Median Antibody Levels Research Articles

Vaccination Against SARS-CoV-2 and Mortality in Hemodialysis Patients: Three is Good

This study has investigated the vaccination rates against SARS-CoV-2 infection, antibody response to vaccine types, and factors affecting mortality in maintenance hemodialysis patients.98 of 143 patients undergoing hemodialysis in our clinic had 3 doses of BNT162b2 (Pfizer-BioNTechh) or CoronaVac (Sinovac Life Sciences) vaccine. Of these 98 patients, blood samples were obtained from 52 patients who agreed to obtain serum samples before and after vaccination. The serum samples were analyzed using the Abbott SARS-CoV-2 immunoassay designed to detect IgG antibodies against the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2. The rate of vaccination with at least one dose of vaccine was 85.3%, and the frequency of SARS-CoV-2 infection was 58.7%. The patients whose antibody titer was obtained after the third dose of vaccine (n=52) were divided into two groups according to the last vaccine type, as BioNTechh group of 16 patients and the Sinovac group of 36 patients. Considering all 52 patients with 3 doses of vaccine, the median antibody level was 397.3 (min-max) (4.5-40000) before the third vaccine dose, while 1325.3 (min-max) (10.5-40000) after the third vaccine dose (P

#4843 EFFECT OF MORNING VACCINATION COMPARED WITH AFTERNOON/EVENING VACCINATION ON HUMORAL RESPONSE TO COVID-19 VACCINE IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Patients with ESKD who are undergoing hemodialysis have impaired immunogenicity to SARS-CoV-2 vaccination. Age, dialysis vintage, use of immunosuppressive drugs, serum albumin, lymphocyte count, vaccine type, and COVID-19 experience have been identified to be associated with humoral and cellular responses. A recent review highlights that vaccination responses also exhibit circadian rhythmicity. However, the benefits of vaccination in the morning compared with later times in the day among hemodialysis patients remain unclear. Therefore, we aimed to determine if morning vaccination with a COVID-19 vaccine was able to induce a higher antibody response than afternoon/evening vaccination among hemodialysis patients. Method We conducted a prospective observational study in the hemodialysis unit of Taipei Tzu Chi Hospital, Taiwan. Prevalent hemodialysis patients aged 20 years or over with no history of SARS-CoV-2 infection were eligible for enrollment. Patients were excluded if they had been vaccinated, refused vaccination, had inadequate dialysis, or declined to participate. Patients with current use of immunosuppressants were also excluded. All participants received a priming dose of ChAdOx1 nCoV-19, an adenovirus-vectored vaccine, on June 16 or 17, 2021 during the hemodialysis session. IgG antibodies to the receptor binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 were measured using the AdviseDx SARS-CoV-2 IgG II assay (Abbot Laboratories, Abbott Park, IL, USA) at Day 28 and Day 56 after vaccination. The cutoff value for positivity was set at ≥50 arbitrary units per mL (AU/mL) based on manufacturer's recommendations. Multivariate logistic regression analyses were used to evaluate the relationship between time of day of vaccination and antibody response. Covariates identified by prior studies as significant predictors of vaccine response or with a P value <0.1 between responders and nonresponders were fitted. Results A total of 201 participants were included, with a male to female distribution of 52% to 48%, a mean age of 67 years, and a median dialysis vintage of 7.7 years. Among the participants, 70 were dialyzed in the morning (between 7:00 AM and 12:00 PM), 69 in the afternoon (between 12:00 and 5:00 PM), and 62 in the evening (between 5:00 and 10:00 PM). Overall, 137 (68.2%) participants developed antibodies against the SARS-CoV-2 spike protein after a single dose of ChAdOx1 nCoV-19. The median antibody level was 184.6 AU/mL. In the multivariate model, morning vaccination, age, coronary artery disease, and lymphocyte count independently predicted a humoral response at Day 28. Participants who received morning vaccination were more likely to develop seroconversion compared with those who received afternoon/evening doses (odds ratio 3.81, 95% confidence interval 1.59–9.15; P = 0.003). Anti-spike antibody titers were measured in 198 participants at Day 56. The median antibody level was 153.7 AU/mL. A significantly higher proportion of morning-vaccinated hemodialysis patients remained seropositive (odds ratio 2.54, 95% confidence interval 1.15–5.61; P = 0.021). Conclusion Our preliminary results showed that circadian rhythms might be harnessed to optimize vaccination strategies for hemodialysis patients. Future studies with larger sample size are required to validate our findings.

