Immunogenicity trends 1 and 3 months after second BNT162B2 vaccination among healthcare workers in Israel

ObjectivesWe evaluated the antibody response to the BNT162B2 vaccine among healthcare workers (HCWs) to identify factors associated with decreased immunogenicity.MethodsThis prospective cohort study included consenting HCWs who completed a questionnaire regarding background illnesses, medications, and post-vaccination allergic reactions or rash. All HCWs were tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) 1 and 3 months after the second vaccine dose. A multivariate mixed linear model was adjusted to participants' data and fit to predict antibody levels after the second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 months and 1 month. Multivariate analyses identified factors associated with lower antibody levels.ResultsIn total 1506 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Older age was associated with lower mean antibody levels (–1.22 AU/mL, p < 0.001, 95%CI –1.43 to –1.01). In addition, male sex (–22.16 AU/mL, p < 0.001, 95%CI –27.93 to –16.39), underlying condition (–10.86 AU/mL, p 0.007, 95%CI –18.81 to –2.91) and immunosuppressive treatment (–28.57 AU/mL, p 0.002, 95%CI –46.85 to –10.29) were associated with significantly lower mean antibody levels. Allergic reactions after vaccine administration or peri-vaccination glucocorticosteroid treatment were not correlated with antibody levels.ConclusionsMost HCWs had measurable antibodies at 3 months. Risk factors for lower antibody levels were older age, male sex, underlying condition, and immunosuppressive treatment. These factors may be considered when planning booster doses during vaccine shortages.     

Quantitative SARS-CoV-2 anti-spike responses to Pfizer–BioNTech and Oxford–AstraZeneca vaccines by previous infection status

ObjectivesWe investigated determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer–BioNTech or Oxford–AstraZeneca vaccines.MethodsHCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥50 AU/mL). We used multivariable logistic regression to identify predictors of seropositivity and generalized additive models to track antibody responses over time.Results3570/3610 HCWs (98.9%) were seropositive >14 days post first vaccination and prior to second vaccination: 2706/2720 (99.5%) were seropositive after the Pfizer–BioNTech and 864/890 (97.1%) following the Oxford–AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after the second vaccination were seropositive. Quantitative antibody responses were higher after previous infection: median (IQR) >21 days post first Pfizer–BioNTech 14 604 (7644–22 291) AU/mL versus 1028 (564–1985) AU/mL without prior infection (p < 0.001). Oxford–AstraZeneca vaccine recipients had lower readings post first dose than Pfizer–BioNTech recipients, with and without previous infection, 10 095 (5354–17 096) and 435 (203–962) AU/mL respectively (both p < 0.001 versus Pfizer–BioNTech). Antibody responses >21 days post second Pfizer vaccination in those not previously infected, 10 058 (6408–15 582) AU/mL, were similar to those after prior infection followed by one vaccine dose.ConclusionsSARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.     

SARS-CoV-2 new infections among health-care workers after the first dose of the BNT162b2 mRNA COVID-19 vaccine. A hospital-wide cohort study

ObjectivesTo evaluate the effect of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on the incidence of new SARS-CoV-2 infections in health-care workers (HCW).MethodsThe evolution of the incident rate of microbiologically confirmed SARS-CoV-2 infection in a cohort of 2590 HCW after BNT162b2 mRNA SARS-CoV-2 vaccination, compared with the rate in the community (n = 170 513) was evaluated by mixed Poisson regression models.ResultsA total of 1820 HCW (70.3% of total) received the first dose of the BNT162b2 mRNA vaccine between 10 January and 16 January 2021, and 296 (11.4%) received it the following week. All of them completed vaccination 3 weeks later. Incidence rates of SARS-CoV-2 infection after the first dose of mRNA SARS-CoV-2 vaccine declined by 71% (Incidence Rate Ratio (IRR) 0.286, 95% CI 0.174–0.468; p < 0.001) and by 97% (IRR 0.03, 95% CI 0.013–0.068; p < 0.001) after the second dose, compared with the perivaccine time. SARS-CoV-2 incidence rates in the community (with a negligible vaccination rate) had a much lower decline: 2% (IRR 0.984, 95% CI 0.943–1.028; p 0.47) and 61% (IRR 0.390, 95% CI 0.375–0.406; p < 0.001) for equivalent periods. Adjusting for the decline in the community, the reduction in the incident rates among HCW were 73% (IRR 0.272, 95% CI 0.164–0.451 p < 0.001) after the first dose of the vaccine and 92% (IRR 0.176, 95% CI 0.033–0.174; p < 0.001) after the second dose.ConclusionsmRNA SARS-CoV-2 vaccination is associated with a dramatic decline in new SARS-CoV-2 infection among HCW, even before the administration of the second dose of the vaccine.     

Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study

ObjectivesTo evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19).MethodsWe measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay.ResultsAntibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7–87.8), 3 (103.2 U/mL, 95%CI: 87.9–121.2; p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4–147.0; p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9–24.0), 3 (15.2 AU/mL, 95%CI: 13.2–17.6; p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7–11.4; p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics.ConclusionsNeutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.     

Seroprevalence of SARS-CoV-2 antibodies and reduced risk of reinfection through 6 months: a Danish observational cohort study of 44 000 healthcare workers

ObjectivesAntibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor in protecting against coronavirus disease 2019 (COVID-19). We examined longitudinal changes in seroprevalence in healthcare workers (HCWs) in Copenhagen and the protective effect of antibodies against SARS-CoV-2.MethodsIn this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCWs three times over 6 months. HCW characteristics were obtained by questionnaires. The study was registered at ClinicalTrials.gov, NCT04346186.ResultsFrom April to October 2020 we screened 44 698 HCWs, of whom 2811 were seropositive at least once. The seroprevalence increased from 4.0% (1501/37 452) to 7.4% (2022/27 457) during the period (p < 0.001) and was significantly higher than in non-HCWs. Frontline HCWs had a significantly increased risk of seropositivity compared to non-frontline HCWs, with risk ratios (RRs) at the three rounds of 1.49 (95%CI 1.34–1.65, p < 0.001), 1.52 (1.39–1.68, p < 0.001) and 1.50 (1.38–1.64, p < 0.001). The seroprevalence was 1.42- to 2.25-fold higher (p < 0.001) in HCWs from dedicated COVID-19 wards than in other frontline HCWs. Seropositive HCWs had an RR of 0.35 (0.15–0.85, p 0.012) of reinfection during the following 6 months, and 2115 out of 2248 (95%) of those who were seropositive during rounds one or two remained seropositive after 4–6 months. The 133 of 2248 participants (5.0%) who seroreverted were slightly older and reported fewer symptoms than other seropositive participants.ConclusionsHCWs remained at increased risk of infection with SARS-CoV-2 during the 6-month period. Seropositivity against SARS-CoV-2 persisted for at least 6 months in the vast majority of HCWs and was associated with a significantly lower risk of reinfection.     

Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs

ObjectivesThe aim was to determine the antibody response against SARS-CoV-2 spike protein and nucleoprotein using four automated immunoassays and three ELISAs for the detection of total Ig antibodies (Roche) or IgG (Abbott, Diasorin, Snibe, Euroimmun, Mikrogen) in COVID-19 patients.MethodsSensitivity and dynamic trend to seropositivity were evaluated in 233 samples from 114 patients with moderate, severe or critical COVID-19 confirmed with PCR on nasopharyngeal swab. Specificity was evaluated in 113 samples collected before January 2020, including 24 samples from patients with non-SARS coronavirus infection.ResultsSensitivity for all assays was 100% (95% confidence interval 83.7–100) 3 weeks after onset of symptoms. Specificity varied between 94.7% (88.7–97.8) and 100% (96.1–100). Calculated at the cut-offs that corresponded to a specificity of 95% and 97.5%, Roche had the highest sensitivity (85.0% (79.8–89.0) and 81.1% (76.6–85.7), p < 0.05 except vs. Abbott). Seroconversion occurred on average 2 days earlier for Roche total Ig anti-N and the three IgG anti-N assays (Abbott, Mikrogen, Euroimmun) than for the two IgG anti-S assays (Diasorin, Euroimmun) (≥50% seroconversion day 9–10 vs. day 11–12 and p < 0.05 for percent seropositive patients day 9–10 to 17–18). There was no significant difference in the IgG antibody time to seroconversion between critical and non-critical patients.DiscussionSeroconversion occurred within 3 weeks after onset of symptoms with all assays and on average 2 days earlier for assays detecting IgG or total Ig anti-N than for IgG anti-S. The specificity of assays detecting anti-N was comparable to anti-S and excellent in a challenging control population.     

