key: cord-0695987-5dcdos2k authors: Castelló, Isabel Beneyto; Maestre, Elena Moreno; Escorihuela, David Ramos; Reig, Jordi Espí; Galiano, Ana Ventura; Cebrián, María Ramos; Espinosa, Marta Moreno; Borrás, Pablo González-Calero; Jaras, Julio Hernández title: SARS-CoV-2 Infection after vaccination: kidney transplant recipient profile and disease evolution in a single centre. date: 2022-01-07 journal: Transplant Proc DOI: 10.1016/j.transproceed.2021.12.013 sha: b3d730ce1dffbb526b3a3f99901f920c186eaea3 doc_id: 695987 cord_uid: 5dcdos2k Background SARS-CoV-2 infection has had a major impact on kidney transplant patients. Recent evidence suggests that solid organ transplant recipients who received mRNA vaccines reach low immunization rates. There are only few reports about the risk factors and severity of COVID-19 disease in these patients. Our single centre experience describes the patient profile and disease evolution observed in this vulnerable group after inoculation. Material and methods Retrospective cohort study with kidney transplant patients who received a COVID-19 vaccine before testing positive for SARS-CoV-19 using polymerase chain reaction (PCR). Demographic characteristics and clinical information are described and compared with our previous series of patients who were infected before the initiation of the vaccination rollout. Results Sixteen kidney transplant recipients diagnosed with COVID-19 after being vaccinated were included and compared with our previous series of 76 unvaccinated positive patients. No differences were found among risk factors such as age, time after transplant, hypertension and obesity between groups (p-value > 0.05). After COVID-19 diagnosis among inoculated patients, ten patients were hospitalized, and 4 of whom met the criteria for admission to the intensive care unit (ICU). Three patients died due to COVID-19 complications. Despite this, the incidence of infections has decreased after vaccination rollout (p-value < 0.05). Conclusion Patients’ risk profiles remain constant among positive COVID-19 recipients between waves. We did not find significant differences in hospitalization and severity rates in this reduced group of patients. However, the overall incidence in our kidney transplant population has decreased. March 2020, all countries around the world have registered a large number of cases in different waves that have brought their health-care systems to the limit of saturation. Several factors such as advanced age, obesity, diabetes mellitus, hypertension and cardiovascular pathology have been associated with disease severity in the general population. Against this backdrop, solid organ transplant patients are a major risk group given the high prevalence of these factors in addition to their chronic immunosuppressive state [1, 2] . The mortality rates among kidney transplant patients vary in different reports, but are high, especially in the elderly and in the early post-transplant period [3, 4] . A report of the Spanish Registry shows differences in overall mortality between the first (March-June) and second (July-December) wave (27.4% vs 15.1%) but similar rates in critical patients [5] . After initiation of the vaccination rollout in kidney transplant patients, several reports have indicated an impaired anti-SARS-CoV-2 antibody response in the context of maintenance immunosuppression [6] . This situation raised concerns about their protective effect and the susceptibility and severity of the disease after vaccination in these patients. The aim of this communication is to describe, and provide a first approach to, the profile of the kidney transplant recipient diagnosed of SARS-CoV-2 after vaccination in our unit looking into their evolution, severity of the disease and differences with respect to unvaccinated patients of the previous COVID-19 waves. Retrospective cohort study that included all adult kidney transplant recipients with a functioning allograft who tested positive for SARS-CoV-2 between March 16th 2020 and September 6th 2021. For the purpose of analysis, data was divided into two groups: our previous series of 76 patients, infected between March 16th 2020 and February 11th 2021 before vaccination rollout, and the 16 recipients who tested positive between May 18th 2021 and September 6th 2021 after receiving the vaccine at our centre. Our first goal was to describe and compare the characteristics and evolution of these patients. Since the recipients in the first group completely differ from those in the second group, we treated them as independent measures. Secondly, in order to know if the proportion of contagions had decreased between waves in our overall population of functioning allografts after vaccination rollout, data was treated as paired. The information about demographic, clinical, laboratory and comorbidity data was extracted from electronic medical records at our centre. SARS-CoV-2 diagnosis was based on the polymerase chain reaction (PCR) test by means of a nasopharyngeal swab. Categorical variables were summarized with counts and percentages, while quantitative variables included minimum-maximum, means (standard deviation) and medians (IQRs), where appropriate. Chi-squared test was performed for qualitative variable comparison, replaced by Fisher exact test when cell value < 5. Differences between quantitative variables were assessed with the non-parametric Mann-Whitney U test, regarding the lack of normality and appeal to the Central Limit Theorem due to the small sample size. The analysis of infection proportion change between waves in our 1500 functioning allografts was