mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern.

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.

SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.

Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.

Weight, habitual fibre intake, and microbiome composition predict tolerance to fructan supplementation.

Fructans are commonly used as dietary fibre supplements for their ability to promote the growth of beneficial gut microbes. However, fructan consumption has been associated with various dosage-dependent side effects. We characterised side effects in an exploratory analysis of a randomised trial in healthy adults (n = 40) who consumed 18 g/day inulin or placebo. We found that individuals weighing more or habitually consuming higher fibre exhibited the best tolerance. Furthermore, we identified associations between gut microbiome composition and host tolerance. Specifically, higher levels of Christensenellaceae R-7 group were associated with gastrointestinal discomfort, and a machine-learning-based approach successfully predicted high levels of flatulence, with [Ruminococcus] torques group and (Oscillospiraceae) UCG-002 sp. identified as key predictive taxa. These data reveal trends that can help guide personalised recommendations for initial inulin dosage. Our results support prior ecological findings indicating that fibre supplementation has the greatest impact on individuals whose baseline fibre intake is lowest.

The role of extracorporeal membrane oxygenation in adult kidney transplant patients: A qualitative systematic review of literature.

BACKGROUND: A paucity of evidence exists regarding the risks and benefits of Extracorporeal Membrane Oxygenation (ECMO) in adult kidney transplantation. METHODS: This was a systematic review conducted from Jan 1, 2000 to April 24, 2020 of adult kidney transplant recipients (pre- or post- transplant) and donors who underwent veno-arterial or veno-venous ECMO cannulation. Death and graft function were the primary outcomes, with complications as secondary outcomes. RESULTS: Twenty-three articles were identified that fit inclusion criteria. 461 donors were placed on ECMO, with an overall recipient 12-month mortality rate of 1.3% and a complication rate of 61.5%, the majority of which was delayed graft function. Fourteen recipients were placed on ECMO intraoperatively or postoperatively, with infection as the most common indication for ECMO. The 90-day mortality rate for recipients on ECMO was 42.9%, with multisystem organ failure and infection as the ubiquitous causes of death. 35.7% of patients experienced rejection within 6 months of decannulation, yet all were successfully treated. CONCLUSIONS: ECMO use in adult kidney transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO mirrors that of recipients from standard criteria donors. The morbidity and mortality of recipients placed on ECMO are also similar to other patient populations requiring ECMO.

The role of extracorporeal membrane oxygenation in adult liver transplant patients: A qualitative systematic review of literature.

BACKGROUND: A paucity of evidence exists regarding risks and benefits of extracorporeal membrane oxygenation (ECMO) in adult liver transplantation. METHODS: This was a systematic review conducted from January 1, 2000 to April 24, 2020 of adult liver transplant recipients (pre- or post-transplant) and donors who underwent Veno-arterial or Veno-venous ECMO cannulation. Death was the primary outcome, with graft function and complications as secondary outcomes. RESULTS: Forty-one articles were identified that fit criteria. A total of 183 donors were placed on ECMO, with recipient complication profiles and mortality that mirrored rates from standard criteria donors. Sixty-one recipients were placed on ECMO intraoperatively or postoperatively. Most patients experienced at least one complication with infections as the most common cause and minimal complications specifically related to ECMO use. Multisystem organ failure (MSOF) and infections were more common among liver recipients who died compared to those who survived. Overall mortality at 90 days was 45.9%. Causes of death were most commonly MSOF and infections. CONCLUSIONS: ECMO use in adult liver transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO parallel that of recipients from standard criteria donors, and morbidity and mortality of recipients placed on ECMO are similar to other ECMO populations.

The role of extracorporeal membrane oxygenation in pediatric abdominal transplant patients: A qualitative systematic review of literature.

