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1. Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer

Author

Chen, Daniel G, Xie, Jingyi, Choi, Jongchan, Ng, Rachel H, Zhang, Rongyu, Li, Sarah, Edmark, Rick, Zheng, Hong, Solomon, Ben, Campbell, Katie M, Medina, Egmidio, Ribas, Antoni, Khatri, Purvesh, Lanier, Lewis L, Mease, Philip J, Goldman, Jason D, Su, Yapeng, and Heath, James R

Subjects
Biological Sciences, Rare Diseases, Autoimmune Disease, Infectious Diseases, Prevention, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Good Health and Well Being, CD8-Positive T-Lymphocytes, Humans, Communicable Diseases, Neoplasms, Autoimmune Diseases, Inflammation, Autoimmunity, Immunologic Memory, CD8(+) T cells, CP: Immunology, NKG2A, autoimmune disease, cancer, infectious disease, multi-disease, plasma proteomics, single-cell multi-omics, systems immunology, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.

Published
2024

2. Researching COVID to enhance recovery (RECOVER) adult study protocol: Rationale, objectives, and design

Author

Horwitz, Leora I, Thaweethai, Tanayott, Brosnahan, Shari B, Cicek, Mine S, Fitzgerald, Megan L, Goldman, Jason D, Hess, Rachel, Hodder, SL, Jacoby, Vanessa L, Jordan, Michael R, Krishnan, Jerry A, Laiyemo, Adeyinka O, Metz, Torri D, Nichols, Lauren, Patzer, Rachel E, Sekar, Anisha, Singer, Nora G, Stiles, Lauren E, Taylor, Barbara S, Ahmed, Shifa, Algren, Heather A, Anglin, Khamal, Aponte-Soto, Lisa, Ashktorab, Hassan, Bassett, Ingrid V, Bedi, Brahmchetna, Bhadelia, Nahid, Bime, Christian, Bind, Marie-Abele C, Black, Lora J, Blomkalns, Andra L, Brim, Hassan, Castro, Mario, Chan, James, Charney, Alexander W, Chen, Benjamin K, Chen, Li Qing, Chen, Peter, Chestek, David, Chibnik, Lori B, Chow, Dominic C, Chu, Helen Y, Clifton, Rebecca G, Collins, Shelby, Costantine, Maged M, Cribbs, Sushma K, Deeks, Steven G, Dickinson, John D, Donohue, Sarah E, Durstenfeld, Matthew S, Emery, Ivette F, Erlandson, Kristine M, Facelli, Julio C, Farah-Abraham, Rachael, Finn, Aloke V, Fischer, Melinda S, Flaherman, Valerie J, Fleurimont, Judes, Fonseca, Vivian, Gallagher, Emily J, Gander, Jennifer C, Gennaro, Maria Laura, Gibson, Kelly S, Go, Minjoung, Goodman, Steven N, Granger, Joey P, Greenway, Frank L, Hafner, John W, Han, Jenny E, Harkins, Michelle S, Hauser, Kristine SP, Heath, James R, Hernandez, Carla R, Ho, On, Hoffman, Matthew K, Hoover, Susan E, Horowitz, Carol R, Hsu, Harvey, Hsue, Priscilla Y, Hughes, Brenna L, Jagannathan, Prasanna, James, Judith A, John, Janice, Jolley, Sarah, Judd, SE, Juskowich, Joy J, Kanjilal, Diane G, Karlson, Elizabeth W, Katz, Stuart D, Kelly, J Daniel, Kelly, Sara W, Kim, Arthur Y, Kirwan, John P, Knox, Kenneth S, Kumar, Andre, Lamendola-Essel, Michelle F, Lanca, Margaret, Lee-lannotti, Joyce K, Lefebvre, R Craig, and Levy, Bruce D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Clinical Research, Emerging Infectious Diseases, Infectious Diseases, Infection, Good Health and Well Being
Abstract

Abstract: Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility– and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross– validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

Published
2023

3. Multiple early factors anticipate post-acute COVID-19 sequelae

Author

Su, Yapeng, Yuan, Dan, Chen, Daniel G, Ng, Rachel H, Wang, Kai, Choi, Jongchan, Li, Sarah, Hong, Sunga, Zhang, Rongyu, Xie, Jingyi, Kornilov, Sergey A, Scherler, Kelsey, Pavlovitch-Bedzyk, Ana Jimena, Dong, Shen, Lausted, Christopher, Lee, Inyoul, Fallen, Shannon, Dai, Chengzhen L, Baloni, Priyanka, Smith, Brett, Duvvuri, Venkata R, Anderson, Kristin G, Li, Jing, Yang, Fan, Duncombe, Caroline J, McCulloch, Denise J, Rostomily, Clifford, Troisch, Pamela, Zhou, Jing, Mackay, Sean, DeGottardi, Quinn, May, Damon H, Taniguchi, Ruth, Gittelman, Rachel M, Klinger, Mark, Snyder, Thomas M, Roper, Ryan, Wojciechowska, Gladys, Murray, Kim, Edmark, Rick, Evans, Simon, Jones, Lesley, Zhou, Yong, Rowen, Lee, Liu, Rachel, Chour, William, Algren, Heather A, Berrington, William R, Wallick, Julie A, Cochran, Rebecca A, Micikas, Mary E, Unit, the ISB-Swedish COVID-19 Biobanking, Wrin, Terri, Petropoulos, Christos J, Cole, Hunter R, Fischer, Trevan D, Wei, Wei, Hoon, Dave SB, Price, Nathan D, Subramanian, Naeha, Hill, Joshua A, Hadlock, Jennifer, Magis, Andrew T, Ribas, Antoni, Lanier, Lewis L, Boyd, Scott D, Bluestone, Jeffrey A, Chu, Helen, Hood, Leroy, Gottardo, Raphael, Greenberg, Philip D, Davis, Mark M, Goldman, Jason D, and Heath, James R

Subjects
Clinical Research, Prevention, Infectious Diseases, Good Health and Well Being, Adaptive Immunity, Adolescent, Adult, Aged, Aged, 80 and over, Autoantibodies, Biomarkers, Blood Proteins, CD8-Positive T-Lymphocytes, COVID-19, Convalescence, Disease Progression, Female, Humans, Immunity, Innate, Longitudinal Studies, Male, Middle Aged, Risk Factors, SARS-CoV-2, Transcriptome, Young Adult, Post-Acute COVID-19 Syndrome, ISB-Swedish COVID-19 Biobanking Unit, PASC, RNAemia, antibodies, auto-antibodies, computational biology, immune system, immunology, long COVID, metabolomics, multi-omics, proteomics, single cell, single-cell CITE-seq, single-cell RNA-seq, single-cell TCR-seq, single-cell secretome, symptoms, transcriptome, viremia, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Published
2022

4. Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

Author

Heldman, Madeleine R, Kates, Olivia S, Safa, Kassem, Kotton, Camille N, Multani, Ashrit, Georgia, Sarah J, Steinbrink, Julie M, Alexander, Barbara D, Blumberg, Emily A, Haydel, Brandy, Hemmige, Vagish, Hemmersbach-Miller, Marion, La Hoz, Ricardo M, Moni, Lisset, Condor, Yesabeli, Flores, Sandra, Munoz, Carlos G, Guitierrez, Juan, Diaz, Esther I, Diaz, Daniela, Vianna, Rodrigo, Guerra, Giselle, Loebe, Matthias, Yabu, Julie M, Kramer, Kailey Hughes, Tanna, Sajal D, Ison, Michael G, Rakita, Robert M, Malinis, Maricar, Azar, Marwan M, McCort, Margaret E, Singh, Pooja P, Velioglu, Arzu, Mehta, Sapna A, van Duin, David, Goldman, Jason D, Lease, Erika D, Wald, Anna, Limaye, Ajit P, Fisher, Cynthia E, and UW Covid-19 SOT Study Team

Subjects
UW Covid-19 SOT Study Team, Lung, Transplantation, Prevention, Organ Transplantation, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Microbiology
Abstract

IntroductionMost studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined.MethodsWe used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90.ResultsVital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

Published
2022

5. Changing trends in mortality among solid organ transplant recipients hospitalized for COVID‐19 during the course of the pandemic

Author

Heldman, Madeleine R, Kates, Olivia S, Safa, Kassem, Kotton, Camille N, Georgia, Sarah J, Steinbrink, Julie M, Alexander, Barbara D, Hemmersbach‐Miller, Marion, Blumberg, Emily A, Multani, Ashrit, Haydel, Brandy, La Hoz, Ricardo M, Moni, Lisset, Condor, Yesabeli, Flores, Sandra, Munoz, Carlos G, Guitierrez, Juan, Diaz, Esther I, Diaz, Daniela, Vianna, Rodrigo, Guerra, Giselle, Loebe, Matthias, Rakita, Robert M, Malinis, Maricar, Azar, Marwan M, Hemmige, Vagish, McCort, Margaret E, Chaudhry, Zohra S, Singh, Pooja P, Kramer, Kailey Hughes, Velioglu, Arzu, Yabu, Julie M, Morillis, Jose A, Mehta, Sapna A, Tanna, Sajal D, Ison, Michael G, Derenge, Ariella C, Duin, David, Maximin, Adrienne, Gilbert, Carlene, Goldman, Jason D, Lease, Erika D, Fisher, Cynthia E, Limaye, Ajit P, and Team, the UW COVID‐19 SOT Study

Subjects
Transplantation, Good Health and Well Being, COVID-19, Humans, Organ Transplantation, Pandemics, SARS-CoV-2, Transplant Recipients, clinical research, practice, infection and infectious agents, viral, infectious disease, organ transplantation in general, quality of care, care delivery, UW COVID-19 SOT Study Team, clinical research/practice, infection and infectious agents - viral, quality of care/care delivery, Medical and Health Sciences, Surgery
Abstract

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p

Published
2022

6. COVID-19 in solid organ transplant: A multi-center cohort study

Author

Kates, Olivia S, Haydel, Brandy M, Florman, Sander S, Rana, Meenakshi M, Chaudhry, Zohra S, Ramesh, Mayur S, Safa, Kassem, Kotton, Camille Nelson, Blumberg, Emily A, Besharatian, Behdad D, Tanna, Sajal D, Ison, Michael G, Malinis, Maricar, Azar, Marwan M, Rakita, Robert M, Morilla, Jose A, Majeed, Aneela, Sait, Afrah S, Spaggiari, Mario, Hemmige, Vagish, Mehta, Sapna A, Neumann, Henry, Badami, Abbasali, Goldman, Jason D, Lala, Anuradha, Hemmersbach-Miller, Marion, McCort, Margaret E, Bajrovic, Valida, Ortiz-Bautista, Carlos, Friedman-Moraco, Rachel, Sehgal, Sameep, Lease, Erika D, Fisher, Cynthia E, Limaye, Ajit P, Arya, Akanksha, Jeng, Amy, Kuo, Alexander, Luk, Alfred, Puing, Alfredo G, Rossi, Ana P, Brueckner, Andrew J, Multani, Ashrit, Keller, Brian C, Derringer, Darby, Florescu, Diana F, Dominguez, Edward A, Sandoval, Elena, Bilgili, Erin P, Hashim, Faris, Silveira, Fernanda P, Haidar, Ghady, Joharji, Hala G, Murad, Haris F, Gani, Imran Yaseen, el-amm, Jose-Marie, Kahwaji, Joseph, Popoola, Joyce, Yabu, Julie M, Hughes, Kailey, Saharia, Kapil K, Gajurel, Kiran, Bowman, Lyndsey J, Veroux, Massimiliano, Morales, Megan K, Fung, Monica, Theodoropoulos, Nicole M, de la Cruz, Oveimar, Kapoor, Rajan, La Hoz, Ricardo M, Allam, Sridhar R, Vora, Surabhi B, McCarty, Todd P, Anderson-Haag, Tracy, Malhotra, Uma, Kelly, Ursula M, Bhandaram, Vidya, Bennett, William M, and Lominadze, Zurabi

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Clinical Trials and Supportive Activities, Organ Transplantation, Transplantation, Clinical Research, Good Health and Well Being, COVID-19, Cohort Studies, Humans, Male, Middle Aged, SARS-CoV-2, Transplant Recipients, UW COVID-19 SOT Study Team, coronavirus, solid organ transplantation, transplantation, Biological Sciences, Medical and Health Sciences, Microbiology, Clinical sciences
Abstract

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described.MethodsWe performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients.ResultsFour hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P

Published
2021

7. Large libraries of single-chain trimer peptide-MHCs enable antigen-specific CD8+ T cell discovery and analysis

Author

Chour, William, Choi, Jongchan, Xie, Jingyi, Chaffee, Mary E., Schmitt, Thomas M., Finton, Kathryn, DeLucia, Diana C., Xu, Alexander M., Su, Yapeng, Chen, Daniel G., Zhang, Rongyu, Yuan, Dan, Hong, Sunga, Ng, Alphonsus H. C., Butler, Jonah Z., Edmark, Rick A., Jones, Lesley C., Murray, Kim M., Peng, Songming, Li, Guideng, Strong, Roland K., Lee, John K., Goldman, Jason D., Greenberg, Philip D., and Heath, James R.

Published
2023
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8. COVID‐19 in hospitalized lung and non‐lung solid organ transplant recipients: A comparative analysis from a multicenter study

Author

Heldman, Madeleine R, Kates, Olivia S, Safa, Kassem, Kotton, Camille N, Georgia, Sarah J, Steinbrink, Julie M, Alexander, Barbara D, Hemmersbach‐Miller, Marion, Blumberg, Emily A, Crespo, Maria M, Multani, Ashrit, Lewis, Angelica V, Beaird, Omer Eugene, Haydel, Brandy, La Hoz, Ricardo M, Moni, Lisset, Condor, Yesabeli, Flores, Sandra, Munoz, Carlos G, Guitierrez, Juan, Diaz, Esther I, Diaz, Daniela, Vianna, Rodrigo, Guerra, Giselle, Loebe, Matthias, Rakita, Robert M, Malinis, Maricar, Azar, Marwan M, Hemmige, Vagish, McCort, Margaret E, Chaudhry, Zohra S, Singh, Pooja, Hughes, Kailey, Velioglu, Arzu, Yabu, Julie M, Morillis, Jose A, Mehta, Sapna A, Tanna, Sajal D, Ison, Michael G, Tomic, Rade, Derenge, Ariella Candace, Duin, David, Maximin, Adrienne, Gilbert, Carlene, Goldman, Jason D, Sehgal, Sameep, Weisshaar, Dana, Girgis, Reda E, Nelson, Joanna, Lease, Erika D, Limaye, Ajit P, Fisher, Cynthia E, and Team, the UW COVID‐19 SOT Study

Subjects
Transplantation, Organ Transplantation, Infectious Diseases, Lung, Clinical Research, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Adult, Aged, COVID-19, Cohort Studies, Humans, SARS-CoV-2, Transplant Recipients, clinical research, practice, infection and infectious agents, viral, infectious disease, lung (allograft) function, dysfunction, lung disease, infectious, lung transplantation, pulmonology, organ transplantation in general, UW COVID-19 SOT Study Team, clinical research/practice, infection and infectious agents - viral, lung (allograft) function/dysfunction, lung disease: infectious, lung transplantation/pulmonology, Medical and Health Sciences, Surgery
Abstract

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.

