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1. Registered Nurses' Knowledge and Attitudes Towards Psychedelics in Healthcare: Statewide Survey Results.

Author

Graefe, Anna C., Weirick, Madison E., Harpin, Scott B., Dorsen, Caroline, and Porta, Carolyn M.

Subjects
*MENTAL health services, *NURSES' attitudes, *PSYCHIATRIC nursing, *NURSES, *LEGAL opinions
Abstract

ABSTRACT Introduction Aim/Question Method Results Discussion Limitations Implications Recommendations Psychedelic science is re‐emerging to address mental health conditions, of which certain populations in the United States experience disparities. However, the perspectives of registered nurses (RNs), who have important roles within mental health care, towards psychedelics are largely unknown.To assess attitudes, knowledge, and beliefs of a large, state‐wide sample of RNs towards psychedelics in healthcare settings.RNs were randomly selected from a statewide directory to participate in a cross‐sectional, multi‐method online survey.793 RNs completed all items, with generally positive attitudes towards psychedelics but mixed opinions regarding the legal landscape, including decriminalisation. Few (12.7%) reported psychedelic content in their training, and most expressed low confidence in their knowledge.Findings generally align with previous research regarding provider attitudes towards psychedelics. Participants in this study had slightly more favourable attitudes and higher knowledge scores.The study has potential selection bias, lacks a priori power analysis, and is limited to one state.As psychedelic science emerges as a potential treatment option for several mental health conditions, RNs must be prepared to support individuals and communities.Additional education in this emerging area of mental health nursing is warranted to ensure RN competence and confidence. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Measures of Population Immunity Can Predict the Dominant Clade of Influenza A (H3N2) in the 2017–2018 Season and Reveal Age‐Associated Differences in Susceptibility and Antibody‐Binding Specificity.

Author

Kim, Kangchon, Vieira, Marcos C., Gouma, Sigrid, Weirick, Madison E., Hensley, Scott E., and Cobey, Sarah

Abstract

Background: For antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared with others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross‐sectional antibody‐derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season. Methods: We collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains using focus reduction neutralization tests (FNRT) and enzyme‐linked lectin assays (ELLA). We estimated relative population‐average and age‐specific susceptibilities to circulating viral clades and compared those estimates to changes in clade frequencies in the following 2017–2018 season. Results: The clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titer correlations between viral strains varied by age, suggesting age‐associated differences in epitope targeting driven by shared past exposures. Yet substantial unexplained variation remains within age groups. Conclusions: This study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza. [ABSTRACT FROM AUTHOR]

Published
2024
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3. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer

Author

Bange, Erin M., Han, Nicholas A., Wileyto, Paul, Kim, Justin Y., Gouma, Sigrid, Robinson, James, Greenplate, Allison R., Hwee, Madeline A., Porterfield, Florence, Owoyemi, Olutosin, Naik, Karan, Zheng, Cathy, Galantino, Michael, Weisman, Ariel R., Ittner, Caroline A. G., Kugler, Emily M., Baxter, Amy E., Oniyide, Olutwatosin, Agyekum, Roseline S., Dunn, Thomas G., Jones, Tiffanie K., Giannini, Heather M., Weirick, Madison E., McAllister, Christopher M., Babady, N. Esther, Kumar, Anita, Widman, Adam J., DeWolf, Susan, Boutemine, Sawsan R., Roberts, Charlotte, Budzik, Krista R., Tollett, Susan, Wright, Carla, Perloff, Tara, Sun, Lova, Mathew, Divij, Giles, Josephine R., Oldridge, Derek A., Wu, Jennifer E., Alanio, Cécile, Adamski, Sharon, Garfall, Alfred L., Vella, Laura A., Kerr, Samuel J., Cohen, Justine V., Oyer, Randall A., Massa, Ryan, Maillard, Ivan P., Maxwell, Kara N., Reilly, John P., Maslak, Peter G., Vonderheide, Robert H., Wolchok, Jedd D., Hensley, Scott E., Wherry, E. John, Meyer, Nuala J., DeMichele, Angela M., Vardhana, Santosha A., Mamtani, Ronac, and Huang, Alexander C.

Published
2021
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4. Immunologic Predictors of Vaccine Responsiveness in Patients With Lymphoma and Chronic Lymphocytic Leukemia.

Author

Chong, Elise A, Kumashie, Kingsley Gideon, Chong, Emeline R, Fabrizio, Joseph, Gupta, Aditi, Svoboda, Jakub, Barta, Stefan K, Walsh, Kristy M, Napier, Ellen B, Lundberg, Rachel K, Nasta, Sunita D, Gerson, James N, Landsburg, Daniel J, Gonzalez, Joyce, Gaano, Andrew, Weirick, Madison E, McAllister, Christopher M, Awofolaju, Moses, John, Gavin N, and Kammerman, Shane C

Subjects
SARS-CoV-2, T helper cells, VACCINE effectiveness, CHRONIC lymphocytic leukemia, IMMUNOGLOBULIN M
Abstract

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19–directed chimeric antigen receptor–modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing. [ABSTRACT FROM AUTHOR]

Published
2024
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5. SARS-CoV-2 Seropositivity and Seroconversion in Patients Undergoing Active Cancer-Directed Therapy