Not all COVID-19 pandemic waves are alike

ObjectiveWe aimed to assess differences in patients' profiles in the first two surges of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Barcelona, Spain.MethodsWe prospectively collected data from all adult patients with SARS-CoV-2 infection diagnosed at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. All the patients were diagnosed through nasopharyngeal swab PCR. The first surge spanned from 1st March to 13th August 2020, while surge two spanned from 14th August to 8th December 2020.ResultsThere were 2479 and 852 patients with microbiologically proven SARS-CoV-2 infection in surges one and two, respectively. Patients from surge two were significantly younger (median age 52 (IQR 35) versus 59 (40) years, respectively, p < 0.001), had fewer comorbidities (379/852, 44.5% versus 1237/2479, 49.9%, p 0.007), and there was a shorter interval between onset of symptoms and diagnosis (median 3 (5) versus 4 (5) days, p < 0.001). All-cause in-hospital mortality significantly decreased for both the whole population (24/852, 2.8% versus 218/2479, 8.8%, p < 0.001) and hospitalized patients (20/302, 6.6% versus 206/1570, 13.1%, p 0.012). At adjusted logistic regression analysis, predictors of in-hospital mortality were older age (per year, adjusted odds ratio (aOR) 1.079, 95%CI 1.063–1.094), male sex (aOR 1.476, 95%CI 1.079–2.018), having comorbidities (aOR 1.414, 95%CI 0.934–2.141), ICU admission (aOR 3.812, 95%CI 1.875–7.751), mechanical ventilation (aOR 2.076, 95%CI 0.968–4.454), and coronavirus disease 2019 (COVID-19) during surge one (with respect to surge two) (aOR 2.176, 95%CI 1.286–3.680).ConclusionsFirst-wave SARS-CoV-2-infected patients had a more than two-fold higher in-hospital mortality than second-wave patients. The causes are likely multifactorial.     

Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses

ObjectivesThis study sought to correlate the SARS-CoV-2 IgG antibody response level to the BNT162b2 (Pfizer BioNTech) mRNA vaccine after the first and second doses with the reported adverse events.MethodsThis cohort study examined the adverse events profiles of people vaccinated with BNT162b2 in our institute between late 2020 and May 2021. Adverse events, age, and sex were reported using an electronic questionnaire, and their SARS-CoV-2 IgG antibody levels were retrieved from the hospital database.ResultsBetween 20 December 2020 and 31 May 2021, the adverse events questionnaire was completed by 9700 individuals who received the first vaccine dose and 8321 who received the second dose. After the first and second doses, the average antibody levels were 62.34 AU/mL (mean 4–373) and 188.19 AU/mL (mean 20–392), respectively. All of the adverse events, except local pain, were more common after the second vaccine dose. Multivariate analysis showed that after the first vaccine dose, female sex and younger age (but not IgG titres) were associated with a higher probability of adverse events (OR 2.377, 95% CI, 1.607–3.515, p = 0.000; OR 0.959, 95% CI, 0.944–0.977, p £0.000; OR 1.002, 95% CI, 0.995–1.008, p £0.601; respectively); however, all three parameters were associated with the incidence of adverse events after the second dose (OR 2.332, 95% CI, 1.636–3.322, p = 0.000; OR 0.984, 95% CI, 0.970–0.999, p £0.039; OR 1.004, 95% CI, 1.001–1.007, p £0.022; respectively).DiscussionAdverse events are significantly more common after the second BNT162b2 vaccine dose than after the first dose. We found an association between sex, age, and SARS-CoV-2 IgG antibody titre with the incidence of adverse events.     

Humoral serological response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation

ObjectivesTo assess the humoral immune response to the BNT162b2 vaccine after allogeneic haematopoietic cell transplantation (HCT).MethodsThis is a prospective cohort study. The SARS-CoV-2 IgGII Quant (Abbott©) assay was performed 4–6 weeks after the second BNT162b2 vaccine for quantitative measurement of anti-spike antibodies.ResultsThe cohort included 106 adult patients. Median time from HCT to vaccination was 42 (range 4–439) months. Overall, 15/106 (14%, 95% confidence interval (CI) 7–21%) were seronegative despite vaccination, 14/52 patients on immunosuppression (27%, 95%CI 19–35%) compared to only 1/54 patients off immunosuppression (1.8%, 95%CI 1–4%) (p 0.0002). The proportion of seronegative patients declined with time; it was 46% (6/13) during the first year, 12.5% (3/24) during the second year and 9% (6/69) beyond 2 years from transplant. Patients with acute graft-versus-host disease (GVHD) (odds ratio (OR) 3.3, 95%CI 0.97–11.1, p 0.06) and moderate to severe chronic GVHD (OR 5.9, 95%CI 1.2–29, p 0.03) were more likely to remain seronegative. Vaccination was well tolerated by most patients. However, 7% (7/106) reported that GVHD-related symptoms worsened within days following vaccination.ConclusionA significant proportion of allogeneic HCT recipients receiving immunosuppression demonstrated an inadequate humoral response to the BNT162b2 vaccine. These patients should be recognized and instructed to take appropriate precautions. Recipients who were off immunosuppression had a humoral response that was comparable to that of the general population.     

