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Dr. Elizabeth Anderson
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

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0 Influenza
0 Viral evolution
0 antibody responses
0 vaccine effectiveness
0 HIV persistence

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Journal article
Published: 23 August 2021 in JCI Insight
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Some studies suggest that recent common coronavirus (CCV) infections are associated with reduced COVID-19 severity upon SARS-CoV-2 infection. We completed serological assays using samples collected from health care workers to identify antibody types associated with SARS-CoV-2 protection and COVID-19 symptom duration. Rare SARS-CoV-2 cross-reactive antibodies elicited by past CCV infections were not associated with protection; however, the duration of symptoms following SARS-CoV-2 infections was significantly reduced in individuals with higher common betacoronavirus (βCoV) antibody titers. Since antibody titers decline over time after CCV infections, individuals in our cohort with higher βCoV antibody titers were more likely recently infected with common βCoVs compared to individuals with lower antibody titers. Therefore, our data suggest that recent βCoV infections potentially limit the duration of symptoms following SARS-CoV-2 infections through mechanisms that do not involve cross-reactive antibodies. Our data are consistent with the emerging hypothesis that cellular immune responses elicited by recent common βCoV infections transiently reduce symptom duration following SARS-CoV-2 infections.

ACS Style

Sigrid Gouma; Madison E. Weirick; Marcus J. Bolton; Claudia P. Arevalo; Eileen C. Goodwin; Elizabeth M. Anderson; Christopher M. McAllister; Shannon R. Christensen; Debora Dunbar; Danielle Fiore; Amanda Brock; JoEllen Weaver; John S. Millar; Stephanie DerOhannessian; The Upenn Covid Processing Unit; Ian Frank; Daniel J. Rader; E. John Wherry; Scott E. Hensley. Health care worker seromonitoring reveals complex relationships between common coronavirus antibodies and COVID-19 symptom duration. JCI Insight 2021, 6, 1 .

AMA Style

Sigrid Gouma, Madison E. Weirick, Marcus J. Bolton, Claudia P. Arevalo, Eileen C. Goodwin, Elizabeth M. Anderson, Christopher M. McAllister, Shannon R. Christensen, Debora Dunbar, Danielle Fiore, Amanda Brock, JoEllen Weaver, John S. Millar, Stephanie DerOhannessian, The Upenn Covid Processing Unit, Ian Frank, Daniel J. Rader, E. John Wherry, Scott E. Hensley. Health care worker seromonitoring reveals complex relationships between common coronavirus antibodies and COVID-19 symptom duration. JCI Insight. 2021; 6 (16):1.

Chicago/Turabian Style

Sigrid Gouma; Madison E. Weirick; Marcus J. Bolton; Claudia P. Arevalo; Eileen C. Goodwin; Elizabeth M. Anderson; Christopher M. McAllister; Shannon R. Christensen; Debora Dunbar; Danielle Fiore; Amanda Brock; JoEllen Weaver; John S. Millar; Stephanie DerOhannessian; The Upenn Covid Processing Unit; Ian Frank; Daniel J. Rader; E. John Wherry; Scott E. Hensley. 2021. "Health care worker seromonitoring reveals complex relationships between common coronavirus antibodies and COVID-19 symptom duration." JCI Insight 6, no. 16: 1.

Journal article
Published: 01 April 2021 in Cell
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the coronavirus disease 2019 (COVID-19) pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection.

ACS Style

Elizabeth M. Anderson; Eileen C. Goodwin; Anurag Verma; Claudia P. Arevalo; Marcus J. Bolton; Madison E. Weirick; Sigrid Gouma; Christopher M. McAllister; Shannon R. Christensen; JoEllen Weaver; Philip Hicks; Tomaz B. Manzoni; Oluwatosin Oniyide; Holly Ramage; Divij Mathew; Amy E. Baxter; Derek A. Oldridge; Allison R. Greenplate; Jennifer E. Wu; Cécile Alanio; Kurt D’Andrea; Oliva Kuthuru; Jeanette Dougherty; Ajinkya Pattekar; Justin Kim; Nicholas Han; Sokratis A. Apostolidis; Alex C. Huang; Laura A. Vella; Leticia Kuri-Cervantes; M. Betina Pampena; Michael R. Betts; E. John Wherry; Nuala J. Meyer; Sara Cherry; Paul Bates; Daniel J. Rader; Scott E. Hensley. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell 2021, 184, 1858 -1864.e10.

AMA Style

Elizabeth M. Anderson, Eileen C. Goodwin, Anurag Verma, Claudia P. Arevalo, Marcus J. Bolton, Madison E. Weirick, Sigrid Gouma, Christopher M. McAllister, Shannon R. Christensen, JoEllen Weaver, Philip Hicks, Tomaz B. Manzoni, Oluwatosin Oniyide, Holly Ramage, Divij Mathew, Amy E. Baxter, Derek A. Oldridge, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Kurt D’Andrea, Oliva Kuthuru, Jeanette Dougherty, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sokratis A. Apostolidis, Alex C. Huang, Laura A. Vella, Leticia Kuri-Cervantes, M. Betina Pampena, Michael R. Betts, E. John Wherry, Nuala J. Meyer, Sara Cherry, Paul Bates, Daniel J. Rader, Scott E. Hensley. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell. 2021; 184 (7):1858-1864.e10.

