Publications by authors named "Aaron A R Tobian"

249 Publications

Declining HIV incidence in sub-Saharan Africa: a systematic review and meta-analysis of empiric data.

J Int AIDS Soc 2021 Oct;24(10):e25818

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Introduction: UNAIDS models suggest HIV incidence is declining in sub-Saharan Africa. The objective of this study was to assess whether modelled trends are supported by empirical evidence.

Methods: We conducted a systematic review and meta-analysis of adult HIV incidence data from sub-Saharan Africa by searching Embase, Scopus, PubMed and OVID databases and technical reports published between 1 January 2010 and 23 July 2019. We included prospective and cross-sectional studies that directly measured incidence from blood samples. Incidence data were abstracted according to population risk group, geographic location, sex, intervention arm and calendar period. Weighted regression models were used to assess incidence trends across general population studies by sex. We also identified studies reporting greater than or equal to three incidence measurements since 2010 and assessed trends within them.

Results: Total 291 studies, including 22 sub-Saharan African countries, met inclusion criteria. Most studies were conducted in South Africa (n = 102), Uganda (n = 46) and Kenya (n = 41); there were 26 countries with no published incidence data, most in western and central Africa. Data were most commonly derived from prospective observational studies (n = 163; 56%) and from geographically defined populations with limited demographic or risk-based enrolment criteria other than age (i.e., general population studies; n = 151; 52%). Across general population studies, average annual incidence declines since 2010 were 0.12/100 person-years (95% CI: 0.06-0.18; p = 0.001) among men and 0.10/100 person-years (95% CI: -0.02-0.22; p = 0.093) among women in eastern Africa, and 0.25/100 person-years (95% CI: 0.17-034; p < 0.0001) among men and 0.42/100 person-years (95% CI: 0.23-0.62; p = 0.0002) among women in southern Africa. In nine of 10 studies with multiple measurements, incidence declined over time, including in two studies of key populations. Across all population risk groups, the highest HIV incidence estimates were observed among men who have sex with men, with rates ranging from 1.0 to 15.4/100 person-years. Within general population studies, incidence was typically higher in women than men with a median female-to-male incidence rate ratio of 1.47 (IQR: 1.11 to 1.83) with evidence of a growing sex disparity over time.

Conclusions: Empirical incidence data show the rate of new HIV infections is declining in eastern and southern Africa. However, recent incidence data are non-existent or very limited for many countries and key populations.
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http://dx.doi.org/10.1002/jia2.25818DOI Listing
October 2021

A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients.

medRxiv 2021 Oct 13. Epub 2021 Oct 13.

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.
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http://dx.doi.org/10.1101/2021.08.11.21261914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528082PMC
October 2021

Prevalence in the United States: National Inpatient Sample, 2016 to 2018.

Open Forum Infect Dis 2021 Sep 30;8(9):ofab409. Epub 2021 Jul 30.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Data from the National Inpatient Sample indicate that prevalence decreased from 10.1 (95% confidence interval [CI] = 9.9-10.3) to 8.6 (95% CI = 8.5-8.8) per 1000 hospital discharges between 2016 and 2018, after accounting for age, sex, and race. There was heterogeneity in the prevalence and decrease in prevalence by geographic region in the United States.
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http://dx.doi.org/10.1093/ofid/ofab409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522265PMC
September 2021

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential.

Cell Rep 2021 Oct 5;37(3):109838. Epub 2021 Oct 5.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma. Conversely, near-complete protection is observed in animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.
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http://dx.doi.org/10.1016/j.celrep.2021.109838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491932PMC
October 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Serosurveillance in Blood Donor Populations.

J Infect Dis 2021 Oct 9. Epub 2021 Oct 9.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

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http://dx.doi.org/10.1093/infdis/jiab517DOI Listing
October 2021

Blood transfusion trends in the United States: national inpatient sample, 2015 to 2018.

Blood Adv 2021 Oct;5(20):4179-4184

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.