Severe immunosuppression is related to poorer immunogenicity to SARS-CoV-2 vaccines among people living with HIV

ObjectivesThe aim of this study was to assess the immunogenicity of SARS-CoV-2 available vaccines among people living with HIV (PLWH) after a complete vaccination scheme, and determine predictors of seroconversion.MethodsThis multicentre prospective cohort study included 420 PLWH who had received a standard immunization, either with mRNA or adenoviral-vectored COVID-19 vaccines. Antibody response was evaluated within 1 to 2 months after the last dose of the vaccine with a quantitative determination of antitrimeric spike protein-specific IgG antibodies and IgG neutralizing antibodies.ResultsOverall, 384 of 420 PLWH (91%) showed antibody response to vaccination. Seroconversion was observed in 308 of 326 individuals with cluster of differentiation 4 (CD4) counts ≥350 cells/mm³ (95%), 55 of 61 PLWH with 200 to 349 cells/mm³ (90%), and 21 of 33 PLWH with CD4 counts <200 cells/mm³ (64%; p < 0.001). The median log₁₀ IgG neutralization levels were 2.4 IU/mL (Q1–Q3, 1.0–3.1) among PLWH with CD4 counts <200 cells/mm³, 3.1 IU/mL (Q1–Q3, 2.8–3.4) for the 200 to 349 cells/mm³ group, and 3.1 IU/mL (Q1–Q3, 2.7–3.4) for PLWH with CD4 counts ≥350 cells/mm³ (p = 0.016). In the multivariate analysis, CD4 counts ≥350 cells/mm³ (OR: 7.10; 95% CI, 1.91–26.46; p = 0.004) and receiving mRNA-vectored COVID-19 vaccines (OR: 8.19; 95% CI, 3.24–20.70; p ≤ 0.001) were independently associated with a higher probability of response to vaccination.DiscussionHIV-related immunosuppression impairs the antibody response to SARS-CoV-2 vaccines. Specific vaccination schemes should be urgently tailored in this setting, particularly in patients with CD4 cell counts <200 cells/μL. Adenoviral-vectored vaccines should be avoided in PLWH whenever possible.     

Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study

ObjectiveWe aimed to assess the impact of early versus late third-trimester maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on transplacental transfer and neonatal levels of SARS-CoV-2 antibodies.MethodsMaternal and cord blood sera were collected following term delivery after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination, with the first vaccine dose administered between 27 and 36 weeks of gestation. SARS-CoV-2 spike protein (S) and receptor-binding domain (RBD) -specific, IgG levels and neutralizing potency were evaluated in maternal and cord blood samples.ResultsThe study cohort consisted of 171 parturients—median age 31 years (interquartile range (IQR) 27–35 years); median gestational age 39⁺⁵ weeks (IQR 38⁺⁵–40⁺⁴ weeks)–83 (48.5%) were immunized in early thrird-trimester (first dose at 27–31 weeks) and 88 (51.5%) were immunized in late third trimester (first dose at 32–36 weeks). All mother–infant paired sera were positive for anti S- and anti-RBD-specific IgG. Anti-RBD-specific IgG concentrations in neonatal sera were higher following early versus late third-trimester vaccination (median 9620 AU/mL (IQR 5131–15332 AU/mL) versus 6697 AU/mL (IQR 3157–14731 AU/mL), p 0.02), and were positively correlated with increasing time since vaccination (r = 0.26; p 0.001). Median antibody placental transfer ratios were increased following early versus late third-trimester immunization (anti-S ratio: 1.3 (IQR 1.1–1.6) versus 0.9 (IQR 0.6–1.1); anti-RBD-specific ratio: 2.3 (IQR 1.7–3.0) versus 0.7 (IQR 0.5–1.2), p < 0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late third-trimester immunization (median 1.9 (IQR 1.7–2.5) versus 0.8 (IQR 0.5–1.1), p < 0.001), and was positively associated with longer duration from vaccination (r = 0.77; p < 0.001).ConclusionsEarly compared with late third-trimester maternal SARS-CoV-2 immunization enhanced transplacental antibody transfer and increased neonatal neutralizing antibody levels. Our findings highlight that vaccination of pregnant women early in the third trimester may enhance neonatal seroprotection.     