Chicago/Turabian Style

Elizabeth M. Anderson; Eileen C. Goodwin; Anurag Verma; Claudia P. Arevalo; Marcus J. Bolton; Madison E. Weirick; Sigrid Gouma; Christopher M. McAllister; Shannon R. Christensen; JoEllen Weaver; Philip Hicks; Tomaz B. Manzoni; Oluwatosin Oniyide; Holly Ramage; Divij Mathew; Amy E. Baxter; Derek A. Oldridge; Allison R. Greenplate; Jennifer E. Wu; Cécile Alanio; Kurt D’Andrea; Oliva Kuthuru; Jeanette Dougherty; Ajinkya Pattekar; Justin Kim; Nicholas Han; Sokratis A. Apostolidis; Alex C. Huang; Laura A. Vella; Leticia Kuri-Cervantes; M. Betina Pampena; Michael R. Betts; E. John Wherry; Nuala J. Meyer; Sara Cherry; Paul Bates; Daniel J. Rader; Scott E. Hensley. 2021. "Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection." Cell 184, no. 7: 1858-1864.e10.

Research article
Published: 02 March 2021 in Science Immunology
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Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.

ACS Style

Laura A. Vella; Josephine R. Giles; Amy E. Baxter; Derek A. Oldridge; Caroline Diorio; Leticia Kuri-Cervantes; Cécile Alanio; M. Betina Pampena; Jennifer E. Wu; Zeyu Chen; Yinghui Jane Huang; Elizabeth M. Anderson; Sigrid Gouma; Kevin O. McNerney; Julie Chase; Chakkapong Burudpakdee; Jessica H. Lee; Sokratis A. Apostolidis; Alexander C. Huang; Divij Mathew; Oliva Kuthuru; Eileen C. Goodwin; Madison E. Weirick; Marcus J. Bolton; Claudia P. Arevalo; Andre Ramos; Cj Jasen; Peyton E Conrey; Samir Sayed; Heather M. Giannini; Kurt D’Andrea; Nuala J. Meyer; Edward M. Behrens; Hamid Bassiri; Scott E. Hensley; Sarah E. Henrickson; David T. Teachey; Michael R. Betts; E. John Wherry; The Upenn Covid Processing Unit†. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Science Immunology 2021, 6, eabf7570 .

AMA Style

Laura A. Vella, Josephine R. Giles, Amy E. Baxter, Derek A. Oldridge, Caroline Diorio, Leticia Kuri-Cervantes, Cécile Alanio, M. Betina Pampena, Jennifer E. Wu, Zeyu Chen, Yinghui Jane Huang, Elizabeth M. Anderson, Sigrid Gouma, Kevin O. McNerney, Julie Chase, Chakkapong Burudpakdee, Jessica H. Lee, Sokratis A. Apostolidis, Alexander C. Huang, Divij Mathew, Oliva Kuthuru, Eileen C. Goodwin, Madison E. Weirick, Marcus J. Bolton, Claudia P. Arevalo, Andre Ramos, Cj Jasen, Peyton E Conrey, Samir Sayed, Heather M. Giannini, Kurt D’Andrea, Nuala J. Meyer, Edward M. Behrens, Hamid Bassiri, Scott E. Hensley, Sarah E. Henrickson, David T. Teachey, Michael R. Betts, E. John Wherry, The Upenn Covid Processing Unit†. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Science Immunology. 2021; 6 (57):eabf7570.

Chicago/Turabian Style

Laura A. Vella; Josephine R. Giles; Amy E. Baxter; Derek A. Oldridge; Caroline Diorio; Leticia Kuri-Cervantes; Cécile Alanio; M. Betina Pampena; Jennifer E. Wu; Zeyu Chen; Yinghui Jane Huang; Elizabeth M. Anderson; Sigrid Gouma; Kevin O. McNerney; Julie Chase; Chakkapong Burudpakdee; Jessica H. Lee; Sokratis A. Apostolidis; Alexander C. Huang; Divij Mathew; Oliva Kuthuru; Eileen C. Goodwin; Madison E. Weirick; Marcus J. Bolton; Claudia P. Arevalo; Andre Ramos; Cj Jasen; Peyton E Conrey; Samir Sayed; Heather M. Giannini; Kurt D’Andrea; Nuala J. Meyer; Edward M. Behrens; Hamid Bassiri; Scott E. Hensley; Sarah E. Henrickson; David T. Teachey; Michael R. Betts; E. John Wherry; The Upenn Covid Processing Unit†. 2021. "Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19." Science Immunology 6, no. 57: eabf7570.

Journal article
Published: 08 December 2020 in Blood Advances
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Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.

ACS Style

Caroline Diorio; Kevin O. McNerney; Michele Lambert; Michele Paessler; Elizabeth M. Anderson; Sarah E. Henrickson; Julie Chase; Emily J. Liebling; Chakkapong Burudpakdee; Jessica H. Lee; Frances B. Balamuth; Allison M. Blatz; Kathleen Chiotos; Julie C. Fitzgerald; Therese M. Giglia; Kandace Gollomp; Audrey R. Odom John; Cristina Jasen; Tomas Leng; Whitney Petrosa; Laura A. Vella; Char Witmer; Kathleen E. Sullivan; Benjamin L. Laskin; Scott E. Hensley; Hamid Bassiri; Edward M. Behrens; David T. Teachey. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Advances 2020, 4, 6051 -6063.