#5520 EFFICACY OF MRNA VACCINE BNT162B2 AGAINST NOVEL SARS-COV-2 VIRUS IN END-STAGE KIDNEY DISEASE

Abstract Background and Aims Covid-19 pandemic affected more than 600 million people worldwide. Chronic kidney disease was shown to be a significant risk factor for disease severity. The introduction of the novel mRNA vaccines against SARS-CoV-2 prompted studies to evaluate their efficacy and safety. This study aims to assess the humoral response to the BNT162b2 vaccine, its durability, the booster effect, and breakthrough infections among end-stage renal disease patients (ESRD). Methods A one-year, single center, observational prospective study was conducted between 2021 and 2022. The cohort included adult dialysis patients (n = 143), kidney transplant recipients (11), and healthy controls (n = 75). Demographic and clinical data were retrieved from electronic medical records. All participants received 30 µg/dose of BNT162b2 mRNA vaccine, at 0 and 3 weeks. A third vaccine (booster) was administered at least 6 months after the first dose. SARS-CoV-2 infection was diagnosed based on PCR test of nasal and oropharyngeal swabs. Infections that occurred from January 2022 were attributed to omicron variant. Longitudinal blood samples were collected as indicated in Figure after the first vaccine dose (V1) and after the booster dose (V3). Humoral immune response was assessed by measuring serum IgG antibodies against the receptor-binding domain of the SARS-CoV-2 S1 subunit, using the ABBOTT kit. The study protocol was approved by the Institutional Review Board and was conducted in adherence to the Declaration of Helsinki. Results Twenty-eight weeks after two doses of vaccine, the median antibody levels were significantly lower in dialysis and transplant patients compared with healthy controls (122 AU/mL (2–4,557) and 6 AU/mL (1–217) vs 831 AU/mL (117–40,000), respectively). Furthermore, only 75% of dialysis patients developed positive antibody response (>50 AU/mL) as compared to 100% in controls (see Figure 1). A significant waning of immunity was seen over time in both dialysis and healthy participants (p < .0001). Four weeks after a booster dose, antibody levels surged and did not differ between dialysis and healthy participants 13,840 ± 15,126 AU/mL vs 18,080 ± 13,354 AU/mL, respectively (p = .283). Non-responder rate among dialysis patients dropped from 21% after a 2-dose vaccination to 7% after a booster dose. Lower antibody levels measured at 28-week after the first vaccination were associated with higher risk for Covid-19 infection (p = .021). Of note, all infection cases occurred in subjects with antibody levels below 1050 AU/mL. However, no association was found between antibody levels and Covid-19-omicron variant infection rate among dialysis patients and healthy controls (p = 0.650). Conclusions Dialysis patients had a blunted humoral immune response after two doses of BNT162b2 vaccine compared with healthy controls, which improved after a booster dose. Based on the observed omicron variant breakthrough infections, further studies are needed to improve the vaccines' efficacy against the evolving SARS-CoV-2 variants.

Sleep Quality Affects Humoral Response in Recipients of Two-Dose Sinovac Vaccines

To curb the COVID-19 pandemic, the government distributed Sinovac vaccines. Sleep mediates immune function, including post-vaccination antibody response. This study aimed to analyze whether there was a difference in post-vaccination antibody levels in Sinovac vaccine recipients with poor and good sleep quality. This study used analytical observations of recipients of the two-dose Sinovac vaccine in 2021. Primary data included age, sex, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and post-vaccination IgG-SARS-CoV-2 antibody levels. The PSQI and IgG SARS-CoV-2 antibody levels were measured a month after the second vaccination. Participants with non-reactive antibody levels before the first vaccination were included, and participants with incomplete data were excluded. The Mann-Whitney test was used to look for associations between sleep quality and post-vaccination IgG SARS-CoV-2 levels. Univariate analysis showed that of 54 participants, 37 (68.5%) were male, and 28 (51.9%) had poor sleep quality. 15 participants (27.78%) were in the 36-45 age group, and median antibody levels in participants who received the second Sinovac Vaccine was 223.5 (199.01) units/mL. Post-vaccination IgG SARS-CoV-2 antibody levels were significantly associated with sleep quality (p=0.036).

