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2. Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection

Author

Dandekar, Satya, Dandekar, S ( Satya ), Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Ulyte, Agne; https://orcid.org/0000-0001-7419-9778, Radtke, Thomas; https://orcid.org/0000-0002-1723-1070, Haile, Sarah R; https://orcid.org/0000-0002-4704-6570, Ammann, Priska, Raineri, Alessia; https://orcid.org/0009-0007-7128-9656, Rueegg, Sonja, Epp, Selina, Berger, Christoph; https://orcid.org/0000-0002-2373-8804, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Manrique, Amapola; https://orcid.org/0000-0003-3982-398X, Audigé, Annette, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schreiber, Peter W; https://orcid.org/0000-0001-8123-2601, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Fehr, Jan; https://orcid.org/0000-0003-1113-9895, Weber, Jacqueline, Rusert, Peter, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Puhan, Milo A; https://orcid.org/0000-0003-4721-1879, Kriemler, Susi; https://orcid.org/0000-0002-3384-7940, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Dandekar, Satya, Dandekar, S ( Satya ), Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Ulyte, Agne; https://orcid.org/0000-0001-7419-9778, Radtke, Thomas; https://orcid.org/0000-0002-1723-1070, Haile, Sarah R; https://orcid.org/0000-0002-4704-6570, Ammann, Priska, Raineri, Alessia; https://orcid.org/0009-0007-7128-9656, Rueegg, Sonja, Epp, Selina, Berger, Christoph; https://orcid.org/0000-0002-2373-8804, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Manrique, Amapola; https://orcid.org/0000-0003-3982-398X, Audigé, Annette, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schreiber, Peter W; https://orcid.org/0000-0001-8123-2601, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Fehr, Jan; https://orcid.org/0000-0003-1113-9895, Weber, Jacqueline, Rusert, Peter, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Puhan, Milo A; https://orcid.org/0000-0003-4721-1879, Kriemler, Susi; https://orcid.org/0000-0002-3384-7940, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, and Pasin, Chloé; https://orcid.org/0000-0001-8730-790X

Abstract

Knowledge of the interplay between human coronavirus (HCoV) immunity and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is critical to understanding the coexistence of current endemic coronaviruses and to building knowledge potential future zoonotic coronavirus transmissions. This study, which retrospectively analyzed a large cohort of individuals first exposed to SARS-CoV-2 in Switzerland in 2020–2021, revealed several key findings. Pre-existing HCoV immunity, particularly mucosal antibody responses, played a significant role in improving SARS-CoV-2 immune response upon infection and reducing symptoms development. Mucosal neutralizing activity against SARS-CoV-2, although low in magnitude, retained activity against SARS-CoV-2 variants underlining the importance of maintaining local mucosal immunity to SARS-CoV-2. While the cross-protective effect of HCoV immunity was not sufficient to block infection by SARS-CoV-2, the present study revealed a remarkable impact on limiting symptomatic disease. These findings support the feasibility of generating pan-protective coronavirus vaccines by inducing potent mucosal immune responses.

Published
2024

3. Incidence of sexually transmitted infections and association with behavioural factors: Time-to-event analysis of a large pre-exposure prophylaxis (PrEP) cohort

Author

Hovaguimian, Frédérique; https://orcid.org/0000-0003-4181-2948, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Schmidt, Axel J; https://orcid.org/0000-0002-6910-4399, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Stoeckle, Marcel; https://orcid.org/0000-0002-0088-5078, Surial, Bernard; https://orcid.org/0000-0002-1402-974X, Christinet, Vanessa, Darling, Katharine E A; https://orcid.org/0000-0003-1449-3873, Depmeier, Carsten, Läuchli, Severin, Reinacher, Matthias, Rasi, Manuela, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Bruggmann, Philip, Haerry, David, Bize, Raphaël; https://orcid.org/0000-0001-5626-4628, Low, Nicola; https://orcid.org/0000-0003-4817-8986, Vock, Florian, El Amari, Emmanuelle Boffi, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Bosshard, Philipp P; https://orcid.org/0000-0002-1154-2281, Fehr, Jan S, Hampel, Benjamin, SwissPrEPared Cohort Study, Hovaguimian, Frédérique; https://orcid.org/0000-0003-4181-2948, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Schmidt, Axel J; https://orcid.org/0000-0002-6910-4399, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Stoeckle, Marcel; https://orcid.org/0000-0002-0088-5078, Surial, Bernard; https://orcid.org/0000-0002-1402-974X, Christinet, Vanessa, Darling, Katharine E A; https://orcid.org/0000-0003-1449-3873, Depmeier, Carsten, Läuchli, Severin, Reinacher, Matthias, Rasi, Manuela, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Bruggmann, Philip, Haerry, David, Bize, Raphaël; https://orcid.org/0000-0001-5626-4628, Low, Nicola; https://orcid.org/0000-0003-4817-8986, Vock, Florian, El Amari, Emmanuelle Boffi, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Bosshard, Philipp P; https://orcid.org/0000-0002-1154-2281, Fehr, Jan S, Hampel, Benjamin, and SwissPrEPared Cohort Study