Published
2021

9. Organ-specific immunity: A tissue analysis framework for investigating local immune responses to SARS-CoV-2

Author

Ng, Alphonsus H.C., Hu, Huiqian, Wang, Kai, Scherler, Kelsey, Warren, Sarah E., Zollinger, Daniel R., McKay-Fleisch, Jill, Sorg, Kristina, Beechem, Joseph M., Ragaglia, Emily, Lacy, J. Matthew, Smith, Kelly D., Marshall, Desiree A., Bundesmann, Michael M., López de Castilla, Diego, Corwin, David, Yarid, Nicole, Knudsen, Beatrice S., Lu, Yue, Goldman, Jason D., and Heath, James R.

Published
2023
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10. Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19

Author

Su, Yapeng, Chen, Daniel, Yuan, Dan, Lausted, Christopher, Choi, Jongchan, Dai, Chengzhen L, Voillet, Valentin, Duvvuri, Venkata R, Scherler, Kelsey, Troisch, Pamela, Baloni, Priyanka, Qin, Guangrong, Smith, Brett, Kornilov, Sergey A, Rostomily, Clifford, Xu, Alex, Li, Jing, Dong, Shen, Rothchild, Alissa, Zhou, Jing, Murray, Kim, Edmark, Rick, Hong, Sunga, Heath, John E, Earls, John, Zhang, Rongyu, Xie, Jingyi, Li, Sarah, Roper, Ryan, Jones, Lesley, Zhou, Yong, Rowen, Lee, Liu, Rachel, Mackay, Sean, O’Mahony, D Shane, Dale, Christopher R, Wallick, Julie A, Algren, Heather A, Zager, Michael A, Unit, the ISB-Swedish COVID19 Biobanking, Wei, Wei, Price, Nathan D, Huang, Sui, Subramanian, Naeha, Wang, Kai, Magis, Andrew T, Hadlock, Jenn J, Hood, Leroy, Aderem, Alan, Bluestone, Jeffrey A, Lanier, Lewis L, Greenberg, Philip D, Gottardo, Raphael, Davis, Mark M, Goldman, Jason D, and Heath, James R

Subjects
Infectious Diseases, Clinical Research, Prevention, Inflammatory and immune system, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, COVID-19, Female, Genomics, Humans, Male, Middle Aged, RNA-Seq, SARS-CoV-2, Severity of Illness Index, Single-Cell Analysis, ISB-Swedish COVID19 Biobanking Unit, CITE-seq, immune response, infection, metabolomics, multi-omics, proteomics, single-cell RNA-seq, single-cell TCR-seq, single-cell secretome, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

Published
2020

11. Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

Author

Su, Yapeng, Chen, Daniel, Lausted, Christopher, Yuan, Dan, Choi, Jongchan, Dai, Cheng, Voillet, Valentin, Scherler, Kelsey, Troisch, Pamela, Duvvuri, Venkata R, Baloni, Priyanka, Qin, Guangrong, Smith, Brett, Kornilov, Sergey, Rostomily, Clifford, Xu, Alex, Li, Jing, Dong, Shen, Rothchild, Alissa, Zhou, Jing, Murray, Kim, Edmark, Rick, Hong, Sunga, Jones, Lesley, Zhou, Yong, Roper, Ryan, Mackay, Sean, O’Mahony, D Shane, Dale, Christopher R, Wallick, Julie A, Algren, Heather A, Michael, Zager A, Magis, Andrew, Wei, Wei, Price, Nathan D, Huang, Sui, Subramanian, Naeha, Wang, Kai, Hadlock, Jennifer, Hood, Leroy, Aderem, Alan, Bluestone, Jeffrey A, Lanier, Lewis L, Greenberg, Phil, Gottardo, Raphael, Davis, Mark M, Goldman, Jason D, Heath, James R, and Unit, the ISB-Swedish COVID19 Biobanking

Subjects
Emerging Infectious Diseases, Infectious Diseases, Infection, Inflammatory and immune system, Good Health and Well Being
Abstract

Host immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8 + and CD4 + T cells, and cytotoxic CD4 + T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

Published
2020

12. Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19

Author

Lee, Jihoon W., Su, Yapeng, Baloni, Priyanka, Chen, Daniel, Pavlovitch-Bedzyk, Ana Jimena, Yuan, Dan, Duvvuri, Venkata R., Ng, Rachel H., Choi, Jongchan, Xie, Jingyi, Zhang, Rongyu, Murray, Kim, Kornilov, Sergey, Smith, Brett, Magis, Andrew T., Hoon, Dave S. B., Hadlock, Jennifer J., Goldman, Jason D., Price, Nathan D., Gottardo, Raphael, Davis, Mark M., Hood, Leroy, Greenberg, Philip D., and Heath, James R.

Published
2022
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16. 1993. Donor-Derived Transmission of Candida species: 10-year Analysis from the OPTN ad hoc Disease Transmission Advisory Committee (DTAC)

Author

Goldman, Jason D, primary, Woolley, Ann E, additional, Heun Lee, Dong, additional, Wood, R Patrick, additional, Liveli, Taylor, additional, Anesi, Judith A, additional, Berry, Gerald J, additional, Dunn, Kelly E, additional, Fisher, Cynthia E, additional, Ho, Chak-Sum, additional, Kittleson, Michelle, additional, Sellers, Marty T, additional, Taimur, Sarah, additional, Te, Helen S, additional, Trindade, Anil J, additional, Zaffiri, Lorenzo, additional, Levi, Marilyn E, additional, Klassen, David, additional, La Hoz, Ricardo M, additional, Pouch, Stephanie M, additional, and Danziger-Isakov, Lara A, additional

Published
2023
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17. Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design

