Publications by authors named "Thomas C Quinn"

387 Publications

A tribute to John G. Bartlett, MD (1937-2021).

J Clin Invest 2021 Mar;131(6)

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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http://dx.doi.org/10.1172/JCI148371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954592PMC
March 2021

A high prevalence of potential HIV elite controllers identified over 30 years in Democratic Republic of Congo.

EBioMedicine 2021 Mar 2;65:103258. Epub 2021 Mar 2.

Infectious Diseases Research, Abbott Diagnostics, Abbott Park, IL, United States.

Background: In-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates.

Methods: 10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting.

Findings: Our data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends.

Interpretation: Viral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression.

Funding: Abbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.
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http://dx.doi.org/10.1016/j.ebiom.2021.103258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992073PMC
March 2021

CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants.

medRxiv 2021 Feb 12. Epub 2021 Feb 12.

This study examined whether CD8+ T-cell responses from COVID-19 convalescent individuals(n=30) potentially maintain recognition of the major SARS-CoV-2 variants. Out of 45 mutations assessed, only one from the B.1.351 Spike overlapped with a low-prevalence CD8+ epitope, 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/10.1101/2021.02.11.21251585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885937PMC
February 2021

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality.

J Clin Invest 2021 04;131(7)

Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection.
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http://dx.doi.org/10.1172/JCI146927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011893PMC
April 2021

Cytokine and Chemokine Levels in Coronavirus Disease 2019 Convalescent Plasma.

Open Forum Infect Dis 2021 Feb 26;8(2):ofaa574. Epub 2020 Nov 26.

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

Background: The efficacy of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors.

Methods: A cross-sectional study was conducted among 20 prepandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection-based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n = 35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percentage of detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher's exact and Wilcoxon rank-sum tests, respectively.

Results: Among CCP donors (n = 140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days (interquartile range = 38-50) and 9% (n = 12) were hospitalized due to COVID-19. Compared with healthy blood donor controls, CCP donors had significantly higher plasma levels of interferon (IFN)-γ, interleukin (IL)-10, IL-15, IL-21, and macrophage-inflammatory protein-1, but lower levels of IL-1RA, IL-8, IL-16, and vascular endothelial growth factor-A ( < .0014). The distributions of plasma levels of IL-8, IL-15, and IFN-inducible protein-10 were significantly higher among CCP donors with high (≥160) versus low (<40) anti-SARS-CoV-2 neutralizing antibody titers ( < .0014). The median levels of IL-6 were significantly higher among CCP donors who were hospitalized versus nonhospitalized ( < .0014).

Conclusions: Heterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.
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http://dx.doi.org/10.1093/ofid/ofaa574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717355PMC
February 2021

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Status in Decedents Undergoing Forensic Postmortem Examination in Maryland, May 24 to June 30, 2020.

Open Forum Infect Dis 2021 Jan 15;8(1):ofaa611. Epub 2020 Dec 15.

Office of the Chief Medical Examiner, Maryland Department of Health, Baltimore, Maryland, USA.

Seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies was 10% among the subset of decedents undergoing forensic postmortem examination in June in Maryland. Decedents of motor vehicle crashes had similar seroprevalence compared with those with a natural death (including decedents with SARS-CoV-2 infection). Decedents of motor vehicle crashes may be a sentinel surveillance population.
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http://dx.doi.org/10.1093/ofid/ofaa611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798730PMC
January 2021

Validation of the Asante HIV-1 Rapid Recency Assay for Detection of Recent HIV-1 Infections in Uganda.

AIDS Res Hum Retroviruses 2021 Feb 25. Epub 2021 Feb 25.

Rakai Health Sciences Program, Kalisizo, Uganda.