Abstract

OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.

Published
2024

5. Similar But Different: Integrated Phylogenetic Analysis of Austrian and Swiss HIV-1 Sequences Reveal Differences in Transmission Patterns of the Local HIV-1 Epidemics

Author

Kusejko, Katharina, Tschumi, Nadine, Chaudron, Sandra E., Nguyen, Huyen, Battegay, Manuel, Bernasconi, Enos, Böni, Jürg, Huber, Michael, Calmy, Alexandra, Cavassini, Matthias, Egle, Alexander, Grabmeier-Pfistershammer, Katharina, Haas, Bernhard, Hirsch, Hans, Klimkait, Thomas, Öllinger, Angela, Perreau, Matthieu, Ramette, Alban, Flury, Baharak Babouee, Sarcletti, Mario, Scherrer, Alexandra, Schmid, Patrick, Yerly, Sabine, Zangerle, Robert, Günthard, Huldrych F., and Kouyos, Roger D.

Published
2022
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6. Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection

Author

Abela, Irene A., primary, Schwarzmüller, Magdalena, additional, Ulyte, Agne, additional, Radtke, Thomas, additional, Haile, Sarah R., additional, Ammann, Priska, additional, Raineri, Alessia, additional, Rueegg, Sonja, additional, Epp, Selina, additional, Berger, Christoph, additional, Böni, Jürg, additional, Manrique, Amapola, additional, Audigé, Annette, additional, Huber, Michael, additional, Schreiber, Peter W., additional, Scheier, Thomas, additional, Fehr, Jan, additional, Weber, Jacqueline, additional, Rusert, Peter, additional, Günthard, Huldrych F., additional, Kouyos, Roger D., additional, Puhan, Milo A., additional, Kriemler, Susi, additional, Trkola, Alexandra, additional, and Pasin, Chloé, additional

Published
2024
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7. Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity

Author

Abela, Irene A., Pasin, Chloé, Schwarzmüller, Magdalena, Epp, Selina, Sickmann, Michèle E., Schanz, Merle M., Rusert, Peter, Weber, Jacqueline, Schmutz, Stefan, Audigé, Annette, Maliqi, Liridona, Hunziker, Annika, Hesselman, Maria C., Niklaus, Cyrille R., Gottschalk, Jochen, Schindler, Eméry, Wepf, Alexander, Karrer, Urs, Wolfensberger, Aline, Rampini, Silvana K., Meyer Sauteur, Patrick M., Berger, Christoph, Huber, Michael, Böni, Jürg, Braun, Dominique L., Marconato, Maddalena, Manz, Markus G., Frey, Beat M., Günthard, Huldrych F., Kouyos, Roger D., and Trkola, Alexandra

Published
2021
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8. Host genomics of the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment

Author

Thorball, Christian W., Borghesi, Alessandro, Bachmann, Nadine, Von Siebenthal, Chantal, Vongrad, Valentina, Turk, Teja, Neumann, Kathrin, Beerenwinkel, Niko, Bogojeska, Jasmina, Roth, Volker, Kok, Yik Lim, Parbhoo, Sonali, Wieser, Mario, Böni, Jürg, Perreau, Matthieu, Klimkait, Thomas, Yerly, Sabine, Battegay, Manuel, Rauch, Andri, Schmid, Patrick, Bernasconi, Enos, Cavassini, Matthias, Kouyos, Roger D., Günthard, Huldrych F., Metzner, Karin J., and Fellay, Jacques