Blood transfusions are among the most common therapeutic procedures performed in hospitalized patients. This study evaluates contemporary national trends in red blood cell (RBC), plasma, platelet, and cryoprecipitate transfusions. National Inpatient Sample, the largest all-payer inpatient database representing 94% to 97% of the US population, was evaluated from the fourth quarter (Q4) of 2015 through 2018. Quarterly trends for the percentage of hospitalizations with a transfusion procedure were separately examined for each blood product using log binomial regression and reported as quarterly percent change (QPC). The percentage of hospitalizations with an RBC transfusion decreased from 4.22% (2015Q4) to 3.79% (2018Q4) (QPC = -0.72; 95% confidence interval [CI], -1.26 to -0.19; Ptrend = .008). Although plasma transfusions also decreased, QPC = -1.33 (95% CI, -2.00 to -0.65; Ptrend < .001), platelet transfusions remained stable QPC = -0.13 (95% CI, -0.99 to 0.73; Ptrend = .766). In contrast, hospitalizations with cryoprecipitate utilization significantly increased QPC = 2.01 (95% CI, 0.57 to 3.44; Ptrend = .006). Significant quarterly reductions in RBC transfusions were also seen among many, but not all, strata of sex, race/ethnicity, patient risk severity, and admission type (elective vs nonelective). Despite significant declines in RBC transfusions among older adults, there were no significant changes among pediatric age-group (<18 years) and those 18 to 49 years. The decline in RBC and plasma transfusions suggests steady incorporation of robust evidence base showing safety of restrictive transfusions. Increased cryoprecipitate use may be reflective of wider adoption of hypofibrinogenemia management and hemostasis testing for coagulopathic patients.
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http://dx.doi.org/10.1182/bloodadvances.2021005361DOI Listing
October 2021

A hemagglutination-based, semi-quantitative test for point-of-care determination of SARS-CoV-2 antibody levels.

J Clin Microbiol 2021 Sep 1:JCM0118621. Epub 2021 Sep 1.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Serologic, point-of-care tests to detect antibodies against SARS-CoV-2 are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a novel antibody test leveraging hemagglutination, employing a dry card format currently used for typing ABO blood groups. 200 COVID-19 patient and 200 control plasma samples were reconstituted with O-negative RBCs to form whole blood and added to dried viral-antibody fusion protein, followed by a stirring step and a tilting step, 3-minute incubation, and a second tilting step. The sensitivity for the hemagglutination test, Euroimmun IgG ELISA test and RBD-based CoronaChek lateral flow assay was 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing pre-pandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (p<0.0001). Strong agglutinations were observed within 1 minute of testing, and this shorter assay time also increased specificity to 98.5%. In conclusion, we developed a novel rapid, point-of-care RBC agglutination test for the detection of SARS-CoV-2 antibodies that can yield semi-quantitative information on neutralizing antibody titer in patients. The five-minute test may find use in determination of serostatus prior to vaccination, post-vaccination surveillance and travel screening.
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http://dx.doi.org/10.1128/JCM.01186-21DOI Listing
September 2021

Potential donor characteristics and decisions made by organ procurement organization staff: Results of a discrete choice experiment.

Transpl Infect Dis 2021 Aug 30:e13721. Epub 2021 Aug 30.

Department of Health Policy and Management, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.

Organ procurement organizations (OPOs) evaluate referrals for deceased organ donation in the United States. Efforts to expand the donor pool, such as the HIV organ policy equity (HOPE) Act that permits transplants from HIV-positive donors to HIV-positive recipients, can only succeed if OPOs pursue referrals. However, relatively little is known about how OPO staff evaluate referrals. To better understand this process, OPO staff completed a discrete choice experiment to quantify the relative importance of seven donor characteristics on the decision to pursue a theoretical donor. Relative importance was defined by Partworth utility using a hierarchical Bayesian conditional logit model. There were 51 respondents from 36 of 58 OPOs in the United States. Of the seven attributes, organ and tissue potential were the most influential, followed by age, type of death, HIV status, donor registration, and Hepatitis C status. To be preferred to an HIV-negative donor, an HIV-positive donor needed to have the potential to donate two additional organs. These data provide insight into the preferences of OPO referral staff and may help explain the lower than expected number of HIV-positive transplants performed since the passage of the HOPE Act.
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http://dx.doi.org/10.1111/tid.13721DOI Listing
August 2021

National Landscape of HIV+ Deceased Organ Donors in the United States.