Author

Horwitz, Leora I., primary, Thaweethai, Tanayott, additional, Brosnahan, Shari B., additional, Cicek, Mine S., additional, Fitzgerald, Megan L., additional, Goldman, Jason D., additional, Hess, Rachel, additional, Hodder, S. L., additional, Jacoby, Vanessa L., additional, Jordan, Michael R., additional, Krishnan, Jerry A., additional, Laiyemo, Adeyinka O., additional, Metz, Torri D., additional, Nichols, Lauren, additional, Patzer, Rachel E., additional, Sekar, Anisha, additional, Singer, Nora G., additional, Stiles, Lauren E., additional, Taylor, Barbara S., additional, Ahmed, Shifa, additional, Algren, Heather A., additional, Anglin, Khamal, additional, Aponte-Soto, Lisa, additional, Ashktorab, Hassan, additional, Bassett, Ingrid V., additional, Bedi, Brahmchetna, additional, Bhadelia, Nahid, additional, Bime, Christian, additional, Bind, Marie-Abele C., additional, Black, Lora J., additional, Blomkalns, Andra L., additional, Brim, Hassan, additional, Castro, Mario, additional, Chan, James, additional, Charney, Alexander W., additional, Chen, Benjamin K., additional, Chen, Li Qing, additional, Chen, Peter, additional, Chestek, David, additional, Chibnik, Lori B., additional, Chow, Dominic C., additional, Chu, Helen Y., additional, Clifton, Rebecca G., additional, Collins, Shelby, additional, Costantine, Maged M., additional, Cribbs, Sushma K., additional, Deeks, Steven G., additional, Dickinson, John D., additional, Donohue, Sarah E., additional, Durstenfeld, Matthew S., additional, Emery, Ivette F., additional, Erlandson, Kristine M., additional, Facelli, Julio C., additional, Farah-Abraham, Rachael, additional, Finn, Aloke V., additional, Fischer, Melinda S., additional, Flaherman, Valerie J., additional, Fleurimont, Judes, additional, Fonseca, Vivian, additional, Gallagher, Emily J., additional, Gander, Jennifer C., additional, Gennaro, Maria Laura, additional, Gibson, Kelly S., additional, Go, Minjoung, additional, Goodman, Steven N., additional, Granger, Joey P., additional, Greenway, Frank L., additional, Hafner, John W., additional, Han, Jenny E., additional, Harkins, Michelle S., additional, Hauser, Kristine S. P., additional, Heath, James R., additional, Hernandez, Carla R., additional, Ho, On, additional, Hoffman, Matthew K., additional, Hoover, Susan E., additional, Horowitz, Carol R., additional, Hsu, Harvey, additional, Hsue, Priscilla Y., additional, Hughes, Brenna L., additional, Jagannathan, Prasanna, additional, James, Judith A., additional, John, Janice, additional, Jolley, Sarah, additional, Judd, S. E., additional, Juskowich, Joy J., additional, Kanjilal, Diane G., additional, Karlson, Elizabeth W., additional, Katz, Stuart D., additional, Kelly, J. Daniel, additional, Kelly, Sara W., additional, Kim, Arthur Y., additional, Kirwan, John P., additional, Knox, Kenneth S., additional, Kumar, Andre, additional, Lamendola-Essel, Michelle F., additional, Lanca, Margaret, additional, Lee-lannotti, Joyce K., additional, Lefebvre, R. Craig, additional, Levy, Bruce D., additional, Lin, Janet Y., additional, Logarbo, Brian P., additional, Logue, Jennifer K., additional, Longo, Michele T., additional, Luciano, Carlos A., additional, Lutrick, Karen, additional, Malakooti, Shahdi K., additional, Mallett, Gail, additional, Maranga, Gabrielle, additional, Marathe, Jai G., additional, Marconi, Vincent C., additional, Marshall, Gailen D., additional, Martin, Christopher F., additional, Martin, Jeffrey N., additional, May, Heidi T., additional, McComsey, Grace A., additional, McDonald, Dylan, additional, Mendez-Figueroa, Hector, additional, Miele, Lucio, additional, Mittleman, Murray A., additional, Mohandas, Sindhu, additional, Mouchati, Christian, additional, Mullington, Janet M., additional, Nadkarni, Girish N., additional, Nahin, Erica R., additional, Neuman, Robert B., additional, Newman, Lisa T., additional, Nguyen, Amber, additional, Nikolich, Janko Z., additional, Ofotokun, Igho, additional, Ogbogu, Princess U., additional, Palatnik, Anna, additional, Palomares, Kristy T. S., additional, Parimon, Tanyalak, additional, Parry, Samuel, additional, Parthasarathy, Sairam, additional, Patterson, Thomas F., additional, Pearman, Ann, additional, Peluso, Michael J., additional, Pemu, Priscilla, additional, Pettker, Christian M., additional, Plunkett, Beth A., additional, Pogreba-Brown, Kristen, additional, Poppas, Athena, additional, Porterfield, J. Zachary, additional, Quigley, John G., additional, Quinn, Davin K., additional, Raissy, Hengameh, additional, Rebello, Candida J., additional, Reddy, Uma M., additional, Reece, Rebecca, additional, Reeder, Harrison T., additional, Rischard, Franz P., additional, Rosas, Johana M., additional, Rosen, Clifford J., additional, Rouphael, Nadine G., additional, Rouse, Dwight J., additional, Ruff, Adam M., additional, Saint Jean, Christina, additional, Sandoval, Grecio J., additional, Santana, Jorge L., additional, Schlater, Shannon M., additional, Sciurba, Frank C., additional, Selvaggi, Caitlin, additional, Seshadri, Sudha, additional, Sesso, Howard D., additional, Shah, Dimpy P., additional, Shemesh, Eyal, additional, Sherif, Zaki A., additional, Shinnick, Daniel J., additional, Simhan, Hyagriv N., additional, Singh, Upinder, additional, Sowles, Amber, additional, Subbian, Vignesh, additional, Sun, Jun, additional, Suthar, Mehul S., additional, Teunis, Larissa J., additional, Thorp, John M., additional, Ticotsky, Amberly, additional, Tita, Alan T. N., additional, Tragus, Robin, additional, Tuttle, Katherine R., additional, Urdaneta, Alfredo E., additional, Utz, P. J., additional, VanWagoner, Timothy M., additional, Vasey, Andrew, additional, Vernon, Suzanne D., additional, Vidal, Crystal, additional, Walker, Tiffany, additional, Ward, Honorine D., additional, Warren, David E., additional, Weeks, Ryan M., additional, Weiner, Steven J., additional, Weyer, Jordan C., additional, Wheeler, Jennifer L., additional, Whiteheart, Sidney W., additional, Wiley, Zanthia, additional, Williams, Natasha J., additional, Wisnivesky, Juan P., additional, Wood, John C., additional, Yee, Lynn M., additional, Young, Natalie M., additional, Zisis, Sokratis N., additional, and Foulkes, Andrea S., additional

Published
2023
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19. Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative

Author

Bonilla, Hector, primary, Peluso, Michael J., additional, Rodgers, Kathleen, additional, Aberg, Judith A., additional, Patterson, Thomas F., additional, Tamburro, Robert, additional, Baizer, Lawrence, additional, Goldman, Jason D., additional, Rouphael, Nadine, additional, Deitchman, Amelia, additional, Fine, Jeffrey, additional, Fontelo, Paul, additional, Kim, Arthur Y., additional, Shaw, Gwendolyn, additional, Stratford, Jeran, additional, Ceger, Patricia, additional, Costantine, Maged M., additional, Fisher, Liza, additional, O’Brien, Lisa, additional, Maughan, Christine, additional, Quigley, John G., additional, Gabbay, Vilma, additional, Mohandas, Sindhu, additional, Williams, David, additional, and McComsey, Grace A., additional