Point of care rapid recency testing for HIV-1 may be a cost-effective tool to identify recently infected individuals for incidence estimation, and focused HIV prevention through intensified contact tracing. We validated the Asante™ HIV-1 rapid recency assay for use in Uganda. Archived specimens (serum/plasma), collected from longitudinally observed HIV-1 recently and long-term infected participants, were tested with the Asante HIV-1 rapid recency assay per manufacturer's instructions. Previously identified antiretroviral therapy (ART)-naive samples with known seroconversions within 6 months of follow-up were tested in independent laboratories: the Rakai Health Sciences Program (RHSP) and the Uganda Virus Research Institute HIV Reference Laboratory (UVRI-HRL). In addition, samples from participants who seroconverted within 6-18 months and samples from individuals with chronic HIV-1 infection of at least 18 months duration were classified into three categories: ART naive, ART exposed with suppressed viral loads, and ART exposed with detectable viremia. Of the 85 samples seroconverting in ≤6 months, 27 and 42 samples were identified as "recent" by the Asante HIV-1 rapid recency test at the RHSP laboratory and UVRI-HRL, corresponding to sensitivities of 32% and 49%, respectively. There was 72% agreement between the laboratories (Cohen's kappa = 0.481, 95% CI = 0.317-0.646,  < .0001). Specificity was 100% (200/200) among chronically infected ART-naive samples. The Asante HIV-1 rapid recency assay had low sensitivity for detection of recent HIV-1 infections in Uganda, with substantial interlaboratory variability due to differential interpretation of the test strip bands. Specificity was excellent. Assessment of assay performance in other settings is needed to guide decisions on test utility.
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http://dx.doi.org/10.1089/AID.2020.0279DOI Listing
February 2021

ABO blood group and SARS-CoV-2 antibody response in a convalescent donor population.

Vox Sang 2021 Jan 25. Epub 2021 Jan 25.

Division of Transfusion Medicine, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.

Background And Objectives: ABO blood group may affect risk of SARS-CoV-2 infection and/or severity of COVID-19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS-CoV-2 vary by ABO blood group.

Materials And Methods: Among eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti-SARS-CoV-2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non-parametric Kruskal-Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS-CoV-2 diagnosis.

Results: Of the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti-spike IgA or anti-spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1-3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4-1·0], P = 0·053).

Conclusion: Eligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID-19 severity are needed.
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http://dx.doi.org/10.1111/vox.13070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012988PMC
January 2021

Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study.

J Infect Dis 2021 Apr;223(7):1150-1160

Rakai Health Sciences Program, Entebbe, Uganda.

Background: There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa.

Methods: Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression.

Results: There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15-29 vs 40-49 years; adjRR = 1.80; 95% CI = 1.19-2.71), male sex (adjRR = 2.09, 95% CI = 1.47-2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34-2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34-2.73) were factors associated with persistent viremia.

Conclusions: Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.
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http://dx.doi.org/10.1093/infdis/jiab021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030722PMC
April 2021

SARS-CoV-2-specific CD8+ T cell responses in convalescent COVID-19 individuals.

J Clin Invest 2021 03;131(5)

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.

Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2-specific CD8+ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8+ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2-specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection.
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http://dx.doi.org/10.1172/JCI145476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919723PMC
March 2021

Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai, Uganda: A pragmatic, cluster-randomized trial.

PLoS Med 2021 Jan 6;18(1):e1003475. Epub 2021 Jan 6.

Rakai Health Sciences Program, Rakai, Uganda.

Background: Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services.

Methods And Findings: The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect.

Conclusions: A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control.

Trial Registration: ClinicalTrials.gov NCT02556957.
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http://dx.doi.org/10.1371/journal.pmed.1003475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787382PMC
January 2021

Seroprevalence of Chlamydia trachomatis among female adults in the United States: The National Health and Nutrition Examination Surveys.

Clin Infect Dis 2020 Dec 23. Epub 2020 Dec 23.

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

Background: Chlamydia trachomatis is the most common nationally notifiable sexually transmitted infectious disease in the United States; however, the seroprevalence of C. trachomatis infection is unknown.

Methods: This cross-sectional study was conducted among 1725 females aged 18-39 years who provided serum and urine samples in the 2013-2016 National Health and Nutrition Examination Surveys (NHANES). Presence of anti-C. trachomatis Pgp3 IgG was determined using both an enzyme-linked immunosorbent assay (ELISA) and multiplex bead array (MBA). Weighted seroprevalence estimates were calculated. Correlates of seroprevalence were examined by multivariable Poisson regression.