AMA Style

Caroline Diorio, Kevin O. McNerney, Michele Lambert, Michele Paessler, Elizabeth M. Anderson, Sarah E. Henrickson, Julie Chase, Emily J. Liebling, Chakkapong Burudpakdee, Jessica H. Lee, Frances B. Balamuth, Allison M. Blatz, Kathleen Chiotos, Julie C. Fitzgerald, Therese M. Giglia, Kandace Gollomp, Audrey R. Odom John, Cristina Jasen, Tomas Leng, Whitney Petrosa, Laura A. Vella, Char Witmer, Kathleen E. Sullivan, Benjamin L. Laskin, Scott E. Hensley, Hamid Bassiri, Edward M. Behrens, David T. Teachey. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Advances. 2020; 4 (23):6051-6063.

Chicago/Turabian Style

Caroline Diorio; Kevin O. McNerney; Michele Lambert; Michele Paessler; Elizabeth M. Anderson; Sarah E. Henrickson; Julie Chase; Emily J. Liebling; Chakkapong Burudpakdee; Jessica H. Lee; Frances B. Balamuth; Allison M. Blatz; Kathleen Chiotos; Julie C. Fitzgerald; Therese M. Giglia; Kandace Gollomp; Audrey R. Odom John; Cristina Jasen; Tomas Leng; Whitney Petrosa; Laura A. Vella; Char Witmer; Kathleen E. Sullivan; Benjamin L. Laskin; Scott E. Hensley; Hamid Bassiri; Edward M. Behrens; David T. Teachey. 2020. "Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations." Blood Advances 4, no. 23: 6051-6063.

Journal article
Published: 29 September 2020 in Annual Review of Virology
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Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and there is clearly room for improvement. Here, we review the history of seasonal influenza vaccines, describe challenges associated with producing influenza vaccine antigens, and discuss the inherent difficulties of updating influenza vaccine strains each influenza season. We argue that seasonal influenza vaccines can be dramatically improved by modernizing antigen production processes and developing models that are better at predicting viral evolution. Resources should be specifically dedicated to improving seasonal influenza vaccines while developing entirely new vaccine platforms.

ACS Style

Sigrid Gouma; Elizabeth M. Anderson; Scott E. Hensley. Challenges of Making Effective Influenza Vaccines. Annual Review of Virology 2020, 7, 495 -512.

AMA Style

Sigrid Gouma, Elizabeth M. Anderson, Scott E. Hensley. Challenges of Making Effective Influenza Vaccines. Annual Review of Virology. 2020; 7 (1):495-512.

Chicago/Turabian Style

Sigrid Gouma; Elizabeth M. Anderson; Scott E. Hensley. 2020. "Challenges of Making Effective Influenza Vaccines." Annual Review of Virology 7, no. 1: 495-512.

Journal article
Published: 04 September 2020 in Pediatric Blood & Cancer
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There are no proven safe and effective therapies for children who develop life‐threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS‐CoV‐2, but has theoretical risks.We present the first report of CP in children with life‐threatening coronavirus disease 2019 (COVID‐19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody‐dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.

ACS Style

Caroline Diorio; Elizabeth M. Anderson; Kevin O. McNerney; Eileen C. Goodwin; Julie C. Chase; Marcus J. Bolton; Claudia P. Arevalo; Madison E. Weirick; Sigrid Gouma; Laura A. Vella; Sarah E. Henrickson; Kathleen Chiotos; Julie C. Fitzgerald; Todd J. Kilbaugh; Audrey R. Odom John; Allison M. Blatz; Michele P. Lambert; Kathleen E. Sullivan; Margaret R. Tartaglione; Danielle Zambrano; Meghan Martin; Jessica H. Lee; Pampee Young; David Friedman; Deborah A. Sesok‐Pizzini; Scott E. Hensley; Edward M. Behrens; Hamid Bassiri; David T. Teachey. Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome. Pediatric Blood & Cancer 2020, 67, 1 .

AMA Style

Caroline Diorio, Elizabeth M. Anderson, Kevin O. McNerney, Eileen C. Goodwin, Julie C. Chase, Marcus J. Bolton, Claudia P. Arevalo, Madison E. Weirick, Sigrid Gouma, Laura A. Vella, Sarah E. Henrickson, Kathleen Chiotos, Julie C. Fitzgerald, Todd J. Kilbaugh, Audrey R. Odom John, Allison M. Blatz, Michele P. Lambert, Kathleen E. Sullivan, Margaret R. Tartaglione, Danielle Zambrano, Meghan Martin, Jessica H. Lee, Pampee Young, David Friedman, Deborah A. Sesok‐Pizzini, Scott E. Hensley, Edward M. Behrens, Hamid Bassiri, David T. Teachey. Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome. Pediatric Blood & Cancer. 2020; 67 (11):1.

Chicago/Turabian Style

Caroline Diorio; Elizabeth M. Anderson; Kevin O. McNerney; Eileen C. Goodwin; Julie C. Chase; Marcus J. Bolton; Claudia P. Arevalo; Madison E. Weirick; Sigrid Gouma; Laura A. Vella; Sarah E. Henrickson; Kathleen Chiotos; Julie C. Fitzgerald; Todd J. Kilbaugh; Audrey R. Odom John; Allison M. Blatz; Michele P. Lambert; Kathleen E. Sullivan; Margaret R. Tartaglione; Danielle Zambrano; Meghan Martin; Jessica H. Lee; Pampee Young; David Friedman; Deborah A. Sesok‐Pizzini; Scott E. Hensley; Edward M. Behrens; Hamid Bassiri; David T. Teachey. 2020. "Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome." Pediatric Blood & Cancer 67, no. 11: 1.

Other
Published: 18 August 2020
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SARS-CoV-2 antibody responses in children remain poorly characterized. Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients.