The effect of a third-dose BNT162b2 vaccine on anti-SARS-CoV-2 antibody levels in immunosuppressed patients

ObjectivesThe recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.MethodsThis was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.ResultsOf the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti–SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1–69) to 243 (IQR, 2–4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25–184.5) to 1824 (IQR, 161–9686)), followed by the rheumatology (from 22 (IQR, 1–106) to 1291 (IQR, 6–6231)) and haemato-oncology (from 1 (IQR, 0.1–7) to 7.5 (IQR, 0.1–407.5)) cohorts. The χ² test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%–46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%–71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%–60.5%)) and haemato-oncology (29.7% (95% CI, 22%–38.8%); χ² = 11.87; p = 0.003) patients.DiscussionA third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.     

The temporal course of T- and B-cell responses to vaccination with BNT162b2 and mRNA-1273

ObjectivesTo investigate the response of the immune system (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273.Methods531 vaccinees, recruited from healthcare professionals, donated samples before, in between, and after the administration of the two doses of the vaccine. T- and B-cell responses were examined via interferon-γ (IFN-γ) release assay, and antibodies against different epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (S1 and NCP) were detected via ELISA and surrogate neutralization assay. Results were correlated with influencing factors such as age, sex, prior infection, vaccine received (BNT162b2 or mRNA-1273), and immunosuppression. Furthermore, antinuclear antibodies (ANAs) were measured to screen for autoimmune responses following vaccination with an mRNA vaccine.ResultsNo markers of immunity against SARS-CoV-2 were found before the first vaccination. Two weeks after it, specific responses against SARS-CoV-2 were already measurable (median ± median absolute deviation (MAD): anti-S1 IgG 195.5 ± 172.7 BAU/mL; IgA 6.7 ± 4.9 OD; surrogate neutralization 39 ± 23.7%), and were significantly increased two weeks after the second dose (anti-S1 IgG 3744 ± 2571.4 BAU/mL; IgA 12 ± 0 OD; surrogate neutralization 100 ± 0%, IFN-γ 1897.2 ± 886.7 mIU/mL). Responses were stronger for younger participants (this difference decreasing after the second dose). Further influences were previous infection with SARS-CoV-2 (causing significantly stronger responses after the first dose compared to unexposed individuals (p ≤ 0.0001)) and the vaccine received (significantly stronger reactions for recipients of mRNA-1273 after both doses, p < 0.05–0.0001). Some forms of immunosuppression significantly impeded the immune response to the vaccination (with no observable immune response in three immunosuppressed participants). There was no significant induction of ANAs by the vaccination (no change in qualitative ANA results (p 0.2592) nor ANA titres (p 0.08) from pre-to post-vaccination.ConclusionsBoth vaccines elicit strong and specific immune responses against SARS-CoV-2 which become detectable one week (T-cell response) or two weeks (B-cell response) after the first dose.     

Long term SARS-CoV-2-specific cellular immunity after COVID-19 in liver transplant recipients

PurposeLong-term immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunosuppressed patients is not well characterized. We aimed to explore the long-term natural immunity against SARS-CoV-2 in liver transplant (LT) recipients compared to the non-transplanted population (control group).MethodsFifteen LT recipients and 15 controls matched according to variables associated with disease severity were included at 12 months following the coronavirus disease 2019 (COVID-19) onset. Peripheral blood mononuclear cells were stimulated with peptide pools covering spike (S), nucleocapside (N), and membrane (M) proteins. Reactive CD4+ and CD8+ T cells were identified using flow cytometry, and cytokine production was evaluated in the culture supernatants using cytometric bead array. Serum anti-N and anti-S IgG antibodies were detected with chemiluminescence.ResultsThe percentage of patients with a positive response in both CD4+ and CD8+ T cells against each viral protein and IL2, IL10, TNF-α, and IFN-γ levels was similar between LT recipients and controls. IFN-γ levels were positively correlated with the percentage of reactive CD4+ (p = 0.022) and CD8+ (p = 0.043) T cells to a mixture of M + N + S peptide pools. The prevalence and levels of anti-N and anti-S IgG antibodies were slightly lower in the LT recipients, but the difference was not statistically significant.ConclusionLT recipients exhibited a similar T cell response compared to non-transplanted individuals one year after COVID-19 diagnosis.     