Published
2023
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20. Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report

Author

Goldman, Jason D., primary, Wang, Kai, additional, Röltgen, Katharina, additional, Nielsen, Sandra C. A., additional, Roach, Jared C., additional, Naccache, Samia N., additional, Yang, Fan, additional, Wirz, Oliver F., additional, Yost, Kathryn E., additional, Lee, Ji-Yeun, additional, Chun, Kelly, additional, Wrin, Terri, additional, Petropoulos, Christos J., additional, Lee, Inyoul, additional, Fallen, Shannon, additional, Manner, Paula M., additional, Wallick, Julie A., additional, Algren, Heather A., additional, Murray, Kim M., additional, Hadlock, Jennifer, additional, Chen, Daniel, additional, Dai, Chengzhen L., additional, Yuan, Dan, additional, Su, Yapeng, additional, Jeharajah, Joshua, additional, Berrington, William R., additional, Pappas, George P., additional, Nyatsatsang, Sonam T., additional, Greninger, Alexander L., additional, Satpathy, Ansuman T., additional, Pauk, John S., additional, Boyd, Scott D., additional, and Heath, James R., additional

Published
2022
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22. Reszinate—A Phase 1/2 Randomized Clinical Trial of Zinc and Resveratrol Utilizing Home Patient-Obtained Nasal and Saliva Viral Sampling

Author

Kaplan, Henry G., Wang, Kai, Reeves, Kimberly M., Scanlan, James M., Nunn, Christopher C., Kieper, Douglas A., Mark, Joshua L., Lee, Inyoul, Liu, Rachel, Jin, Ruyun, Bolton, Michael J., and Goldman, Jason D.

Abstract

Background: Safe, effective, and inexpensive treatment for COVID-19 is an urgent unmet medical need. Zinc and resveratrol have been reported to have antiviral activity, and resveratrol may increase zinc activity at the site of replication by increasing intracellular zinc concentrations.Methods: A 1:1 randomized, placebo-controlled trial of zinc 150 mg plus resveratrol 4 g daily for 5 days versus placebos in outpatients with SARS-CoV-2 was carried out from 9/21/2020–1/22/2021 in Seattle, Washington. Viral shedding was followed with patient self-collected nasal and saliva samples by measuring qRT-PCR for SARS-CoV-2 N gene days 1–7, 10, and 14. Patients filled out a web-based questionnaire on days 1–14 to report symptoms, vital signs and adherence to the study intervention. The study was posted as Clinical Trials.gov NCT04542993 on 9 September 2020.Results: A total of 30 participants (14 treatment; 16 placebos) had ≥1 day of the protocol treatment and were evaluable for the primary or secondary outcome. There was no difference in viral shedding between groups, nor in the resolution of symptoms. There was a trend toward a more rapid decrease in symptoms in the treatment group, though this was not statistically significant in the GLM model. Viral shedding was similar between patient self-collected mid-turbinate nasal swabs and expectorated saliva samples with a good correlation.Conclusion: SARS-CoV-2 shedding and COVID-19 symptoms were not statistically significantly decreased by treatment. Viral shedding correlates well between patient-obtained home nasal swabs and saliva sampling.

Published
2022
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23. Hydroxychloroquine for Prevention of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: Challenges to Trial Conduct During the Global Pandemic

Author

Goldman, Jason D

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Hydroxychloroquine, Virology, Pre-exposure prophylaxis, Health personnel, Infectious Diseases, Pandemic, Medicine, business, medicine.drug
Published
2020
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24. Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study

Author

Kates, Olivia S, Haydel, Brandy M, Florman, Sander S, Rana, Meenakshi M, Chaudhry, Zohra S, Ramesh, Mayur S, Safa, Kassem, Kotton, Camille Nelson, Blumberg, Emily A, Besharatian, Behdad D, Tanna, Sajal D, Ison, Michael G, Malinis, Maricar, Azar, Marwan M, Rakita, Robert M, Morilla, Jose A, Majeed, Aneela, Sait, Afrah S, Spaggiari, Mario, Hemmige, Vagish, Mehta, Sapna A, Neumann, Henry, Badami, Abbasali, Goldman, Jason D, Lala, Anuradha, Hemmersbach-Miller, Marion, McCort, Margaret E, Bajrovic, Valida, Ortiz-Bautista, Carlos, Friedman-Moraco, Rachel, Sehgal, Sameep, Lease, Erika D, Fisher, Cynthia E, Limaye, Ajit P, Arya, Akanksha, Jeng, Amy, Kuo, Alexander, Luk, Alfred, Puing, Alfredo G, Rossi, Ana P, Brueckner, Andrew J, Multani, Ashrit, Keller, Brian C, Derringer, Darby, Florescu, Diana F, Dominguez, Edward A, Sandoval, Elena, Bilgili, Erin P, Hashim, Faris, Silveira, Fernanda P, Haidar, Ghady, Joharji, Hala G, Murad, Haris F, Gani, Imran Yaseen, el-amm, Jose-Marie, Kahwaji, Joseph, Popoola, Joyce, Yabu, Julie M, Hughes, Kailey, Saharia, Kapil K, Gajurel, Kiran, Bowman, Lyndsey J, Veroux, Massimiliano, Morales, Megan K, Fung, Monica, Theodoropoulos, Nicole M, de la Cruz, Oveimar, Kapoor, Rajan, La Hoz, Ricardo M, Allam, Sridhar R, Vora, Surabhi B, McCarty, Todd P, Anderson-Haag, Tracy, Malhotra, Uma, Kelly, Ursula M, Bhandaram, Vidya, Bennett, William M, and Lominadze, Zurabi

Subjects
Male, Microbiology (medical), medicine.medical_specialty, medicine.medical_treatment, Clinical Trials and Supportive Activities, coronavirus, 030230 surgery, Logistic regression, Medical and Health Sciences, Microbiology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, Clinical endpoint, Humans, Medicine, Lung, solid organ transplantation, UW COVID-19 SOT Study Team, Mechanical ventilation, Transplantation, SARS-CoV-2, business.industry, COVID-19, Immunosuppression, Organ Transplantation, Biological Sciences, Middle Aged, medicine.disease, Comorbidity, Transplant Recipients, Good Health and Well Being, Infectious Diseases, 030211 gastroenterology & hepatology, business, Solid organ transplantation, transplantation, Cohort study
Abstract

Background The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. Methods We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. Results Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46–57), median time post-transplant was 5 years (IQR 2–10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7–5.5, P Conclusions Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Published
2020
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25. Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping

Author

Duvvuri, Venkata R., primary, Baumgartner, Andrew, additional, Molani, Sevda, additional, Hernandez, Patricia V., additional, Yuan, Dan, additional, Roper, Ryan T., additional, Matos, Wanessa F., additional, Robinson, Max, additional, Su, Yapeng, additional, Subramanian, Naeha, additional, Goldman, Jason D., additional, Heath, James R., additional, and Hadlock, Jennifer J., additional

Published
2022
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26. Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report.