Published
2020
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17. Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART

Author

Bachmann, Nadine, von Siebenthal, Chantal, Vongrad, Valentina, Turk, Teja, Neumann, Kathrin, Beerenwinkel, Niko, Bogojeska, Jasmina, Fellay, Jaques, Roth, Volker, Kok, Yik Lim, Thorball, Christian W., Borghesi, Alessandro, Parbhoo, Sonali, Wieser, Mario, Böni, Jürg, Perreau, Matthieu, Klimkait, Thomas, Yerly, Sabine, Battegay, Manuel, Rauch, Andri, Hoffmann, Matthias, Bernasconi, Enos, Cavassini, Matthias, Kouyos, Roger D., Günthard, Huldrych F., Metzner, Karin J., and the Swiss HIV Cohort Study

Published
2019
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21. Sustained Effect on Hepatitis C Elimination Among Men Who Have Sex With Men in the Swiss HIV Cohort Study: A Systematic Re-Screening for Hepatitis C RNA Two Years Following a Nation-Wide Elimination Program

Author

Kusejko, Katharina, Salazar-Vizcaya, Luisa, Shah, Cyril, Stöckle, Marcel, Béguelin, Charles, Schmid, Patrick, Ongaro, Marie, Darling, Katherine, Bernasconi, Enos, Rauch, Andri, Kouyos, Roger D, Günthard, Huldrych F, Böni, Jürg, Fehr, Jan S, Braun, Dominique L, Swiss HIV Cohort Study, and University of Zurich

Subjects
10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 610 Medicine & health, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI)
Published
2022

22. A Systematic Molecular Epidemiology Screen Reveals Numerous Human Immunodeficiency Virus (HIV) Type 1 Superinfections in the Swiss HIV Cohort Study

Author

Chaudron, Sandra E, Leemann, Christine, Kusejko, Katharina, Nguyen, Huyen, Tschumi, Nadine, Marzel, Alex, Huber, Michael, Böni, Jürg, Perreau, Matthieu, Klimkait, Thomas, Yerly, Sabine, Ramette, Alban, Hirsch, Hans H, Rauch, Andri, Calmy, Alexandra, Vernazza, Pietro, Bernasconi, Enos, Cavassini, Matthias, Metzner, Karin J, Kouyos, Roger D, Günthard, Huldrych F, and University of Zurich

Subjects
10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 2723 Immunology and Allergy, 610 Medicine & health, 2725 Infectious Diseases
Published
2022

24. Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity

Author

Bertels, Frederic, Marzel, Alex, Leventhal, Gabriel, Mitov, Venelin, Fellay, Jacques, Günthard, Huldrych F, Böni, Jürg, Yerly, Sabine, Klimkait, Thomas, Aubert, Vincent, Battegay, Manuel, Rauch, Andri, Cavassini, Matthias, Calmy, Alexandra, Bernasconi, Enos, Schmid, Patrick, Scherrer, Alexandra U, Müller, Viktor, Bonhoeffer, Sebastian, Kouyos, Roger, and Regoes, Roland R

Published
2018
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25. Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study

Author

Swiss HIV Cohort Study, Drescher, Sara M., von Wyl, Viktor, Yang, Wan-Lin, Böni, Jürg, Yerly, Sabine, Shah, Cyril, Aubert, Vincent, Klimkait, Thomas, Taffé, Patrick, Furrer, Hansjakob, Battegay, Manuel, Ambrosioni, Juan, Cavassini, Matthias, Bernasconi, Enos, Vernazza, Pietro L., Ledergerber, Bruno, Günthard, Huldrych F., and Kouyos, Roger D.