evaluated using the McNemar test for paired data. A P-value of < 0.05 was considered significant. Analyses were performed using R Statistical Software (version 4.0.4). Since the outbreak of the pandemic in March 2020 until February 2021, 76 kidney transplant recipients were diagnosed with COVID-19 before the vaccine rollout started ( Table 1) . Between April and May 2021, the patients at our centre received a COVID-19 vaccine. As of May 18th, 16 of whom developed SARS-CoV-2 infection after vaccination. Thus, a total of 92 patients out of 1500 functioning allografts (6.13%) at our centre were infected since the start of the pandemic. "For several reasons, we were unable to obtain the results regarding antibodies in all of our functioning allografts (a total of 1500). Thus, only a small percentage of patients infected with SARS-CoV-2 after vaccination had this parameter tested, making it unfeasible to draw any type of correlation and therefore this information was not included. This is the reason why we adopted a conservative attitude regarding the effectiveness of the vaccine, focusing instead on the patient's profile and possible differences among risk profile between waves." Out of 16 patients, 75% were male, while the remaining 25% were female between 36 and 75 years of age, with a mean of 55.4. Regarding blood type, 9 (56.25%) were type A, 6 (37.50%) were type O and 1 (6.25%) belonged to type AB. The most common cause of Regarding laboratory parameters on admission, creatinine (mg/dL), C-reactive protein (CRP) (mg/L), lymphocyte ( x 10 3 /μL), leucocyte ( x 10 3 /μL) and D-dimer (ng/mL) were recorded. Thus, creatinine levels for vaccinated patients showed a median of 1.9 mg/dL and IQR (1.6-3.7 mg/dL), while leucocyte presented a median of 6.5 x 10 3 /μL and IQR (5.2-7.7 x 10 3 /μL). 90% of the patients had lymphopenia (< 1 x 10 3 /μL), with the median for all patients being 0.7 x 10 3 /μL and IQR (0.5-0.7 x 10 3 /μL). Median and IQR for CRP and D-dimer were 67.9 mg/L (35.8-103.4 mg/L) and 600 ng/mL (360-657 ng/mL), respectively. Table 2 shows clinical and laboratory characteristics among vaccinated and unvaccinated recipients who required hospitalization. It is noteworthy that originally, and among non-vaccinated patients, a total of 48 were hospitalized. However, laboratory and clinical information during admission of two of whom could not be obtained. Therefore, information in Table 2 will refer to the 46 remaining subjects. Significant differences were not found between both groups regarding laboratory results (p-value > 0.05). Seven patients (70%) experienced acute renal failure, and four of whom required hemodialysis. These four also met the criteria for admission to the intensive care unit (ICU), followed by a torpid evolution, after which three of whom died. None of the patients experienced acute rejection or allograft loss. Treatment changed between the waves with more frequent use of ritonavir/lopinavir, hydroxychloroquine, and azithromycin in the first wave and with more frequent use of remdesivir and steroids in the second wave. Patients with cytoquine storm received tocilizumab in the initial stages but not in next waves. High steroid doses were used as treatment for pneumonia and hyper-inflammatory state mainly in the last wave. Asymptomatic patients did not receive specific drugs against COVID-19 and did not require immunosuppression adjustment. In patients with pneumonia, the reduction of immunosuppressive treatment was made according to the published recommendations of the DESCARTES Group [7] . According to the protocol established, ventilatory support via nasal cannula with reservoir was provided to patients whose SpO2 rate ≤ 92%, aiming at a SpO2 rate towards 96%. If this was insufficient, a high flow nasal cannula or Venturi Mask was provided. Non-invasive mechanical ventilation was the next step in order to consider whether respiratory failure continued, unless immediate intubation criteria existed. Thus, five patients (50%) needed oxygen support throughout the hospitalization period, four of whom required intubation. Table 3 shows detailed clinical information regarding vaccinated patients. Based on the results of the analysis of our previous series through Lasso selection and multivariate logistic regression in which age, time after transplant, hypertension, overweight/obesity and the need of supplementary oxygen at admission were shown as risk factors related to hospitalization and poor disease evolution, we studied these factors in the group of infected patients after immunization. No significant differences were found between unvaccinated and vaccinated patients among these variables (p-value > 0.05). Thus, the profile of the infected kidney transplant recipient regarding risk factors remains constant between waves: a patient with a mean age above 55 years, hypertensive, with a similar percentage of overweight and obesity and with a median post-transplant time of around 90 months. Regarding the need of supplementary oxygen at admission, when SpO2 ≤ 92%, although the percentage has decreased from 28.3% among non-vaccinated to 20% among vaccinated, these differences were not significant (p-value > 0.05). On the other hand, we observed that the risk factors related to a worse disease evolution in our previous series are presented to a great extent among the four vaccinated recipients who required ICU admission. These patients were elderly, between 59 and 75 years (mean = 65.25) of age, all of whom being hypertensive and with overweight/obesity. Two of whom (50%) needed oxygen support on admission. Although diabetes did