Author

Goldman, Jason D., Wang, Kai, Röltgen, Katharina, Nielsen, Sandra C. A., Roach, Jared C., Naccache, Samia N., Yang, Fan, Wirz, Oliver F., Yost, Kathryn E., Lee, Ji-Yeun, Chun, Kelly, Wrin, Terri, Petropoulos, Christos J., Lee, Inyoul, Fallen, Shannon, Manner, Paula M., Wallick, Julie A., Algren, Heather A., Murray, Kim M., and Hadlock, Jennifer

Subjects
HUMORAL immunity, REINFECTION, SARS-CoV-2, B cells, VIRAL shedding
Abstract

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection

Author

Jiang, Yonghou, primary, Duffy, Fergal, additional, Hadlock, Jennifer, additional, Raappana, Andrew, additional, Styrchak, Sheila, additional, Beck, Ingrid, additional, Mast, Fred D., additional, Miller, Leslie R., additional, Chour, William, additional, Houck, John, additional, Armistead, Blair, additional, Duvvuri, Venkata R., additional, Yeung, Winnie, additional, Haglund, Micaela, additional, Wallner, Jackson, additional, Wallick, Julie A., additional, Hardy, Samantha, additional, Oldroyd, Alyssa, additional, Ko, Daisy, additional, Gervassi, Ana, additional, Murray, Kim M., additional, Kaplan, Henry, additional, Aitchison, John D., additional, Heath, James R., additional, Sather, D. Noah, additional, Goldman, Jason D., additional, Frenkel, Lisa, additional, and Harrington, Whitney E., additional

Published
2021
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28. LB3. Baricitinib plus Standard of Care for Hospitalized Adults with COVID-19 on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation: Results of a Randomized, Placebo-Controlled Trial

Author

Ely, E Wesley, primary, Ramanan, Athimalaipet V, additional, Kartman, Cynthia E, additional, de Bono, Stephanie, additional, Liao, Ran, additional, Piruzeli, Maria Lucia B, additional, Goldman, Jason D, additional, Saraiva, José Francisco Kerr, additional, Chakladar, Sujatro, additional, and Marconi, Vincent, additional

Published
2021
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29. 126. Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection and Vaccination

Author

Snyder, Thomas M, primary, Gittelman, Rachel M, additional, Klinger, Mark, additional, May, Damon H, additional, Osborne, Edward J, additional, Taniguchi, Ruth, additional, Jabran Zahid, H, additional, Elyanow, Rebecca, additional, Dalai, Sudeb C, additional, Kaplan, Ian M, additional, Dines, Jennifer N, additional, Noakes, Matthew T, additional, Pandya, Ravi, additional, Baldo, Lance, additional, Semprini, Simona, additional, Cerchione, Claudio, additional, Nicolini, Fabio, additional, Mazza, Massimiliano, additional, Delmonte, Ottavia M, additional, Dobbs, Kerry, additional, Laguna-Goya, Rocio, additional, Carreño-Tarragona, Gonazalo, additional, Barrio, Santiago, additional, Imberti, Luisa, additional, Sottini, Alessandra, additional, Quiros-Roldan, Eugenia, additional, Rossi, Camillo, additional, Biondi, Andrea, additional, Bettini, Laura Rachele, additional, D’Angio, Mariella, additional, Bonfanti, Paolo, additional, Tompkins, Miranda F, additional, Alba, Camille, additional, Dalgard, Clifton, additional, Sambri, Vittorio, additional, Martinelli, Giovanni, additional, Goldman, Jason D, additional, Heath, James R, additional, Su, Helen C, additional, Notarangelo, Luigi D, additional, Paz-Artal, Estela, additional, Martinez-Lopez, Joaquin, additional, Carlson, Jonathan M, additional, and Robins, Harlan S, additional

Published
2021
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30. Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19

Author

Lee, Jihoon W., primary, Su, Yapeng, additional, Baloni, Priyanka, additional, Chen, Daniel, additional, Pavlovitch-Bedzyk, Ana Jimena, additional, Yuan, Dan, additional, Duvvuri, Venkata R., additional, Ng, Rachel H., additional, Choi, Jongchan, additional, Xie, Jingyi, additional, Zhang, Rongyu, additional, Murray, Kim, additional, Kornilov, Sergey, additional, Smith, Brett, additional, Magis, Andrew T., additional, Hoon, Dave S. B., additional, Hadlock, Jennifer J., additional, Goldman, Jason D., additional, Price, Nathan D., additional, Gottardo, Raphael, additional, Davis, Mark M., additional, Hood, Leroy, additional, Greenberg, Philip D., additional, and Heath, James R., additional

Published
2021
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32. Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection

Author

Harrington, Whitney E., Jiang, Yonghou, Duffy, Fergal, Hadlock, Jennifer, Raappana, Andrew, Styrchak, Sheila, Beck, Ingrid, Chour, William, Houck, John, Duvvuri, Venkata, Yeung, Winnie, Haglund, Micaela, Wallner, Jackson, Wallick, Julie A., Hardy, Samantha, Oldroyd, Alyssa, Ko, Daisy, Gervassi, Ana, Murray, Kim M., Kaplan, Henry, Aitchison, John D., Heath, James R., Sather, D. Noah, Goldman, Jason D., Frenkel, Lisa, Harrington, Whitney E., Jiang, Yonghou, Duffy, Fergal, Hadlock, Jennifer, Raappana, Andrew, Styrchak, Sheila, Beck, Ingrid, Chour, William, Houck, John, Duvvuri, Venkata, Yeung, Winnie, Haglund, Micaela, Wallner, Jackson, Wallick, Julie A., Hardy, Samantha, Oldroyd, Alyssa, Ko, Daisy, Gervassi, Ana, Murray, Kim M., Kaplan, Henry, Aitchison, John D., Heath, James R., Sather, D. Noah, Goldman, Jason D., and Frenkel, Lisa

Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab). Methods: We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls. Results: There were no significant differences between cases and controls. However, there were trends toward a higher proportion with AT1R-Ab positivity among severe cases versus controls (32% vs. 11%, p=0.1) and higher levels in those with mild COVID-19 compared to controls (median 9.5U/mL vs. 5.9U/mL, p=0.06). Conclusions: These findings suggest that AT1R-Ab are not consistently associated with COVID-19 but do not exclude a contribution to endothelial pathology in a subset of people.

Published
2021

33. Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

Author

Kates, Olivia S, Kates, Olivia S, Haydel, Brandy M, Florman, Sander S, Rana, Meenakshi M, Chaudhry, Zohra S, Ramesh, Mayur S, Safa, Kassem, Kotton, Camille Nelson, Blumberg, Emily A, Besharatian, Behdad D, Tanna, Sajal D, Ison, Michael G, Malinis, Maricar, Azar, Marwan M, Rakita, Robert M, Morilla, Jose A, Majeed, Aneela, Sait, Afrah S, Spaggiari, Mario, Hemmige, Vagish, Mehta, Sapna A, Neumann, Henry, Badami, Abbasali, Goldman, Jason D, Lala, Anuradha, Hemmersbach-Miller, Marion, McCort, Margaret E, Bajrovic, Valida, Ortiz-Bautista, Carlos, Friedman-Moraco, Rachel, Sehgal, Sameep, Lease, Erika D, Fisher, Cynthia E, Limaye, Ajit P, UW COVID-19 SOT Study Team, Kates, Olivia S, Kates, Olivia S, Haydel, Brandy M, Florman, Sander S, Rana, Meenakshi M, Chaudhry, Zohra S, Ramesh, Mayur S, Safa, Kassem, Kotton, Camille Nelson, Blumberg, Emily A, Besharatian, Behdad D, Tanna, Sajal D, Ison, Michael G, Malinis, Maricar, Azar, Marwan M, Rakita, Robert M, Morilla, Jose A, Majeed, Aneela, Sait, Afrah S, Spaggiari, Mario, Hemmige, Vagish, Mehta, Sapna A, Neumann, Henry, Badami, Abbasali, Goldman, Jason D, Lala, Anuradha, Hemmersbach-Miller, Marion, McCort, Margaret E, Bajrovic, Valida, Ortiz-Bautista, Carlos, Friedman-Moraco, Rachel, Sehgal, Sameep, Lease, Erika D, Fisher, Cynthia E, Limaye, Ajit P, and UW COVID-19 SOT Study Team