Published
2014

26. Determinants of HIV-1 broadly neutralizing antibody induction

Author

Rusert, Peter, Kouyos, Roger D, Kadelka, Claus, Ebner, Hanna, Schanz, Merle, Huber, Michael, Braun, Dominique L, Hozé, Nathanael, Scherrer, Alexandra, Magnus, Carsten, Weber, Jacqueline, Uhr, Therese, Cippa, Valentina, Thorball, Christian W, Kuster, Herbert, Cavassini, Matthias, Bernasconi, Enos, Hoffmann, Matthias, Calmy, Alexandra, Battegay, Manuel, Rauch, Andri, Yerly, Sabine, Aubert, Vincent, Klimkait, Thomas, Böni, Jürg, Fellay, Jacques, Regoes, Roland R, Günthard, Huldrych F, Trkola, Alexandra, Bucher, Heiner C, Ciuffi, Angela, Dollenmaier, Günther, Egger, Matthias, Elzi, Luigia, Fehr, Jan, Furrer, Hansjakob, Fux, Christoph A, Haerry, David, Hasse, Barbara, Hirsch, Hans H, Hösli, Irene, Kahlert, Christian, Kaiser, Laurent, Keiser, Olivia, Kovari, Helen, Ledergerber, Bruno, Martinetti, Gladys, de Tejada, Begoña Martinez, Marzolini, Catia, Metzner, Karin J, Müller, Nicolas, Nicca, Dunja, Pantaleo, Giuseppe, Paioni, Paolo, Rudin, Christoph, Schmid, Patrick, Speck, Roberto, Stöckle, Marcel, Tarr, Philip, Vernazza, Pietro, Wandeler, Gilles, and Weber, Rainer

Subjects
Host-virus relationships, HIV infections -- Development and progression -- Care and treatment, Antibodies -- Observations, Immune response -- Observations, Biological sciences, Health
Abstract

Broadly neutralizing antibodies (bnAbs) are a focal component of HIV-1 vaccine design, yet basic aspects of their induction remain poorly understood. Here we report on viral, host and disease factors that steer bnAb evolution using the results of a systematic survey in 4,484 HIV-1-infected individuals that identified 239 bnAb inducers. We show that three parameters that reflect the exposure to antigen--viral load, length of untreated infection and viral diversity--independently drive bnAb evolution. Notably, black participants showed significantly (P = 0.0086-0.038) higher rates of bnAb induction than white participants. Neutralization fingerprint analysis, which was used to delineate plasma specificity, identified strong virus subtype dependencies, with higher frequencies of CD4-binding-site bnAbs in infection with subtype B viruses (P = 0.02) and higher frequencies of V2-glycan-specific bnAbs in infection with non-subtype B viruses (P = 1 x 10[sup.-5]). Thus, key host, disease and viral determinants, including subtype-specific envelope features that determine bnAb specificity, remain to be unraveled and harnessed for bnAb-based vaccine design., Author(s): Peter Rusert [1]; Roger D Kouyos [1, 2]; Claus Kadelka [1, 2]; Hanna Ebner [1]; Merle Schanz [1]; Michael Huber [1]; Dominique L Braun [1, 2]; Nathanael Hozé [3]; [...]

Published
2016
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27. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Author

Marconato, Maddalena, primary, Abela, Irene A., additional, Hauser, Anthony, additional, Schwarzmüller, Magdalena, additional, Katzensteiner, Rheliana, additional, Braun, Dominique L., additional, Epp, Selina, additional, Audigé, Annette, additional, Weber, Jacqueline, additional, Rusert, Peter, additional, Schindler, Eméry, additional, Pasin, Chloé, additional, West, Emily, additional, Böni, Jürg, additional, Kufner, Verena, additional, Huber, Michael, additional, Zaheri, Maryam, additional, Schmutz, Stefan, additional, Frey, Beat M., additional, Kouyos, Roger D., additional, Günthard, Huldrych F., additional, Manz, Markus G., additional, and Trkola, Alexandra, additional

Published
2022
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28. Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection

Author

Metzner, Karin J., Scherrer, Alexandra U., Preiswerk, Benjamin, Joos, Beda, von Wyl, Viktor, Leemann, Christine, Rieder, Philip, Braun, Dominique, Grube, Christina, Kuster, Herbert, Böni, Jürg, Yerly, Sabine, Klimkait, Thomas, Aubert, Vincent, Furrer, Hansjakob, Battegay, Manuel, Vernazza, Pietro L., Cavassini, Matthias, Calmy, Alexandra, Bernasconi, Enos, Weber, Rainer, and Günthard, Huldrych F.