Author

Sun, Lova, Surya, Sanjna, Goodman, Noah G., Le, Anh N., Kelly, Gregory, Owoyemi, Olutosin, Desai, Heena, Zheng, Cathy, DeLuca, Shannon, Good, Madeline L., Hussain, Jasmin, Jeffries, Seth D., Kry, Yolanda R., Kugler, Emily M., Mansour, Maikel, Ndicu, John, Osei-Akoto, AnnaClaire, Prior, Timothy, Pundock, Stacy L., Varughese, Lisa A., Weaver, JoEllen, Doucette, Abigail, Dudek, Scott, Verma, Shefali Setia, Gouma, Sigrid, Weirick, Madison E., McAllister, Christopher M., Bange, Erin, Gabriel, Peter, Ritchie, Marylyn, Rader, Daniel J., Vonderheide, Robert H., Schuchter, Lynn M., Verma, Anurag, Maillard, Ivan, Mamtani, Ronac, Hensley, Scott E., Gross, Robert, Wileyto, E. Paul, Huang, Alexander C., Maxwell, Kara N., and DeMichele, Angela

Published
2021
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7. Immunologic predictors of vaccine responsiveness in patients with lymphoma and CLL

Author

Chong, Elise A, primary, Kumashie, Kingsley Gideon, additional, Chong, Emeline R, additional, Fabrizio, Joseph, additional, Gupta, Aditi, additional, Svoboda, Jakub, additional, Barta, Stefan K, additional, Walsh, Kristy M, additional, Napier, Ellen, additional, Lundburg, Rachel, additional, Nasta, Sunita D, additional, Gerson, James N, additional, Landsburg, Daniel J, additional, Gonzalez, Joyce, additional, Gaano, Andrew, additional, Weirick, Madison E, additional, McAllister, Christopher M, additional, Awofolaju, Moses, additional, John, Gavin N, additional, Kammerman, Shane C, additional, Novaceck, Josef, additional, Pajarillo, Raymone, additional, Lundgreen, Kendall A, additional, Tanenbaum, Nicole, additional, Gouma, Sigrid, additional, Drapeau, Elizabeth M, additional, Adamski, Sharon, additional, D Andrea, Kurt, additional, Pattekar, Ajinkya, additional, Hicks, Amanda, additional, Korte, Scott, additional, Sharma, Harsh, additional, Herring, Sarah, additional, Williams, Justine C, additional, Hamilton, Jacob T, additional, Bates, Paul, additional, Hensley, Scott E, additional, Luning Prak, Eline T, additional, Greenplate, Allison R, additional, Wherry, E John, additional, Schuster, Stephen J, additional, Ruella, Marco, additional, and Vella, Laura A, additional

Published
2023
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11. Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection

Author

Flannery, Dustin D., primary, Gouma, Sigrid, additional, Dhudasia, Miren B., additional, Mukhopadhyay, Sagori, additional, Pfeifer, Madeline R., additional, Woodford, Emily C., additional, Briker, Sara M., additional, Triebwasser, Jourdan E., additional, Gerber, Jeffrey S., additional, Morris, Jeffrey S., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Hensley, Scott E., additional, and Puopolo, Karen M., additional

Published
2022
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13. Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

Author

Goel, Rishi R., primary, Painter, Mark M., additional, Lundgreen, Kendall A., additional, Apostolidis, Sokratis A., additional, Baxter, Amy E., additional, Giles, Josephine R., additional, Mathew, Divij, additional, Pattekar, Ajinkya, additional, Reynaldi, Arnold, additional, Khoury, David S., additional, Gouma, Sigrid, additional, Hicks, Philip, additional, Dysinger, Sarah, additional, Hicks, Amanda, additional, Sharma, Harsh, additional, Herring, Sarah, additional, Korte, Scott, additional, KC, Wumesh, additional, Oldridge, Derek A., additional, Erickson, Rachel I., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Awofolaju, Moses, additional, Tanenbaum, Nicole, additional, Dougherty, Jeanette, additional, Long, Sherea, additional, D’Andrea, Kurt, additional, Hamilton, Jacob T., additional, McLaughlin, Maura, additional, Williams, Justine C., additional, Adamski, Sharon, additional, Kuthuru, Oliva, additional, Drapeau, Elizabeth M., additional, Davenport, Miles P., additional, Hensley, Scott E., additional, Bates, Paul, additional, Greenplate, Allison R., additional, and Wherry, E. John, additional

Published
2022
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14. Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Author

Lederer, Katlyn, primary, Bettini, Emily, additional, Parvathaneni, Kalpana, additional, Painter, Mark M., additional, Agarwal, Divyansh, additional, Lundgreen, Kendall A., additional, Weirick, Madison, additional, Muralidharan, Kavitha, additional, Castaño, Diana, additional, Goel, Rishi R., additional, Xu, Xiaoming, additional, Drapeau, Elizabeth M., additional, Gouma, Sigrid, additional, Ort, Jordan T., additional, Awofolaju, Moses, additional, Greenplate, Allison R., additional, Le Coz, Carole, additional, Romberg, Neil, additional, Trofe-Clark, Jennifer, additional, Malat, Gregory, additional, Jones, Lisa, additional, Rosen, Mark, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Besharatian, Behdad, additional, Kaminiski, Mary, additional, Hensley, Scott E., additional, Bates, Paul, additional, Wherry, E. John, additional, Naji, Ali, additional, Bhoj, Vijay, additional, and Locci, Michela, additional

Published
2022
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15. Evolution of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroprevalence among employees of a US academic children’s hospital during coronavirus disease 2019 (COVID-19) pandemic

