ABSTRACT
Background: Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. Methods: We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4-10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. Findings: The study included 3607 KTRs (59 [48-70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31-57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Interpretation: Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic. Funding: CEPI and internal funds.
ABSTRACT
Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.
ABSTRACT
RATIONALE & OBJECTIVE: Studies published from countries with a high prevalence of COVID-19 have found increased incidence and a more severe disease course of coronavirus disease 2019 (COVID-19) in kidney transplant recipients than in the general population. We investigated how the first wave of the COVID-19 pandemic affected the everyday life of kidney transplant recipients in a country with a low infection burden. STUDY DESIGN: Prospective case-control study. SETTING & PARTICIPANTS: All adult kidney transplant recipients in Norway with a functioning graft and listed in the public phone registry (n = 3,060) and a group of randomly recruited individuals >18 years from the general population (n = 20,000) were invited to participate in the study by an SMS text message. In parallel, all kidney transplant recipients in Norway were invited to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG from mid-June to October 2020. PREDICTORS: The participants were asked to fill out a questionnaire focused on everyday life, travel history, exposure to known COVID-19 cases, and demographics. ANALYTICAL APPROACH: Groups were compared with independent tests using 2-sided 0.05 significance levels. RESULTS: A total of 1,007 kidney transplant recipients and 4,409 controls answered the questionnaire. The kidney transplant recipients reported being more concerned about SARS-CoV-2 infection (27%) than the control group (7%; P value < 0.001); ie, they behaved more carefully in their everyday life (not going to the grocery store, 5.9% vs 0.9%, P < 0.001; keeping at least 1 meter distance, 16.6% vs 5.8%, P < 0.001). Of the kidney transplant responders, 81% had a SARS-CoV-2 IgG taken; all were negative. LIMITATIONS: Mortality data is not reliable because of the low number of SARS-CoV-2 infected kidney transplant recipients in Norway. The relatively low questionnaire response rate for kidney transplant recipients is not optimal. CONCLUSIONS: The questionnaire shows that kidney transplant recipients have behaved more carefully compared with the general population with less social interaction and a very high degree of adherence to governmental advice.