Published
2013
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29. An Approach to Quantifying the Interaction between Behavioral and Transmission Clusters

Author

Salazar-Vizcaya, Luisa, Kusejko, Katharina, Günthard, Huldrych F, Böni, Jürg, Metzner, Karin J, Braun, Dominique L, Nicca, Dunja, Bernasconi, Enos, Calmy, Alexandra, Darling, Katharine E A, Wandeler, Gilles, Kouyos, Roger D, Rauch, Andri, Swiss HIV Cohort Study, University of Zurich, and Salazar-Vizcaya, Luisa

Subjects
10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 2406 Virology, 610 Medicine & health, 2725 Infectious Diseases
Published
2022

30. Secondary attack rates from asymptomatic and symptomatic influenza virus shedders in hospitals: Results from the TransFLUas influenza transmission study

Author

Tamò, Raphaël; https://orcid.org/0000-0002-2098-9392, Turk, Teja; https://orcid.org/0000-0003-3065-8578, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Schmutz, Stefan; https://orcid.org/0000-0002-1955-7007, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Shah, Cyril, Bischoff-Ferrari, Heike A, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Battegay, Edouard; https://orcid.org/0000-0001-9202-5034, Giovanoli, Pietro, Guckenberger, Matthias; https://orcid.org/0000-0002-7146-9071, Kohler, Malcolm; https://orcid.org/0000-0003-1800-8003, Müller, Rouven, Petry, Heidi; https://orcid.org/0000-0001-5220-4273, Ruschitzka, Frank; https://orcid.org/0000-0001-5972-0596, McGeer, Allison, Sax, Hugo; https://orcid.org/0000-0002-1532-2198, Weber, Rainer, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Kuster, Stefan P; https://orcid.org/0000-0002-0525-6529, Tamò, Raphaël; https://orcid.org/0000-0002-2098-9392, Turk, Teja; https://orcid.org/0000-0003-3065-8578, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Schmutz, Stefan; https://orcid.org/0000-0002-1955-7007, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Shah, Cyril, Bischoff-Ferrari, Heike A, Distler, Oliver; https://orcid.org/0000-0002-0546-8310, Battegay, Edouard; https://orcid.org/0000-0001-9202-5034, Giovanoli, Pietro, Guckenberger, Matthias; https://orcid.org/0000-0002-7146-9071, Kohler, Malcolm; https://orcid.org/0000-0003-1800-8003, Müller, Rouven, Petry, Heidi; https://orcid.org/0000-0001-5220-4273, Ruschitzka, Frank; https://orcid.org/0000-0001-5972-0596, McGeer, Allison, Sax, Hugo; https://orcid.org/0000-0002-1532-2198, Weber, Rainer, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, and Kuster, Stefan P; https://orcid.org/0000-0002-0525-6529

Abstract

OBJECTIVE: Nosocomial transmission of influenza is a major concern for infection control. We aimed to dissect transmission dynamics of influenza, including asymptomatic transmission events, in acute care. DESIGN: Prospective surveillance study during 2 influenza seasons. SETTING: Tertiary-care hospital. PARTICIPANTS: Volunteer sample of inpatients on medical wards and healthcare workers (HCWs). METHODS: Participants provided daily illness diaries and nasal swabs for influenza A and B detection and whole-genome sequencing for phylogenetic analyses. Contacts between study participants were tracked. Secondary influenza attack rates were calculated based on spatial and temporal proximity and phylogenetic evidence for transmission. RESULTS: In total, 152 HCWs and 542 inpatients were included; 16 HCWs (10.5%) and 19 inpatients (3.5%) tested positive for influenza on 109 study days. Study participants had symptoms of disease on most of the days they tested positive for influenza (83.1% and 91.9% for HCWs and inpatients, respectively). Also, 11(15.5%) of 71 influenza-positive swabs among HCWs and 3 (7.9%) of 38 influenza-positive swabs among inpatients were collected on days without symptoms; 2 (12.5%) of 16 HCWs and 2 (10.5%) of 19 inpatients remained fully asymptomatic. The secondary attack rate was low: we recorded 1 transmission event over 159 contact days (0.6%) that originated from a symptomatic case. No transmission event occurred in 61 monitored days of contacts with asymptomatic influenza-positive individuals. CONCLUSIONS: Influenza in acute care is common, and individuals regularly shed influenza virus without harboring symptoms. Nevertheless, both symptomatic and asymptomatic transmission events proved rare. We suggest that healthcare-associated influenza prevention strategies that are based on preseason vaccination and barrier precautions for symptomatic individuals seem to be effective.

