ABSTRACT
BACKGROUND AND AIMS COVID-19 infection in solid organ transplant recipients (SOT) is associated with increased morbidity and mortality due to comorbidities and immunosuppression state (Chaudhry ZS et al, 2020). Although vaccines represent the greatest hope to control COVID-19 pandemic, several studies showed the low immunogenicity of a two-dose mRNA COVID-19 vaccine regimen in SOT as compared with general population (Boyarsky BJ et al, 2021). Based on this evidence, on September 2021, the Italian Medicine Agency (AIFA) authorized a third vaccine administration as additional primary dose to immunocompromised patients. The aim of this study is to evaluate the seroconversion rate after the third dose of BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine in kidney transplant recipients (KTRs) and to investigate the baseline factors associated with the absence of the antibody response. METHOD we performed a prospective and observational study on a monocentric cohort of 329 consecutive Caucasian KTRs given three doses of the BNT162b2 COVID-19 vaccine. Key exclusion criteria were a previous history of COVID-19 infection and transplantation or having underwent chemotherapy treatment within the last year. Antibody response against the spike protein was tested on blood sample collected before the administration of vaccine (T0), at 15 and 90 days after the second dose (T2 and T3, respectively) and one month after the third dose (T5). The level of antibodies was assessed using the Roche Elecsys anti–SARS-CoV-2 S enzyme immunoassay (positive cut-off ≥ 0.8 U/mL). A total of 22 patients were excluded from the analysis because categorized as SARS-CoV-2-pre-immunized according to the antibodies’ baseline status (T0) above the positivity cut-off. The Local Ethics Committees approved the study protocol and written informed consent was obtained before enrolment. RESULTS The study population of 307 KTRs was 57.10 ± 13.10 years, with a predominance of male sex (64.2%). Median time from transplantation to vaccine was 10 [IQR 5–17] years. Blood analysis at baseline revealed mean eGFR assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to be 56.95 ± 23.04 mL/min/1.73 m2. The standard immunosuppressive regimen consisted of glucocorticoids in all patients, calcineurin inhibitors (88.6% of patients), antimetabolites (73.3% of patients) and mTOR inhibitors (in 15.6% of patients). The first two doses were administered 21 days apart, and the third dose was administrated 172 ± 4 days after the second dose. In our cohort, 43.3% patients (133/307) responded to the vaccine at T2. The proportion of responders increased to 68.4% (186/272) at T3 (median antibody level: 5.2 [0.40–74.07]). One month after the third dose, a positive antibody titer was detected in 251 of 307 patients (81.8%) (median antibody titre: 1137.50 [9.32–4189.75]). The response curve starting at T2 and increasing at T3 makes apparent that there is a distinctive kinetic of humoral response in immunocompromised patients compared to immunocompetent individuals (Walsh EE et al., 2020). A multivariate analysis showed that the negative response to the third primary dose was associated with antimetabolite immunosuppressants (P = .001), lower estimated glomerular filtration rate (P < .001) and female sex (P = .04) (Figure 1). No serious adverse events were reported. Neither denovo DSAs nor change in proteinuria were reported after vaccination.FIGURE 1: Univariate and multivariate analysis of factors associated with vaccine response one month after third dose of SARS-CoV-2 mRNA vaccine. The limitation of this study is the absence of assays for cellular immune response. CONCLUSION Although the exact threshold of antibody titer for protection against SARS-CoV-2 infection remains unclear, the ability of the additional mRNA COVID-19 vaccine dose to increase both immune response (Figure 2A) and the prevalence of seroconversion rate (Figure 2B) associated with the acceptable safety profile s pports its use after an initial 2-dose mRNA COVID-19 primary vaccine series in immunocompromised patients.FIGURE 2: Antibody Response. Panel A shows the anti-SARS-CoV-2 antibody titers at different timepoints T0, T2, T3 and T5. Panel B shows prevalence of responders and noresponders at different timepoints T0, T2, T3 and T5.