Author

Fisher, Brian T., primary, Sharova, Anna, additional, Boge, Craig L. K., additional, Gouma, Sigrid, additional, Kamrin, Audrey, additional, Blumenstock, Jesse, additional, Shuster, Sydney, additional, Gianchetti, Lauren, additional, Collins, Danielle, additional, Akaho, Elikplim, additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Bolton, Marcus J., additional, Arevalo, Claudia P., additional, Goodwin, Eileen C., additional, Anderson, Elizabeth M., additional, Christensen, Shannon R., additional, Balamuth, Fran, additional, John, Audrey R. Odom, additional, Li, Yun, additional, Coffin, Susan, additional, Gerber, Jeffrey S., additional, and Hensley, Scott E., additional

Published
2021
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16. Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Author

Lederer, Katlyn, primary, Parvathaneni, Kalpana, additional, Painter, Mark M., additional, Bettini, Emily, additional, Agarwal, Divyansh, additional, Lundgreen, Kendall A., additional, Weirick, Madison, additional, Goel, Rishi R., additional, Xu, Xiaoming, additional, Drapeau, Elizabeth M., additional, Gouma, Sigrid, additional, Greenplate, Allison R., additional, Coz, Carole Le, additional, Romberg, Neil, additional, Jones, Lisa, additional, Rosen, Mark, additional, Besharatian, Behdad, additional, Kaminiski, Mary, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Hensley, Scott E., additional, Bates, Paul, additional, Wherry, E. John, additional, Naji, Ali, additional, Bhoj, Vijay, additional, and Locci, Michela, additional

Published
2021
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17. Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination

Author

Painter, Mark M., primary, Mathew, Divij, additional, Goel, Rishi R., additional, Apostolidis, Sokratis A., additional, Pattekar, Ajinkya, additional, Kuthuru, Oliva, additional, Baxter, Amy E., additional, Herati, Ramin S., additional, Oldridge, Derek A., additional, Gouma, Sigrid, additional, Hicks, Philip, additional, Dysinger, Sarah, additional, Lundgreen, Kendall A., additional, Kuri-Cervantes, Leticia, additional, Adamski, Sharon, additional, Hicks, Amanda, additional, Korte, Scott, additional, Giles, Josephine R., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Dougherty, Jeanette, additional, Long, Sherea, additional, D’Andrea, Kurt, additional, Hamilton, Jacob T., additional, Betts, Michael R., additional, Bates, Paul, additional, Hensley, Scott E., additional, Grifoni, Alba, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Greenplate, Allison R., additional, and Wherry, E. John, additional

Published
2021
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18. Health care worker seromonitoring reveals complex relationships between common coronavirus antibodies and COVID-19 symptom duration

Author

Gouma, Sigrid, primary, Weirick, Madison E., additional, Bolton, Marcus J., additional, Arevalo, Claudia P., additional, Goodwin, Eileen C., additional, Anderson, Elizabeth M., additional, McAllister, Christopher M., additional, Christensen, Shannon R., additional, Dunbar, Debora, additional, Fiore, Danielle, additional, Brock, Amanda, additional, Weaver, JoEllen, additional, Millar, John, additional, DerOhannessian, Stephanie, additional, Unit, The UPenn COVID Processing, additional, Frank, Ian, additional, Rader, Daniel J., additional, Wherry, E. John, additional, and Hensley, Scott E., additional

Published
2021
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19. CD8

Author

Bange, Erin M., Han, Nicholas A., Wileyto, Paul, Kim, Justin Y., Gouma, Sigrid, Robinson, James, Greenplate, Allison R., Hwee, Madeline A., Porterfield, Florence, Owoyemi, Olutosin, Naik, Karan, Zheng, Cathy, Galantino, Michael, Weisman, Ariel R., Ittner, Caroline A.G., Kugler, Emily M., Baxter, Amy E., Oniyide, Olutwatosin, Agyekum, Roseline S., Dunn, Thomas G., Jones, Tiffanie K., Giannini, Heather M., Weirick, Madison E., McAllister, Christopher M., Babady, N. Esther, Kumar, Anita, Widman, Adam J., DeWolf, Susan, Boutemine, Sawsan R., Roberts, Charlotte, Budzik, Krista R, Tollett, Susan, Wright, Carla, Perloff, Tara, Sun, Lova, Mathew, Divij, Giles, Josephine R., Oldridge, Derek A., Wu, Jennifer E., Alanio, Cécile, Adamski, Sharon, Garfall, Alfred L., Vella, Laura A, Kerr, Samuel J., Cohen, Justine V., Oyer, Randall A., Massa, Ryan, Maillard, Ivan P., Maxwell, Kara N., Reilly, John P., Maslak, Peter G., Vonderheide, Robert H., Wolchok, Jedd D., Hensley, Scott E., Wherry, E. John, Meyer, Nuala J., DeMichele, Angela M., Vardhana, Santosha A., Mamtani, Ronac, and Huang, Alexander C.

Subjects
Male, B-Lymphocytes, Immunity, Cellular, SARS-CoV-2, COVID-19, CD8-Positive T-Lymphocytes, Middle Aged, Antibodies, Viral, Article, Immunity, Humoral, Immunophenotyping, Cohort Studies, Survival Rate, Logistic Models, Hematologic Neoplasms, Neoplasms, Multivariate Analysis, Humans, Female, Prospective Studies, Aged, Proportional Hazards Models
Abstract

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.

