Vaccine Effectiveness in Immunocompromised Patients

Key Points are meant to be a scientific, factual summary of the available information, focusing on monovalent Pfizer- BioNTech COVID-19 Vaccine or mRNA COVID-19 vaccines, as supported by referenced publications within this section. Conclusions should not be drawn from the inclusion or absence of information.

• Immunocompromised (IC) populations may be susceptible to impaired immune response to vaccination and to severe outcomes, such as hospitalization or death.^1-6 CDC guidelines for monovalent BNT162b2 currently recommend a 3- dose vaccine primary series, followed by an updated bivalent booster dose for those who are moderately or severely immunocompromised and aged 5 years or older.⁷

• Vaccine effectiveness (VE) of monovalent BNT162b2 vaccine has been evaluated in Real-World Evidence (RWE) studies of diverse IC populations, including those with a history of malignancy, organ transplantation, immune-mediated disorders, and immunodeficiencies.^1,4-6

• RWE Studies in IC patient populations:
  • Participants with a history of cancer, rheumatologic disorders, immunodeficiencies, and organ transplantation:
    • Three RWE studies conducted in the US described VE of 2^1-3 and 3 doses^2,3 of monovalent mRNA vaccines against confirmed COVID-19 infection and hospitalization in immunocompromised (those with solid and hematologic malignancies; rheumatologic or inflammatory disorders; organ or stem cell transplant; other intrinsic immune conditions or immunodeficiencies; HIV infection with and without AIDS; previous splenectomy, and use of immunosuppressive medications) and immunocompetent adults, during a Delta (B.1.617.2) predominant period.¹
    • Vaccine Effectiveness, in % (95% CI), in these populations is summarized below. The listed studies cannot be compared due to differences in study design and methodologies.

  Study	Embi et al, MMWR 1			Tenforde et al, MMWR 2			Tartof et al, Lancet Reg Health Am 3
  Population	≥ 18 years, immunocompetent and immunocompromised			≥ 18 years, immunocompetent and immunocompromised			≥ 18 years, immunocompetent and immunocompromised
  Endpoint time period	≥ 14 days after 2nd dose [Reference: unvaccinated]			≥28 days after 2nd dose, ≥ 180 days after 2nd dose, ≥7 days after 3rd dose [Reference: unvaccinated]			≥ 7 days after 2nd dose; ≥ 14 days after 3rd dose [Reference: unvaccinated; ≥ 6 months after 2nddose]
  Study period	January 2021- September 2021 (Delta B.1.617.2 variant)			August 2021- December 2021 (Delta B.1.617.2 variant)			December 2020- December 2021 (Delta B.1.617.2 variant)
  Vaccine effectiveness (VE) outcome:	VE% (95%CI)     VE% (95%CI)			VE% (95%CI)     VE% (95%CI)			VE% (95%CI)     VE% (95%CI)
  Confirmed infection* *Confirmed infection= laboratory-confirmed infection with positive SARS-CoV-2 RT-PCR.	Not reported in this study			Not reported in this study			Vaccine: BNT162b2	Immunocompetent (N= 3,042,930)	Immunocompromised (N=90,145)
  							≥ 7 days after 2nd dose*	64 (59-68)	65 (27-83)
  							≥ 14 days after 3rd dose*	88 (86-90)	84 (75-90)
  							≥ 14 days after 3rd dose**	76 (72-79	68 (49-80)
  Hospitalization	Vaccine:	Immunocompetent (N= 69,116)	Immunocompromised (N=20,101)	Vaccine: Any mRNA Vaccine	Immunocompetent (N= 1,875)	Immunocompromised (N=1,077)	Vaccine: BNT162b2	Immunocompetent (N= 3,042,930)	Immunocompromised (N=90,145)
  	BNT162b2 (≥ 18 years)	88 (86-89)	71 (65-76)	≥ 28 days after 2nd dose	Not reported	69 (57-78)	≥ 7 days after 2nd dose*	85 (75-91)	87 (4-98)
  	Any mRNA Vaccine (≥ 18 years)	90 (89-91)	77 (74-80)	≥ 180 days after 2nd dose	82 (77-86)	Not reported	≥ 14 days after 3rd dose*	98 (96-99)	87 (70-95)
  	Any mRNA Vaccine (18-64 years)	93 (92-94)	80 (74-84)	≥ 7 days after 3rd dose	97 (95-99)	88 (81-93)	≥ 14 days after 3rd dose**	79 (56-90)	55 (-11-82)
  	Any mRNA Vaccine (≥ 65 years)	87 (86-88)	75 (70-79)

  *Compared to unvaccinated; **Compared to ≥ 6 months after 2nd dose

  
  
• Participants with history of organ transplantation, inflammatory bowel disease (IBD), and immune-mediated inflammatory disease:
  • RWE studies have described VE of monovalent BNT162b2 or other mRNA vaccines in solid organ and islet transplant recipients⁴, in participants with inflammatory bowel disease and exposure to immunosuppressive medications⁵, and in participants with immune-mediated inflammatory diseases⁶. Vaccine Effectiveness, in % (95% CI), in these IC populations, compared to unvaccinated participants, is summarized in the table below. The listed studies cannot be compared due to differences in study design and methodologies.

a RA= Rheumatoid arthritis; b IBD= Inflammatory Bowel Disease; c AS= Ankylosing Spondylitis; d NR= not reported due to near zero exposures among test- positive cases and imprecise 95% confidence intervals.

• IC participants were observed to have lower VE against SARS-CoV-2 infection³ and hospitalization^1-3, compared to immunocompetent participants, in some of the studies described in this summary.
• Solid organ transplant recipients were observed to have lower VE against confirmed COVID-19 infection⁴, than the other IC populations^5,6 in the studies described in this summary.
• Two or three doses of monovalent mRNA COVID-19 vaccine provided protection against confirmed COVID-19 infection, and hospitalization or death in participants with immune- mediated inflammatory disease (IBD, RA, AS, psoriasis).^5,6 After two monovalent vaccine doses, effectiveness against infection generally peaked 31–60 days after vaccination and waned gradually with each additional month.⁶

References: (1) Embi; (2) Tenforde;(3) Tartof;(4) Callaghan;(5) Khan; (5) Widdifield;(7) COVID-19 Vaccines for People Who Are Moderately or Severely Immunocompromised | CDC