Five-month impact of tozinameran (BNT162b2) vaccine on kidney transplant and dialysis patients: Serology and clinical outcomes

Background: Dialysis-treated (DT) and kidney transplant (TX) patients face higher morbidly and mortality risks than the general population during COVID-19 pandemic. Determining humoral response and associated COVID-19 morbidity after vaccination will guide risk assessment and changes in vaccination policy in this vulnerable population. Methods: Prospective cohort study up to 5 months follow-up after Tozinameran or SARS-CoV-2 infection. Primary outcomes: qualitative and quantitative anti S1/ S2 antibody (ABs) and disease rates during follow up. Anti-SARS-2 IgG ABs were quantified using LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin) immunoassay in serum of TX, DT and treating team at our hospital. Demographics and clinical data were collected from participants files. Results: 174 DT patients (40% women, age 65±15 years) 253 TX patients (33%, 53±14 years) and 71 control participants (65%, 44±14 years) were recruited. 3 months or more after vaccination we detected anti S1/S2 ABs in 81% of DT (95%CI, 72-90%), 43% of TX (95%CI, 29-57%) and 100% of controls. After COVID-19 respective rates were 94% (95%CI, 83-100%), 75% (95%CI, 60-90%) and 100%. Quantitative titers were in line with qualitative ones. Predictors of negative serology were older age, diabetes, cancer history, lower lymphocyte count and lower vitamin D. Peritoneal dialysis predicted higher titers compared to hemodialysis. In TX, hypertension and higher levels of immnosupression predicated lower titers. Vaccination was associated with fewer subsequent COVID-19 infections (HR=0.23, 95% CI 0.05-0.99, p<0.05). Higher antibody titers associated with fewer events, HR 0.41/unit increase in log10 titer (p<0.05). Conclusions: Patients with ESRD, particularly TX, mounted delayed and diminished antibody response to vaccination, and lesser response was associated with more infections. Thus, measures to protect non-responsive patients are urgently required.

Serologic response to COVID-19 infection and/or vaccine in cancer patients on active treatment.

BACKGROUND: It was shown that immunocompromised patients have significantly reduced immunologic responses to COVID-19 vaccines. The immunogenicity of COVID-19 vaccine/infection in patients with solid tumors is reduced. We evaluated the immunologic response to COVID-19 and/or the BNT162b2 mRNA COVID-19 vaccine among cancer patients on active treatments and reviewed previous literature to identify subgroups that may require third vaccination. PATIENTS AND METHODS: Anti-SARS-CoV-2 S1/S2 antibodies were measured in a cohort of 202 cancer patients on active treatment with chemotherapy (96), immunologic (52), biologic (46), and hormonal (12) treatments for early (n = 66, 32.7%) or metastatic disease (n = 136, 67.3%). Of those, 172 had received two vaccine doses, and 30 had COVID-19 infection (20/30 also received one dose of vaccine). Specific anti-S receptor-binding domain antibodies were further measured in patients with equivocal anti-S1/S2 results. RESULTS: Among cancer patients, the SARS-CoV-2 antibody response rate was 89.1% (180/202) after COVID-19 vaccination or infection and 87.2% (150/172) in patients after vaccination without a history of COVID-19, compared with 100% positive serologic tests in a control group of 30 health care workers (P < 0.001). Chemotherapy treatment was independently associated with significantly reduced humoral response to infection or vaccination, with an 81.3% response rate, compared with 96.2% in patients on other treatments (P = 0.001). In vaccinated patients on chemotherapy, the positive response rate was 77.5%. In a multiple regression model, a neutralizing antibody titer (>60 AU/ml) was more likely with immunotherapy (odds ratio 2.44) and less likely with chemotherapy (odds ratio 0.39). CONCLUSIONS: Overall, both COVID-19 vaccine and natural infection are highly immunogenic among cancer patients. Our study, however, identifies those under chemotherapy as significantly less responsive, and with lower antibody levels. These findings justify close virological and serological surveillance along with consideration of these patients for booster (third dose) vaccine prioritization, as new highly spreading SARS-CoV-2 variants emerge.

Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection.

INTRODUCTION: Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control the COVID-19 pandemic. Because of the overwhelming use of SARS-CoV-2 reverse transcription (RT)-PCR tests worldwide, the availability of test kits has become a major bottleneck and the need to increase testing throughput is rising. We aim to overcome these challenges by pooling samples together, and performing RNA extraction and RT-PCR in pools. METHODS: We tested the efficiency and sensitivity of pooling strategies for RNA extraction and RT-PCR detection of SARS-CoV-2. We tested 184 samples both individually and in pools to estimate the effects of pooling. We further implemented Dorfman pooling with a pool size of eight samples in large-scale clinical tests. RESULTS: We demonstrated pooling strategies that increase testing throughput while maintaining high sensitivity. A comparison of 184 samples tested individually and in pools of eight samples showed that test results were not significantly affected. Implementing the eight-sample Dorfman pooling to test 26 576 samples from asymptomatic individuals, we identified 31 (0.12%) SARS-CoV-2 positive samples, achieving a 7.3-fold increase in throughput. DISCUSSION: Pooling approaches for SARS-CoV-2 testing allow a drastic increase in throughput while maintaining clinical sensitivity. We report the successful large-scale pooled screening of asymptomatic populations.