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Humans display substantial interindividual clinical variability after SARS-CoV-2 infection 1-3 , the genetic and immunological basis of which has begun to be deciphered 4 . However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells-from 222 healthy donors of diverse ancestries-that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk., (© 2023. The Author(s).)

Objective: Mammographic screening for breast cancer is an early use case for artificial intelligence (AI) in healthcare. This is an active area of research, mostly focused on the development and evaluation of individual algorithms. A growing normative literature argues that AI systems should reflect human values, but it is unclear what this requires in specific AI implementation scenarios. Our objective was to understand women's values regarding the use of AI to read mammograms in breast cancer screening., Methods: We ran eight online discussion groups with a total of 50 women, focused on their expectations and normative judgements regarding the use of AI in breast screening., Results: Although women were positive about the potential of breast screening AI, they argued strongly that humans must remain as central actors in breast screening systems and consistently expressed high expectations of the performance of breast screening AI. Women expected clear lines of responsibility for decision-making, to be able to contest decisions, and for AI to perform equally well for all programme participants. Women often imagined both that AI might replace radiographers and that AI implementation might allow more women to be screened: screening programmes will need to communicate carefully about these issues., Conclusions: To meet women's expectations, screening programmes should delay implementation until there is strong evidence that the use of AI systems improves screening performance, should ensure that human expertise and responsibility remain central in screening programmes, and should avoid using AI in ways that exacerbate inequities., (© The Author(s) 2023.)

Background: Although numerous studies have shown the potential of artificial intelligence (AI) systems in drastically improving clinical practice, there are concerns that these AI systems could replicate existing biases., Objective: This paper provides a brief overview of 'algorithmic bias', which refers to the tendency of some AI systems to perform poorly for disadvantaged or marginalised groups., Discussion: AI relies on data generated, collected, recorded and labelled by humans. If AI systems remain unchecked, whatever biases that exist in the real world that are embedded in data will be incorporated into the AI algorithms. Algorithmic bias can be considered as an extension, if not a new manifestation, of existing social biases, understood as negative attitudes towards or the discriminatory treatment of some groups. In medicine, algorithmic bias can compromise patient safety and risks perpetuating disparities in care and outcome. Thus, clinicians should consider the risk of bias when deploying AI-enabled tools in their practice.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.

There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use single-cell RNA-sequencing to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. We show widespread inter-individual variability in the percentage of IAV-infected monocytes. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3 , MX1 and OAS3 . Upon IAV challenge, we find that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. We also uncover a stronger resistance of CD16 + monocytes to IAV infection, together with CD16 + -specific mRNA expression of IL6 and TNF in response to IAV. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16 + monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Based on these data, we hypothesize that higher basal monocyte activation, driven by environmental factors and/or weak-effect genetic variants, underlies the lower cellular susceptibility to IAV infection of individuals of African ancestry relative to those of European ancestry. Further studies are now required to investigate how such cellular differences in IAV susceptibility translate into population differences in clinical outcomes and susceptibility to severe influenza., Competing Interests: JP was employed by DIACCURATE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 O’Neill, Quach, Pothlichet, Aquino, Bisiaux, Zidane, Deschamps, Libri, Hasan, Zhang, Zhang, Matuozzo, Cobat, Abel, Casanova, Naffakh, Rotival and Quintana-Murci.)

Background: Acinetobacter baumannii is a pathogen of importance worldwide., Methods: From January 2011 until January 2012, environmental and surveillance cultures were collected from patients admitted to our intensive care units (ICUs). Surveillance cultures were obtained on admission to the ICU and weekly thereafter. Environmental cultures of high-touch surfaces were performed on an alternating basis every week. A room was designated as contaminated if at least 1 object was positive for carbapenem-resistant A baumannii. We only evaluated the rooms belonging to patients who tested positive for Acinetobacter infection., Results: Five hundred eighty-six rooms were cultured across the 5 ICUs surveyed, of which 134 (22.9%) had patients who tested positive for infection with Acinetobacter. Among patients colonized in the rectum, the odds of having bed rails contaminated with A baumannii were 2.55 times the odds of those with only respiratory colonization (P = .03). The odds of having intravenous pumps contaminated with A baumannii among patients with only respiratory colonization were 2.72 times the odds of contamination among patients colonized in the rectum (P = .03)., Conclusions: There was a significant difference in the degree of contamination of bedrails and intravenous pumps based on the occupant's anatomic source of A baumannii infection., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Our institution continued to experience a hyperendemic situation with carbapenem-resistant Acinetobacter baumannii despite a bundle of interventions. We aim to describe the effect of the subsequent implementation of electronic dissemination of the weekly findings of a bundle of interventions., Methods: This was a quasiexperimental study performed at a 1,500-bed, public, teaching hospital. From January 2011 to March 2012, weekly electronic communications were sent to the hospital leadership and intensive care units (ICUs). These communications aimed to describe, interpret, and package the findings of the previous week's active surveillance cultures, environmental cultures, environmental disinfection, and hand cultures. Additionally, action plans based on these findings were shared with recipients., Results: During 42 months and 1,103,900 patient-days, we detected 438 new acquisitions of carbapenem-resistant A baumannii. Hospital wide, the rate of acquisition decreased from 5.13 ± 0.39 to 1.93 ± 0.23 per 10,000 patient-days, during the baseline and postintervention periods, respectively (P < .0001). This effect was also observed in the medical and trauma ICUs, with decreased rates from 67.15 ± 10.56 to 17.4 ± 4.6 (P < .0001) and from 55.9 ± 8.95 to 14.71 ± 4.45 (P = .0004), respectively., Conclusion: Weekly and systematic dissemination of the findings of a bundle of interventions was successful in decreasing the rates of carbapenem-resistant A baumannii across a large public hospital., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

We aimed to determine the association between environmental exposure to carbapenem-resistant Acinetobacter baumannii and the subsequent risk of acquiring this organism. Patients exposed to a contaminated hospital environment had 2.77 times the risk of acquiring carbapenem-resistant A. baumannii than did unexposed patients (relative risk, 2.77 [95% confidence interval, 1.50-5.13]; P = .002).