Published
2022

31. A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits

Author

Nadeau, Sarah; https://orcid.org/0000-0003-1008-8918, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kouyos, Roger; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Yerly, Sabine; https://orcid.org/0000-0003-1668-696X, Perreau, Matthieu, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Vernazza, Pietro; https://orcid.org/0000-0002-6849-6941, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Mitov, Venelin; https://orcid.org/0000-0002-5227-5191, Stadler, Tanja; https://orcid.org/0000-0001-6431-535X, Swiss HIV Cohort Study (SHCS), Nadeau, Sarah; https://orcid.org/0000-0003-1008-8918, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kouyos, Roger; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Yerly, Sabine; https://orcid.org/0000-0003-1668-696X, Perreau, Matthieu, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Vernazza, Pietro; https://orcid.org/0000-0002-6849-6941, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Mitov, Venelin; https://orcid.org/0000-0002-5227-5191, Stadler, Tanja; https://orcid.org/0000-0001-6431-535X, and Swiss HIV Cohort Study (SHCS)

Abstract

Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. However, pathogen effects on a trait can be heritable from donor to recipient in transmission chains. Thus, residuals in GWAS association tests for host genetic effects may not be independent due to shared pathogen ancestry. We propose a new method to estimate and remove heritable pathogen effects on a trait based on the pathogen phylogeny prior to host GWAS, thus restoring independence of samples. In simulations, we show this additional step can increase GWAS power to detect truly associated host variants when pathogen effects are highly heritable, with strong phylogenetic correlations. We applied our framework to data from two different host-pathogen systems, HIV in humans and X. arboricola in A. thaliana. In both systems, the heritability and thus phylogenetic correlations turn out to be low enough such that qualitative results of GWAS do not change when accounting for the pathogen shared ancestry through a correction step. This means that previous GWAS results applied to these two systems should not be biased due to shared pathogen ancestry. In summary, our framework provides additional information on the evolutionary dynamics of traits in pathogen populations and may improve GWAS if pathogen effects are highly phylogenetically correlated amongst individuals in a cohort.

Published
2022

32. Detecting Selection in the HIV-1 Genome during Sexual Transmission Events

Author

Seifert, David; https://orcid.org/0000-0003-4739-5110, Joos, Beda; https://orcid.org/0000-0002-3082-8875, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Oberle, Corinna S, Schenkel, Corinne D, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Grube, Christina, Böni, Jürg, Yerly, Sabine, Aubert, Vincent; https://orcid.org/0000-0003-0352-9797, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Beerenwinkel, Niko; https://orcid.org/0000-0002-0573-6119, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Swiss HIV Cohort Study, Seifert, David; https://orcid.org/0000-0003-4739-5110, Joos, Beda; https://orcid.org/0000-0002-3082-8875, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Oberle, Corinna S, Schenkel, Corinne D, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Grube, Christina, Böni, Jürg, Yerly, Sabine, Aubert, Vincent; https://orcid.org/0000-0003-0352-9797, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Beerenwinkel, Niko; https://orcid.org/0000-0002-0573-6119, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, and Swiss HIV Cohort Study

Abstract

Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population. We analyzed 30 transmitter-recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes. We developed a new statistical test to detect selection during transmission, called Selection Test in Transmission (SeTesT), based on comparing the transmitter and recipient virus population and accounting for the transmission bottleneck. We performed extensive simulations and found that sensitivity of detecting selection during transmission is limited by the strong population bottleneck of few transmitted virions. When pooling individual test results across patients, we found two candidate HIV-1 genomic features for affecting transmission, namely amino acid positions 3 and 18 of Vpu, which were significant before but not after correction for multiple testing. In summary, SeTesT provides a general framework for detecting selection based on genomic sequencing data of transmitted viruses. Our study shows that a higher number of transmitter-recipient pairs is required to improve sensitivity of detecting selection.