Factors associated with asymptomatic infection in health-care workers with severe acute respiratory syndrome coronavirus 2 infection in Wuhan,China: a multicentre retrospective cohort study

ObjectivesTo describe the fraction of asymptomatic health-care workers (HCWs) in two designated hospitals for coronavirus disease 2019 (COVID-19) treatment in Wuhan and explore the factors associated with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsAll HCWs in Wuhan Union Hospital and Wuhan Red Cross Hospital with either positive SARS-CoV-2 nucleic acid or positive antibody test before 18 April 2020 were included. Exposure, epidemiological and demographic information were retrospectively collected by a structured questionnaire. Medical records were also reviewed for clinical characteristics and CT images of HCWs.ResultsAs of 18 April 2020, a total of 424 HCWs were identified. Among them, 276 (65.1%) were symptomatic and 148 (34.9%) were asymptomatic. Fifty-five (19.9%) families of the symptomatic HCWs and 16 (10.8%) families of the asymptomatic HCWs were infected with SARS-CoV-2. HCWs with infected family members tended to be symptomatic (OR 2.053, 95% CI 1.130–3.730; p 0.018). Multivariable logistic regression analysis exhibited that performing tracheal intubation or extubation (OR 4.057, 95% CI 1.183–13.909; p 0.026) was associated with an increased likelihood of symptomatic SARS-CoV-2 infection, whereas consistent use of N95 respirators (OR 0.369, 95% CI 0.201–0.680; p 0.001) and eye protection (OR 0.217, 95% CI 0.116–0.404; p < 0.001) were associated with an increased likelihood of asymptomatic SARS-CoV-2 infection.ConclusionsAsymptomatic SARS-CoV-2 infection in HCWs comprised a considerable proportion of HCW infections during the pandemic of COVID-19. Those who performed tracheal intubation or extubation were most likely to develop related symptoms, whereas those taking aggressive measures, including consistent use of N95 masks and eye protection, tended to be asymptomatic cases.     

Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic,multicentre, randomized,controlled trial

ObjectivesMany transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB.MethodsWe performed this multicentre, randomized, open-label trial in kidney transplant recipients who had ASB and were ≥2 months post-transplantation. We randomly assigned participants to receive antibiotics or no therapy. The primary outcome was the incidence of symptomatic UTI over the subsequent 12 months.ResultsOne hundred and ninety-nine kidney transplant recipients with ASB were randomly assigned to antibiotics (100 participants) or no therapy (99 participants). There was no significant difference in the occurrence of symptomatic UTI between the antibiotic and no-therapy groups (27%, 27/100 versus 31%, 31/99; univariate Cox model: hazard ratio 0.83, 95%CI: 0.50–1.40; log-rank test: p 0.49). Over the 1-year study period, antibiotic use was five times higher in the antibiotic group than in the no-therapy group (30 antibiotic days/participant, interquartile range 20–41, versus 6, interquartile range 0–15, p < 0.001). Overall, 155/199 participants (78%) had at least one further episode of bacteriuria during the follow-up. Compared with the participant's baseline episode of ASB, the second episode of bacteriuria was more frequently caused by bacteria resistant to clinically relevant antibiotics (ciprofloxacin, cotrimoxazole, third-generation cephalosporin) in the antibiotic group than in the no-therapy group (18%, 13/72 versus 4%, 3/83, p 0.003).ConclusionsApplying a screen-and-treat strategy for ASB does not reduce the occurrence of symptomatic UTI in kidney transplant recipients who are more than 2 months post-transplantation. Furthermore, this strategy increases antibiotic use and promotes the emergence of resistant organisms.     

