-shaped cleft palate, lower lip cleft, and micrognathia. However, father was not present during the telehealth encounter. Mother was counseled regarding the possibility of an autosomal dominant condition with the potential risk to the pregnancy of up to 50%. It was recommended that the FOB have a clinical genetics evaluation, which could potentially provide a specific diagnosis and inform recurrence risk and management guidance. Follow-up MFM genetic counseling telephone visit occurred with the mother at 31 6/7 weeks gestation due to multiple congenital anomalies evident on fetal ultrasound. A 25 week fetal ultrasound revealed hypotelorism and a thickened nuchal translucency. A repeat study at 29 weeks revealed a V-shaped palate with a possible cleft, micrognathia, and midline mandibular cleft. FOB’s history was revisited. It was determined that he had 3 previous “no shows” to Genetics clinic appointments and did not pursue evaluation after the last counseling appointment. Again, it was emphasized that in order to best make a diagnosis for the family, an affected person would need to undergo a thorough evaluation, including medical and family history review, physical examination, and any indicated genetic testing. The parents were comfortable with the likelihood that the baby had the same condition as the father, but variable expressivity and broad range pf phenotypic presentation were explained. Recommendations for postnatal evaluation of the infant and pertinent genetic testing were provided. Consultative Genetics evaluation of the infant at 2 days of age revealed a short, broad forehead with supraorbital fullness leading to a horizontal brow indentation;mask-like facial appearance;hypotelorism;very deep set eyes with blepharophimosis;deep, creased nasal bridge;small, upturned nose with hypoplastic alae and narrow nares;microstomia with pursed lips;glossoptosis;micrognathia;2 deep vertical chin creases;short neck with excess nuchal skin;inverted and wide spaced nipples;clenched hands with 5th digits overlying 4th and 2nd overlying 3rd, bilaterally;bilateral vertical talus;2nd toes longer and overlying rd toes;clinodactyly of 4th and 5th toes bilaterally;and deep gluteal crease with no visible sinus. There were no evident contractures. The father has a complex history with no medical assessments prior to age 18. He reported that he did “not look like anyone else” in his family. He has a diagnosis of autistic spectrum disorder, a submucous cleft, vision issues, hearing loss necessitating a hearing aid on the left, and a history of cholesteatomas and of mastoidectomy. On brief examination, he had a mask-like face, blepharophimosis, left microphthalmia, left esotropia, narrowing of his midface, deep vertical crease on the mandibular region, microstomia, broad great toes, single flexor creases on the thumbs, and contracture of right thumb. Maxillofacial CT of the infant revealed hypoplastic mandibular body, ramus, and condyles bilaterally with micrognathia and retrognathia;hypoplastic maxilla bilaterally;and enophthalmos with retracted appearance of globes in the bony orbits bilaterally. Multiple facial bone abnormalities were seen, including microsomia, micrognathia, retrognathia, orbital hypotelorism and enophthalmos Genetic testing was performed via a custom Whole Exome Slice at GeneDx laboratories and included the MYH3 and TNNI2 genes. Results revealed a heterozygous pathogenic change in MYH3 (c.2015 G>A;p. R6724) consistent with the diagnosis of Freeman-Sheldon syndrome. Conclusion: The presentation of “midline mandibular cleft” on fetal ultrasound was the most specific prenatal finding. This is a very rare fetal finding. Thus, it should prompt further evaluation to assess for true clefting versus ridging or creasing. Additionally, targeted assessment for other findings or clinical clues for Freeman-Sheldon syndrome, such as contractures, “windmill vane” hand, and mouth size, could aid in the differential diagnosis considerations and the diagnostic process. Admittedly, these are position and quality dependent, and are challenging to assess even in ideal situations. The phenotype of the father was immediately recognizable. However, due to COVID-19 pandemic restrictions, prior to the infant’s birth, only telehealth visits were conducted and the father’s participation was by telephone. This limited the ability to narrow the differential diagnosis without visualization of his distinct phenotypic features. Finally, missed opportunities to diagnose the father prior to this pregnancy occurred. Many clinics send “no show” letters to referring providers and patients, as we do. Emphasizing the importance of diagnosis prior to pregnancy for individuals concerned about having a genetic disorder should be considered as part of the information shared in these letters.