Abstract

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described.MethodsWe performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients.ResultsFour hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality.ConclusionsMortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Published
2021

34. Use of convalescent plasma in hospitalized patients with COVID-19: case series

Author

Hegerova, Livia, Gooley, Ted A., Sweerus, Kelly A., Maree, Cynthia, Bailey, Neil, Bailey, Megumi, Dunleavy, Vanessa, Patel, Krish, Alcorn, Kirsten, Haley, Rebecca, Johnsen, Jill M., Konkle, Barbara A., Lahti, Annamarie C., Alexander, Morgan L., Goldman, Jason D., Lipke, Anne, Lim, Sun-jung, Sullivan, Mark D., Pauk, John S., and Pagel, John M.

Published
2020
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37. COVID-19 in solid organ transplant: A multi-center cohort study

Author

Kates, Olivia S, Haydel, Brandy M, Florman, Sander S, Rana, Meenakshi M, Chaudhry, Zohra S, Ramesh, Mayur S, Safa, Kassem, Kotton, Camille Nelson, Blumberg, Emily A, Besharatian, Behdad D, Tanna, Sajal D, Ison, Michael G, Malinis, Maricar, Azar, Marwan M, Rakita, Robert M, Morillas, Jose A, Majeed, Aneela, Sait, Afrah S, Spaggiari, Mario, Hemmige, Vagish, Mehta, Sapna A, Neumann, Henry, Badami, Abbasali, Goldman, Jason D, Lala, Anuradha, Hemmersbach-Miller, Marion, McCort, Margaret E, Bajrovic, Valida, Ortiz-Bautista, Carlos, Friedman-Moraco, Rachel, Sehgal, Sameep, Lease, Erika D, Fisher, Cynthia E, and Limaye, Ajit P

Subjects
Immunomodulation, AcademicSubjects/MED00290, Tissue and Organ Procurement, SARS-CoV-2, Major Article, coronavirus, COVID-19, Humans, Organ Transplantation, solid organ transplantation, transplantation
Abstract

Background The COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described. Methods We performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. Results Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p

Published
2020

38. Remdesivir for 5 or 10 Days in Patients With Severe Covid-19

Author

Goldman, Jason D., Lye, David C.B., Hui, David S., Marks, Kristen M., Bruno, Raffaele, Montejano, Rocio, Spinner, Christoph D., Galli, Massimo, Ahn, Mi‑Young, Nahass, Ronald G., Chen, Yao-Shen, SenGupta, Devi, Hyland, Robert H., Osinusi, Anu O., Cao, Huyen, Blair, Christiana, Wei, Xuelian, Gaggar, Anuj, Brainard, Diana M., Towner, William J., Muñoz Gutiérrez, José, Mullane, Kathleen M., Marty, Francisco M., Tashima, Karen T., Diaz, George, Subramanian, Aruna, and GS-US-540-5773 Investigators

Subjects
Adult, Male, Adenosine monophosphate, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, 030204 cardiovascular system & hematology, Pharmacology, Antiviral Agents, Drug Administration Schedule, Betacoronavirus, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Clinical trials, Humans, Medicine, In patient, 030212 general & internal medicine, Pandemics, Aged, Alanine, biology, SARS-CoV-2, business.industry, Oxygen Inhalation Therapy, COVID-19, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Adenosine Monophosphate, In vitro, COVID-19 Drug Treatment, Hospitalization, Clinical trial, Pneumonia, Treatment Outcome, Editorial, chemistry, RNA Polymerase Inhibitor, Original Article, Female, Coronavirus Infections, business, Assaigs clínics
Abstract

Background Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. Results In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P=0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P=0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). Conclusions In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.)

Published
2020

39. Shared Antigen-specific CD8⁺ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants

Author

Chour, William, Xu, Alexander M., Ng, Alphonsus H. C., Choi, Jongchan, Xie, Jingyi, Yuan, Dan, Delucia, Diane C., Edmark, Rick A., Jones, Lesley C., Schmitt, Thomas M., Chaffee, Mary E., Duvvuri, Venkata R., Murray, Kim M., Peng, Songming, Wallick, Julie, Algren, Heather A., Berrington, William R., O'Mahoney, D. Shane, Lee, John K., Greenberg, Philip D., Goldman, Jason D., Heath, James R., Chour, William, Xu, Alexander M., Ng, Alphonsus H. C., Choi, Jongchan, Xie, Jingyi, Yuan, Dan, Delucia, Diane C., Edmark, Rick A., Jones, Lesley C., Schmitt, Thomas M., Chaffee, Mary E., Duvvuri, Venkata R., Murray, Kim M., Peng, Songming, Wallick, Julie, Algren, Heather A., Berrington, William R., O'Mahoney, D. Shane, Lee, John K., Greenberg, Philip D., Goldman, Jason D., and Heath, James R.

Abstract

We report here on antigens from the SARS-CoV-2 virus spike protein, that when presented by Class I MHC, can lead to cytotoxic CD8⁺ T cell anti-viral responses in COVID-19 patients. We present a method in which the SARS-CoV-2 spike protein is converted into a library of peptide antigen-Major Histocompatibility Complexes (pMHCs) as single chain trimers that contain the peptide antigen, the MHC HLA allele, and the β-2 microglobulin sub-unit. That library is used to detect the evolution of virus-specific T cell populations from two COVID-19 patients, at two time points over the course of infection. Both patients exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. These results can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the variations in immune system trajectories observed in different COVID-19 patients.