Assessment of BIV1-CovIran inactivated vaccine–elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern

ObjectivesThe BIV1-CovIran vaccine is highly effective against COVID-19. The neutralizing potency of all SARS-CoV-2 vaccines seems to be decreased against variants of concern. We assessed the sensitivity of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants to neutralizing antibodies (NAbs) present in sera from individuals who had received the BIV1-CovIran candidate vaccine compared with an original Wuhan-related strain.MethodsThe ability of vaccine serum to neutralize the variants was measured using the conventional virus neutralization test. The correlation of spike (S) protein antibody and anti-receptor binding domain with neutralizing activity was investigated.ResultsThe current study demonstrated that 29 of 32 (90.6%; 95% CI: 75.0–98.0) of the vaccinees developed NAbs against a Wuhan-related strain. It is noteworthy that 28 (87.50%) and 24 of 32 (75%) of the recipients were able to produce NAbs against Alpha, Beta, and Delta variants, respectively. Serum virus-neutralizing titres for different SARS-CoV-2 strains were weakly correlated with anti–receptor binding domain antibodies (Spearman r = 36-42, p < 0.05), but not S-binding antibodies (p > 0.05).DiscussionAlthough there was a reduction in neutralization titres against the Alpha, Beta, and Delta variants compared with the Wuhan strain, BIV1-CovIran still exhibited potent neutralizing activity against the SARS-CoV-2 variants of concern.     

Seroprevalence of SARS-CoV-2 specific IgG antibodies among eye care workers in South India

PurposeHealth care workers are at higher risk of acquiring the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This study aims to understand the seroprevalence of anti-SARS-CoV-2 IgG antibody among the eye care workers in South India.MethodsThe participants included eye care workers from the nine eye care centres. All the participants were interviewed with a questionnaire to obtain essential information about socio-demographics, past contact with COVID-19 patients and additional information as recommended by Indian Council of Medical Research, India. Serum samples were tested for anti-SARS-CoV-2 IgG antibodies by ELISA.ResultsA total of 1313 workers were included and 207 (15.8%) were positive for the SARS-CoV-2 IgG antibody. The seropositivity was higher in the moderate risk group (19.5%) followed by low (18.6%) and high risk (13.7%) groups. The seropositivity was significantly higher among i) day scholars compared to hostellers (OR - 2.22, 1.56 to 3.15, P ​< ​0.0001), ii) individuals with history of flu-like illness (4.57, 3.08–6.78, P ​< ​0.001) or who were symptomatic or in contact with COVID 19 positive cases (2.2, 1.02–4.75, P – 0.043) and iii) individuals with history of systemic illness (2.11, 1.39–3.21, P ​< ​0.001). Individuals (11.97%) who had no history of contact or any illness were also seropositive.ConclusionsThe effectiveness of the protective measures taken against COVID infection was evident from the lower percentage of seropositivity in the high risk group. The study highlighted the need to create awareness among individuals to follow strict safety measures even in non-work hours and also in social circles.     

Relationships between self-management strategies and physical activity and diet quality in women with polycystic ovary syndrome

ObjectiveTo determine the relationships of self-management strategies and physical activity (PA) and diet quality in women with PCOS.MethodsAn online cross-sectional study involving women (n = 501), 18–45 years in the general Australian community with a self-reported PCOS diagnosis. The self-management and lifestyle behaviour questionnaires were completed between August 2017 and March 2018.ResultsImplementation of PA related self-management strategies increased the odds of meeting PA recommendations [Odds ratio (OR): 2.929 (95%CI: 2.172, 3.951), p < 0.001] but had no association with body mass index (BMI) [OR: 0.–0.984 (95%CI: ? 1.010, 0.959), p = 0.217] nor perception of self weight [OR: 1.382 (95% CI: 0.700, 2.725), p = 0.352]. Nutrition related self-management strategies were inversely associated with BMI [OR: ? 0.115 (95%CI: ? 7.159, ? 0.980), p = 0.010] but had no association with diet quality [OR: 0.183 (95%CI: ? 2.328, 2.800), p = 0.855], energy intake [OR: ? 0.092 (95%CI: ? 1204.443, 527.496) p = 0.438] or weight [OR: ? 0.034 (95%CI: ? 4.020, 1.930), p = 0.491].ConclusionsPA self-management strategies were associated with meeting PA recommendations. Nutrition strategies were associated with lower BMI but not diet quality, energy intake or weight in women with PCOS.Practice implicationsOther behaviour change determinants (e.g. education, skills and self-efficacy) should be considered when designing a PCOS lifestyle programme in conjunction with self-management strategies.