We describe 1,132 contacts between anesthesiologists and the operating room. Objects most commonly touched included anesthesia machines and keyboards. Only 13 hand hygiene events were witnessed during 8 hours of observations. Line insertions, bronchoscopies, or blood exposures were not followed by hand hygiene. Stopcocks were accessed 66 times and only disinfected on 10 (15%) of these occasions., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: To establish the presence of air contamination with Acinetobacter baumannii in the trauma ICU., Design: Point prevalence microbiological surveillances., Settings: A 1,500-bed public teaching hospital in the Miami metro area., Patients: Trauma ICU patients., Measurements: Pulsed field electrophoresis was performed on environmental and clinical isolates to determine the association of any isolates from the air with clinical isolates., Main Results: Out of 53 patient areas cultured, 12 (22.6%) had their air positive for A. baumannii. The presence of an A. baumannii-positive patient (underneath the plate) was associated with positive air cultures for A. baumannii (11 of 21 [52.4%] vs 0 of 25 [0%]; p < 0.0001). However, we were not able to find differences in air contamination based on the presence of A. baumannii in respiratory secretions versus absence (p = 1.0). Air and clinical isolates were found to be clonally related., Conclusions: Aerosolization of A. baumannii in the ICUs is a concern, and its role in the transmission of this organism among patients should be further clarified.

We aimed to determine the association between the presence of Acinetobacter baumannii in patient rooms and the carrier status of the occupants. Fifty-six (39%) of 143 rooms with A. baumannii-positive patients had results positive for A. baumannii. Only 49 (10%) of 485 rooms with A. baumannii-negative patients were positive (odds ratio, 5.72 [95% confidence interval, 3.66-8.96]; [Formula: see text]). Clinical and environmental isolates shared pulsed-field gel electrophoresis patterns.

Background: Uniforms are potential reservoirs for hospital organisms, potentially reinfecting the hands of health care workers (HCWs). The study aimed to determine the association between the bacterial contamination of HCWs' hands and uniforms (white coats and scrubs)., Methods: HCWs working in 5 intensive care units had cultures obtained from their hands and uniforms (white coats or scrubs). Pathogens were defined as any gram-negative bacilli, Staphylococcus aureus, and enterococci., Results: Bacterial growth was detected on 103 hands (86%); 13 (11%) grew S aureus, 7 (6%) grew Acinetobacter spp, 2 (2%) grew enterococci, and 83 (70%) grew only skin flora. The presence of pathogens on the hands was associated with a greater likelihood of the presence of pathogens on white coats (κ = 0.81; P < .001), but not on scrubs (κ = 0.31; P = .036). Similarly, the presence of Acinetobacter on HCWs' hands was associated with a greater likelihood of Acinetobacter contamination of white coats (κ = 0.70; P < .001), but not of scrubs (κ = 0.36; P = .024)., Conclusions: Contamination of provider's hands with pathogens or Acinetobacter baumannii was associated with contamination of white coats. This association was not observed between hands and scrubs, however., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: Potential transmission of organisms from the environment to patients is a concern, especially in enclosed settings, such as operating rooms, in which there are multiple and frequent contacts between patients, provider's hands, and environmental surfaces. Therefore, adequate disinfection of operating rooms is essential. We aimed to determine the change in both the thoroughness of environmental cleaning and the proportion of environmental surfaces within operating rooms from which pathogenic organisms were recovered., Design: Prospective environmental study using feedback with UV markers and environmental cultures., Setting: A 1,500-bed county teaching hospital., Participants: Environmental service personnel, hospital administration, and medical and nursing leadership., Results: The proportion of UV markers removed (cleaned) increased from 0.47 (284 of 600 markers; 95% confidence interval [CI], 0.42-0.53) at baseline to 0.82 (634 of 777 markers; 95% CI, 0.77-0.85) during the last month of observations ([Formula: see text]). Nevertheless, the percentage of samples from which pathogenic organisms (gram-negative bacilli, Staphylococcus aureus, and Enterococcus species) were recovered did not change throughout our study. Pathogens were identified on 16.6% of surfaces at baseline and 12.5% of surfaces during the follow-up period ([Formula: see text]). However, the percentage of surfaces from which gram-negative bacilli were recovered decreased from 10.7% at baseline to 2.3% during the follow-up period ([Formula: see text])., Conclusions: Feedback using Gram staining of environmental cultures and UV markers was successful at improving the degree of cleaning in our operating rooms.

We compared cleaning rates associated with use of a white ultraviolet (UV) powder versus a transparent UV gel among units with various degrees of previous experience with UV powder. The study outcome was the presence of discordant cleaning (removal of powder without the removal of gel, or vice versa). We found higher frequency of discordance in high-experience units (31%) than in no-experience units (8%) (P < .001). In 92% of discordant findings, the powder was removed but not the gel (P < .001). These findings suggest preferential cleaning of visible UV targets among units with high levels of previous experience with powder.