Skeletal muscles and Covid-19: a systematic review of rhabdomyolysis and myositis in SARS-CoV-2 infection

OBJECTIVES: Myalgia is a widely publicised feature of Covid-19, but severe muscle injury can occur. This systematic review summarises relevant evidence for skeletal muscle involvement in Covid-19. METHODS: A systematic search of OVID and Medline databases was conducted on 16/3/2021 and updated on 28/10/2021 to identify case reports or observational studies relating to skeletal muscle manifestations of Covid-19 (PROSPERO: CRD42020198637). Data from rhabdomyolysis case reports were combined and summary descriptive statistics calculated. Data relating to other manifestations were analysed for narrative review. RESULTS: 1920 articles were identified. From these, 61 case reports/series met inclusion criteria, covering 86 rhabdomyolysis cases. Median age of rhabdomyolysis patients was 50 years, (range 6-89). 49% had either hypertension, diabetes mellitus or obesity. 77% were male. Symptoms included myalgia (74%), fever (69%), cough (59%), dyspnoea (68%). Median peak CK was 15,783U/L. 28% required intravenous haemofiltration and 36% underwent mechanical ventilation. 62% recovered to discharge and 30% died. Dyspnoea, elevated CRP and need for intravenous haemofiltration increased risk of fatal outcome. Additional articles relating to skeletal muscular pathologies include 6 possible concomitant diagnoses or relapses of idiopathic inflammatory myopathies and 10 reports of viral-induced muscle injuries without rhabdomyolysis. Localised myositis and rhabdomyolysis with SARS-CoV-2 vaccination have been reported. CONCLUSIONS: Rhabdomyolysis is an infrequent but important complication of Covid-19. Increased mortality was associated with a high CRP, renal replacement therapy and dyspnoea. The idiopathic inflammatory myopathies (IIM) may have viral environmental triggers. However, to date the limited number of case reports do not confirm an association with Covid-19.

Cardiac arrhythmias in the critically ill

Arrhythmias are a common problem in the critically ill and they can have significant effects on patient outcome. They often require immediate and swift action and it is, therefore, essential that clinicians have a structured approach to the recognition and management of arrhythmias. Here, we provide a framework for the appropriate management of the more frequently encountered cardiac arrhythmias in critical care. We include the algorithms from the 2015 Resuscitation Council Guidelines for reference.

Skeletal muscle involvement in COVID-19infection: A case report and systematic review