Analysis of trough levels of total IgG, IgG subclasses, measles neutralizing antibodies and IgG antibodies to encapsulated pathogens after infusion of a 5% or 10% intravenous immunoglobulin

IntroductionPatients with primary immunodeficiency (PI) are at risk of infection due to low IgG levels. We report trough levels of total IgG, IgG subclasses, measles neutralizing antibody (MVab) titers, Haemophilus influenzae type B and seven Streptococcus pneumoniae serotypes in PI patients receiving a 5% and 10% intravenous immunoglobulin (IVIG) formulation. MethodsGMX07 was a bioequivalence trial comparing Gammaplex 10% IVIG with Gammaplex 5% IVIG in patients with PI. Adult patients received the 5% for ≥ five infusions, then the 10% for ≥ five infusions, or vice versa. Pediatric patients received the 10% for 5 infusions. Doses were 300–800 mg/kg/infusion. Trough IgG levels were measured before each infusion. Trough levels for MVab, H. influenzae and S. pneumoniae titers were measured after the last infusion. Results33 adults received the 5%, 32 received the 10%. 15 pediatric patients received the 10%. In adults, median IgG trough levels = 952.5 mg/dL for the 10% and 937.0 mg/dL for the 5%. In pediatric patients, median trough level = 879.5 mg/dL. Trough levels of IgG subclasses were comparable across formulations and age groups. Adult patients had a mean MVab titer of 2908 mIU/mL with the 5% vs 3213 mIU/mL for the 10%. In pediatric patients, mean MVab titer was 2122 mIU/mL. In adults, median trough levels of IgG antibodies to H. influenzae were 2.80 µg/mL for the 5% and 2.76 µg/mL for the 10%. Trough levels of IgG antibodies to all S. pneumoniae serotypes were consistent across formulations and age groups. No clinically meaningful differences were noted between formulations, 21-day vs 28-day regimens, or age groups. DiscussionMaintaining IgG trough levels and mean MVab trough titers above protective thresholds is critical for patients with PI. No trough levels or titers fell below the protective thresholds. While thresholds for protective levels for H. influenzae or S. pneumoniae are not clearly defined, delivery of these antibodies to PI patients was demonstrated. ConclusionOur results indicate protective trough levels of IgG and antibody titers are delivered with the 5% and 10% formulations of this IVIG product, with similar results for adult and pediatric PI patients.

Evaluation of humoral immune response after ChAdOx1 nCoV-19 vaccination among health care workers.

We assessed the immunogenicity of ChAdOx1 nCoV-19 vaccination by evaluating the levels of SARS-CoV-2 IgG after vaccination and investigated the effect of diverse factors such as gender, age, and adverse reactions after vaccination. The study included a total of 1028 serum samples from 452 healthcare workers. SARS-CoV-2 IgG levels were assessed using the SARS-CoV-2 IgG II Quant assay. Participants completed a questionnaire regarding the intensity and duration of adverse reactions after vaccination. The seropositive rates after the first and second doses were 95.5% and 100%, respectively. The median antibody levels after the second dose showed a 4.2-fold increase compared with the first. Five months after the second dose, the median antibody levels decreased by 3.5-fold. The antibody levels in men were lower than those in women after the first dose and were higher after the second dose. There was no difference according to age groups after the first dose, but after the second dose, in subjects aged 50 and above, the rise in antibody levels was less than that in other age groups. The antibody levels among participants with moderate or severe symptoms were significantly higher than those among participants with mild symptoms after the first dose. There were no statistically significant differences according to the duration of symptoms. We could assume that different age groups and genders might have different immunogenicity following vaccination. The intensity of adverse symptoms was positively correlated with the antibody levels, implying that higher immunogenicity is related to the intensity of adverse symptoms after vaccination.

COVID-19 vaccine antibody responses in community-dwelling adults to 48 weeks post primary vaccine series

We report a decentralized prospective cohort study of self-reported adverse events and antibody responses to COVID vaccines derived from dried blood spots. Data are presented for 911 older (aged >70 years) and 375 younger (30-50 years) recruits to 48weeks after the primary vaccine series. After a single vaccine, 83% younger and 45% older participants had overall seropositivity (p<0.0001) increasing to 100/98% with the second dose, respectively (p= 0.084). A cancer diagnosis (p= 0.009), no mRNA-1273 vaccine doses (p <0 .0001), and older age (p <0 .0001) predicted lower responses. Antibody levels declined in both cohorts at 12 and 24weeks increasing with booster doses. At 48weeks, for participants with 3 vaccine doses, the median antibody levels were higher in the older cohort (p= 0.04) with any dose of mRNA-1273 (p <0 .0001) and with COVID infection (p <0 .001). The vaccines were well tolerated. Breakthrough COVID infections were uncommon (16% older cohort, 29% younger cohort; p<0.0001) and mild.