ACS Style

Elizabeth M. Anderson; Caroline Diorio; Eileen C. Goodwin; Kevin O. McNerney; Madison E. Weirick; Sigrid Gouma; Marcus J. Bolton; Claudia P. Arevalo; Julie Chase; Philip Hicks; Tomaz B. Manzoni; Amy E. Baxter; Kurt P. Andrea; Chakkapong Burudpakdee; Jessica H. Lee; Laura A. Vella; Sarah E. Henrickson; Rebecca M. Harris; E. John Wherry; Paul Bates; Hamid Bassiri; Edward M. Behrens; David T. Teachey; Scott E. Hensley. SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19. 2020, 1 .

AMA Style

Elizabeth M. Anderson, Caroline Diorio, Eileen C. Goodwin, Kevin O. McNerney, Madison E. Weirick, Sigrid Gouma, Marcus J. Bolton, Claudia P. Arevalo, Julie Chase, Philip Hicks, Tomaz B. Manzoni, Amy E. Baxter, Kurt P. Andrea, Chakkapong Burudpakdee, Jessica H. Lee, Laura A. Vella, Sarah E. Henrickson, Rebecca M. Harris, E. John Wherry, Paul Bates, Hamid Bassiri, Edward M. Behrens, David T. Teachey, Scott E. Hensley. SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19. . 2020; ():1.

Chicago/Turabian Style

Elizabeth M. Anderson; Caroline Diorio; Eileen C. Goodwin; Kevin O. McNerney; Madison E. Weirick; Sigrid Gouma; Marcus J. Bolton; Claudia P. Arevalo; Julie Chase; Philip Hicks; Tomaz B. Manzoni; Amy E. Baxter; Kurt P. Andrea; Chakkapong Burudpakdee; Jessica H. Lee; Laura A. Vella; Sarah E. Henrickson; Rebecca M. Harris; E. John Wherry; Paul Bates; Hamid Bassiri; Edward M. Behrens; David T. Teachey; Scott E. Hensley. 2020. "SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19." , no. : 1.

Reports
Published: 29 July 2020 in Science Immunology
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Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important for determining SARS-CoV-2 exposures within both individuals and populations. We validated a SARS-CoV-2 spike receptor binding domain serological test using 834 pre-pandemic samples and 31 samples from COVID-19 recovered donors. We then completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate exposure to SARS-CoV-2 within the community.

ACS Style

Dustin D. Flannery; Sigrid Gouma; Miren B. Dhudasia; Sagori Mukhopadhyay; Madeline R. Pfeifer; Emily C. Woodford; Jeffrey S. Gerber; Claudia P. Arevalo; Marcus J. Bolton; Madison E. Weirick; Eileen C. Goodwin; Elizabeth M. Anderson; Allison R. Greenplate; Justin Kim; Nicholas Han; Ajinkya Pattekar; Jeanette Dougherty; Oliva Kuthuru; Divij Mathew; Amy E. Baxter; Laura A. Vella; JoEllen Weaver; Anurag Verma; Rita Leite; Jeffrey S. Morris; Daniel J. Rader; Michal A. Elovitz; E. John Wherry; Karen M. Puopolo; Scott E. Hensley. SARS-CoV-2 seroprevalence among parturient women in Philadelphia. Science Immunology 2020, 5, eabd5709 .

AMA Style

Dustin D. Flannery, Sigrid Gouma, Miren B. Dhudasia, Sagori Mukhopadhyay, Madeline R. Pfeifer, Emily C. Woodford, Jeffrey S. Gerber, Claudia P. Arevalo, Marcus J. Bolton, Madison E. Weirick, Eileen C. Goodwin, Elizabeth M. Anderson, Allison R. Greenplate, Justin Kim, Nicholas Han, Ajinkya Pattekar, Jeanette Dougherty, Oliva Kuthuru, Divij Mathew, Amy E. Baxter, Laura A. Vella, JoEllen Weaver, Anurag Verma, Rita Leite, Jeffrey S. Morris, Daniel J. Rader, Michal A. Elovitz, E. John Wherry, Karen M. Puopolo, Scott E. Hensley. SARS-CoV-2 seroprevalence among parturient women in Philadelphia. Science Immunology. 2020; 5 (49):eabd5709.

Chicago/Turabian Style

Dustin D. Flannery; Sigrid Gouma; Miren B. Dhudasia; Sagori Mukhopadhyay; Madeline R. Pfeifer; Emily C. Woodford; Jeffrey S. Gerber; Claudia P. Arevalo; Marcus J. Bolton; Madison E. Weirick; Eileen C. Goodwin; Elizabeth M. Anderson; Allison R. Greenplate; Justin Kim; Nicholas Han; Ajinkya Pattekar; Jeanette Dougherty; Oliva Kuthuru; Divij Mathew; Amy E. Baxter; Laura A. Vella; JoEllen Weaver; Anurag Verma; Rita Leite; Jeffrey S. Morris; Daniel J. Rader; Michal A. Elovitz; E. John Wherry; Karen M. Puopolo; Scott E. Hensley. 2020. "SARS-CoV-2 seroprevalence among parturient women in Philadelphia." Science Immunology 5, no. 49: eabd5709.

Research article
Published: 15 July 2020 in Science Immunology
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Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.