Published
2022

33. An Approach to Quantifying the Interaction between Behavioral and Transmission Clusters

Author

Salazar-Vizcaya, Luisa; https://orcid.org/0000-0003-0527-0141, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Bernasconi, Enos, Calmy, Alexandra, Darling, Katharine E A, Wandeler, Gilles, Kouyos, Roger D, Rauch, Andri, Swiss HIV Cohort Study, Salazar-Vizcaya, Luisa; https://orcid.org/0000-0003-0527-0141, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Bernasconi, Enos, Calmy, Alexandra, Darling, Katharine E A, Wandeler, Gilles, Kouyos, Roger D, Rauch, Andri, and Swiss HIV Cohort Study

Abstract

We hypothesize that patterns of sexual behavior play a role in the conformation of transmission networks, i.e., the way you behave might influence whom you have sex with. If that was the case, behavioral grouping might in turn correlate with, and potentially predict transmission networking, e.g., proximity in a viral phylogeny. We rigorously present an intuitive approach to address this hypothesis by quantifying mapped interactions between groups defined by similarities in sexual behavior along a virus phylogeny while discussing power and sample size considerations. Data from the Swiss HIV Cohort Study on condom use and hepatitis C virus (HCV) sequences served as proof-of-concept. In this case, a strict inclusion criteria contrasting with low HCV prevalence hindered our possibilities to identify significant relationships. This manuscript serves as guide for studies aimed at characterizing interactions between behavioral patterns and transmission networks. Large transmission networks such as those of HIV or COVID-19 are prime candidates for applying this methodological approach.

Published
2022

34. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

Author

Marconato, Maddalena, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Katzensteiner, Rheliana, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Epp, Selina, Audigé, Annette, Weber, Jacqueline, Rusert, Peter, Schindler, Eméry, Pasin, Chloé, West, Emily, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Kufner, Verena; https://orcid.org/0000-0003-4233-5952, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Schmutz, Stefan; https://orcid.org/0000-0002-1955-7007, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Marconato, Maddalena, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Katzensteiner, Rheliana, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Epp, Selina, Audigé, Annette, Weber, Jacqueline, Rusert, Peter, Schindler, Eméry, Pasin, Chloé, West, Emily, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Kufner, Verena; https://orcid.org/0000-0003-4233-5952, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Schmutz, Stefan; https://orcid.org/0000-0002-1955-7007, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, and Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X

Abstract

BACKGROUNDNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated. METHODSWe conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends. RESULTSIn this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034). CONCLUSIONOur data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies. TRIAL REGISTRATIONClinicalTrials.gov NCT04869072. FUNDINGThis study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program "

Published
2022

35. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study

Author

Wittkop, Linda, Arsandaux, Julie, Trevino, Ana, Schim van der Loeff, Maarten, Anderson, Jane, van Sighem, Ard, Böni, Jürg, Brun-Vezinet, Françoise, Soriano, Vicente, Boufassa, Faroudy, Brockmeyer, Norbert, Calmy, Alexandra, Dabis, François, Jarrin, Inma, Dorrucci, Maria, Duque, Vitor, Fätkenheuer, Gerd, Zangerle, Robert, Ferrer, Elena, Porter, Kholoud, Judd, Ali, Sipsas, Nikolaos V., Lambotte, Olivier, Shepherd, Leah, Leport, Catherine, Morrison, Charles, Mussini, Cristina, Obel, Niels, Ruelle, Jean, Schwarze-Zander, Carolyne, Sonnerborg, Anders, Teira, Ramon, Torti, Carlo, Valadas, Emilia, Colin, Celine, Friis-Møller, Nina, Costagliola, Dominique, Thiebaut, Rodolphe, Chene, Geneviève, and Matheron, Sophie

Published
2017
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41. Ambiguous Nucleotide Calls From Population-based Sequencing of HIV-1 are a Marker for Viral Diversity and the Age of Infection

Author

the Swiss HIV Cohort Study, Kouyos, Roger D., von Wyl, Viktor, Yerly, Sabine, Böni, Jürg, Rieder, Philip, Joos, Beda, Taffé, Patrick, Shah, Cyril, Bürgisser, Philippe, Klimkait, Thomas, Weber, Rainer, Hirschel, Bernard, Cavassini, Matthias, Rauch, Andri, Battegay, Manuel, Vernazza, Pietro L., Bernasconi, Enos, Ledergerber, Bruno, Bonhoeffer, Sebastian, and Günthard, Huldrych F.

