SARS-CoV-2 messenger RNA vaccine antibody response and reactogenicity in heart and lung transplant recipients

Abstract

Background: While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. Methods: US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. Results: Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p<0.001). Priming dose antibody response was associated with younger recipient age (p=0.04), transplant-to-vaccination time ≥ 6 years (p<0.01), and lack of anti-metabolite maintenance immunosuppression (p<0.001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. Conclusions: HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…Forty-seven studies described immunogenicity across various solid organ transplant populations ( n = 5974), mostly in kidney transplant recipients ( n = 3534, 59.2%) ( Table S5 ) [ 18 , [20] , [21] , [22] , [23] , [24] , [25] , [26] , 29 , 34 , 40 , [56] , [57] , [58] ], [ 62 , 63 , 65 , 66 , 69 , 72 , 73 , 75 , 77 , 79 , 81 , 120 , 126 ], [ [136] , [137] , [138] , [139] , [140] , [141] , [142] , [143] , [144] , [145] , [146] , [147] , [148] , [149] , [150] , [151] , [152] , [153] , [154] , [155] , [156] , [157] , [158] , [159] , [160] ]. Twenty-four of those studies included a control group representing overall 1399 participants [ 21 , 34 , 57 , 63 , 66 , 69 , 72 , 73 , 75 , 79 , ...…”

“…Solid organ transplant-specific treatments (calcineurin inhibitors, antimetabolites, corticosteroids) were often associated with a higher non-response rate or lower antibody titres [ 20 , 21 , 24 , 40 , 56 , 62 , 65 , 69 , 72 , 75 , 81 , 136 , [138] , [139] , [140] , [141] , [142] , 144 , 145 , 148 , [154] , [155] , [156] , [157] , 159 , 160 ] ( Table S5 ). Older age and lower estimated glomerular filtration rate were repeatedly associated with a non-responder status [ 21 , 24 , 79 , 120 , 138 , 142 , 144 , 155 ].…”

“…We found conflicting results regarding the impact of time since transplantation on vaccine response: seven studies found higher non-response rates or lower antibody titres in patients with recent transplantation, Rozen-Zvi et al. [ 138 ] found a longer time from transplantation was associated with lower antibody titres [ 21 , 62 , 79 , 139 , 141 , 143 , 155 , 160 ].…”

Efficacy of COVID-19 vaccines in patients taking immunosuppressants

“…Studies have shown that COVID-19 vaccines have reduced immunogenicity in immunosuppressed individuals compared with immunocompetent individuals. [5][6][7][8] In the limited epidemiological research thus far, the approved vaccines appear to be less effective in immunosuppressed individuals relative to the general population. [9][10][11] However, these studies were all limited by either small sample size, individuals with a specific condition, a single vaccine or a short study period before the Delta variant became dominant and booster dose approved.…”

“…Since approval, the vaccines have been highly effective at preventing SARS-CoV-2 infection and severe illness,4 but there is still limited evidence regarding vaccine effectiveness in immunosuppressed individuals. Studies have shown that COVID-19 vaccines have reduced immunogenicity in immunosuppressed individuals compared with immunocompetent individuals 5–8. In the limited epidemiological research thus far, the approved vaccines appear to be less effective in immunosuppressed individuals relative to the general population 9–11.…”