Results: In 2013-2016, overall seroprevalence of C. trachomatis Pgp3 IgG was 30.0%(95%CI=25.5%-35.0%) as measured by ELISA and 29.4%(95%CI=25.8%-33.0%) as measured by the MBA assay. Overall agreement between tests was 87.1%(1503/1725). There was a high positive agreement by the MBA assay with current detection of chlamydia in urine (86%[36/42]), a past-year diagnosis of chlamydia (82%[27/33]), and a history of treatment for pelvic inflammatory disease (61%[37/61]). Seroprevalence of C. trachomatis Pgp3 IgG, as measured by MBA, was significantly higher among non-Hispanic Blacks (68.0%; aPR=2.7[95%CI=2.3-3.3]), Mexican Americans (30.9%; aPR=1.5[95% CI=1.2-1.9]), and other Hispanics (35.0%; aPR=1.9[95%CI=1.4-2.5]) as compared to non-Hispanic Whites (21.4%). Seroprevalence was also associated with a higher lifetime number of sexual partners and a younger age at sexual debut.

Conclusion: Both the ELISA and MBA serologic assays revealed a high prevalence of antibodies to C. trachomatis Pgp3 in young adult females in the U.S. household population. There were major racial/ethnic disparities in exposure to C. trachomatis, with increased vulnerability among non-Hispanic Blacks.
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http://dx.doi.org/10.1093/cid/ciaa1879DOI Listing
December 2020

Sex-specific associations between cerebrospinal fluid inflammatory marker levels and cognitive function in antiretroviral treated people living with HIV in rural Uganda.

Brain Behav Immun 2021 Mar 24;93:111-118. Epub 2020 Dec 24.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States.

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies.
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http://dx.doi.org/10.1016/j.bbi.2020.12.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023502PMC
March 2021

Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality.

medRxiv 2020 Dec 18. Epub 2020 Dec 18.

Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

COVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, has been successfully used for treatment of COVID-19. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-S titer but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.
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http://dx.doi.org/10.1101/2020.12.16.20248294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755150PMC
December 2020

Temporal trends of early mortality and its risk factors in HIV-infected adults initiating antiretroviral therapy in Uganda.

EClinicalMedicine 2020 Nov 7;28:100600. Epub 2020 Nov 7.

Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Background: A decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improvements in early mortality due to improved patient care.

Methods: We conducted a retrospective cohort study of HIV-infected individuals ages 18 and older who initiated ART at the Mengo HIV Counseling and Home Care Clinic between 2006 and 2016. We conducted a mediation analysis using generalized structural equation models with inverse odds ratio weighting to estimate the natural direct and indirect effects of ART initiation time on early mortality.

Findings: Among 6,847 patients, most were female (69%), with a median age of 32 (interquartile range [IQR] = 28-38), versus a median age of 38 (IQR = 32-45) for males. The median CD4 count at ART initiation increased from 142 cells/ul (95% confidence interval [CI] = 135-150) in 2006-2010 to 302 cells/ul (95% CI = 283-323) in 2015-2016 ( < 0·001). The number of patients at WHO clinical stages I/II increased from 52% in 2006-2010 to 78% in 2015-2016 ( < 0·001). Annual early mortality decreased from 8·8 deaths/100 person years (PYS) in 2006 to 2.5 deaths/100 pys in 2016 ( < 0·001). Mediation by CD4 counts and WHO clinical stages accounted for 54% of the total effect of ART initiation timing on early mortality. In comparison, 46% remained as the direct effect, reflecting the contribution of improved patient care.

Interpretation: Improved patient care practices should be promoted as a strategy for reducing early mortality after ART initiation, above and beyond the effects from ART initiation at higher CD4 counts and less advanced WHO clinical stage alone.

Funding: This research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR), the National Institute of Allergy and Infectious Diseases Division of Intramural Research, and the National Cancer Institute.
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http://dx.doi.org/10.1016/j.eclinm.2020.100600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700951PMC
November 2020

Similar frequency and inducibility of intact HIV-1 proviruses in blood and lymph nodes.

J Infect Dis 2020 Dec 3. Epub 2020 Dec 3.

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Background: The HIV-1 latent reservoir (LR) in resting CD4 + T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes.

Methods: We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from ten HIV-1-infected patients on ART using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay.

