Kinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects (preprint)

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination. Methods: This prospective study enrolled 208 healthcare workers from the Liege University Hospital (CHU) of Liege in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naive (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN-gamma on peripheral blood lymphocytes using the QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naive and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naive HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses.

Proteinuria in COVID-19: prevalence, characterization and prognostic role (preprint)

Background: Proteinuria has been commonly reported in patients with COVID-19, suggesting a renal involvement in this infection. However, only dipstick tests have been used thus far. Here, the quantification and characterization of proteinuria and hematuria are investigated. Their potential association with mortality was assessed. Methods: This retrospective, observational and monocentric study includes 153 patients hospitalized with COVID-19 between March 28th and April 30th 2020, in whom total proteinuria and urine α1-microglobulin (a marker of tubular injury) have been measured. Association with mortality was evaluated with a follow-up until May 7th 2020. Results: According to the Kidney Disease Improving Global Outcomes staging, 14% (n=21) had stage 1 proteinuria (<150 mg/g of urine creatinine), 42% (n=64) had stage 2 (between 150 and 500 mg/g) and 44% (n=68) had stage 3 (over 500 mg/g). Urine α1-microglobulin concentration was higher than 10 or 15 mg/g in 94% and 89% of patients, respectively. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urine α1-microglobulin (as continuous and/or categorical variables) were associated with mortality in unadjusted and adjusted models. This association was even stronger in subgroups of patients with normal renal function or without urinary catheter. Conclusions: Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin with increased urine α1-microglobulin. Tubular proteinuria seems associated with mortality in COVID-19.