Investigators have identified several risk factors for diminished antibody response to COVID-19 vaccination in solid organ transplant (SOT) recipients.

Nitipong Permpalung, MD, MPH, of Johns Hopkins University School of Medicine, Baltimore, Maryland, who is the study’s corresponding author, and colleagues performed a systematic review of 83 studies and a meta-analysis of 29 studies involving 11,713 SOT recipients who received at least 1 dose of a COVID-19 vaccine. Mean humoral response for antispike antibodies after receipt of an mRNA vaccine was 10.4% after 1 dose, 44.9% after 2 doses, and 63.1% after 3 doses, the investigators reported in JAMA Network Open. In 2 studies, 50% of SOT recipients with no or minimal antibody response after 3 doses of an mRNA vaccine mounted an antibody response after a fourth dose.

Responders were nearly 4 years younger on average than nonresponders, the investigators reported. Deceased donor status, recent antithymocyte globulin exposure, antimetabolite use, and recent rituximab exposure were significantly associated with 34%, 68%, 79%, and 79% lower odds of response, respectively.

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“We hypothesize that lower seroconversion with these agents could be caused by direct suppression of B-lymphocyte function or suppression of T-lymphocyte-dependent B-lymphocyte activation,” the investigators stated. They noted that several current trials are investigating immunogenicity in SOT recipients after modulation of immunosuppression.

In December 2021, the FDA issued an emergency use authorization for tixagevimab-cilgavimab, a combination of long-acting monoclonal antibodies for preexposure prophylaxis in patients who are immunocompromised, including SOT recipients. The risk factors identified in this study for lower seroconversion rates may help clinicians and patients make decisions about active vs passive immunization from monoclonal antibodies.

In an accompanying editorial, Alan Koff, MBBS, of the University of California Davis School of Medicine in Sacramento, and colleagues commented:

“As COVID-19 hospitalizations decline and states reopen businesses, relax mask requirements, and loosen travel restrictions, studies like this one by Manothummetha et al remind us that we continue to have a moral obligation to protect the members of our society at highest risk of severe disease and death.”

The editorialists added that novel vaccination strategies, prophylactic, and therapeutic agents are needed to protect those with suboptimal response or contraindications to COVID-19 vaccination.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Manothummetha K, Chuleerarux N, Sanguankeo A, et al. Immunogenicity and risk factors associated with poor humoral immune response of SARS-CoV-2 vaccines in recipients of solid organ transplant. JAMA Network Open. Published online April 12, 2022. doi:10.1001/jamanetworkopen.2022.6822

Koff A, Malinis M. Suboptimal antispike antibody levels following vaccination in recipients of solid organ transplant—variance of concern. JAMA Network Open. Published online April 12, 2022. doi:10.1001/jamanetworkopen.2022.6880