key: cord-0751486-df4k1ki7
authors: Hoffman, Thijs W.; Meek, B.; Rijkers, G.T.; van Kessel, D.A.
title: Poor Serologic Response to 2 Doses of an mRNA-based SARS-CoV-2 Vaccine in Lung Transplant Recipients
date: 2021-10-01
journal: Transplantation
DOI: 10.1097/tp.0000000000003966
sha: 8da4e3b165d4e0e362a3ae30bf0c561a51cf194c
doc_id: 751486
cord_uid: df4k1ki7

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Thijs W. Hoffman, MD, 1 B. Meek, PhD, 2 G.T. Rijkers, PhD, 3 and D.A. van Kessel, MD, PhD 1, 4 L ung transplant recipients are at an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination against SARS-CoV-2 has been recommended, 1 but an impaired response has been observed in solid organ transplant recipients. 2 For lung transplant recipients, impaired response to vaccination might be an especially pressing issue, as they usually receive more intensive immunosuppressive therapy compared with other solid organ transplant recipients. However, lung transplant recipients only represented a small proportion of the solid organ transplant recipients in whom the response to SARS-CoV-2 vaccines has been studied.

In this study, we analyzed the serologic response to 2 doses of an mRNA-based SARS-CoV-2 vaccine in our cohort of 91 lung transplant recipients who were vaccinated in April and May 2021 (BNT162b2 [n = 2] or mRNA-1273 [n = 89]). The median time since lung transplantation was 5.35 y (interquartile range, 1.87-9.71 y). SARS-CoV-2 spike S1/S2 protein-specific immunoglobulin G antibody levels were measured before, 4 wk after the first dose and 6 wk after the second dose on the Liaison platform (DiaSorin, Saluggia, Italy). All patients gave written informed consent for the use of their data in clinical research. The study was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki.

In patients without COVID-19 before vaccination, the serologic response rate after 2 vaccine doses was 27% ( Figure 1) . Notably, in patients who had COVID-19 before vaccination (n = 12), the response rate was significantly higher at 75% (P = 0.002). This confirms that immunological memory is induced during and after the infection even in this immunocompromised patient population. This would argue for repeated exposure to SARS-CoV-2 antigens as a method for obtaining an improved serologic response. Importantly, 2 recent studies showed a clear improvement in serologic responses after a third dose of a SARS-CoV-2 vaccine in solid organ transplant recipients. 3, 4 In contrast, there were 3 patients who had COVID-19 before vaccination but did not develop measurable antibodies after the vaccinations. Thus, even having had COVID-19 is not likely to be protective in all solid organ transplant patients. We have not witnessed breakthrough infections in our patients thus far, but these have been reported in other solid organ transplant recipients who had received a complete vaccination schedule. 5 A positive serologic response was also associated with younger age (P = 0.002), not using tacrolimus as an immunosuppressant (P = 0.04), and a normal response to previous pneumococcal vaccination (P = 0.03). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone. In a multivariate model, both age at vaccination and having had COVID-19 before vaccination retained statistical significance (P = 0.002 and P = 0.002, respectively).

In conclusion, and important for clinical practice, the response to mRNA-based SARS-CoV-2 vaccines is poor in lung transplant recipients. Factors associated with a positive serologic response were younger age at vaccination, having had COVID-19 before vaccination, and not using tacrolimus as an immunosuppressant. Lung transplant recipients will likely remain at risk for severe COVID-19, even after SARS-CoV-2 vaccination. Future studies will have to determine the optimal vaccination schedule.

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Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients

Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients

Clinically significant COVID-19 following SARS-CoV-2 vaccination in kidney transplant recipients

All values below the lower detection limit of the assay were set to 0. After the second vaccination, antibody levels were significantly higher in patients who had had COVID-19 before vaccination (n = 12) compared with patients who had not had COVID-19 (n = 80; median 800 AU/mL

The dashed line represents the 2.5th percentile value of anti-SARS-CoV-2 IgG antibodies after the first and second vaccination in 102 healthy volunteers, as provided by the manufacturer (after the first vaccination, the 2.5th percentile was 25 AU/mL, and the median value 138 AU/mL; after the second vaccination, the 2.5th percentile was 372 AU/mL and the median value 1706 AU/mL

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2