Clin Infect Dis 2021 Aug 28. Epub 2021 Aug 28.

New York University Langone Transplant Institute, New York University Grossman School of Medicine, New York, NY, USA.

Background: Organ transplantation from donors with HIV to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV+ donors is critical for safety.

Methods: We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) testing within the HOPE in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262; NCT03500315; NCT03734393). We compared clinical characteristics in HIV+ versus FP donors. We measured CD4+ T cells, HIV viral load (VL), drug resistance mutations (DRMs), co-receptor tropism, and serum antiretroviral therapy (ART) detection using mass spectrometry in HIV+ donors.

Results: Between 03/2016-03/2020, 92 donors (58 HIV+, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidney, 46 liver). Each year the number of donors increased. Prevalence of hepatitis B (16% vs. 0%), syphilis (16% vs. 0%), and cytomegalovirus (91% vs. 58%) was higher in HIV+ versus FP donors; hepatitis C viremia was similar (2% vs. 6%). Most HIV+ donors (71%) had known HIV diagnosis, of whom 90% were prescribed ART and 68% had VL<400 copies/mL. Median CD4 count was 194 cells/uL (IQR=77-331); median CD4% was 27.0 (IQR=16.8-36.1). Major HIV DRMs were detected in 42%, including non-nucleoside reverse transcriptase inhibitors (33%), integrase strand transfer inhibitor (INSTI, 4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history.

Conclusion: Utilization of HIV+ donor organs is increasing. HIV DRMs are common, yet resistance that would compromise INSTI-based regimens is rare, which is reassuring regarding safety.
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http://dx.doi.org/10.1093/cid/ciab743DOI Listing
August 2021

Antibody Response to a Fourth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.

Transplantation 2021 Aug 24. Epub 2021 Aug 24.

Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1097/TP.0000000000003934DOI Listing
August 2021

Trends and Correlates of Age-Disparate Sexual Partnerships in the United States: The National Health and Nutrition Examination Surveys.

Sex Transm Dis 2021 Aug 16. Epub 2021 Aug 16.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Baltimore, MD.

Abstract: This national survey demonstrates age-disparate (≥5 years; AD-5) sexual partnerships remain common among males and females aged 20-29 years in the U.S. (2005-2016). Females reported more older AD-5 partners and males reported more younger AD-5 partners. Having AD-5 partners was associated with greater lifetime and recent number of sexual partners.
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http://dx.doi.org/10.1097/OLQ.0000000000001529DOI Listing
August 2021

Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2.

medRxiv 2021 Aug 8. Epub 2021 Aug 8.

While antibodies provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. In this study, we employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These predictive models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.
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http://dx.doi.org/10.1101/2021.08.06.21261710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366811PMC
August 2021

Patients' Experiences With HIV-positive to HIV-positive Organ Transplantation.

Transplant Direct 2021 Sep 6;7(9):e745. Epub 2021 Aug 6.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: HIV donor (HIV D) to HIV recipient (HIV R) transplantation involves ethical considerations related to safety, consent, stigma, and privacy, which could be better understood through studying patients' actual experiences.

Methods: We interviewed kidney and liver transplant recipients enrolled in clinical trials evaluating HIV D/R transplantation at 4 centers regarding their decision-making process, the informed consent process, and posttransplant experiences. Participants were interviewed at-transplant (≤3 wk after transplant), posttransplant (≥3 mo after transplant), or both time points. Interviews were analyzed thematically using constant comparison of inductive and deductive coding.

Results: We conducted 35 interviews with 22 recipients (15 at-transplant; 20 posttransplant; 13 both time points; 85% participation). Participants accepted HIV D organs because of perceived benefits and situational factors that increased their confidence in the trials and outweighed perceived clinical and social risks. Participants reported positive experiences with the consent process and the trial. Some described HIV-related stigma and emphasized the need for privacy; others believed HIV D/R transplantation could help combat such stigma. There were some indications of possible therapeutic misestimation (overestimation of benefits or underestimation of risks of a study). Some participants believed that HIV transplant candidates were unable to receive HIV-noninfected donor organs.

