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

EBioMedicine. 2021 Dec:74:103705. doi: 10.1016/j.ebiom.2021.103705. Epub 2021 Nov 30.


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.

Keywords: CAR-T; HIV; Immunocompromised patients; Primary Immunodeficiency; chronic lymphocytic leukemia; human stem-cell transplantation; mRNA BNT162b2 vaccine; solid organ transplantation.

Publication types

  • Clinical Trial

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Antibodies, Viral / blood
  • BNT162 Vaccine / adverse effects*
  • BNT162 Vaccine / immunology*
  • COVID-19 / prevention & control
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunocompromised Host / immunology*
  • Immunogenicity, Vaccine / immunology*
  • Immunotherapy, Adoptive
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / therapeutic use
  • Organ Transplantation
  • Piperidines / adverse effects
  • Piperidines / therapeutic use
  • Primary Immunodeficiency Diseases / immunology
  • Prospective Studies
  • SARS-CoV-2 / immunology*
  • Seroconversion
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination / adverse effects
  • Vaccine Efficacy


  • Antibodies, Viral
  • Piperidines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ibrutinib
  • Mycophenolic Acid
  • Adenine
  • BNT162 Vaccine