Published
2021

20. Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios

Author

Flannery, Dustin D., primary, Gouma, Sigrid, additional, Dhudasia, Miren B., additional, Mukhopadhyay, Sagori, additional, Pfeifer, Madeline R., additional, Woodford, Emily C., additional, Triebwasser, Jourdan E., additional, Gerber, Jeffrey S., additional, Morris, Jeffrey S., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Bolton, Marcus J., additional, Arevalo, Claudia P., additional, Anderson, Elizabeth M., additional, Goodwin, Eileen C., additional, Hensley, Scott E., additional, and Puopolo, Karen M., additional

Published
2021
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21. Rapid induction of antigen-specific CD4+T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination

Author

Painter, Mark M., primary, Mathew, Divij, additional, Goel, Rishi R., additional, Apostolidis, Sokratis A., additional, Pattekar, Ajinkya, additional, Kuthuru, Oliva, additional, Baxter, Amy E., additional, Herati, Ramin S., additional, Oldridge, Derek A., additional, Gouma, Sigrid, additional, Hicks, Philip, additional, Dysinger, Sarah, additional, Lundgreen, Kendall A., additional, Kuri-Cervantes, Leticia, additional, Adamski, Sharon, additional, Hicks, Amanda, additional, Korte, Scott, additional, Giles, Josephine R., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Dougherty, Jeanette, additional, Long, Sherea, additional, D’Andrea, Kurt, additional, Hamilton, Jacob T., additional, Betts, Michael R., additional, Bates, Paul, additional, Hensley, Scott E., additional, Grifoni, Alba, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Greenplate, Allison R., additional, and Wherry, E. John, additional

Published
2021
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22. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination

Author

Goel, Rishi R., primary, Apostolidis, Sokratis A., additional, Painter, Mark M., additional, Mathew, Divij, additional, Pattekar, Ajinkya, additional, Kuthuru, Oliva, additional, Gouma, Sigrid, additional, Hicks, Philip, additional, Meng, Wenzhao, additional, Rosenfeld, Aaron M., additional, Dysinger, Sarah, additional, Lundgreen, Kendall A., additional, Kuri-Cervantes, Leticia, additional, Adamski, Sharon, additional, Hicks, Amanda, additional, Korte, Scott, additional, Oldridge, Derek A., additional, Baxter, Amy E., additional, Giles, Josephine R., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Dougherty, Jeanette, additional, Long, Sherea, additional, D’Andrea, Kurt, additional, Hamilton, Jacob T., additional, Betts, Michael R., additional, Luning Prak, Eline T., additional, Bates, Paul, additional, Hensley, Scott E., additional, Greenplate, Allison R., additional, and Wherry, E. John, additional

Published
2021
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23. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection

Author

Anderson, Elizabeth M., primary, Goodwin, Eileen C., additional, Verma, Anurag, additional, Arevalo, Claudia P., additional, Bolton, Marcus J., additional, Weirick, Madison E., additional, Gouma, Sigrid, additional, McAllister, Christopher M., additional, Christensen, Shannon R., additional, Weaver, JoEllen, additional, Hicks, Philip, additional, Manzoni, Tomaz B., additional, Oniyide, Oluwatosin, additional, Ramage, Holly, additional, Mathew, Divij, additional, Baxter, Amy E., additional, Oldridge, Derek A., additional, Greenplate, Allison R., additional, Wu, Jennifer E., additional, Alanio, Cécile, additional, D’Andrea, Kurt, additional, Kuthuru, Oliva, additional, Dougherty, Jeanette, additional, Pattekar, Ajinkya, additional, Kim, Justin, additional, Han, Nicholas, additional, Apostolidis, Sokratis A., additional, Huang, Alex C., additional, Vella, Laura A., additional, Kuri-Cervantes, Leticia, additional, Pampena, M. Betina, additional, Betts, Michael R., additional, Wherry, E. John, additional, Meyer, Nuala J., additional, Cherry, Sara, additional, Bates, Paul, additional, Rader, Daniel J., additional, and Hensley, Scott E., additional

Published
2021
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24. Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

Author

Mathew, Divij, Giles, Josephine R., Baxter, Amy E., Greenplate, Allison R., Wu, Jennifer E., Alanio, Cécile, Oldridge, Derek A., Kuri-Cervantes, Leticia, Pampena, M. Betina, D’Andrea, Kurt, Manne, Sasikanth, Chen, Zeyu, Huang, Yinghui Jane, Reilly, John P., Weisman, Ariel R, Ittner, Caroline A.G., Kuthuru, Oliva, Dougherty, Jeanette, Nzingha, Kito, Han, Nicholas, Kim, Justin, Pattekar, Ajinkya, Goodwin, Eileen C., Anderson, Elizabeth M., Weirick, Madison E., Gouma, Sigrid, Arevalo, Claudia P., Bolton, Marcus J., Chen, Fang, Lacey, Simon F., Hensley, Scott E., Apostolidis, Sokratis, Huang, Alexander C., Vella, Laura A., Betts, Michael R., Meyer, Nuala J., and Wherry, E. John

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Time Factors, Coronavirus disease 2019 (COVID-19), T cell, T-Lymphocytes, Plasma Cells, Pneumonia, Viral, Psychological intervention, B-Lymphocyte Subsets, Adaptive Immunity, CD8-Positive T-Lymphocytes, medicine.disease_cause, Antibodies, Viral, Lymphocyte Activation, Severity of Illness Index, Article, Immune profiling, Betacoronavirus, Young Adult, Immune system, T-Lymphocyte Subsets, medicine, Humans, Pandemics, B cell, Aged, Aged, 80 and over, B-Lymphocytes, business.industry, SARS-CoV-2, COVID-19, T-Lymphocytes, Helper-Inducer, Immune dysregulation, Middle Aged, medicine.anatomical_structure, Immunology, Cytokines, Female, business, Coronavirus Infections, Cytometry, Immunologic Memory
Abstract

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ∼200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.