Results: The frequencies of CD4 + T cells with intact proviruses were not significantly different in PB vs LN (61vs104/10 6CD4 + cells), and were substantially lower than frequencies of CD4 + T cells with defective proviruses. The frequencies of CD4 + T cells induced to produce high levels of viral RNA were not significantly different in PB vs LN (4.3/10 6 vs 7.9/10 6), but were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples.

Conclusions: These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs.
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http://dx.doi.org/10.1093/infdis/jiaa736DOI Listing
December 2020

Evaluation of Serological SARS-CoV-2 Lateral Flow Assays for Rapid Point-of-Care Testing.

J Clin Microbiol 2021 01 21;59(2). Epub 2021 Jan 21.

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

Rapid point-of-care tests (POCTs) for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies vary in performance. A critical need exists to perform head-to-head comparisons of these assays. The performances of 15 different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies were compared on a well-characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (collected an average of 45 days after symptom onset) were used to assess sensitivity. Sixty samples from the prepandemic era (negative control) that were known to represent infections with other respiratory viruses (rhinoviruses A, B, and C and/or coronavirus 229E, HKU1, and NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed using five lateral flow assays (LFAs) and a panel of 272 longitudinal samples from 47 patients for whom the time since symptom onset was known. Among the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55% to 97% and from 78% to 100%, respectively. Assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0% to 88% and 80% to 100% for IgM and from 25% to 95% and 90% to 100% for IgG, respectively. Longitudinal testing revealed that the median times after symptom onset to a positive result were 7 days (interquartile range [IQR], 5.4 to 9.8) for IgM and 8.2 days (IQR, 6.3 to 11.3) for IgG. The testing performances differed widely among LFAs, with greatest amount of variation related to the sensitivity of the assays. The IgM band was the band most likely to misclassify prepandemic samples. The appearances of IgM and IgG bands occurred almost simultaneously.
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http://dx.doi.org/10.1128/JCM.02020-20DOI Listing
January 2021

The association of α4β7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

EBioMedicine 2020 Dec 7;62:103102. Epub 2020 Nov 7.

Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Background: α4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4 T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID).

Methods: MSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (1:1 and 1:3, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of α4β7 expression on CD4 T cells. Multivariable conditional logistic regression was used to compare α4β7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the association of α4β7 expression pre-seroconversion with HIV disease progression.

Findings: In MSM and transgender women (n = 103 cases, 103 controls), there was no statistically significant difference in the levels of α4β7 expression on CD4 T cells between cases and controls (adjusted odds ratio [adjOR] =1.10, 95% confidence interval [CI]=0.94,1.29; p = 0.246). Interestingly, in PWID (n = 49 cases, 143 controls), cases had significantly lower levels of α4β7 expression compared to their matched controls (adjOR = 0.80, 95% CI = 0.68, 0.93; p = 0.004). Among HIV-positive PWID (n = 47), there was no significant association in HIV disease progression in individuals above or below the median level of α4β7 expression (log-rank p = 0.84).

Interpretation: In contrast to findings in heterosexual women, higher α4β7 expression does not predict HIV acquisition or disease progression in PWID or MSM.

Funding: This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.
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http://dx.doi.org/10.1016/j.ebiom.2020.103102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658649PMC
December 2020

Comparative Performance of Five Commercially Available Serologic Assays To Detect Antibodies to SARS-CoV-2 and Identify Individuals with High Neutralizing Titers.

J Clin Microbiol 2021 01 21;59(2). Epub 2021 Jan 21.

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

Accurate serological assays to detect antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donation. This study compared the performances of commercial enzyme immunoassays (EIAs) with respect to detection of IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAbs). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) for detection of IgG or total antibodies to SARS-CoV-2 was evaluated using cross-sectional samples from potential CCP donors who had prior molecular confirmation of SARS-CoV-2 infection ( = 214) and samples from prepandemic emergency department patients without SARS-CoV-2 infection ( = 1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority ( = 16 [7.5%]) had been hospitalized due to COVID-19; 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. Performed according to the protocols of the manufacturers to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff value of ≥160 as the reference representing a positive test result ( = 140 CCP donors), the empirical area under the receiver operating curve for each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAb titers. Some but not all commercial EIAs may be useful in the identification of individuals with high nAb titers among convalescent individuals.
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http://dx.doi.org/10.1128/JCM.02257-20DOI Listing
January 2021

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation.

bioRxiv 2020 Oct 8. Epub 2020 Oct 8.