Conclusions: Despite overall positive experiences, some ethical concerns remain that should be mitigated going forward. For instance, based on our findings, targeted education for HIV transplant candidates regarding available treatment options and for transplant teams regarding privacy and stigma concerns would be beneficial.
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http://dx.doi.org/10.1097/TXD.0000000000001197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352618PMC
September 2021

CD8+ T-Cell Responses in COVID-19 Convalescent Individuals Target Conserved Epitopes From Multiple Prominent SARS-CoV-2 Circulating Variants.

Open Forum Infect Dis 2021 Jul 30;8(7):ofab143. Epub 2021 Mar 30.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

This study examined whether CD8+ T-cell responses from coronavirus disease 2019 convalescent individuals (n = 30) potentially maintain recognition of the major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (alpha, beta, gamma; n = 45 mutations assessed). Only 1 mutation found in Beta variant-spike overlapped with a previously identified epitope (1/52), suggesting that virtually all anti-SARS-CoV-2 CD8+ T-cell responses should recognize these newly described variants.
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http://dx.doi.org/10.1093/ofid/ofab143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083629PMC
July 2021

Prescription Antibiotic Use Among the US population 1999-2018: National Health and Nutrition Examination Surveys.

Open Forum Infect Dis 2021 Jul 13;8(7):ofab224. Epub 2021 May 13.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Antibiotic resistance has been identified as a public health threat both in the United States and globally. The United States published the National Strategy for Combating Antibiotic Resistance in 2014, which included goals to reduce inappropriate outpatient antibiotic use.

Methods: This cross-sectional study was conducted using National Health and Nutrition Examination Surveys (NHANES) years 1999-2018. Weighted prevalence of past 30-day nontopical outpatient antibiotic use was calculated, as well as the change in prevalence from 1999-2002 to 2015-2018 and 2007-2010 to 2015-2018, both overall and for subgroups. Associations with past 30-day nontopical outpatient antibiotic use in 2015-2018 were examined using predictive margins calculated by multivariable logistic regression.

Results: The overall prevalence of past 30-day nontopical outpatient antibiotic use adjusted for age, sex, race/ethnicity, poverty status, time of year of the interview, and insurance status from 1999-2002 to 2015-2018 changed significantly from 4.9% (95% CI, 3.9% to 5.0%) to 3.0% (95% CI, 2.6% to 3.0%), with the largest decrease among children age 0-1 years. From 2007-2010 to 2015-2018, there was no significant change (adjusted prevalence ratio [adjPR], 1.0; 95% CI, 0.8 to 1.2). Age was significantly associated with antibiotic use, with children age 0-1 years having significantly higher antibiotic use than all other age categories >6 years. Being non-Hispanic Black was negatively associated with antibiotic use as compared with being non-Hispanic White (adjPR, 0.6; 95% CI, 0.4 to 0.8).

Conclusions: While there were declines in antibiotic use from 1999-2002 to 2015-2018, there were no observed declines during the last decade.
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http://dx.doi.org/10.1093/ofid/ofab224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291435PMC
July 2021

Transplant of SARS-CoV-2-infected Living Donor Liver: Case Report.

Transplant Direct 2021 Aug 8;7(8):e721. Epub 2021 Jul 8.

Division of Transplant Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Given the high community prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant programs will encounter SARS-CoV-2 infections in living donors or recipients in the perioperative period. There is limited data on SARS-CoV-2 viremia and organotropism beyond the respiratory tract to inform the risk of transplant transmission of SARS-CoV-2. We report a case of a living donor liver transplant recipient who received a right lobe graft from a living donor with symptomatic PCR-confirmed SARS-CoV-2 infection 3 d following donation. The donor was successfully treated with remdesivir, dexamethasone, and coronavirus disease 2019 (COVID-19) convalescent plasma. No viral transmission was identified, and both donor and recipient had excellent postoperative outcomes.
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http://dx.doi.org/10.1097/TXD.0000000000001178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270633PMC
August 2021

Sequential dosing of convalescent COVID-19 plasma with significant temporal clinical improvements in a persistently SARS-COV-2 positive patient.