Published
2020

25. Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

Author

Goel, Rishi R., primary, Apostolidis, Sokratis A., additional, Painter, Mark M., additional, Mathew, Divij, additional, Pattekar, Ajinkya, additional, Kuthuru, Oliva, additional, Gouma, Sigrid, additional, Kuri-Cervantes, Leticia, additional, Meng, Wenzhao, additional, Adamski, Sharon, additional, Baxter, Amy E., additional, Giles, Josephine R., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Hicks, Amanda, additional, Korte, Scott, additional, Dougherty, Jeanette, additional, Long, Sherea, additional, D’Andrea, Kurt, additional, Hamilton, Jacob T., additional, Luning Prak, Eline T, additional, Betts, Michael R., additional, Bates, Paul, additional, Hensley, Scott E., additional, Greenplate, Allison R., additional, and Wherry, E. John, additional

Published
2021
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26. CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer

Author

Bange, Erin, primary, Han, Nicholas, additional, Wileyto, E. Paul, additional, Kim, Justin, additional, Gouma, Sigrid, additional, Robinson, James, additional, Greenplate, Allison, additional, Porterfield, Florence, additional, Owoyemi, Olutosin, additional, Naik, Karan, additional, Zheng, Cathy, additional, Galantino, Michael, additional, Weisman, Ariel, additional, Ittner, Carolin, additional, Kugler, Emily, additional, Baxter, Amy, additional, Weirick, Madison, additional, McAllister, Christopher, additional, Babady, Ngolela Esther, additional, Kumar, Anita, additional, Widman, Adam, additional, Dewolf, Susan, additional, Boutemine, Sawsan, additional, Roberts, Charlotte, additional, Budzik, Krista, additional, Tollett, Susan, additional, Wright, Carla, additional, Perloff, Tara, additional, Sun, Lova, additional, Mathew, Divij, additional, Giles, Josephine, additional, Oldridge, Derek, additional, Wu, Jennifer, additional, Alanio, Cecile, additional, Adamski, Sharon, additional, Vella, Laura, additional, Kerr, Samuel, additional, Cohen, Justine, additional, Oyer, Randall, additional, Massa, Ryan, additional, Maillard, Ivan, additional, Maxwell, Kara, additional, Maslak, Peter, additional, Vonderheide, Robert, additional, Wolchok, Jedd D., additional, Hensley, Scott, additional, Wherry, E., additional, Meyer, Nuala, additional, DeMichele, Angela, additional, Oniyide, Oluwatosin, additional, Agyekum, Roseline, additional, Dunn, Thomas, additional, Jones, Tiffanie, additional, Giannini, Heather, additional, Garfall, Alfred, additional, Reilly, John, additional, Vardhana, Santosha, additional, Mamtani, Ronac, additional, and Huang, Alexander, additional

Published
2021
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27. SARS-CoV-2 seropositivity and seroconversion in patients undergoing active cancer-directed therapy

Author

Sun, Lova, primary, Surya, Sanjna, additional, Goodman, Noah G., additional, Le, Anh N., additional, Kelly, Gregory, additional, Owoyemi, Olutosin, additional, Desai, Heena, additional, Zheng, Cathy, additional, DeLuca, Shannon, additional, Good, Madeline L., additional, Hussain, Jasmin, additional, Jeffries, Seth D., additional, Kry, Yolanda R., additional, Kugler, Emily M., additional, Mansour, Maikel, additional, Ndicu, John, additional, Osei-Akoto, AnnaClaire, additional, Prior, Timothy, additional, Pundock, Stacy L., additional, Varughese, Lisa A., additional, Weaver, JoEllen, additional, Doucette, Abigail, additional, Dudek, Scott, additional, Verma, Shefali Setia, additional, Gouma, Sigrid, additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Bange, Erin, additional, Gabriel, Peter, additional, Ritchie, Marylyn, additional, Rader, Daniel J., additional, Vonderheide, Robert H., additional, Schuchter, Lynn M, additional, Verma, Anurag, additional, Maillard, Ivan, additional, Mamtani, Ronac, additional, Hensley, Scott E., additional, Gross, Robert, additional, Wileyto, E. Paul, additional, Huang, Alexander C., additional, Maxwell, Kara N., additional, and DeMichele, Angela, additional

Published
2021
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28. Evolution of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroprevalence among employees of a US academic children’s hospital during coronavirus disease 2019 (COVID-19) pandemic

Author

Fisher, Brian T., Sharova, Anna, Boge, Craig L. K., Gouma, Sigrid, Kamrin, Audrey, Blumenstock, Jesse, Shuster, Sydney, Gianchetti, Lauren, Collins, Danielle, Akaho, Elikplim, Weirick, Madison E., McAllister, Christopher M., Bolton, Marcus J., Arevalo, Claudia P., Goodwin, Eileen C., Anderson, Elizabeth M., Christensen, Shannon R., Balamuth, Fran, John, Audrey R. Odom, Li, Yun, Coffin, Susan, Gerber, Jeffrey S., and Hensley, Scott E.