Background/AimsIt is increasingly understood that COVID-19 has a very broad range ofmulti-system manifestations. Myalgia is a widely publicised feature ofSARS-CoV-2 infection, however, more severe muscle injury can occur.There are several case reports of rhabdomyolysis with markedelevation in creatine kinase (CK) and myoglobinuria, leading to acuterenal failure, but also reports of myositis characterised by weakness, mildly raised CK and muscle oedema on MRI. We present a systematicliterature search to evaluate the clinical characteristics of skeletalmuscle involvement.MethodsA systematic search for terms related to "SARS-CoV-2" and "myalgia", "myositis", "rhabdomyolysis" or "muscle" was performed across foursearch engines (Web of Science, Pubmed, Mednar and Medrxiv) on10/09/2020. Only original research published or translated in Englishwas included. Information relating to skeletal muscle injury inconfirmed SARS-CoV-2 infection was summarised.ResultsThe search protocol identified 980 articles of which 200 wereappropriate for abstract review. 21 case reports covering 22 patientswith rhabdomyolysis were found. Other muscular pathology notdefined as rhabdomyolysis by authors, included 1 case of acutemyositis leading to compartment syndrome, 2 cases of myositis withclassical proximal weakness, elevated creatine kinase and proximalmuscle oedema on imaging, and one series of 7 patients withparaspinal myositis on MRI imaging. A histopathological study foundevidence of incidental myositis in 2 cases. Critical care myopathy andpolyneuropathy are described, along with many other neurologicalmanifestations. While 91 cohort studies were identified, none looked indetail at skeletal muscle involvement. There are 8 meta-analyses whichfind the prevalence of myalgia between 19-33%. The age ofrhabdomyolysis patients appears lower than expected for covid-19admissions at 46.7 years, but ranged from 16 to 88. Baselinecharacteristics mirror those at higher risk of severe covid-19: halfhad either hypertension, type 2 diabetes or obesity and 86.4% weremale. Common accompanying symptoms were myalgia (81.8%), fever(68.2%), cough (59.1%), dyspnoea (40.9%). Median peak CK was22, 511IU/L. 68.2% had changes consistent with covid-19 on chestimaging. Intravenous haemofiltration or mechanical ventilation wereeach required by 4 patients. Short term prognosis showed 18 (81.8%)being discharged, 2 deaths (9.1%) and 2 unknown outcomes. ConclusionSevere skeletal manifestations such rhabdomyolysis occur in covid-19. More research is needed to discover if this is through direct viralinvasion of the tissues, or indirectly via systemic cytokine release, hyperlactataemia and hypo-oxygenation. CK should be routinelychecked in those critically unwell or with severe myalgia or weaknessto identify treatable rhabdomyolysis early. Chronic autoimmuneconditions such as the idiopathic inflammatory myopathies may haveviral environmental triggers, and one case tested positive for a myositisspecific antibody. Whether patients with acute covid-19 relatedmyositis experience ongoing long-term muscle inflammation has notyet been reported.

Handmaidens and pioneers: Three female anaesthetists and their contribution to anaesthesia in South Africa.

The period during and after World War II saw enormous changes in the practice and status of anaesthesia, as well as in female participation. This article offers an account of three South African (SA) women who trained in anaesthetics before and during the War and participated in these changes. By the mid-1960s, they presided over the three independent anaesthetic departments at Johannesburg's three main teaching hospitals, teaching generations of junior doctors. The first woman to register as a specialist anaesthetist in SA, Miriam (Mollie) Barlow, broke the glass ceiling in her own career by lobbying for the professional rights of medical women, although working within the constraints of the medical and political establishment. She also contributed to important SA research on malignant hyperthermia. Hilde Ginsberg collaborated with Barlow in the 1950s, reducing intraoperative and perioperative mortality at Coronation Hospital, and fought for key interventions in anaesthetic practice and policy through the South African Society of Anaesthetists (SASA), becoming its most long-serving and honoured female member. Kathleen Barbara Vetten's exemplary career in academic medicine, including pioneering animal research (developing anaesthetic techniques for open-heart surgery in dogs and protocols for liver transplantation in primates) and a successful operation to separate craniopagus twins, shows both the achievement of and limits to female achievement at the end of this period. This article also offers a short account of factors that hindered black women from entering anaesthesia training, contributing to this history before the 1990s.

Keep your (social) distance: Pathogen concerns and social perception in the time of COVID-19.

Previous research suggests that individual differences in pathogen disgust sensitivity and social anxiety predict avoidance behavior, especially of pathogen cues, and reduced tolerance for social ambiguity. Conversely, generalized social trust is associated with approach behavior and a greater tolerance for social ambiguity. We conducted an online study (N = 1078) to test these predictions in the context of the COVID-19 global pandemic. Specifically, we assessed whether individual differences in pathogen disgust sensitivity, social anxiety and generalized social trust predicted judgments of trustworthiness, desired social distance and perceptions of sickness of target faces wearing surgical masks. Our results showed that (a) high sensitivity to pathogen disgust predicted lower judgments of trustworthiness and lower social desirability; (b) high social anxiety predicted higher perceptions of illness and lower judgments of trustworthiness; and (c) generalized social trust predicted higher judgments of trustworthiness and lower perceptions of illness of target faces. Further, we found that mask wearers were perceived as more likely to be ill, more trustworthy and more socially desirable than the same faces presented to a control group, without the surgical mask superimposed. Results are discussed in terms of perceived compliance with an emerging social norm overriding the intrinsic untrustworthiness of masked faces.