Evaluation of catch-up growth in severe pediatric Hashimoto's hypothyroidism

BackgroundWe aimed to evaluate catch-up growth in children with severe Hashimoto's hypothyroidism (HH) after thyroid hormone replacement therapy (HRT). MethodsA multicenter retrospective study was conducted including children referred for growth slowdown that led to the diagnosis of HH between 1998 and 2017. ResultsA total of 29 patients were included, with a median age of 9.7 years (13–172 months). Median height at diagnosis was -2.7 [-4.6; -0.1] standard deviation score (SDS), with a height loss of 2.5 [0.7; 5.4] SDS compared to height before growth deflection (p<0.0001). At diagnosis, the median TSH level was 819.5 mIU/L [100; 1844], the median FT4 level was 0 pmol/L [undetectable; 5.4], and the median anti-thyroperoxidase antibody level was 1601 UI/L [47; 25,500].In the 20 patients treated only with HRT, there were significant differences between height at diagnosis and height at 1 year (n = 19, p<0.0001), 2 years (n = 13, p = 0.0005), 3 years (n = 9, p = 0.0039), 4 years (n = 10, p = 0.0078), and 5 years (n = 10, p = 0.0018) of treatment but not in the case of final height (n = 6, p = 0.0625). Median final height was -1.4 [-2.7; 1,5] SDS (n = 6), with a significant difference between height loss at diagnosis and total catch-up growth (p = 0.003).The other nine patients were also given growth hormone (GH). They were smaller at diagnosis (p = 0.01); however, there was no difference in final height between those two groups (p = 0.68). ConclusionSevere HH can lead to a major height deficit, and catch-up growth seems to be insufficient after treatment with HRT alone. In the most severe cases, administration of GH may enhance this catch-up.

Hacettepe Health Cohort (HU-CoVaCS): Study Design, Baseline Characteristics and the First 3-Month-Follow Up of COVID-19 Vaccinated Students

Objective: This study included participants from Hacettepe University 4th, 5th, and 6th-grade students of Medical School and 4th and 5th-grade students of Dental School; and aimed to evaluate the general health status, COVID-19 history, vaccination status, and SARS-CoV-2 antibody levels of the participants to support their physical and social health, during the pandemic period. Methods: A prospective cohort study was conducted with an integrated, matched, nested case-control study. Sociodemographic characteristics, life habits, COVID-19 history, vaccination status, compliance with mask-distance-hygiene rules, and risks (if any) for COVID-19 were inquired via online questionnaires. Physical examinations, complete blood count, biochemistry tests, and anti-SARS-CoV-2 anti-spike antibody tests were conducted for all consenting participants. All analyses were established using depersonalized data. Results: Of the 778 participants completing the baseline visit in June-July 2021, the percentages of those vaccinated with at least one, two, and three/more doses of COVID-19 vaccine were 99.1%, 98.0%, and 11.7%, respectively; one had four doses. The median (minimum-maximum) time since the last vaccination was 134 (34-166) days for those vaccinated with two doses [CoronaVac (Sinovac Life Sciences, Beijing, China)] and 25 (14-56) days for those vaccinated with three doses [two doses of CoronaVac and a last dose of Pfizer-BioNTech mRNA vaccine (Comirnaty®). The third dose was applied at a median of 164 (151-202) days after the second dose, and all were heterologous in type. The median (minimum-maximum) antibody level for the overall group was 53.55(0-5680) BAU/mL: 47.19 BAU/mL in those who received two doses, with a more than 100 times increase after a third dose (4943.64 BAU/mL). Of the 522 participants followed up to October 1, 2021, 6 PCR-positive symptomatic participants were diagnosed with COVID-19: the incidence rate was 4/1000 person-months. Conclusion: A 100-fold neutralizing antibody level following the third dose demonstrated the importance of a booster dose. Given the time lag between doses, antibody measurements of BioNTech recipients should be repeated in the upcoming months. Booster selection should involve antibody level, variant sensitivity of the vaccine, and individual characteristics of the recipient.