Abstract

AbstractObjective:To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.Design, setting, and participants:Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.Methods:Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.Results:In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.Conclusions:Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

Published
2022
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29. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Antibody Responses in Children With Multisystem Inflammatory Syndrome in Children (MIS-C) and Mild and Severe Coronavirus Disease 2019 (COVID-19)

Author

Anderson, Elizabeth M, primary, Diorio, Caroline, additional, Goodwin, Eileen C, additional, McNerney, Kevin O, additional, Weirick, Madison E, additional, Gouma, Sigrid, additional, Bolton, Marcus J, additional, Arevalo, Claudia P, additional, Chase, Julie, additional, Hicks, Philip, additional, Manzoni, Tomaz B, additional, Baxter, Amy E, additional, Andrea, Kurt P, additional, Burudpakdee, Chakkapong, additional, Lee, Jessica H, additional, Vella, Laura A, additional, Henrickson, Sarah E, additional, Harris, Rebecca M, additional, Wherry, E John, additional, Bates, Paul, additional, Bassiri, Hamid, additional, Behrens, Edward M, additional, Teachey, David T, additional, and Hensley, Scott E, additional

Published
2020
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30. Transplacental Transfer of SARS-CoV-2 Antibodies

Author

Flannery, Dustin D., primary, Gouma, Sigrid, additional, Dhudasia, Miren B., additional, Mukhopadhyay, Sagori, additional, Pfeifer, Madeline R., additional, Woodford, Emily C., additional, Triebwasser, Jourdan E., additional, Gerber, Jeffrey S., additional, Morris, Jeffrey S., additional, Weirick, Madison E., additional, McAllister, Christopher M., additional, Bolton, Marcus J., additional, Arevalo, Claudia P., additional, Anderson, Elizabeth M., additional, Goodwin, Eileen C., additional, Hensley, Scott E., additional, and Puopolo, Karen M., additional

Published
2020
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31. Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome

Author

Diorio, Caroline, primary, Anderson, Elizabeth M., additional, McNerney, Kevin O., additional, Goodwin, Eileen C., additional, Chase, Julie C., additional, Bolton, Marcus J., additional, Arevalo, Claudia P., additional, Weirick, Madison E., additional, Gouma, Sigrid, additional, Vella, Laura A., additional, Henrickson, Sarah E., additional, Chiotos, Kathleen, additional, Fitzgerald, Julie C., additional, Kilbaugh, Todd J., additional, John, Audrey R. Odom, additional, Blatz, Allison M., additional, Lambert, Michele P., additional, Sullivan, Kathleen E., additional, Tartaglione, Margaret R., additional, Zambrano, Danielle, additional, Martin, Meghan, additional, Lee, Jessica H., additional, Young, Pampee, additional, Friedman, David, additional, Sesok‐Pizzini, Deborah A., additional, Hensley, Scott E., additional, Behrens, Edward M., additional, Bassiri, Hamid, additional, and Teachey, David T., additional

Published
2020
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32. SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19

Author

Anderson, Elizabeth M., primary, Diorio, Caroline, additional, Goodwin, Eileen C., additional, McNerney, Kevin O., additional, Weirick, Madison E., additional, Gouma, Sigrid, additional, Bolton, Marcus J., additional, Arevalo, Claudia P., additional, Chase, Julie, additional, Hicks, Philip, additional, Manzoni, Tomaz B., additional, Baxter, Amy E., additional, Andrea, Kurt P., additional, Burudpakdee, Chakkapong, additional, Lee, Jessica H., additional, Vella, Laura A., additional, Henrickson, Sarah E., additional, Harris, Rebecca M., additional, John Wherry, E., additional, Bates, Paul, additional, Bassiri, Hamid, additional, Behrens, Edward M., additional, Teachey, David T., additional, and Hensley, Scott E., additional

Published
2020
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33. Convalescent plasma for pediatric patients with COVID-19 associated acute respiratory distress syndrome

Author

Diorio, Caroline, primary, Anderson, Elizabeth, additional, McNerney, Kevin, additional, Goodwin, Eileen, additional, Chase, Julie, additional, Bolton, Marcus, additional, Arevalo, Claudia, additional, Weirick, Madison, additional, Gouma, Sigrid, additional, Vella, Laura, additional, Henrickson, Sarah, additional, Chiotos, Kathleen, additional, Fitzgerald, Julie, additional, Kilbaugh, Todd, additional, John, Audrey Odom, additional, Blatz, Allison, additional, Lambert, Michele, additional, Sullivan, Kathleen, additional, Tartaglione, Margaret, additional, Zambrano, Danielle, additional, Martin, Meghan, additional, Lee, Jessica, additional, Young, Pampee, additional, Friedman, David, additional, Pizzini, Deborah Sesok, additional, Hensley, Scott, additional, Behrens, Edward, additional, Bassiri, Hamid, additional, and Teachey, David, additional

Published
2020
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34. SARS-CoV-2 Seroprevalence Among Parturient Women

Author

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

Published
2020
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35. Comprehensive mapping of immune perturbations associated with severe COVID-19

Author

Kuri-Cervantes, Leticia, primary, Pampena, Maria Betina, additional, Meng, Wenzhao, additional, Rosenfeld, Aaron M., additional, Ittner, Caroline A. G., additional, Weisman, Ariel R., additional, Agyekum, Roseline S., additional, Mathew, Divij, additional, Baxter, Amy E., additional, Vella, Laura A., additional, Kuthuru, Oliva, additional, Apostolidis, Sokratis A., additional, Bershaw, Luanne, additional, Dougherty, Jeanette, additional, Greenplate, Allison R., additional, Pattekar, Ajinkya, additional, Kim, Justin, additional, Han, Nicholas, additional, Gouma, Sigrid, additional, Weirick, Madison E., additional, Arevalo, Claudia P., additional, Bolton, Marcus J., additional, Goodwin, Eileen C., additional, Anderson, Elizabeth M., additional, Hensley, Scott E., additional, Jones, Tiffanie K., additional, Mangalmurti, Nilam S., additional, Luning Prak, Eline T., additional, Wherry, E. John, additional, Meyer, Nuala J., additional, and Betts, Michael R., additional

Published
2020
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36. SARS-CoV-2 seroprevalence among parturient women in Philadelphia

Author

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

Published
2020
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37. Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Author

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

Published
2020
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41. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Antibody Responses in Children With Multisystem Inflammatory Syndrome in Children (MIS-C) and Mild and Severe Coronavirus Disease 2019 (COVID-19).