Transfus Apher Sci 2021 Oct 3;60(5):103180. Epub 2021 Jun 3.

Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA; Division of Transfusion Medicine, Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA; Mississippi Valley Regional Blood Center, Davenport, IA, USA. Electronic address:

The current global pandemic, SARS-CoV-2 infection, is still extending across the world affecting millions of lives to the date. While new successful vaccines are available with promising outcomes to minimize the spread and to reduce the severity of the disease, optimal therapeutic options still remain elusive. COVID-19 convalescent plasma (CCP) is an investigational treatment option which studies suggesting signals of efficacy and favorable outcomes only for patients treated very early in course of the disease. Benefits of the use of CCP later in the disease remain highly debated and therefore are not common practice. We hereby report a case of severe SARS-CoV-2 infection in a young male patient with prolonged COVID-19 positivity who received repeat doses of CCP treatments later in the disease with temporal clinical improvement. This patient's case highlights the need of further studies evaluating efficacy of repeated dosing of CCP. This also suggests a potential of successful use of CCP later in the disease in selected COVID-19 patients.
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http://dx.doi.org/10.1016/j.transci.2021.103180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173591PMC
October 2021

Blood transfusions in gunshot-wound-related emergency department visits and hospitalizations in the United States.

Transfusion 2021 08 2;61(8):2277-2289. Epub 2021 Jul 2.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients.

Methods: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion.

Results: There were 168,315 ED visits and 58,815 hospitalizations (age = 18-90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18-24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15-5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10-2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission.

Conclusions: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.
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http://dx.doi.org/10.1111/trf.16552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366522PMC
August 2021

Barriers experienced by organ procurement organizations in implementing the HOPE act and HIV-positive organ donation.

AIDS Care 2021 Jun 28:1-7. Epub 2021 Jun 28.

Department of Health Policy and Management, Johns Hopkins School of Public Health, Baltimore, MD, USA.

In the seven years since the HIV Organ Policy Equity (HOPE) Act made HIV-positive organ donation to HIV-positive recipients legally permissible in the United States, there have been fewer HIV-positive organ donations than expected. Organ procurement organizations (OPOs) play a key role in the transplant system and barriers at OPOs may be partly responsible for the relatively low number of HIV-positive donors. To understand potential OPO barriers, we conducted semi-structured interviews with 20 OPO staff members. Interviews were recorded, transcribed, and analyzed using a conventional content analytic approach with two coders. OPO staff had high levels of knowledge about HOPE. Many had evaluated referrals of HIV-positive donors and approached families for authorization. Barriers to HIV-positive organ recovery identified included obtaining authorization for donation, potentially disclosing HIV status to next-of-kin, and fear of HIV infection among those engaged in organ recovery. Strategies to overcome these barriers include providing continuing education about the specific tasks required to procure organs from HIV-positive donors, implementing targeted interventions to reduce fear of infection, and developing partnerships with HIV advocacy and care organizations. Given the central role OPOs play, HIV-positive donations are unlikely to occur in significant numbers unless these barriers can be overcome.
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http://dx.doi.org/10.1080/09540121.2021.1945999DOI Listing
June 2021

Immunogenicity and Reactogenicity After SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients Taking Belatacept.

Transplantation 2021 09;105(9):2119-2123

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept.

Methods: Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response.

Results: Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01).

Conclusions: Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.
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http://dx.doi.org/10.1097/TP.0000000000003824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380692PMC
September 2021

Demographic and clinical correlates of acute and convalescent SARS-CoV-2 infection among patients of a U.S. emergency department.

Am J Emerg Med 2021 Oct 30;48:261-268. Epub 2021 Apr 30.

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, MD, United States of America; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.

Background: Emergency Departments (EDs) have served as critical surveillance sites for infectious diseases. We sought to determine the prevalence and temporal trends of acute (by PCR) and convalescent (by antibody [Ab]) SARS-CoV-2 infection during the earliest phase of the pandemic among patients in an urban ED in Baltimore City.

