DOI: 10.1111/ajt.16855 LETTER TO THE EDITOR AJT Reconciling short-­term clinical and immunological outcomes of SARS-­CoV-­2 vaccination in solid organ transplant recipients To the Editor: S2), independently of the progressive reduction of infection rates ob- Relevant concerns are being raised regarding the weak serological served over the same time period in the general population (Figure response of solid organ transplant (SOT) recipients after receiving S1). Notably, the same adjusted incidences of patients requiring hos- two doses of messenger RNA-­ based vaccine against the severe pitalization, ICU admission, and deaths related to COVID-­19 signifi- acute respiratory syndrome coronavirus 2 (SARS-­CoV-­2)1 and some cantly decreased after vaccination (Table S2). Therefore, we did not severe cases of coronavirus disease (COVID-­19) occurring after vac- make any recommendation for further vaccine booster aimed at im- cination. 2 Thus, additional preventive booster doses are proposed to proving this initial protection during this initial timeframe. 3,4 enhance anti-­viral immunity. Interestingly, the reduction in COVID-­ 19 infections, did also In this regard, recent reports have shown the immunological overlap with less restrictive community measures and a marked response to a third dose of the two main mRNA-­based vaccines reduction of virus circulation, thus suggesting on the one hand a (BNT162b2; Pfizer–­ BioNTech or mRNA-­ 1273; Moderna) leading progressive generation of herd immunity (due to a widespread vacci- to an increase in IgG seroconversion rates from 40% to 50%–­70% nation policy) and less viral infectivity, and on the other, the relative 4 weeks after, especially among those with detectable antibodies role of other protective immunological mechanisms such as virus-­ after the two doses. Despite that no SARS-­CoV-­2 infections oc- specific cellular immunity controlling viral replication. Altogether, curred, these data suggest the need of booster doses in this par- while generalized booster vaccinations seem to be likely necessary ticularly vulnerable patient population. Nevertheless, while this among SOT in view of the low seroconversion rates, especially with evidence points toward an impaired adaptive immune response to the now-­predominant Delta variant, the question is whether a vac- vaccination in SOT patients,5 the short-­term clinical scenario of the cine should treat numbers or improve clinical outcomes, thus a bet- incidence of COVID-­19 among SOT after two vaccine doses does ter immune-­risk stratification of SOT patients and the development not fully support this biological feature. of interventional clinical trials aiming at conferring immune protec- To investigate this question, we took advantage of the rapid vac- tion, also involving these biomarkers, is highly warranted. cine prioritization of SOT patients in our country, which was done over a 3-­week period starting late February 2021, and by early May, K E Y WO R D S up to 90% of the total SOT population had received the two doses clinical research/practice, editorial/personal viewpoint, (http://trasp​lanta​ments.gencat.cat). immunosuppression/immune modulation, infection and infectious Remarkably, in our SOT center (the largest in Spain [http://www. agents -­viral, infectious disease, kidney transplantation/ ont.es/infes​ p/Pagin​ as/Memor​ ias.aspx]), the incidence of SARS-­ nephrology, monitoring: immune, vaccine CoV-­2 infection markedly dropped during the 4 months after vaccina- tion (March–­June) (Figure 1, Table S1). Out of the total 117 detected D I S C LO S U R E infections over this 8-­month period, 103 (88%) occurred before and The authors of this manuscript have no conflicts of interest to dis- only 14 (12%) after vaccination occurring 6/14 (42.8%) infections close as described by the American Journal of Transplantation. between the first and second dose. This difference was observed across all types of SOT and remained significant in a multivariate Oriol Bestard1,2 Poisson model accounting for age, gender, and type of SOT and im- Thomas Jouve2 munosuppression (incidence ratio [IR] 0.211, p < .001) (Figure S2). Lluís Castells3,4 To assess the independent effect of the two-­dose vaccination, we Manuel Lopez5 compared COVID-­19 rates between SOT and the general population Marina Muñoz6 in our region (www.dades​covid.cat) using a Poisson regression model Elena Crespo2 analyzing the influence of the investigation period on COVID-­19 in- Nestor Toapanta1 cidences. Interestingly, the effect of vaccination era (before/after) Juliana Esperalba7 had a significant impact on IRs of vaccination (0.50, p < .001) (Table Isabel Campos-­Varela3,4 © 2021 The American Society of Transplantation and the American Society of Transplant Surgeons Am J Transplant. 