Author

Anderson, Elizabeth M, Diorio, Caroline, Goodwin, Eileen C, McNerney, Kevin O, Weirick, Madison E, Gouma, Sigrid, Bolton, Marcus J, Arevalo, Claudia P, Chase, Julie, Hicks, Philip, Manzoni, Tomaz B, Baxter, Amy E, Andrea, Kurt P, Burudpakdee, Chakkapong, Lee, Jessica H, Vella, Laura A, Henrickson, Sarah E, Harris, Rebecca M, Wherry, E John, and Bates, Paul

Subjects
IMMUNOGLOBULINS, COVID-19, SYSTEMIC inflammatory response syndrome, MULTIPLE organ failure, PEDIATRICS, SARS disease
Abstract

Severe acute respiratory syndrome-coronavirus-2 (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 immunoglobulin G (IgG) titers compared with those with severe coronavirus disease 2019, likely reflecting a longer time since the onset of infection in MIS-C patients. [ABSTRACT FROM AUTHOR]

Published
2021
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42. CD8+T cells contribute to survival in patients with COVID-19 and hematologic cancer

Author

Bange, Erin M., Han, Nicholas A., Wileyto, Paul, Kim, Justin Y., Gouma, Sigrid, Robinson, James, Greenplate, Allison R., Hwee, Madeline A., Porterfield, Florence, Owoyemi, Olutosin, Naik, Karan, Zheng, Cathy, Galantino, Michael, Weisman, Ariel R., Ittner, Caroline A. G., Kugler, Emily M., Baxter, Amy E., Oniyide, Olutwatosin, Agyekum, Roseline S., Dunn, Thomas G., Jones, Tiffanie K., Giannini, Heather M., Weirick, Madison E., McAllister, Christopher M., Babady, N. Esther, Kumar, Anita, Widman, Adam J., DeWolf, Susan, Boutemine, Sawsan R., Roberts, Charlotte, Budzik, Krista R., Tollett, Susan, Wright, Carla, Perloff, Tara, Sun, Lova, Mathew, Divij, Giles, Josephine R., Oldridge, Derek A., Wu, Jennifer E., Alanio, Cécile, Adamski, Sharon, Garfall, Alfred L., Vella, Laura A., Kerr, Samuel J., Cohen, Justine V., Oyer, Randall A., Massa, Ryan, Maillard, Ivan P., Maxwell, Kara N., Reilly, John P., Maslak, Peter G., Vonderheide, Robert H., Wolchok, Jedd D., Hensley, Scott E., Wherry, E. John, Meyer, Nuala J., DeMichele, Angela M., Vardhana, Santosha A., Mamtani, Ronac, and Huang, Alexander C.

Abstract

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

Published
2021
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43. Potential Antigenic Mismatch of the H3N2 Component of the 2019 Southern Hemisphere Influenza Vaccine.

Author

Gouma, Sigrid, Weirick, Madison, and Hensley, Scott E

Subjects
*GENETICS, *INFLUENZA vaccines, *INFLUENZA A virus, H3N2 subtype
Abstract

Here, we find that the egg-adapted H3N2 component of the 2019 Southern Hemisphere influenza vaccine elicits an antibody response in ferrets that is highly focused on antigenic site A of hemagglutinin. This is potentially problematic as most H3N2 viruses currently circulating in the Southern Hemisphere possess antigenic site A substitutions. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Measures of population immunity can predict the dominant clade of influenza A (H3N2) in the 2017-2018 season and reveal age-associated differences in susceptibility and antibody-binding specificity.

Author

Kim K, Vieira MC, Gouma S, Weirick ME, Hensley SE, and Cobey S

Abstract

Background: For antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared to others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross-sectional antibody-derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season., Methods: We collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains using Focus Reduction Neutralization Tests (FNRT) and Enzyme-Linked Lectin Assays (ELLA). We estimated relative population-average and age-specific susceptibilities to circulating viral clades and compared those estimates to changes in clade frequencies in the following 2017-18 season., Results: The clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titer correlations between viral strains varied by age, suggesting age-associated differences in epitope targeting driven by shared past exposures. Yet substantial unexplained variation remains within age groups., Conclusions: This study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza., Competing Interests: Competing interests S.E.H. is a co-inventor on patents that describe the use of nucleoside-modified mRNA as a vaccine platform. S.E.H reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. The other authors declare no competing interests.

Published
2024
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45. Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine.

Author

Goel RR, Painter MM, Lundgreen KA, Apostolidis SA, Baxter AE, Giles JR, Mathew D, Pattekar A, Reynaldi A, Khoury DS, Gouma S, Hicks P, Dysinger S, Hicks A, Sharma H, Herring S, Korte S, Kc W, Oldridge DA, Erickson RI, Weirick ME, McAllister CM, Awofolaju M, Tanenbaum N, Dougherty J, Long S, D'Andrea K, Hamilton JT, McLaughlin M, Williams JC, Adamski S, Kuthuru O, Drapeau EM, Davenport MP, Hensley SE, Bates P, Greenplate AR, and Wherry EJ

Abstract

Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ∼9-10 months after the primary 2-dose mRNA vaccine series, as well as for ∼3 months after a 3 rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3 rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ∼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3 rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3 rd dose. In contrast, pre-3 rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.