ACS Style

Leticia Kuri-Cervantes; M. Betina Pampena; Wenzhao Meng; Aaron M. Rosenfeld; Caroline A.G. Ittner; Ariel R. Weisman; Roseline S. Agyekum; Divij Mathew; Amy E. Baxter; Laura A. Vella; Oliva Kuthuru; Sokratis A. Apostolidis; Luanne Bershaw; Jeanette Dougherty; Allison R. Greenplate; Ajinkya Pattekar; Justin Kim; Nicholas Han; Sigrid Gouma; Madison E. Weirick; Claudia P. Arevalo; Marcus J. Bolton; Eileen C. Goodwin; Elizabeth M. Anderson; Scott E. Hensley; Tiffanie K. Jones; Nilam S. Mangalmurti; Eline T. Luning Prak; E. John Wherry; Nuala J. Meyer; Michael R. Betts. Comprehensive mapping of immune perturbations associated with severe COVID-19. Science Immunology 2020, 5, eabd7114 .

AMA Style

Leticia Kuri-Cervantes, M. Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A.G. Ittner, Ariel R. Weisman, Roseline S. Agyekum, Divij Mathew, Amy E. Baxter, Laura A. Vella, Oliva Kuthuru, Sokratis A. Apostolidis, Luanne Bershaw, Jeanette Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, Scott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, Michael R. Betts. Comprehensive mapping of immune perturbations associated with severe COVID-19. Science Immunology. 2020; 5 (49):eabd7114.

Chicago/Turabian Style

Leticia Kuri-Cervantes; M. Betina Pampena; Wenzhao Meng; Aaron M. Rosenfeld; Caroline A.G. Ittner; Ariel R. Weisman; Roseline S. Agyekum; Divij Mathew; Amy E. Baxter; Laura A. Vella; Oliva Kuthuru; Sokratis A. Apostolidis; Luanne Bershaw; Jeanette Dougherty; Allison R. Greenplate; Ajinkya Pattekar; Justin Kim; Nicholas Han; Sigrid Gouma; Madison E. Weirick; Claudia P. Arevalo; Marcus J. Bolton; Eileen C. Goodwin; Elizabeth M. Anderson; Scott E. Hensley; Tiffanie K. Jones; Nilam S. Mangalmurti; Eline T. Luning Prak; E. John Wherry; Nuala J. Meyer; Michael R. Betts. 2020. "Comprehensive mapping of immune perturbations associated with severe COVID-19." Science Immunology 5, no. 49: eabd7114.

Research article
Published: 15 July 2020 in Science
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Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

ACS Style

Divij Mathew; Josephine R. Giles; Amy E. Baxter; Derek A. Oldridge; Allison R. Greenplate; Jennifer E. Wu; Cécile Alanio; Leticia Kuri-Cervantes; M. Betina Pampena; Kurt D’Andrea; Sasikanth Manne; Zeyu Chen; Yinghui Jane Huang; John P. Reilly; Ariel R. Weisman; Caroline A. G. Ittner; Oliva Kuthuru; Jeanette Dougherty; Kito Nzingha; Nicholas Han; Justin Kim; Ajinkya Pattekar; Eileen C. Goodwin; Elizabeth M. Anderson; Madison E. Weirick; Sigrid Gouma; Claudia P. Arevalo; Marcus J. Bolton; Fang Chen; Simon F. Lacey; Holly Ramage; Sara Cherry; Scott E. Hensley; Sokratis A. Apostolidis; Alexander C. Huang; Laura A. Vella; Michael R. Betts; Nuala J. Meyer; E. John Wherry; The Upenn Covid Processing Unit†. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020, 369, eabc8511 .

AMA Style

Divij Mathew, Josephine R. Giles, Amy E. Baxter, Derek A. Oldridge, Allison R. Greenplate, Jennifer E. Wu, Cécile Alanio, Leticia Kuri-Cervantes, M. Betina Pampena, Kurt D’Andrea, Sasikanth Manne, Zeyu Chen, Yinghui Jane Huang, John P. Reilly, Ariel R. Weisman, Caroline A. G. Ittner, Oliva Kuthuru, Jeanette Dougherty, Kito Nzingha, Nicholas Han, Justin Kim, Ajinkya Pattekar, Eileen C. Goodwin, Elizabeth M. Anderson, Madison E. Weirick, Sigrid Gouma, Claudia P. Arevalo, Marcus J. Bolton, Fang Chen, Simon F. Lacey, Holly Ramage, Sara Cherry, Scott E. Hensley, Sokratis A. Apostolidis, Alexander C. Huang, Laura A. Vella, Michael R. Betts, Nuala J. Meyer, E. John Wherry, The Upenn Covid Processing Unit†. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020; 369 (6508):eabc8511.

Chicago/Turabian Style

Divij Mathew; Josephine R. Giles; Amy E. Baxter; Derek A. Oldridge; Allison R. Greenplate; Jennifer E. Wu; Cécile Alanio; Leticia Kuri-Cervantes; M. Betina Pampena; Kurt D’Andrea; Sasikanth Manne; Zeyu Chen; Yinghui Jane Huang; John P. Reilly; Ariel R. Weisman; Caroline A. G. Ittner; Oliva Kuthuru; Jeanette Dougherty; Kito Nzingha; Nicholas Han; Justin Kim; Ajinkya Pattekar; Eileen C. Goodwin; Elizabeth M. Anderson; Madison E. Weirick; Sigrid Gouma; Claudia P. Arevalo; Marcus J. Bolton; Fang Chen; Simon F. Lacey; Holly Ramage; Sara Cherry; Scott E. Hensley; Sokratis A. Apostolidis; Alexander C. Huang; Laura A. Vella; Michael R. Betts; Nuala J. Meyer; E. John Wherry; The Upenn Covid Processing Unit†. 2020. "Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications." Science 369, no. 6508: eabc8511.