BACKGROUND: Advances in ECMO have made it a useful adjunct in critically ill pediatric patients; however, a dearth of evidence exists regarding risks and benefits in pediatric abdominal transplantation. The purpose of this study was to perform a qualitative systematic review of outcomes in pediatric patients undergoing ECMO support pre- or post-abdominal organ transplantation. METHODS: This was a systematic review conducted from Jan 1, 1989, to April 24, 2020, via PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and ClinicalTrials.gov of all pediatric solid abdominal organ transplant recipients (pre- and post-transplant) and donors who underwent V-A or V-V ECMO cannulation. Death was the primary outcome, with graft function and complications as secondary outcomes. RESULTS: Fourteen articles were identified that fit criteria, with 88% being case reports. Three patients were donors placed on ECMO, with no mortality among the 8 recipients of organs from these donors. Nineteen recipients were placed on ECMO. All were liver transplants. Most patients experienced at least one complication (84%), with bleeding as the most common cause (44%). Mortality was 26%. Causes of death included multiorgan system failure (n = 3), heart failure (n = 1), Systemic inflammatory response syndrome (n = 1), abdominal compartment syndrome (n = 3), bleeding (n = 1), septic shock from aspergillus (n = 1), and hepatic artery thrombosis (n = 2). CONCLUSIONS: The data are poor on ECMO usage in pediatric abdominal transplantation. While complications were high, mortality did not appear to be related to ECMO usage and was relatively low given the severity of patient illness.

mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions.

The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy has begun to show differences across the two approved mRNA platforms, BNT162b2 and mRNA-1273; these findings suggest that subtle variation in immune responses induced by the BNT162b2 and mRNA-1273 vaccines may confer differential protection. Given our emerging appreciation for the importance of additional antibody functions beyond neutralization, we profiled the postboost binding and functional capacity of humoral immune responses induced by the BNT162b2 and mRNA-1273 vaccines in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to variants of concern. However, differences emerged across epitope-specific responses, with higher concentrations of receptor binding domain (RBD)- and N-terminal domain-specific IgA observed in recipients of mRNA-1273. Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients. RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector functions induced across the mRNA vaccines. These data provide insights into potential differences in protective immunity conferred by these vaccines.

Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19.

The introduction of vaccines has inspired new hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against COVID-19, thus we profiled the earliest humoral signatures in a large cohort of severe and asymptomatic COVID-19 individuals. While a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, non-survivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibody evolution. Given the conservation of S2 across ß-coronaviruses, we found the early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common ß-coronavirus OC43 humoral immunity in survivors, which was selectively also expanded in individuals that develop paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles.

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

Early cross-coronavirus reactive signatures of humoral immunity against COVID-19.

The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2­specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across ß-coronaviruses, we found that the early development of SARS-CoV-2­specific immunity occurred in tandem with preexisting common ß-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

Toward an Anti-Racist Curriculum: Incorporating Art into Medical Education to Improve Empathy and Structural Competency.

BACKGROUND: There is an urgent need for medical school curricula that address the effects of structural influences, particularly racism, on health, healthcare access, and the quality of care for people of color. Underrepresented racial minorities in the United States receive worse health care relative to their White counterparts. Structural competency, a framework for recognizing and understanding social influences on health, provides a means for understanding the structural violence that results from and perpetuates racism in classroom and clinical education. Some medical schools have incorporated art into their curricula to increase empathy generally, yet few programs use art to address racial disparities in medicine specifically. OBJECTIVE: "Can We Talk About Race?" (CWTAR) aims to increase medical students' empathy for racial minorities and increase the ease and ability of students to address racial issues. CWTAR also provides a unique context for ongoing conversations about racism and structural inequality within the health care system. METHODS: Sixty-four first-year medical students were randomly selected to participate in CWTAR. The on-campus Ackland Art Museum staff and trained student facilitators lead small group discussions on selected artworks. A course evaluation was sent to all participants consisting of 4 questions: (1) Likert scale rating the quality of the program, (2) the most important thing learned from the program, (3) any differences between discussion at this program versus other conversations around race, and (4) suggestions for changes to the program. Free text responses were content coded and analyzed to reveal common themes. RESULTS: Out of 64 students, 63 (98%) responded to at least one course evaluation question. The majority (89%) of participants rated the program quality as either "Very Good" or "Excellent." Of the 37 students who responded to the free text question regarding the most important thing they learned from the program, 16 (44%) responses revealed students felt that they were exposed to perspectives that differed from their own, and 19% of respondents reported actively viewing a subject through another's perspective. Of the 33 students who responded to the free text question regarding any differences between discussion at this program versus other conversations around race, 48% noted an increased comfort level discussing race during the program. A common theme in responses to the question regarding suggested changes to the program was a more explicit connection to medicine in the discussion around race. CONCLUSIONS: Student responses to CWTAR suggest that the program is effective in engaging students in discussions of racial issues. More investigation is needed to determine whether this methodology increases empathy among medical students for racial minorities specifically.