Incidence and Associated Factors of SARS-CoV-2 Infection Post-mRNA-1273 Booster Vaccination in Health-Care Workers.

The COVID-19 pandemic has caused significant morbidity and mortality worldwide, especially among health-care workers. One of the most important preventive measures is vaccination. This study examined factors associated with the incidence rate of SARS-CoV-2 infection after mRNA-1273 booster vaccination (preceded by the CoronaVac primary vaccination) and the antibody profile of health-care workers at one of the tertiary hospitals in Indonesia. This was a combined retrospective cohort and cross-sectional study. Three hundred health-care workers who were given the mRNA-1273 booster vaccine a minimum of 5 months prior to this study were randomly selected. Participants were then interviewed about their history of COVID-19 vaccination, history of SARS-CoV-2 infection, and comorbidities. Blood samples were taken to assess IgG sRBD antibody levels. The median antibody level was found to be 659 BAU/mL (min 37 BAU/mL, max 5680 BAU/mL, QIR 822 BAU/mL) after the booster, and this was not related to age, sex, comorbidities, or adverse events following immunization (AEFI) after the booster. SARS-CoV-2 infection after the booster was correlated with higher antibody levels. In sum, 56 participants (18.6%) experienced SARS-CoV-2 infection after the mRNA-1273 booster vaccination within 5 months. Incidence per person per month was 3.2%. Age, sex, diabetes mellitus type 2, hypertension, obesity, and post-booster AEFI were not related to COVID-19 incidence after the booster. History of SARS-CoV-2 infection before the booster vaccination was significantly associated with a reduced risk of SARS-CoV-2 infection after booster vaccination, with a relative risk (RR) of 0.21 (95% CI 0.09-0.45, p < 0.001).

Comparison of antiphenolic glycolipid-1 antibody levels in seropositive contacts of leprosy after 2 years of single-dose rifampicin as postexposure prophylaxis.

Leprosy is still a global problem, especially in developing countries, including Indonesia. Ineffective prevention of leprosy leads to active transmission of the disease. World Health Organization (WHO) recommend post-exposure prophylaxis (PEP) with single dose of rifampicin (SDR) for leprosy patients. Previous study showed protective effect of SDR against leprosy, especially for the first 2 years. Hence, the use of PEP and IgM anti PGL-1 examination are required to suspend the chain of leprosy transmission. This study evaluated the effectiveness of SDR administration by comparing IgM anti-PGL-1 antibody levels in seropositive household contacts before and after 2 years of SDR administration. Analytical observational laboratory study comparing IgM anti PGL-1 antibody levels before and after 2 years of SDR administration in leprosy contacts, with a prospective follow-up study design. We conducted this study from December 2022 to January 2023 at Dr. Mohammad Hoesin General Hospital Palembang. All seropositive household contacts of leprosy who had been administrated SDR 2 years ago were included, then PGL-1 antibody levels were examined. The use of SDR showed significant improvement in leprosy contacts after 2 years (P=0.000). The median antibody level before SDR administration was 1,209.20 (615.81 - 4,353.60), which decrease to 146.03 (0 - 2,487.80) U/mL after 2 years. There was statistically significant relationship between history of BCG vaccination (P=0.003) and IgM PGL-1 antibody levels after 2 years of SDR administration. There is a significant decrease in IgM anti PGL-1 antibody levels among leprosy contacts after 2 years of SDR chemoprophylaxis administration.

Kinetics of SARS-CoV-2 IgM and IgG Antibodies 3 Months after COVID-19 Onset in Moroccan Patients

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious global public health problems. Characterization of the immune response, particularly antibodies to SARS-CoV-2, is important for establishing vaccine strategies. The purpose of this study was to evaluate longitudinally the kinetics of anti-SARS-CoV-2 antibodies against spike protein (S1) for up to 3 months in a cohort of 169 COVID-19 patients. We enrolled COVID-19 patients at two regional hospitals in Casablanca, Morocco, between March and September 2021. Blood samples were collected and N-specific IgM and S-specific IgG levels were measured by a commercial Euroimmun ELISA. IgM antibodies were assessed 2-5 (D00), 9-12 (D07), 17-20 (D15), and 32-37 (D30) days after symptom onset; IgG antibodies were assessed at these time points plus 60 (D60) and 90 (D90) days after symptom onset. We found that at 3 months after symptom onset, 79% of patients had detectable SARS-CoV-2-specific IgG antibodies, whereas their IgM seropositivity was 19% by 1 month after symptom onset. The IgM level decreased to 0.34 (interquartile range [IQR] 0.19-0.92) at 1 month after symptom onset, whereas the IgG level peaked at D30 (3.10; IQR 1.83-5.64) and remained almost stable at D90 (2.95; IQR 1.52-5.19). IgG levels were significantly higher in patients older than 50 years than in those younger than 50 at all follow-up time points (P < 0.05). Statistical analysis showed no significant difference in median anti-S1 antibody levels among infected patients based on gender or comorbidities. This study provides information on the longevity of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients.