Methods: We tested remnant blood samples from 3255 unique ED patients, collected between March 16th and May 31st 2020 for SARS-CoV-2 Ab. PCR for acute SARS-CoV-2 infection from nasopharyngeal swabs was obtained on any patients based on clinical suspicion. Hospital records were abstracted and factors associated with SARS-CoV-2 infection were assessed.

Results: Of 3255 ED patients, 8.2% (95%CI: 7.3%, 9.2%) individuals had evidence of SARS-CoV-2 infection; 155 PCR+, 78 Ab+, and 35 who were both PCR+ and Ab+. Prevalence of disease increased throughout the study period, ranging from 3.2% (95%CI: 1.8%, 5.2%) PCR+ and 0.6% (95%CI: 0.1%, 1.8%) Ab+ in March, to 6.2% (95%CI: 5.1%, 7.4%) PCR+ and 4.2% (95%CI: 3.3%, 5.3%) Ab+ in May. The highest SARS-CoV-2 prevalence was found in Hispanic individuals who made up 8.4% (95%CI: 7.4%, 9.4%) of individuals screened, but 35% (95%CI: 29%, 41%) of infections (PCR and/or Ab+). Demographic and clinical factors independently associated with acute infection included Hispanic ethnicity, loss of smell or taste, subjective fever, cough, muscle ache and fever. Factors independently associated with convalescent infection were Hispanic ethnicity and low oxygen saturation.

Conclusions: The burden of COVID-19 in Baltimore City increased dramatically over the 11-week study period and was disproportionately higher among Hispanic individuals. ED-based surveillance methods are important for identifying both acute and convalescent SARS-CoV-2 infections and provides important information regarding demographic and clinical correlates of disease in the local community.
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http://dx.doi.org/10.1016/j.ajem.2021.04.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086378PMC
October 2021

A hemagglutination-based, semi-quantitative test for point-of-care determination of SARS-CoV-2 antibody levels.

medRxiv 2021 May 4. Epub 2021 May 4.

Serologic, point-of-care tests to detect antibodies against SARS-CoV-2 are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a new method of COVID-19 antibody testing employing hemagglutination tested on a dry card, similar to that which is already available for rapid typing of ABO blood groups. A fusion protein linking red blood cells (RBCs) to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was placed on the card. 200 COVID-19 patient and 200 control plasma samples were reconstituted with O-negative RBCs to form whole blood and added to the dried protein, followed by a stirring step and a tilting step, 3-minute incubation, and a second tilting step. The sensitivity for the hemagglutination test, Euroimmun IgG ELISA test and RBD-based CoronaChek lateral flow assay was 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing pre-pandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (p<0.0001). Strong agglutinations were observed within 1 minute of testing, and this shorter assay time also increased specificity to 98.5%. In conclusion, we developed a novel rapid, point-of-care RBC agglutination test for the detection of SARS-CoV-2 antibodies that can yield semi-quantitative information on neutralizing antibody titer in patients. The five-minute test may find use in determination of serostatus prior to vaccination, post-vaccination surveillance and travel screening.
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http://dx.doi.org/10.1101/2021.05.01.21256452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109202PMC
May 2021

Markers of Polyfunctional SARS-CoV-2 Antibodies in Convalescent Plasma.