Other
Published: 10 July 2020
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Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ∼1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.One Sentence SummarySix percent of pregnant women delivering from April 4 to June 3, 2020 had serological evidence of exposure to SARS-CoV-2 with notable race/ethnicity differences in seroprevalence rates.

ACS Style

Dustin D. Flannery; Sigrid Gouma; Miren B. Dhudasia; Sagori Mukhopadhyay; Madeline R. Pfeifer; Emily C. Woodford; Jeffrey S. Gerber; Claudia P. Arevalo; Marcus J. Bolton; Madison E. Weirick; Eileen C. Goodwin; Elizabeth M. Anderson; Allison R. Greenplate; Justin Kim; Nicholas Han; Ajinkya Pattekar; Jeanette Dougherty; Olivia Kuthuru; Divij Mathew; Amy E. Baxter; Laura A. Vella; JoEllen Weaver; Anurag Verma; Rita Leite; Jeffrey S. Morris; Daniel J. Rader; Michal A. Elovitz; E. John Wherry; Karen M. Puopolo; Scott E. Hensley. SARS-CoV-2 Seroprevalence Among Parturient Women. 2020, 1 .

AMA Style

Dustin D. Flannery, Sigrid Gouma, Miren B. Dhudasia, Sagori Mukhopadhyay, Madeline R. Pfeifer, Emily C. Woodford, Jeffrey S. Gerber, Claudia P. Arevalo, Marcus J. Bolton, Madison E. Weirick, Eileen C. Goodwin, Elizabeth M. Anderson, Allison R. Greenplate, Justin Kim, Nicholas Han, Ajinkya Pattekar, Jeanette Dougherty, Olivia Kuthuru, Divij Mathew, Amy E. Baxter, Laura A. Vella, JoEllen Weaver, Anurag Verma, Rita Leite, Jeffrey S. Morris, Daniel J. Rader, Michal A. Elovitz, E. John Wherry, Karen M. Puopolo, Scott E. Hensley. SARS-CoV-2 Seroprevalence Among Parturient Women. . 2020; ():1.

Chicago/Turabian Style

Dustin D. Flannery; Sigrid Gouma; Miren B. Dhudasia; Sagori Mukhopadhyay; Madeline R. Pfeifer; Emily C. Woodford; Jeffrey S. Gerber; Claudia P. Arevalo; Marcus J. Bolton; Madison E. Weirick; Eileen C. Goodwin; Elizabeth M. Anderson; Allison R. Greenplate; Justin Kim; Nicholas Han; Ajinkya Pattekar; Jeanette Dougherty; Olivia Kuthuru; Divij Mathew; Amy E. Baxter; Laura A. Vella; JoEllen Weaver; Anurag Verma; Rita Leite; Jeffrey S. Morris; Daniel J. Rader; Michal A. Elovitz; E. John Wherry; Karen M. Puopolo; Scott E. Hensley. 2020. "SARS-CoV-2 Seroprevalence Among Parturient Women." , no. : 1.

Preprint content
Published: 18 May 2020
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Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.One Sentence SummaryBroad immune perturbations in severe COVID-19

ACS Style

Leticia Kuri-Cervantes; M. Betina Pampena; Wenzhao Meng; Aaron M. Rosenfeld; Caroline A.G. Ittner; Ariel R. Weisman; Roseline Agyekum; Divij Mathew; Amy E. Baxter; Laura Vella; Olivia Kuthuru; Sokratis Apostolidis; Luanne Bershaw; Jeannete Dougherty; Allison R. Greenplate; Ajinkya Pattekar; Justin Kim; Nicholas Han; Sigrid Gouma; Madison E. Weirick; Claudia P. Arevalo; Marcus J. Bolton; Eileen C. Goodwin; Elizabeth M. Anderson; Scott E. Hensley; Tiffanie K. Jones; Nilam S. Mangalmurti; Eline T. Luning Prak; E. John Wherry; Nuala J. Meyer; Michael R. Betts. Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection. 2020, 1 .

AMA Style

Leticia Kuri-Cervantes, M. Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A.G. Ittner, Ariel R. Weisman, Roseline Agyekum, Divij Mathew, Amy E. Baxter, Laura Vella, Olivia Kuthuru, Sokratis Apostolidis, Luanne Bershaw, Jeannete Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, Scott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, Michael R. Betts. Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection. . 2020; ():1.

Chicago/Turabian Style

Leticia Kuri-Cervantes; M. Betina Pampena; Wenzhao Meng; Aaron M. Rosenfeld; Caroline A.G. Ittner; Ariel R. Weisman; Roseline Agyekum; Divij Mathew; Amy E. Baxter; Laura Vella; Olivia Kuthuru; Sokratis Apostolidis; Luanne Bershaw; Jeannete Dougherty; Allison R. Greenplate; Ajinkya Pattekar; Justin Kim; Nicholas Han; Sigrid Gouma; Madison E. Weirick; Claudia P. Arevalo; Marcus J. Bolton; Eileen C. Goodwin; Elizabeth M. Anderson; Scott E. Hensley; Tiffanie K. Jones; Nilam S. Mangalmurti; Eline T. Luning Prak; E. John Wherry; Nuala J. Meyer; Michael R. Betts. 2020. "Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection." , no. : 1.