2021;00:1–3.  amjtransplant.com | 1 2 | AJT LETTER TO THE EDITOR (A) F I G U R E 1 SARS-­CoV-­2 infections over time, from November 1, 2020 to June 30, 2021, at Vall d'Hebron University Hospital. Each dot represents an infected patient. (A) Colors represent Infection cases SarsCov2 serology SARS-­CoV2 Spike IgG serologies (blue: Neg unknown serology [due to the lack of Pos sample], red: non detectable SARS-­CoV-­2 Unknown IgG antibodies, and green: detectable SARS-­CoV-­2 Spike IgG antibodies). (B) Colors represent mortality (orange dots Post 2nd dose are patients deceased from COVID-­19). Pre−vaccination Post 1st dose Dashed lines represent the vaccination periods (first and second doses) Nov Dec Jan Feb Mar Apr May Jun Jul Time (B) Infection cases Mortality Survived Deceased Post 2nd dose Pre−vaccination Post 1st dose Nov Dec Jan Feb Mar Apr May Jun Jul Time Teresa Pont8 Barcelona, Barcelona, Spain Oscar Len9 7 Microbiology Department, Vall d'Hebron Hospital Universitari, Magda Campins10 Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Francesc Moreso1,2 Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain 1 8 Kidney Transplant Unit, Nephrology Department, Vall d'Hebron Transplant Coordination Department, Vall d'Hebron Hospital Hospital Universitari, Vall d'Hebron Institut de Recerca Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Autònoma de Barcelona, Barcelona, Spain Barcelona, Barcelona, Spain 2 9 Laboratory of Nephrology and Transplantation, Vall d'Hebron Infectious Disease Department, Vall d'Hebron Hospital Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall Campus, Universitat Autònoma de Barcelona, Barcelona, Spain d'Hebron Barcelona Hospital Campus, Universitat Autònoma de 3 Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona, Barcelona, Spain 10 Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Deparment of Preventive Medicine and Epidemiology, Vall Campus, Universitat Autònoma de Barcelona, Barcelona, Spain d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca 4 Centro de Investigación Biomédica en Red de Enfermedades (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Autònoma de Barcelona, Barcelona, Spain Madrid, Spain 5 Lung Transplant Unit, Vall d'Hebron Hospital Universitari, Vall Correspondence d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Oriol Bestard, Kidney Transplant Unit, Nephrology Hospital Campus, Universitat Autònoma de Barcelona, Department, Vall d'Hebron Hospital Universitari, Vall Barcelona, Spain d'Hebron Institut de Recerca (VHIR), Vall d'Hebron 6 Pediatric Transplant Department, Vall d'Hebron Hospital Barcelona Hospital Campus, Universitat Autònoma de Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall Barcelona, Barcelona, Spain. d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Email: obestard@vhebron.net LETTER TO THE EDITOR AJT | 3 3. Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA ORCID Covid-­19 vaccine in solid-­organ transplant recipients. N Engl J Med. Oriol Bestard https://orcid.org/0000-0001-9468-7920 2021;385:661–­662. Thomas Jouve https://orcid.org/0000-0001-9016-7506 4. Benotmane I, Gautier G, Perrin P, et al. Antibody response after a third dose of the mRNA-­ 1 273 SARS-­ C oV-­2 vaccine in kid- Nestor Toapanta https://orcid.org/0000-0001-5983-6863 ney transplant recipients with minimal serologic response to Isabel Campos-­Varela https://orcid.org/0000-0001-6597-3151 2 doses. JAMA. 2021;326(11):1063. https://doi.org.10.1001/ Teresa Pont https://orcid.org/0000-0003-4409-1189 jama.2021.12339 Francesc Moreso https://orcid.org/0000-0002-7267-3963 5. Rincon-­A revalo H, Choi M, Stefanski A-­L , et al. Impaired hu- moral immunity to SARS-­ C oV-­ 2 BNT162b2 vaccine in kid- ney transplant recipients and dialysis patients. Sci Immunol. REFERENCES 2021;6(60):eabj1031. 1. 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