mBio 2021 04 20;12(2). Epub 2021 Apr 20.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but the antibody characteristics that contribute to efficacy remain poorly understood. This study analyzed plasma samples from 126 eligible convalescent blood donors in addition to 15 naive individuals, as well as an additional 20 convalescent individuals as a validation cohort. Multiplexed Fc Array binding assays and functional antibody response assays were utilized to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody composition and activity. Donor convalescent plasma samples contained a range of antibody cell- and complement-mediated effector functions, indicating the diverse antiviral activity of humoral responses observed among recovered individuals. In addition to viral neutralization, convalescent plasma samples contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis, and antibody-dependent cellular cytotoxicity against SARS-CoV-2. Plasma samples from a fraction of eligible donors exhibited high activity across all activities evaluated. These polyfunctional plasma samples could be identified with high accuracy with even single Fc Array features, whose correlation with polyfunctional activity was confirmed in the validation cohort. Collectively, these results expand understanding of the diversity of antibody-mediated antiviral functions associated with convalescent plasma, and the polyfunctional antiviral functions suggest that it could retain activity even when its neutralizing capacity is reduced by mutations in variant SARS-CoV-2. Convalescent plasma has been deployed globally as a treatment for COVID-19, but efficacy has been mixed. Better understanding of the antibody characteristics that may contribute to its antiviral effects is important for this intervention as well as offer insights into correlates of vaccine-mediated protection. Here, a survey of convalescent plasma activities, including antibody neutralization and diverse effector functions, was used to define plasma samples with broad activity profiles. These polyfunctional plasma samples could be reliably identified in multiple cohorts by multiplex assay, presenting a widely deployable screening test for plasma selection and investigation of vaccine-elicited responses.
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http://dx.doi.org/10.1128/mBio.00765-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092262PMC
April 2021

A rapid, point-of-care red blood cell agglutination assay detecting antibodies against SARS-CoV-2.

Biochem Biophys Res Commun 2021 05 15;553:165-171. Epub 2021 Mar 15.

Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

The COVID-19 pandemic has caused significant morbidity and mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess past infection, evaluate responses to vaccines in development, and determine individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely on traditional technologies such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays, which have not scaled to meet the demand of hundreds of millions of antibody tests so far. Herein, we present an alternative method of antibody testing that depends on one protein reagent being added to patient serum/plasma or whole blood with direct, visual readout. Two novel fusion proteins, RBD-2E8 and B6-CH1-RBD, were designed to bind red blood cells (RBCs) via a single-chain variable fragment (scFv), thereby displaying the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on the surface of RBCs. Mixing mammalian-derived RBD-2E8 and B6-CH1-RBD with convalescent COVID-19 patient serum and RBCs led to visible hemagglutination, indicating the presence of antibodies against SARS-CoV-2 RBD. B6-CH1-RBD made in bacteria was not as effective in inducing agglutination, indicating better recognition of RBD epitopes from mammalian cells. Given that our hemagglutination test uses methods routinely used in hospital clinical labs across the world for blood typing, we anticipate the test can be rapidly deployed at minimal cost. We anticipate our hemagglutination assay may find extensive use in low-resource settings for detecting SARS-CoV-2 antibodies.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959259PMC
May 2021

Development of a Patient Reported Measure of Experimental Transplants with HIV and Ethics in the United States (PROMETHEUS).

J Patient Rep Outcomes 2021 Mar 18;5(1):28. Epub 2021 Mar 18.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Transplantation of HIV-positive (HIV+) donor organs for HIV+ recipients (HIV D+/R+) is now being performed as research in the United States, but raises ethical concerns. While patient-reported outcome measures are increasingly used to evaluate clinical interventions, there is no published measure to aptly capture patients' experiences in the unique context of experimental HIV D+/R+ transplantation. Therefore, we developed PROMETHEUS (patient-reported measure of experimental transplants with HIV and ethics in the United States). To do so, we created a conceptual framework, drafted a pilot battery using existing and new measures related to this context, and refined it based on cognitive and pilot testing. PROMETHEUS was administered 6-months post-transplant in a clinical trial evaluating these transplants. We analyzed data from the first 20 patient-participants for reliability and validity by calculating Cronbach's alpha and reviewing item performance characteristics.

Results: PROMETHEUS 1.0 consisted of 29 items with 5 putative subscales: Emotions; Trust; Decision Making; Transplant; and Decision Satisfaction. Overall, responses were positive. Cronbach's alpha was > 0.8 for all subscales except Transplant, which was 0.38. Two Transplant subscale items were removed due to poor reliability and construct validity.

Conclusions: We developed PROMETHEUS to systematically capture patient-reported experiences with this novel experimental transplantation program, nested it in an actual clinical trial, and obtained preliminary data regarding its performance.
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http://dx.doi.org/10.1186/s41687-021-00297-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973329PMC
March 2021
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