not reach significance as a risk factor for severe disease in our previous series, we observed that 3 out of 4 patients (75%) admitted at ICU and who died were diabetic. From our current series of 16 vaccinated and infected patients, ten required hospital admission (62.5%) and three of them died due to COVID-19 complications. Differences between the hospitalization rate and severity of evolution between both groups of patients could not be found (p-value > 0.05). However, the proportion of contagions among our 1500 kidney transplant recipients decreased significantly from 5% during the first waves to 1% after vaccination rollout (p-value < 0.05). Thus, the profile of the infected patient remains similar between series. We observed that all the significant risk factors regarding hospitalization and poor disease evolution in our previous series were found among the four patients who required ICU admission after vaccination rollout. This is a retrospective cohort study that reflects the experience of a single centre faced with the impact of COVID-19 infection in their kidney transplant vaccinated patients. When we analyze the evolution of COVID-19 affected patients in the pre-vaccination periods, the need for hospitalization was 63.5 % of all affected patients in our series. The mortality rate was 14.5%, a lower percentage with respect to other published series which is above 25% [8, 9] . Only 12 (15.8%) diagnosed patients remained asymptomatic. In the overall series, symptoms like fever, cough and dyspnea are the most common at presentation and hospital admission percentages are similar in previous reports [9, 10] . Among unvaccinated COVID-19 positive patients, old age and hypertension are the main risk factors for hospitalization, while the probability of being hospitalized decreases with time after transplantation. It should be highlighted that 67.1% of our patients were diagnosed after the first post-transplant decade. Advanced age and COVID-19 infection in the first months were associated with severe disease and high mortality in previous series [11, 12] . We also analyzed in our hospitalized patients, which factors at admission could be related to a worse evolution and severe pneumonia. Among all of them, only SpO2 ≤ 92% on admission (OR 8.954, p-value = 0.026) and overweight/obesity (OR 13.453, p-value = 0.001) were predictors of a worse evolution. These observations are similar to the published results from registry series [5, 13] . After having received the COVID-19 vaccine, 16 patients developed infection. When we analyze the disease evolution in these group of patients and we compare it with the previous of non-immunized infected patients, no significant differences were seen in patient risk profile and disease evolution. It should be noted that among the patients who died, an elevated prevalence of diabetes was the case, which underlines the fact that diabetes plays an important role as a risk factor of severe disease, as described in previous reports [14] . Our results are similar to other published reports that analyze COVID-19 infection after vaccination [15, 16] , while in other series a lower rate for hospital and ICU admission [17] in immunized patients was found. Probably all the reports reflect the impaired capacity of achieving an adequate protective immune response in transplant patients. Therefore, it is essential to keep strict protective measures in this population, while at the same time the convenience of a third vaccine dose has to be emphasized to enhance immunization in this vulnerable group of patients. This retrospective cohort study has some limitations. This is a preliminary study of a single centre series with a small sample size. But on the other hand, our own control series group provides the advantage of a follow-up and homogeneous treatment criteria, which can be considered a study strength. Thus, our findings, far from offering definitive conclusions, probably reflect the low immunization rate in this group of patients, especially those with a higher risk, and reinforce the need to improve it. Larger studies are needed to shed more light on this matter. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area COVID-19-related mortality during the first 60 days after kidney transplantation Clinical features of patients infected with 2019 novel coronavirus in Wuhan Respiratory and gastro-intestinal COVID-19 phenotypes in kidney transplant recipients Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry Antibody Response to 2-Dose SARS-CoV-2 mRNA How should I manage immunosuppression in a Kidney transplant patient with COVID-19? An ERA-EDTA DESCARTES expert opinion COVID-19 in solid organ transplant recipients: a single-center case series from Spain COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature. Transplant Rev (Orlando) COVID-19 in elderly kidney transplant recipients COVID-19-related Mortality During the First 60 Days After Kidney Transplantation An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study Occurrence of severe Covid-19 in vaccinated transplant patients Severe consequences of COVID-19 infection among vaccinated kidney transplant recipients E Cuadrado-Payán et al SARS-CoV-2 Infection after full vaccination in kidney transplant recipients SpO2 ≤ 92% (N, %) 13 (28.26%) CRP) (mg/L) We would like to recognize the effort made by healthcare personnel around the world during the health crisis due to SARS-CoV-2 disease. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare not to have any conflicts of interest. Abbreviations: ICU, intensive care unit; RRT, renal replacement therapy.