Published
2020

42. COVID-19 and beyond: a call for action and audacious solidarity to all the citizens and nations, it is humanity’s fight

Author

Auffray, Charles, primary, Balling, Rudi, additional, Blomberg, Niklas, additional, Bonaldo, Myrna C., additional, Boutron, Bertrand, additional, Brahmachari, Samir, additional, Bréchot, Christian, additional, Cesario, Alfredo, additional, Chen, Sai-Juan, additional, Clément, Karine, additional, Danilenko, Daria, additional, Di Meglio, Alberto, additional, Gelemanović, Andrea, additional, Goble, Carole, additional, Gojobori, Takashi, additional, Goldman, Jason D., additional, Goldman, Michel, additional, Guo, Yi-Ke, additional, Heath, James, additional, Hood, Leroy, additional, Hunter, Peter, additional, Jin, Li, additional, Kitano, Hiroaki, additional, Knoppers, Bartha, additional, Lancet, Doron, additional, Larue, Catherine, additional, Lathrop, Mark, additional, Laville, Martine, additional, Lindner, Ariel B., additional, Magnan, Antoine, additional, Metspalu, Andres, additional, Morin, Edgar, additional, Ng, Lisa F.P., additional, Nicod, Laurent, additional, Noble, Denis, additional, Nottale, Laurent, additional, Nowotny, Helga, additional, Ochoa, Theresa, additional, Okeke, Iruka N., additional, Oni, Tolu, additional, Openshaw, Peter, additional, Oztürk, Mehmet, additional, Palkonen, Susanna, additional, Paweska, Janusz T., additional, Pison, Christophe, additional, Polymeropoulos, Mihael H., additional, Pristipino, Christian, additional, Protzer, Ulrike, additional, Roca, Josep, additional, Rozman, Damjana, additional, Santolini, Marc, additional, Sanz, Ferran, additional, Scambia, Giovanni, additional, Segal, Eran, additional, Serageldin, Ismail, additional, Soares, Marcelo Bento, additional, Sterk, Peter, additional, Sugano, Sumio, additional, Superti-Furga, Giulio, additional, Supple, David, additional, Tegner, Jesper, additional, Uhlen, Mathias, additional, Urbani, Andrea, additional, Valencia, Alfonso, additional, Valentini, Vincenzo, additional, van der Werf, Sylvie, additional, Vinciguerra, Manlio, additional, Wolkenhauer, Olaf, additional, and Wouters, Emiel, additional

Published
2020
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45. Patterns of human herpesvirus-8 oral shedding among diverse cohorts of human herpesvirus-8 seropositive persons

Author

Bender Ignacio, Rachel A., primary, Goldman, Jason D., additional, Magaret, Amalia S., additional, Selke, Stacy, additional, Huang, Meei-Li, additional, Gantt, Soren, additional, Johnston, Christine, additional, Phipps, Warren T., additional, Schiffer, Joshua T., additional, Zuckerman, Richard A., additional, McClelland, R. Scott, additional, Celum, Connie, additional, Corey, Larry, additional, Wald, Anna, additional, and Casper, Corey, additional

Published
2016
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47. Patterns of human herpesvirus-8 oral shedding among diverse cohorts of human herpesvirus-8 seropositive persons.

Author

Ignacio, Rachel A. Bender, Goldman, Jason D., Magaret, Amalia S., Selke, Stacy, Meei-Li Huang, Gantt, Soren, Johnston, Christine, Phipps, Warren T., Schiffer, Joshua T., Zuckerman, Richard A., McClelland, R. Scott, Celum, Connie, Corey, Larry, Wald, Anna, and Casper, Corey

Subjects
*STATISTICAL correlation, *HERPESVIRUSES, *HIV infections, *KAPOSI'S sarcoma, *LONGITUDINAL method, *POLYMERASE chain reaction, *RESEARCH funding, *SEROLOGY
Abstract

Background: Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication (“shedding”) at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons. Methods: We quantified HHV-8 oral shedding using PCR among HHV-8 seropositive persons who collected at least 14 days of oral swabs in 22 studies on 3 continents. We excluded persons taking antivirals during sampling or any prior use of antiretrovirals in those who were HIV-infected. Results: 248 participants were enrolled from the US, Peru, Cameroon, Uganda, and Kenya; 61 % were men, 58 % were HIV seropositive, and 16 % had KS. Overall, 3,123 of 10,557 samples (29.6 %) had HHV-8 detected. Quantity of virus shed was highly correlated with shedding rate, (ρ = 0.72, p < 0.0001). HHV-8 was detected in ≥1 sample in 55 % of participants with a median of 7 % of days in the US and Kenya, 0 % in Uganda and Peru, and 18 % in Cameroon. Median episode duration was three days, and episodes with high median quantity lasted longer (42 vs 3 days, p < 0.0001). In persons with multiple observations over time, 66 % of shedding rate variance was attributable to differences between individuals. Conclusions: In HHV-8 infected individuals from diverse settings, oral mucosal shedding rate, quantity, and duration were correlated; individual shedding was highly variable. Studies are needed to determine factors accounting for between-person variation and the relationship of HHV-8 shedding to development of associated diseases. [ABSTRACT FROM AUTHOR]

Published
2016
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48. Correction: A Cluster Randomized Trial of Routine HIV-1 Viral Load Monitoring in Zambia: Study Design, Implementation, and Baseline Cohort Characteristics

Author

Koethe, John R., primary, Westfall, Andrew O., additional, Luhanga, Dora K., additional, Clark, Gina M., additional, Goldman, Jason D., additional, Mulenga, Priscilla L., additional, Cantrell, Ronald A., additional, Chi, Benjamin H., additional, Zulu, Isaac, additional, Saag, Michael S., additional, and Stringer, Jeffrey S. A., additional

Published
2010
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49. A Cluster Randomized Trial of Routine HIV-1 Viral Load Monitoring in Zambia: Study Design, Implementation, and Baseline Cohort Characteristics

Author

Koethe, John R., primary, Westfall, Andrew O., additional, Luhanga, Dora K., additional, Clark, Gina M., additional, Goldman, Jason D., additional, Mulenga, Priscilla L., additional, Cantrell, Ronald A., additional, Chi, Benjamin H., additional, Zulu, Isaac, additional, Saag, Michael S., additional, and Stringer, Jeffrey S. A., additional

Published
2010
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50. HIV, Hepatitis B, and Hepatitis C in Zambia.

Author

Kapembwa, Kenneth C., Goldman, Jason D., Lakhi, Shabir, Banda, Yolan, Bowa, Kasonde, Vermund, Sten H., Mulenga, Joseph, Chama, David, and Chi, Benjamin H.

Subjects
*HIV, *HEPATITIS B, *HEPATITIS C, *HEALTH policy, *MEDICAL screening, *DISEASE prevalence, *PATIENTS
Abstract

Objectives: Epidemiologic data of HIV and viral hepatitis coinfection are needed in sub-Saharan Africa to guide health policy for hepatitis screening and optimized antiretroviral therapy (ART). Materials and Methods: We screened 323 HIV-infected, ART-eligible adults for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV Ab) at a tertiary hospital in Lusaka, Zambia. We collected basic demographic, medical, and laboratory data to determine predictors for coinfection. Results: Of 323 enrolled patients, 32 (9.9%; 95% CI=6.7–13.2%) were HBsAg positive, while 4 (1.2%; 95% CI=0.03–2.4%) were HCV Ab positive. Patients with hepatitis B coinfection were more likely to be <40 years (84.4% vs. 61.4%; P=0.01) when compared to those who were not coinfected. Patients with active hepatitis B were more likely to have mild to moderately elevated AST/ALT (40–199 IU/L, 15.8% vs. 5.4%; P=0.003). Highly elevated liver enzymes (>200 IU/L) was uncommon and did not differ between the two groups (3.4% vs. 2.3%; P=0.5). We were unable to determine predictors of hepatitis C infection due to the low prevalence of disease. Conclusions: HIV and hepatitis B coinfection was common among patients initiating ART at this tertiary care facility. Routine screening for hepatitis B should be considered for HIV-infected persons in southern Africa. [ABSTRACT FROM AUTHOR]

Published
2011
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