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.
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http://dx.doi.org/10.1101/2020.10.08.330688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553170PMC
October 2020

Effectiveness of Voluntary Medical Male Circumcision for HIV prevention in Rakai, Uganda.

Clin Infect Dis 2020 Oct 12. Epub 2020 Oct 12.

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

Background: The efficacy of voluntary male medical circumcision (VMMC) for HIV prevention in men was demonstrated in three randomized trials. This led to the adoption of VMMC as an integral component of the President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real world, programmatic settings is limited.

Methods: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda were followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised versus uncircumcised men.

Results: 3,916 non-Muslim men were followed for 17,088 person-years (py). There were 1338 newly reported VMMCs (9.8/100 py). Over the study period, the median age of men adopting VMMC declined from 28 years (IQR 21-35) to 22 years (IQR 18-29; p-trend <0.001). HIV incidence was 0.40/100 py (20/4992.8 py) among newly circumcised men and 0.98/100 py (118/12095.1 py) among uncircumcised men with an adjusted IRR of 0.47 (95%CI: 0.28-0.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time.

Conclusions: VMMC programs are highly effective in preventing HIV-acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.
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http://dx.doi.org/10.1093/cid/ciaa1533DOI Listing
October 2020

Implementation of global health competencies: A scoping review on target audiences, levels, and pedagogy and assessment strategies.

PLoS One 2020 1;15(10):e0239917. Epub 2020 Oct 1.

Johns Hopkins School of Public Health, Baltimore, MD, United States of America.

Background: As the field of global health expands, the recognition of structured training for field-based public health professionals has grown. Substantial effort has gone towards defining competency domains for public health professionals working globally. However, there is limited literature on how to implement competency-based training into learning curricula and evaluation strategies.

Objectives: This scoping review seeks to collate the current status, degree of consensus, and best practices, as well as gaps and areas of divergence, related to the implementation of competencies in global health curricula. Specifically, we sought to examine (i) the target audience, (ii) the levels or milestones, and (iii) the pedagogy and assessment approaches.

Sources Of Evidence: A review of the published and grey literature was completed to identify published and grey literature sources that presented information on how to implement or support global health and public health competency-based education programs. In particular, we sought to capture any attempts to assign levels or milestones, any evaluation strategies, and the different pedagogical approaches.

Results: Out of 68 documents reviewed, 21 documents were included which contained data related to the implementation of competency-based training programs; of these, 18 were peer-reviewed and three were from the grey literature. Most of the sources focused on post-graduate public health students, professional trainees pursuing continuing education training, and clinical and allied health professionals working in global health. Two approaches were identified to defining skill level or milestones, namely: (i) defining levels of increasing ability or (ii) changing roles across career stages. Pedagogical approaches featured field experience, direct engagement, group work, and self-reflection. Assessment approaches included self-assessment surveys, evaluations by peers and supervisors, and mixed methods assessments.

Conclusions: The implementation of global health competencies needs to respond to the needs of specific agencies or particular groups of learners. A milestones approach may aide these efforts while also support monitoring and evaluation. Further development is needed to understand how to assess competencies in a consistent and relevant manner.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239917PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529249PMC
November 2020

The effect of Mass Drug Administration for trachoma on antibodies to Chlamydia trachomatis pgp3 in children.

Sci Rep 2020 09 16;10(1):15225. Epub 2020 Sep 16.