The Quantity, Quality and Two Major Effector Functions of Antibodies to VAR2CSA and their Association with Pregnancy Outcomes in a Low Malaria Transmission Area

Background: Women produce antibodies to VAR2CSA when infected with Plasmodium falciparum during pregnancy that reduce disease severity in the current and subsequent pregnancies. In addition to antibody quantity, antibody quality (e.g., avidity) and function (e.g., inhibition of binding and opsonic phagocytosis) are immunologically important. Studies comparing the quantity, avidity and effector mechanisms of antibodies to VAR2CSA in the same group of women with pregnancy outcomes, especially in low transmission areas, are limited. Aims: The purpose of this study was to characterize antibodies to VAR2CSA using four assays, determine the correlation among the assays, and relate this to pregnancy outcome. Methods: A panel of 310 plasma samples from women in Yaoundé (a city with low malaria transmission) who had antibodies to full-length VAR2CSA were screened in assays that measured i) level of antibodies to VAR2CSA, ii) antibody avidity, iii) reduction in binding (RiB) of fluorescent VAR2CSA-coupled beads to fluorescent-CSA-coupled beads, and iv) opsonic phagocytosis using VAR2CSA-coupled beads and human THP1 cells. Results from the assays were compared with clinical information from 614 women who were Ab-negative. Results: A modest association was found among the 4 assays, i.e., as the amount of antibodies increased, a small increase in avidity, RiB and phagocytosis was observed; however, the association between RiB and avidity was poor. When results were dichotomized to above and below the median, antibody avidity, but not antibodies in the other assays, was associated with a significant reduction in prevalence of placental malaria and lower placental parasitemia. However, women who had antibody values above the median in amount (p=0.03), avidity (p=0.006), reduction in binding (p=0.018) and probably phagocytosis (p=0.065) had significantly lower placental parasitemia than women who lacked Abs to VAR2CSA. Conclusions: In this urban setting, women with the highest (above the median) antibody levels, in the four assays had a lower prevalence of placental malaria and placental parasitemia than women who lacked anti-VAR2CSA antibodies. Thus, VAR2CA-based vaccine trials in low transmission areas should consider using all four assays before and after vaccination.

Accelerated waning of immune responses to a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases

BackgroundA 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed. Currently it remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses. Methods50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period. ResultsAt week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781–10,208] versus 9650 BAU/ml [6633–16,050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological disease-modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported. ConclusionDue to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.

Humoral and T-cell mediated response after administration of mRNA vaccine BNT162b2 in frail populations

Patients with frailty are considered to be at greater risk to get severe infection from SARS-CoV-2. One of the most effective strategies is vaccination.In our study we evaluated both the humoral immune response elicited by the vaccination at different time points, and the T-cell response in terms of interferon (IFN)-γ production in frail patients and healthy donors.Fifty-seven patients (31 patients undergoing hemodialysis and 26 HIV positive subjects) and 39 healthcare workers were enrolled. All participants received two doses of the mRNA vaccine BNT162b2.Healthcare workers showed a significantly higher antibody titer than patients twenty-one days after the first dose (p < 0.001). From the same time point we observed for both groups a decay of the antibody levels with a steeper slope of decline in the patients group. Regarding T-cell response the only significant difference between non-reactive and reactive subjects was found in median antibody levels, higher in the responders group than in non-responders.The healthcare workers seem to better respond to the vaccination in terms of antibodies production; the lack of T-cell response in about 50% of the participants seems to suggest that in our study population both humoral and cell-mediated response decline over time remarking the importance of the booster doses, particularly for frail patients.

SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study

ObjectivesTo examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions.DesignCohort study.SettingOxford University Hospitals in the United Kingdom.ParticipantsHealthcare workers who had SARS-CoV-2 serological data available...