Journal article
Published: 25 January 2020 in Viruses
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Combination antiretroviral therapy (cART) controls but does not eradicate HIV infection; HIV persistence is the principal obstacle to curing infections. The proportion of defective proviruses increases during cART, but the dynamics of this process are not well understood, and a quantitative analysis of how the proviral landscape is reshaped after cART is initiated is critical to understanding how HIV persists. Here, we studied longitudinal samples from HIV infected individuals undergoing long term cART using multiplexed Droplet Digital PCR (ddPCR) approaches to quantify the proportion of deleted proviruses in lymphocytes. In most individuals undergoing cART, HIV proviruses that contain gag are lost more quickly than those that lack gag. Increases in the fraction of gag-deleted proviruses occurred only after 1–2 years of therapy, suggesting that the immune system, and/or toxicity of viral re-activation helps to gradually shape the proviral landscape. After 10–15 years on therapy, there were as many as 3.5–5 times more proviruses in which gag was deleted or highly defective than those containing intact gag. We developed a provirus-specific ddPCR approach to quantify individual clones. Investigation of a clone of cells containing a deleted HIV provirus integrated in the HORMAD2 gene revealed that the cells underwent a massive expansion shortly after cART was initiated until the clone, which was primarily in effector memory cells, dominated the population of proviruses for over 6 years. The expansion of this HIV-infected clone had substantial effects on the overall proviral population.

ACS Style

Elizabeth M. Anderson; Francesco R. Simonetti; Robert J. Gorelick; Shawn Hill; Monica A. Gouzoulis; Jennifer Bell; Catherine Rehm; Liliana Pérez; Eli Boritz; Xiaolin Wu; Daria Wells; Stephen H. Hughes; Venigalla Rao; John M. Coffin; Mary F. Kearney; Frank Maldarelli. Dynamic Shifts in the HIV Proviral Landscape During Long Term Combination Antiretroviral Therapy: Implications for Persistence and Control of HIV Infections. Viruses 2020, 12, 136 .

AMA Style

Elizabeth M. Anderson, Francesco R. Simonetti, Robert J. Gorelick, Shawn Hill, Monica A. Gouzoulis, Jennifer Bell, Catherine Rehm, Liliana Pérez, Eli Boritz, Xiaolin Wu, Daria Wells, Stephen H. Hughes, Venigalla Rao, John M. Coffin, Mary F. Kearney, Frank Maldarelli. Dynamic Shifts in the HIV Proviral Landscape During Long Term Combination Antiretroviral Therapy: Implications for Persistence and Control of HIV Infections. Viruses. 2020; 12 (2):136.

Chicago/Turabian Style

Elizabeth M. Anderson; Francesco R. Simonetti; Robert J. Gorelick; Shawn Hill; Monica A. Gouzoulis; Jennifer Bell; Catherine Rehm; Liliana Pérez; Eli Boritz; Xiaolin Wu; Daria Wells; Stephen H. Hughes; Venigalla Rao; John M. Coffin; Mary F. Kearney; Frank Maldarelli. 2020. "Dynamic Shifts in the HIV Proviral Landscape During Long Term Combination Antiretroviral Therapy: Implications for Persistence and Control of HIV Infections." Viruses 12, no. 2: 136.

Research article
Published: 25 September 2019 in Science Advances
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HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.

ACS Style

G. Bozzi; F. R. Simonetti; S. A. Watters; E. M. Anderson; M. Gouzoulis; M. F. Kearney; P. Rote; C. Lange; W. Shao; R. Gorelick; B. Fullmer; S. Kumar; S. Wank; S. Hewitt; D. E. Kleiner; J. Hattori; M. J. Bale; S. Hill; J. Bell; C. Rehm; Z. Grossman; R. Yarchoan; T. Uldrick; F. Maldarelli. No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication. Science Advances 2019, 5, eaav2045 .

AMA Style

G. Bozzi, F. R. Simonetti, S. A. Watters, E. M. Anderson, M. Gouzoulis, M. F. Kearney, P. Rote, C. Lange, W. Shao, R. Gorelick, B. Fullmer, S. Kumar, S. Wank, S. Hewitt, D. E. Kleiner, J. Hattori, M. J. Bale, S. Hill, J. Bell, C. Rehm, Z. Grossman, R. Yarchoan, T. Uldrick, F. Maldarelli. No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication. Science Advances. 2019; 5 (9):eaav2045.

Chicago/Turabian Style

G. Bozzi; F. R. Simonetti; S. A. Watters; E. M. Anderson; M. Gouzoulis; M. F. Kearney; P. Rote; C. Lange; W. Shao; R. Gorelick; B. Fullmer; S. Kumar; S. Wank; S. Hewitt; D. E. Kleiner; J. Hattori; M. J. Bale; S. Hill; J. Bell; C. Rehm; Z. Grossman; R. Yarchoan; T. Uldrick; F. Maldarelli. 2019. "No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication." Science Advances 5, no. 9: eaav2045.

Journal article
Published: 23 September 2019 in Journal of Clinical Investigation
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To investigate the possibility that HIV-1 replication in lymph nodes sustains the reservoir during ART, we looked for evidence of viral replication in 5 donors after up to 13 years of viral suppression. We characterized proviral populations in lymph nodes and peripheral blood before and during ART, evaluated the levels of viral RNA expression in single lymph node and blood cells, and characterized the proviral integration sites in paired lymph node and blood samples. Proviruses with identical sequences, identical integration sites, and similar levels of RNA expression were found in lymph nodes and blood samples collected during ART, and no single sequence with significant divergence from the pretherapy population was present in either blood or lymph nodes. These findings show that all detectable persistent HIV-1 infection is consistent with maintenance in lymph nodes by clonal proliferation of cells infected before ART and not by ongoing viral replication during ART.