National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

A serologic test for antibodies to chlamydia may be a useful tool for trachoma surveillance. However, little is known about the longitudinal stability of antibody status, especially following Mass Drug Administration (MDA), which is critical to understanding serostatus in trachoma-endemic areas. A longitudinal cohort of 1908 children ages 1-9 years in Tanzania from 50 communities were followed at baseline and for 6 months after MDA. They were evaluated for clinical trachoma, conjunctival swabs were tested for chlamydial infection using GeneXpert platform, and blood spots were collected on filter paper and dried to test for antibodies to Chlamydia trachomatis pgp3 using the Luminex platform. 6.3% of children in the study had infection, and coverage with MDA was 97%. 670 (35%) were sero-positive for pgp3 antibodies at baseline, and 4.0% of these seroreverted to negative following MDA. Of those seronegative at baseline, 3.6% seroconverted. The individual change in log median fluorescence intensity(MFI-BG) values was -0.15 overall (p < .001). Seroconversion rates were lower following MDA and seroreversion rates were slightly higher compared to rates in this same cohort in the absence of MDA. MDA has a small effect on reduction of MFI-BG.
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http://dx.doi.org/10.1038/s41598-020-71833-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495425PMC
September 2020

Marijuana Use, Sexual Behaviors, and Prevalent Sexually Transmitted Infections Among Sexually Experienced Males and Females in the United States: Findings From the National Health and Nutrition Examination Surveys.

Sex Transm Dis 2020 10;47(10):672-678

From the Department of Pathology, Johns Hopkins University School of Medicine.

Background: Several national guidelines consider illicit drug use as an indication for testing and/or counseling for some sexually transmitted infections (STIs). The legal and social landscape of marijuana use is changing, and its relevance with STI risk is unclear.

Methods: Sex-specific prevalence of T. vaginalis and/or C. trachomatis infection was examined by past-year marijuana use (no vs yes) among 2958 sexually experienced, 20- to 39-year-old participants of the 2013-2016 National Health and Nutrition Examination Surveys. Prevalence ratios (PRs) with 95% confidence intervals [CIs] were estimated by Poisson regression. Adjusted PRs (aPR) were estimated following propensity score covariate-adjustment accounting for sociodemographics, alcohol use, injection drug use, depression, and age at sexual debut.

Results: Past-year marijuana use was reported by 27.3% and 36.3% of females and males, respectively. Male and female past-year marijuana users were more likely to have new and multiple sexual partners in the past year (P < 0.05). Past-year marijuana use was associated with prevalent C. trachomatis and/or T. vaginalis infection among females (7.4% vs. 2.9%; PR, 2.57 [95% CI, 1.62-4.07]) and males (4.0% vs. 1.1%; PR, 3.59 [95% CI, 1.96-6.58]), but this association was attenuated after propensity score covariate adjustment among females (aPR, 1.15 [95% CI, 0.72-1.83]) and males (aPR, 2.10 [95% CI, 0.88-5.02]). Additional adjustment for new or multiple sexual partners further attenuated the associations (aPRs, 1.02 [95% CI, 0.65-1.51] and 1.91 [95% CI, 0.82-4.47] for females and males, respectively).

Conclusions: Sexually transmitted infection prevalence was higher among persons with a past-year history of marijuana use; however, this association was not significant after accounting for measured confounders. Additional work is needed to characterize STI prevalence by the mode, duration, and frequency of marijuana use.
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http://dx.doi.org/10.1097/OLQ.0000000000001229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694737PMC
October 2020

SARS-CoV-2 Antibody Avidity Responses in COVID-19 Patients and Convalescent Plasma Donors.

J Infect Dis 2020 11;222(12):1974-1984

Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Background: Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19-susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood.

Methods: SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression.

Results: Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19-2.12]), independent of age, sex, and hospitalization.

Conclusions: SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.
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http://dx.doi.org/10.1093/infdis/jiaa581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499592PMC
November 2020

Comparative performance of five commercially available serologic assays to detect antibodies to SARS-CoV-2 and identify individuals with high neutralizing titers.

medRxiv 2020 Sep 2. Epub 2020 Sep 2.

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

Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection for sensitivity (n=214) and pre-pandemic emergency department patients for specificity (n=1,102). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers' protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.
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http://dx.doi.org/10.1101/2020.08.31.20184788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480035PMC
September 2020

HIV serologically indeterminate individuals: Future HIV status and risk factors.

PLoS One 2020 26;15(8):e0237633. Epub 2020 Aug 26.

NIAID, Baltimore, MD, United States of America.