Immunogenicity of the Two mRNA SARS-CoV-2 Vaccines in a Large Cohort of Dialysis Patients.

Chronic kidney disease patients, especially those on hemodialysis, are at the highest risk of a severe course and death from COVID-19. Moreover, they appear to have suboptimal response in both cellular and humoral immunity after vaccination. The present study investigated humoral and cellular response and safety after two doses of either of the two authorized mRNA vaccines in a cohort of 310 patients on maintenance dialysis. The antibody response rate was 94.5%, with a median (25th, 75th) antibody titer of 3478 (1236, 8141) AU/mL. Only mild adverse effects were observed. Only vaccine type was independently associated with immunogenicity. Α statistically significant difference in favor of mRNA1273 versus BNT162b2 vaccine was observed. Antibody positivity (100% vs. 94.3%, p &lt; 0.001), median (25th, 75th) antibody levels: 9499 (6118, 20,780) AU/mL vs. 3269 (1220, 7807) AU/mL (p &lt; 0.001). Among the 65 patients tested for T-cell response, 27 (41.5%) had a positive one with a median (25th, 75th) antibody titer of 6007 (3405, 12,068) AU/mL, while 38 with no T-cell response presented a lower median (25th, 75th) antibody titer of 1744 (850, 4176) AU/mL (p &lt; 0.001). Both mRNA vaccines are safe for dialysis patients and can trigger humoral and cellular responses, although with lower titers than those that have been reported to healthy individuals.

Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy.

Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2-4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2-4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138-8732) compared with 4495 (1591-6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150-4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p&lt;0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. NCT04798625.

Immunity After Vaccination Against SARS-CoV-2 in Lung Transplant?

Introduction: SARS-CoV2 infection causes high morbidity and mortality in lung transplant recipients (LT). Vaccination with mRNA vaccines has been shown to play a key role in controlling the severity of infection in the general population. The aim of our study is to analyze whether vaccination with 2 doses of SARS-Cov2 provides immunity in LT.Material and Methods: Retrospective descriptive and analytical study of LTs vaccinated with 2 doses of SARS-CoV2. We analyzed the vaccine received, if they had COVID-19, antibody levels (anti-spike and anti-nucleoprotein), anticalcineurin levels, infections in the last year and the presence of neoplasias.Results: The most commonly administered vaccine was from the Moderna laboratory, with 27% of patients showing immunity with a median antibody levels of 4.81 BAU/ml far from the values considered protective (>34 BAU/ml). Thirteen patients were infected with SARS-CoV2, seven post-vaccination (five of them were anti-spike positive). No relationship was demonstrated between generation of immunity and age and level of immunosuppression.Conclusion: Vaccination against SARS-CoV2 in LT generates limited and ineffective immunity with only 2 doses.

Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections.

Background: Vaccine mediated SARS-CoV-2 antibody responses should be carefully evaluated. With regular follow-up in healthy individuals, we aimed to determine SARS-CoV-2 serological responses post three doses of immunization and prior to breakthrough infections in the Canadian population. Methods: In a prospective cohort study, we enrolled 140 healthy participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor–binding domain were quantified by immunoassay post three doses of immunization. With COVID-19 rapid antigen test, polymerase chain reaction, and whole genome sequencing, 27 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccine (including BNT162b2, AZD1222, and mRNA-1273), the median serum anti-spike protein antibody level was 143.6 BAU/mL (binding antibody unit, interquartile range 79.0–266.6) post the first dose of immunization, 1046.4 BAU/mL (423.9–1738.2) post the second dose, and 1604.7 BAU/mL (700.1–3764.0) post the third dose. Observed differences were significant (p ≤ 0.001). The median antibody level of 1604.7 BAU/mL post third dose is 45.6 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In seven breakthrough cases characterized by whole genome sequencing, prior to infection, antibody concentrations of breakthrough cases were at 3249.4 (Delta), 2748.4 (Delta), 4893.9 (Omicron), 209.1 (Omicron), and 231.5 (Omicron), 725.7 (Omicron), and 2346.6 (Omicron) BAU/mL. Compared with the average antibody concentration of 2057.7 BAU/mL (58 times that of the seroconversion concentration) from above seven cases, 37.2% of triple vaccinated, 19.0% of double vaccinated, and 1.5% single dosed individuals have higher SARS-CoV-2 antibody levels. Conclusions: Most vaccines are effective in producing robust antibody responses when more than one dose is given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants have SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.