ABSTRACT
BACKGROUND AND AIMS SARS-CoV-2 pandemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients, such as nephropathic patients, are still scarce. Patients with chronic kidney disease (CKD) and on haemodialysis (HD) are at risk of a more severe disease course and worst outcomes. Here, we aimed to describe the characteristics and outcomes of CKD and HD patients with SARS-CoV-2 infection, admitted to the Covid Nephrology Unit in the first three pandemic waves, analysing mortality rate and risk factors for mortality in this subgroup of patients. METHOD A Covid Nephrology Unit was organized in March 2020 to manage the high number of CKD and HD patients with SARS-CoV-2 infection. Several ‘spoke’ units were also set to manage HD asymptomatic patients (Hi Hotel and ‘Villa Luce’ Dialysis Center) or with mild symptoms (‘Miulli Hospital’-Acquaviva delle Fonti and ‘Fallacara Hospital’—Triggiano). Clinical and laboratory data in several timepoints were collected using electronic medical records. Primary outcome was to assess the mortality rate. Moreover, we analysed the trend of inflammatory markers in the first 7 days after hospital admission between survivors and non-survivors;finally, risk factors for mortality were analysed by logistic regression. RESULTS From March 2020 to May 2021, a total of 221 patients were admitted to the Covid Nephrology Unit;among these, 112 patients on chronic haemodialysis, 21 with acute kidney injury (AKI), 58 with CKD, 24 kidney transplant recipients and 6 patients on peritoneal dialysis (PD). Median age was 71 years (IQR 62.5–80), while male gender predominated (61.5%). Main comorbidities were arterial hypertension (81%), diabetes mellitus (41.8%) and cardiovascular disease (CVD, 60.6%). At admission, 13.2% of patients required non-invasive ventilatory (NIV) support (CPAP, BiPAP) and about 60% presented interstitial pneumonia at CT scan. A total of 80 patients (36.1%) died during hospital stay with a medium length of stay of 15.8 days. In the first 7 days, 29 patients presented respiratory failure requiring transfer to ICU. Conversely, 100 patients were discharged at home, while 48 patients were transferred to the spoke units (39 patients at Miulli and Fallacara Hospitals, 9 patients at Hi Hotel). Compared to survivors, patients who died were older (median age 75.5 versus 66 years, P < .001), characterized by more comorbidities (diabetes mellitus 54.5% versus 35.2%, P = .01;CVD 81.1% versus 51.4%, P < .001;chronic obstructive pulmonary disease (COPD, 41.5% versus 19%, P = .01;peripheral vasculopathy 58.4% versus 34.2%, P = .01) and more severe respiratory compromission at hospital admission (patients in NIV, 22.6% versus 8.1%, P = .005). As shown in Table 1, in the first 7 days of hospital stay, a significant increase in WBC (8.29 versus 12.6 × 106P < .001) was described in the non-survivor group;similarly, inflammatory markers such as CRP and IL-6 did not improve in the non-survivors at day 7 (CRP 81.8 versus 85.7 mg/L, P = .62;IL-6 63.1 versus 79.4 pg/mL, P = .84), while they significantly improved in survivors (median CRP 42.5 versus 10.1 mg/L, P < .001;median IL-6 32.3 versus 13.7 pg/mL, P = .01). In a multivariate logistic regression model, age (OR 1.062, 95% CI 1.007–1.119, P = .025), history of CVD (OR 8.308, 95%CI 1.704–40.499, P = .009) and dyspnoea at hospital admission (OR 9.465, 95%CI 1.231–72.79, P = .031) were associated with risk of mortality in this population. CONCLUSION To our knowledge, this is the largest study analyzing characteristics and outcomes of CKD and hemodialysis patients to date. A wide heterogeneity of severity of disease has been documented in our cohort;we documented a higher mortality rate in this cohort of patients compared to general population. The presence of several comorbidities, a more severe disease at hospital admission and the persistence of elevated inflammatory markers during hospital stay are risk factors for mortality.
ABSTRACT
BACKGROUND: Solid-organ transplant (SOT) recipients are at a high risk of severe COVID-19, and are priority for vaccination. Here, we describe three cases of severe COVID-19 caused by SARS-CoV-2 B.1.1.7 lineage in vaccinated SOT recipients. METHODS: Three SOT patients were hospitalized in the Policlinico Hospital of Bari (southern Italy) and underwent nasopharyngeal swabs for molecular detection of SARS-CoV-2 genes and spike protein mutations by real-time PCR. One sample was subjected to whole-genome sequencing. RESULTS: One patient was a heart transplant recipient and two were kidney transplant recipients. All were hospitalized with severe COVID-19 between March and May 2021. Two patients were fully vaccinated and one had received only one dose of the BNT162b2 mRNA vaccine. All the patients showed a high viral load at diagnosis, and molecular typing revealed the presence of B.1.1.7 lineage SARS-CoV-2. In all three cases, prolonged viral shedding was reported. CONCLUSIONS: The three cases pose concern about the role of the B.1.1.7 lineage in severe COVID-19 and about the efficacy of COVID-19 vaccination in immunocompromised patients. Protecting immunocompromised patients from COVID-19 is a challenge. SOT recipients show a suboptimal response to standard vaccination, and thus, an additive booster or a combined vaccination strategy with mRNA, protein/subunit, and vector-based vaccines may be necessary. This population should continue to practice strict COVID-19 precautions post-vaccination, until new strategies for protection are available.