A third dose SARS­CoV­2 BNT162b2 mRNA vaccine results in improved immune response in hemodialysis patients.

Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS­CoV­2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time. Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7-15 weeks and 2) 6-8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated. Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7-15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134-1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325-26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5-80), 51.5 (14.8-132), and 19.5 (8.8-54.2) units, respectively, for 6-8 months after dose two, 3 weeks, and 3 months after dose three. Conclusions: Our data show that a third dose of SARS­CoV­2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals.

Three Doses of SARS‑COV‑2 BNT162B2 MRNA Vaccine Results in an Enhanced Immunologic B- And T-Cell Response in Haemodialysis Patients

BACKGROUND AND AIMS The immune system is affected by uremia. Haemodialysis (HD) patients have an increased risk of acquiring infections due to many healthcare contacts and have a suboptimal response to vaccination and a high mortality from COVID-19 infection. Accumulating data indicate that two doses of vaccines are not enough, and most HD-patients have now received a third dose. The aim of the study was to describe the antibody and T-cell response to three doses of SARS‑CoV‑2 BNT162b2 mRNA vaccination and change over time. METHOD Initially, 50 patients (mean age 69.4 years and 62% men) with end-stage kidney disease (ESKD) and haemodialysis treatment, at the dialysis outpatient clinic, Uppsala Academic Hospital, Sweden were enrolled into the study. Administration of SARS‑CoV‑2 BNT162b2 mRNA vaccine began on 28 Decemeber 2020. In September 2021, the patients received their third vaccine dose. During the study four patients died, four received a kidney transplant and two did not receive the third vaccine dose. A total of 41 (82%) patients received three doses of vaccine and were followed up until 3 months after the third dose. The antibody response was measured at four timepoints;7–15 weeks and 6–8 months after the second dose, 3 weeks and 3 months after the third dose, and the T-cell response at three timepoints;7–15 weeks after the second dose, 3 weeks and 3 months after the third dose. SARS-CoV-2 IgG antibody test (Abbott Architect) was performed against Spike antigen (anti-S) positive both after COVID-19 infection and vaccination (quantitative method used in routine diagnostics at Laboratory of Clinical Microbiology, Uppsala) and T-cell reactivity testing against the Spike protein using ELISPOT technology measuring interferon-gamma activity was performed at ABC-labs, Solna. RESULTS After two doses, IgG antibodies (IgG abs) to anti-S were detected in 37 (74%) of 50 patients, 5 (10%) had a borderline response and 8 (16%) were negative. T-cell response were detected in 29 (58%) of 50 patients and in 21 (42%) no response was detected. Before the third dose IgG abs to anti-S were detected in 24 (52%) of 46 patients, 3 (7%) had a borderline response and 19 (41%) were negative. Three weeks after the third dose IgG abs to anti-S were detected in 39 (95%) of 41 patients, and 2 (5%) were negative. T-cell responses were detected in 35 (85%) of 41 patients and in 6 (15%) no response. Three months after the third dose IgG ab to anti-S were still detected in 38 (95%) of 40 patients, and 2 (5%) were negative. Changes in IgG ab to anti-S and T-cell response over time in patients who received all three doses of vaccine and were followed up until 3 months after the latest dose (n = 40 and 37) are displayed in Figures 1 and 2 (preliminary data). CONCLUSION These results highlight the need for at least three doses of the SARS‑CoV‑2 BNT162b2 mRNA vaccine. It also indicates that the effect of the vaccine decreases slower after dose 3 than after dose 2 since almost all patients had a measurable immune response 3 months after dose 3. However, not all patients develop an immunological response. In a clinical setting, it is justified to measure the antibody response after vaccination to identify patients that are not protected and where one needs to take other measures to protect them from infection and/or to give early treatment in case of symptoms.FIGURE 1: Changes in IgG antibodies to anti-S in patients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccine and were followed up until 3 months after the latest dose (n = 40).FIGURE 2: Changes T-cell response patients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccine and were followed up until 3 months after the latest dose (n = 37).

Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients have an increased risk of acquiring infections due to many health care contacts and may, in addition, have a suboptimal response to vaccination and a high mortality from Covid-19 infection. METHODS: In 50 HD patients (mean age 69.4 years, 62% men) administration of SARS-CoV-2BNT162b2 mRNA vaccine began in Dec 2020 and the immune response was evaluated 7-15 weeks after the last dose. Levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using ELISPOT technology were evaluated. RESULTS: Out of 50 patients, anti-S IgG antibodies indicating a vaccine effect or previous Covid-19 infection, were detected in 37 (74%), 5 (10%) had a borderline response and 8 (16%) were negative after two doses of vaccine. T-cell responses were detected in 29 (58%). Of the 37 patients with anti-S antibodies, 25 (68%) had a measurable T-cell response. 2 (40%) out of 5 patients with borderline anti-S and 2 (25%) without anti-S had a concomitant T-cell response. Twenty-seven (54%) had both an antibody and T-cell response. IgG antibodies to anti-N indicating a previous Covid-19 disease were detected in 7 (14%) patients. CONCLUSIONS: Most HD patients develop a B- and/or T-cell response after vaccination against Covid-19 but approx. 20% had a limited immunological response. T-cell reactivity against Covid-19 was only present in a few of the anti-S antibody negative patients.

Diagnostic Potential of a Luminex-Based Coronavirus Disease 2019 Suspension Immunoassay (COVID-19 SIA) for the Detection of Antibodies against SARS-CoV-2.

Due to the current, rapidly increasing Coronavirus disease 2019 (COVID-19) pandemic, efficient and highly specific diagnostic methods are needed. The receptor-binding part of the spike (S) protein, S1, has been suggested to be highly virus-specific; it does not cross-react with antibodies against other coronaviruses. Three recombinant partial S proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) expressed in mammalian or baculovirus-insect cells were evaluated as antigens in a Luminex-based suspension immunoassay (SIA). The best performing antigen (S1; amino acids 16-685) was selected and further evaluated by serum samples from 76 Swedish patients or convalescents with COVID-19 (previously PCR and/or serologically confirmed), 200 pre-COVID-19 individuals (180 blood donors and 20 infants), and 10 patients with acute Epstein-Barr virus infection. All 76 positive samples showed detectable antibodies to S1, while none of the 210 negative controls gave a false positive antibody reaction. We further compared the COVID-19 SIA with a commercially available enzyme immunoassay and a previously evaluated COVID-19 rapid antibody test. The results revealed an overall assay sensitivity of 100%, a specificity of 100% for both IgM and IgG, a quantitative ability at concentrations up to 25 BAU/mL, and a better performance as compared to the commercial assays, suggesting the COVID-19 SIA as a most valuable tool for efficient laboratory-based serology.

Work at inpatient care units is associated with an increased risk of SARS-CoV-2 infection; a cross-sectional study of 8679 healthcare workers in Sweden.

BACKGROUND: During the Covid-19 pandemic, the protection of healthcare workers has been in focus throughout the world, but the availability and quality of personal protective equipment has at times and in some settings been suboptimal. MATERIALS AND METHODS: A total of 8679 healthcare workers and healthcare support staff in the county of Uppsala, north of Stockholm, were included in this cross-sectional study. All subjects were analysed for IgG anti-SARS-CoV-2, and predictors for positive serostatus were analysed in a logistic regression model including demographic parameters and self-reported employment characteristics. RESULTS: Overall, 577 (6.6%) were classified as seropositive, with no statistically significant differences between healthcare workers and support staff. Among healthcare workers, age (OR 0.987 per year, 95% CI 0.980-0.995), time to sampling (OR 1.019 per day, 95% CI 1.004-1.035), and employment at an outpatient care unit (OR 0.620, 95% CI 0.487-0.788) were statistically significantly associated with risk of infection. Covid-19 specific units were not at particular risk, compared to other units with comparable characteristics and staff demography. CONCLUSION: Our findings indicate that SARS-CoV-2 transmission is related to inpatient healthcare work, and illustrate the need for a high standard of basic hygiene routines in all inpatient care settings.