Published
2011
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42. A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits

Author

Nadeau, Sarah, Thorball, Christian W, Kouyos, Roger, Günthard, Huldrych F, Böni, Jürg, Yerly, Sabine, Perreau, Matthieu, Klimkait, Thomas, Rauch, Andri, Hirsch, Hans H, Cavassini, Matthias, Vernazza, Pietro, Bernasconi, Enos, Fellay, Jacques, Mitov, Venelin, Stadler, Tanja, Swiss HIV Cohort Study (SHCS), University of Zurich, and Stadler, Tanja

Subjects
10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, phylogenetic mixed model, 1105 Ecology, Evolution, Behavior and Systematics, genome-wide association study, 1311 Genetics, infectious disease, 1312 Molecular Biology, 570 Life sciences, biology, 610 Medicine & health, heritability
Abstract

Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. However, pathogen effects on a trait can be heritable from donor to recipient in transmission chains. Thus, residuals in GWAS association tests for host genetic effects may not be independent due to shared pathogen ancestry. We propose a new method to estimate and remove heritable pathogen effects on a trait based on the pathogen phylogeny prior to host GWAS, thus restoring independence of samples. In simulations, we show this additional step can increase GWAS power to detect truly associated host variants when pathogen effects are highly heritable, with strong phylogenetic correlations. We applied our framework to data from two different host-pathogen systems, HIV in humans and X. arboricola in A. thaliana. In both systems, the heritability and thus phylogenetic correlations turn out to be low enough such that qualitative results of GWAS do not change when accounting for the pathogen shared ancestry through a correction step. This means that previous GWAS results applied to these two systems should not be biased due to shared pathogen ancestry. In summary, our framework provides additional information on the evolutionary dynamics of traits in pathogen populations and may improve GWAS if pathogen effects are highly phylogenetically correlated amongst individuals in a cohort., Molecular Biology and Evolution, 39 (8), ISSN:0737-4038, ISSN:1537-1719

Published
2022
Full Text
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43. Detecting Selection in the HIV-1 Genome during Sexual Transmission Events

Author

Seifert, David, Joos, Beda, Braun, Dominique L, Oberle, Corinna S, Schenkel, Corinne D, Kuster, Herbert, Grube, Christina, Böni, Jürg, Yerly, Sabine, Aubert, Vincent, Klimkait, Thomas, Günthard, Huldrych F, Beerenwinkel, Niko, Metzner, Karin J, Swiss HIV Cohort Study, University of Zurich, Günthard, Huldrych F, Beerenwinkel, Niko, and Metzner, Karin J

Subjects
10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, HIV-1, transmission, transmitter–recipient pairs, Selection Test in Transmission (SeTesT), Vpu, ZPHI, SHCS, 2406 Virology, 610 Medicine & health, 2725 Infectious Diseases
Abstract

Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population. We analyzed 30 transmitter–recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes. We developed a new statistical test to detect selection during transmission, called Selection Test in Transmission (SeTesT), based on comparing the transmitter and recipient virus population and accounting for the transmission bottleneck. We performed extensive simulations and found that sensitivity of detecting selection during transmission is limited by the strong population bottleneck of few transmitted virions. When pooling individual test results across patients, we found two candidate HIV-1 genomic features for affecting transmission, namely amino acid positions 3 and 18 of Vpu, which were significant before but not after correction for multiple testing. In summary, SeTesT provides a general framework for detecting selection based on genomic sequencing data of transmitted viruses. Our study shows that a higher number of transmitter–recipient pairs is required to improve sensitivity of detecting selection., Viruses, 14 (2), ISSN:1999-4915

Published
2022
Full Text
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45. Molecular Epidemiology Reveals Long-Term Changes in HIV Type 1 Subtype B Transmission in Switzerland

Author

Swiss HIV Cohort Study, Kouyos, Roger D., von Wyl, Viktor, Yerly, Sabine, Böni, Jürg, Taffé, Patrick, Shah, Cyril, Bürgisser, Philippe, Klimkait, Thomas, Weber, Rainer, Hirschel, Bernard, Cavassini, Matthias, Furrer, Hansjakob, Battegay, Manuel, Vernazza, Pietro L., Bernasconi, Enos, Rickenbach, Martin, Ledergerber, Bruno, Bonhoeffer, Sebastian, and Günthard, Huldrych F.

Published
2010

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