Background: Indeterminate HIV test results are common, but little is known about the evolution of indeterminate serology and its sociodemographic and behavioral correlates. We assessed future HIV serological outcomes for individuals with indeterminate results and associated factors in Rakai, Uganda.

Methods: 115,944 serological results, defined by two enzyme immunoassay (EIAs), among 39,440 individuals aged 15-49 years in the Rakai Community Cohort Study were assessed. Indeterminate results were defined as contradictory EIAs. Modified Poisson regression models with generalized estimating equations were used to assess prevalence ratios (PRs) of subsequent HIV serological outcomes and factors associated with HIV indeterminate results.

Results: The prevalence of HIV serologically indeterminate results was 4.9%. Indeterminate results were less likely among women than men (adjPR 0.76, 95% CI 0.71,0.81), in unmarried participants than married participants (adjPR 0.92, 95% CI 0.85,99), and in individuals with primary (adjPR 0.90, 95% CI 0.80,1.02), secondary (adjPR 0.83, 95% CI 0.73,0.96) and post-secondary (adjPR 0.75, 95% CI 0.60,0.94) education, relative to no education. The proportions of persons with indeterminate results progressing to HIV positive, negative or indeterminate results in subsequent visits was 5%, 71% and 24%, respectively.

Conclusion: HIV serologically indeterminate results were associated with gender and marital status. HIV surveillance programs should develop a protocol for reporting individuals with mixed or persistently indeterminate HIV results on multiple follow-up visits. Most indeterminate results became HIV-negative over time, but follow-up is still needed to detect positive serologies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237633PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449388PMC
October 2020

Racial differences in α4β7 expression on CD4+ T cells of HIV-negative men and women who inject drugs.

PLoS One 2020 25;15(8):e0238234. Epub 2020 Aug 25.

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.

Introduction: We performed a cross-sectional study of HIV-uninfected men and women who inject drugs from the ALIVE cohort to examine if black men and women who inject drugs have higher levels of CD4+ T cells expressing the integrin heterodimer α4β7 compared to white men and women.

Materials And Methods: Flow cytometry was used to examine expression of α4β7 and other markers associated with different functional CD4+ T cell subsets in both men and women who inject drugs.

Results: Higher levels of α4β7, CCR5, and CCR6 were observed on CD4+ T cells from black participants compared with white participants. In a multivariable model, α4β7 expression differed by race, but not sex, age, or other factors.

Discussion: Black men and women express higher percentages of α4β7 expressing CD4+ T cells, which may play a role in HIV disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238234PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447027PMC
October 2020

Patient acceptance of HIV testing services in rural emergency departments in South Africa.

South Afr J HIV Med 2020 22;21(1):1105. Epub 2020 Jul 22.

Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States of America.

Background: South Africa faces the highest burden of HIV infection globally. The National Strategic Plan on HIV recommends provider-initiated HIV counselling and testing (HCT) in all healthcare facilities. However, HIV continues to overwhelm the healthcare system. Emergency department (ED)-based HCT could address unmet testing needs.

Objectives: This study examines the reasons for accepting or declining HCT in South African EDs to inform the development of HCT implementation strategies.

Method: We conducted a prospective observational study in two rural EDs, from June to September 2017. Patients presenting to the ED were systematically approached and offered a point-of-care test in accordance with national guidelines. Patients demographics, presenting compaint, medical history and reasons for accepting/declining testing, were recorded. A pooled analysis is presented.

Results: Across sites, 2074 adult, non-critical patients in the ED were approached; 1880 were enrolled in the study. Of those enrolled, 19.7% had a previously known positive diagnosis, and 80.3% were unaware of their HIV status. Of those unaware, 90% patients accepted and 10% declined testing. The primary reasons for declining testing were 'does not want to know status' (37.6%), 'in too much pain' (34%) and 'does not believe they are at risk' (19.9%).

Conclusions: Despite national guidelines, a high proportion of individuals remain undiagnosed, of which a majority are young men. Our study demonstrated high patient acceptance of ED-based HCT. There is a need for investment and innovation regarding effective pain management and confidential service delivery to address patient barriers. Findings support a routine, non-targeted HCT strategy in EDs.
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http://dx.doi.org/10.4102/sajhivmed.v21i1.1105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433237PMC
July 2020