Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
Peter Bergman, MD,
Ola Blennow, MD,
Lotta Hansson, MD,
Stephan Mielke, MD,
Piotr Nowak, MD,
Puran Chen, MD,
Gunnar Söderdahl, MD,
Anders Österborg, MD,
C. I. Edvard Smith, MD,
David Wullimann, MSc,
Jan Vesterbacka, MD,
Gustaf Lindgren, MD,
Lisa Blixt, MD,
Gustav Friman, MD,
Emilie Wahren-Borgström, MD,
Anna Nordlander, MD,
Angelica Cuapio Gomez, MD,
Mira Akber, MSc,
Davide Valentini, MD,
Anna-Carin Norlin, MD,
Anders Thalme, MD,
Gordana Bogdanovic, MD,
Sandra Muschiol, PhD,
Peter Nilsson, PhD,
Sophia Hober, PhD,
Karin Loré, PhD,
Margaret Sällberg Chen, PhD,
Marcus Buggert, PhD,
Hans-Gustaf Ljunggren, MD,
Per Ljungman, MD,
Soo Aleman, MD
Affiliations
Peter Bergman, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden
Ola Blennow, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Lotta Hansson, MD
Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Stephan Mielke, MD
Department of Laboratory Medicine, Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
Piotr Nowak, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Laboratory for Molecular Infection Medicine Sweden MIMS, Umeå University, Sweden
Puran Chen, MD
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Gunnar Söderdahl, MD
Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Anders Österborg, MD
Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
C. I. Edvard Smith, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
David Wullimann, MSc
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Jan Vesterbacka, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Gustaf Lindgren, MD
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
Lisa Blixt, MD
Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Gustav Friman, MD
Department of Transplantation, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Emilie Wahren-Borgström, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Anna Nordlander, MD
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
Angelica Cuapio Gomez, MD
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Mira Akber, MSc
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Davide Valentini, MD
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden
Anna-Carin Norlin, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Anders Thalme, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Gordana Bogdanovic, MD
Dept of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
Sandra Muschiol, PhD
Dept of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Peter Nilsson, PhD
Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden
Sophia Hober, PhD
Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden
Karin Loré, PhD
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Margaret Sällberg Chen, PhD
Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
Marcus Buggert, PhD
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Hans-Gustaf Ljunggren, MD
Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Per Ljungman, MD
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Medicine Huddinge, Hematology, Karolinska Institutet, Stockholm
Soo Aleman, MD
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Corresponding author: Soo Aleman, Department of Infectious Diseases, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity. Funding: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden.