Published
2022
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46. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.

Author

Goel RR, Painter MM, Apostolidis SA, Mathew D, Meng W, Rosenfeld AM, Lundgreen KA, Reynaldi A, Khoury DS, Pattekar A, Gouma S, Kuri-Cervantes L, Hicks P, Dysinger S, Hicks A, Sharma H, Herring S, Korte S, Baxter AE, Oldridge DA, Giles JR, Weirick ME, McAllister CM, Awofolaju M, Tanenbaum N, Drapeau EM, Dougherty J, Long S, D'Andrea K, Hamilton JT, McLaughlin M, Williams JC, Adamski S, Kuthuru O, Frank I, Betts MR, Vella LA, Grifoni A, Weiskopf D, Sette A, Hensley SE, Davenport MP, Bates P, Luning Prak ET, Greenplate AR, and Wherry EJ

Subjects
Humans, COVID-19 Vaccines immunology, Immunologic Memory, SARS-CoV-2 genetics, SARS-CoV-2 immunology, mRNA Vaccines immunology
Abstract

The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2–naïve and –recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4 + and CD8 + T cells, and early CD4 + T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.

Published
2021
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47. Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals.

Author

Lederer K, Parvathaneni K, Painter MM, Bettini E, Agarwal D, Lundgreen KA, Weirick M, Goel RR, Xu X, Drapeau EM, Gouma S, Greenplate AR, Coz CL, Romberg N, Jones L, Rosen M, Besharatian B, Kaminiski M, Weiskopf D, Sette A, Hensley SE, Bates P, Wherry EJ, Naji A, Bhoj V, and Locci M

Abstract

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients. We found that, unlike healthy subjects, KTX recipients presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cells, SARS-CoV-2 receptor-binding-domain-specific memory B cells and neutralizing antibodies. KTX recipients also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.

Published
2021
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48. Rapid induction of antigen-specific CD4 + T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination.

Author

Painter MM, Mathew D, Goel RR, Apostolidis SA, Pattekar A, Kuthuru O, Baxter AE, Herati RS, Oldridge DA, Gouma S, Hicks P, Dysinger S, Lundgreen KA, Kuri-Cervantes L, Adamski S, Hicks A, Korte S, Giles JR, Weirick ME, McAllister CM, Dougherty J, Long S, D'Andrea K, Hamilton JT, Betts MR, Bates P, Hensley SE, Grifoni A, Weiskopf D, Sette A, Greenplate AR, and Wherry EJ

Subjects
2019-nCoV Vaccine mRNA-1273, Adult, Antibodies, Neutralizing blood, Antibodies, Viral blood, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, BNT162 Vaccine, Female, Humans, Immunity, Cellular, Immunity, Humoral, Immunization, Secondary, Immunologic Memory, Lectins, C-Type metabolism, Lymphocyte Activation, Male, Middle Aged, Peptides immunology, Spike Glycoprotein, Coronavirus immunology, Vaccination, Young Adult, CD8-Positive T-Lymphocytes immunology, COVID-19 immunology, COVID-19 Vaccines immunology, SARS-CoV-2 physiology, Th1 Cells immunology
Abstract

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4 + T cell responses in naive subjects after the first dose, whereas CD8 + T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8 + T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4 + T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals., Competing Interests: Declaration of interests S.E.H. has received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merk for work unrelated to this study. E.J.W. is a consultant or an adviser for Merck, Elstar, Janssen, Related Sciences, Synthekine, and Surface Oncology. E.J.W. is a founder of Surface Oncology and Arsenal Biosciences. E.J.W. is an inventor on a patent (U.S. Patent No. 10,370,446) submitted by Emory University that covers the use of PD-1 blockade to treat infections and cancer. A.S. is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus, Oxfordimmunotech, and Avalia. La Jolla Institute for Immunology has filed for patent protection for various aspects of T cell epitope and vaccine design work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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49. mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern.

Author

Goel RR, Painter MM, Apostolidis SA, Mathew D, Meng W, Rosenfeld AM, Lundgreen KA, Reynaldi A, Khoury DS, Pattekar A, Gouma S, Kuri-Cervantes L, Hicks P, Dysinger S, Hicks A, Sharma H, Herring S, Korte S, Baxter AE, Oldridge DA, Giles JR, Weirick ME, McAllister CM, Awofolaju M, Tanenbaum N, Drapeau EM, Dougherty J, Long S, D'Andrea K, Hamilton JT, McLaughlin M, Williams JC, Adamski S, Kuthuru O, Frank I, Betts MR, Vella LA, Grifoni A, Weiskopf D, Sette A, Hensley SE, Davenport MP, Bates P, Luning Prak ET, Greenplate AR, and Wherry EJ

Abstract

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.

Published
2021
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50. Sero-monitoring of health care workers reveals complex relationships between common coronavirus antibodies and SARS-CoV-2 severity.

Author

Gouma S, Weirick ME, Bolton MJ, Arevalo CP, Goodwin EC, Anderson EM, McAllister CM, Christensen SR, Dunbar D, Fiore D, Brock A, Weaver J, Millar J, DerOhannessian S, Frank I, Rader DJ, Wherry EJ, and Hensley SE

Abstract

Recent common coronavirus (CCV) infections are associated with reduced COVID-19 severity upon SARS-CoV-2 infection, however the immunological mechanisms involved are unknown. We completed serological assays using samples collected from health care workers to identify antibody types associated with SARS-CoV-2 protection and COVID-19 severity. 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 severity of 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 disease severity following SARS-CoV-2 infections.

Published
2021
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