SARS-CoV-2 infection in kidney transplant recipients: clinical impact and outcomes - a single center experience.

INTRODUCTION: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. METHODS: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. RESULTS: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. CONCLUSION: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.

Torquetenovirus viral load is associated with anti-spike antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated kidney transplant patients.

INTRODUCTION: Kidney transplant patients (KT) are at high risk for severe COVID-19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre-vaccination TTV viral load and anti-spike total antibody response to SARS-CoV-2 vaccination in KT. MATERIAL AND METHODS: The 114 adult KT recipients enrolled in this prospective single-center cohort study received two doses of SARS-CoV-2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16-45 days after the second dose (T2). Primary endpoint was the development of anti-spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS-CoV-2 antibodies at T2. RESULTS: Ninety-nine patients (86.8%) were naïve for SARS-CoV-2 before vaccination. Fifty-six (56.6%) patients developed anti-spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log10 cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47-19.80; p = .011), after adjusting for age and eGFR at T0. CONCLUSIONS: Higher TTV viral loads before vaccination are associated with reduced anti-spike total antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added-value in the optimization of vaccination regimens in KT.

Differences in Humoral Response After SARS-COV-2 Vaccination Between Kidney Transplant and Peritoneal Dialysis Patients: What is the Impact of Immunosuppression?

BACKGROUND AND AIMS Patients on renal replacement therapy are reported to have altered humoral immunity, which is demonstrated by a decreased response to different vaccines. However, in kidney transplant (KT) patients, vaccines are even less immunogenic in terms of antibody response. Therefore, these patients have a higher risk of critical infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which makes them eligible for early vaccination. The aim of this study was to compare the humoral response after complete vaccination against SARS-CoV-2 between KT patients and peritoneal dialysis (PD) patients. METHOD We conducted a single-center, retrospective study, which included 67 KT recipients and 49 prevalent PD patients. Patients were excluded if they had previously known SARS-CoV-2 infection or positive anti-nucleocapsid IgG or IgM antibodies. Completion of vaccination was defined as two doses of a messenger RNA vaccine (BNT162b2 messenger RNA vaccine [Pfizer-BioNTech] or messenger RNA-1273 [Moderna]), two doses of viral vector vaccine ChadOx1 nCoV-19/AZD1222 (AstraZeneca) or one dose of JNJ-78 436 735 (Janssen) vaccine. Anti-spike (anti-S) IgG antibodies were measured, at least, 21 days after the completion of vaccination and before receiving a `booster’ dose. A value of anti-S >0.8 U/mL was considered positive. Immunogenicity of the vaccine, measured by anti-spike IgG antibodies, was compared between KT recipients and PD patients. RESULTS The mean age of the population was 58.8 ± 13.6 years and 62.0% were males (similar between the two groups). The median interval between completion of vaccination and serologic analysis was 4.1 months in KT patients and 7.1 months in PD patients. In KT patients, the median anti-S level was 1.50 U/mL (IQR 0.0–27.3) versus 97.0 U/mL (IQR 34.5–447.0) in PD patients (P < .001). In the KT group, there were 31 (46.3%) non-responders (patients without detectable levels of anti-S), while in the second there were only two (4.1%). In KT patients, anti-S levels were not associated with time since transplant or immunosuppressive induction therapy. In PD patients, anti-S levels were not associated with time since the beginning of PD. In both groups, anti-S levels were not associated with age, gender, type of administered vaccine or interval between completion of vaccination and serologic analysis. CONCLUSION We found a significant difference in humoral responses to the vaccine between PD and KT transplant patients with no previous exposure to SARS-CoV-2. In PD patients, the vaccine seemed to be effective. On the contrary, KT patients had a significantly weaker rising of anti-S titers, with a high proportion of patients not responding to the vaccine. This study emphasizes the negative impact of immunosuppression on humoral responses, reinforcing the need for a `booster’ dose in this group of patients.

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up.

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign. Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes. Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3-4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2. Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10-05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10-16). Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

Kinetics of torquetenovirus DNA load in a recent kidney transplant recipient with mild SARS-CoV-2 infection and a failed antibody response.

Kidney transplant (KT) recipients are at an increased risk for severe COVID-19 because of their immunosuppressed state. A 42-year-old KT patient was diagnosed with COVID-19 three months after KT. Despite lymphopenia and several risk factors, he had a mild disease course. Nasopharyngeal real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 became negative 48 days after detection. SARS-CoV-2 IgG antibodies became negative after day 40. TTV DNA load increased with the onset COVID-19 and reduced after its resolution. This is the first report where TTV DNA load was measured during the course of COVID-19.