ACS Style

William McManus; Michael J. Bale; Jonathan Spindler; Ann Wiegand; Andrew Musick; Sean C. Patro; Michele D. Sobolewski; Victoria K. Musick; Elizabeth M. Anderson; Joshua C. Cyktor; Elias K. Halvas; Wei Shao; Daria Wells; Xiaolin Wu; Brandon F. Keele; Jeffrey M. Milush; Rebecca Hoh; John W. Mellors; Stephen H. Hughes; Steven G. Deeks; John M. Coffin; Mary Kearney. HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy. Journal of Clinical Investigation 2019, 129, 4629 -4642.

AMA Style

William McManus, Michael J. Bale, Jonathan Spindler, Ann Wiegand, Andrew Musick, Sean C. Patro, Michele D. Sobolewski, Victoria K. Musick, Elizabeth M. Anderson, Joshua C. Cyktor, Elias K. Halvas, Wei Shao, Daria Wells, Xiaolin Wu, Brandon F. Keele, Jeffrey M. Milush, Rebecca Hoh, John W. Mellors, Stephen H. Hughes, Steven G. Deeks, John M. Coffin, Mary Kearney. HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy. Journal of Clinical Investigation. 2019; 129 (11):4629-4642.

Chicago/Turabian Style

William McManus; Michael J. Bale; Jonathan Spindler; Ann Wiegand; Andrew Musick; Sean C. Patro; Michele D. Sobolewski; Victoria K. Musick; Elizabeth M. Anderson; Joshua C. Cyktor; Elias K. Halvas; Wei Shao; Daria Wells; Xiaolin Wu; Brandon F. Keele; Jeffrey M. Milush; Rebecca Hoh; John W. Mellors; Stephen H. Hughes; Steven G. Deeks; John M. Coffin; Mary Kearney. 2019. "HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy." Journal of Clinical Investigation 129, no. 11: 4629-4642.

Review
Published: 23 October 2018 in Retrovirology
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Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research.

ACS Style

Elizabeth M. Anderson; Frank Maldarelli. The role of integration and clonal expansion in HIV infection: live long and prosper. Retrovirology 2018, 15, 71 .

AMA Style

Elizabeth M. Anderson, Frank Maldarelli. The role of integration and clonal expansion in HIV infection: live long and prosper. Retrovirology. 2018; 15 (1):71.

Chicago/Turabian Style

Elizabeth M. Anderson; Frank Maldarelli. 2018. "The role of integration and clonal expansion in HIV infection: live long and prosper." Retrovirology 15, no. 1: 71.

Unit
Published: 25 September 2018 in Current Protocols in Microbiology
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HIV persists, despite effective antiretroviral therapy, in long‐lived cells, posing a major barrier toward a cure. A key step in the HIV replication cycle and a hallmark of the Retroviridae family is the integration of the viral DNA into the host genome. Once integrated, HIV expression is regulated by host machinery and the provirus persists until the cell dies. A reservoir of cells harboring replication‐competent proviruses can survive for years, and mechanisms that maintain that reservoir are under investigation. The majority of integrated proviruses, however, are defective or have large deletions, and the composition of the proviral landscape during therapy remains unknown. Methods to quantify HIV proviruses are useful in investigating HIV persistence. Presented in this unit is a method for total HIV DNA quantification of various HIV genome targets that utilizes the next‐generation PCR platform, digital PCR. The abundance of various HIV gene targets reflects the overall proviral composition. In this protocol, total genomic DNA is isolated from patient‐derived cells and then used as a template for droplet digital PCR, in which the PCR reaction is partitioned into approximately 20,000 individual droplets, PCR amplified to an end point, and subjected to absolute quantification by counting the number of positive and negative droplets. Copy number is directly calculated using straightforward Poisson correction. Additionally, this methodological approach can be used to obtain absolute quantification of other DNA targets. © 2018 by John Wiley & Sons, Inc.

ACS Style

Elizabeth M. Anderson; Frank Maldarelli. Quantification of HIV DNA Using Droplet Digital PCR Techniques. Current Protocols in Microbiology 2018, 51, e62 .

AMA Style

Elizabeth M. Anderson, Frank Maldarelli. Quantification of HIV DNA Using Droplet Digital PCR Techniques. Current Protocols in Microbiology. 2018; 51 (1):e62.

Chicago/Turabian Style

Elizabeth M. Anderson; Frank Maldarelli. 2018. "Quantification of HIV DNA Using Droplet Digital PCR Techniques." Current Protocols in Microbiology 51, no. 1: e62.

Journal article
Published: 11 November 2015 in Retrovirology
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Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT-SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART.

ACS Style

Mary F. Kearney; Elizabeth M. Anderson; Charles Coomer; Luke Smith; Wei Shao; Nicholas Johnson; Christopher Kline; Jonathan Spindler; John W. Mellors; John M. Coffin; Zandrea Ambrose. Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy. Retrovirology 2015, 12, 93 .

AMA Style

Mary F. Kearney, Elizabeth M. Anderson, Charles Coomer, Luke Smith, Wei Shao, Nicholas Johnson, Christopher Kline, Jonathan Spindler, John W. Mellors, John M. Coffin, Zandrea Ambrose. Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy. Retrovirology. 2015; 12 (1):93.

Chicago/Turabian Style

Mary F. Kearney; Elizabeth M. Anderson; Charles Coomer; Luke Smith; Wei Shao; Nicholas Johnson; Christopher Kline; Jonathan Spindler; John W. Mellors; John M. Coffin; Zandrea Ambrose. 2015. "Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy." Retrovirology 12, no. 1: 93.