Anti-spike S1 IgA,anti-spike trimeric IgG,and anti-spike RBD IgG response after BNT162b2 COVID-19 mRNA vaccination in healthcare workers

BackgroundMost studies on immune response after coronavirus disease 2019 (COVID-19) vaccination focused on serum IgG antibodies and cell-mediated immunity, discounting the role of anti-SARS-CoV-2 neutralizing IgA antibodies in preventing viral infection. This study was aimed to quantify serum IgG and IgA neutralizing antibodies after mRNA COVID-19 vaccination in baseline SARS-CoV-2 seronegative healthcare workers.MethodsThe study population consisted of 181 SARSCoV-2 seronegative healthcare workers (median age 42 years, 59.7% women), receiving two doses of Pfizer COVID-19 vaccine BNT162b2 (Comirnaty). Serum samples were collected before receiving the first vaccine dose, 21 days (before the second vaccine dose) and 50 days afterwards. We then measured anti-spike trimeric IgG (Liaison XL, DiaSorin), anti-spike receptor binding domain (RBD) IgG (Access 2, Beckman Coulter) and anti-spike S1 subunit IgA (ELISA, Euroimmun). Results were presented as median and interquartile range (IQR).ResultsVaccine administration elicited all anti-SARS-CoV2 antibodies measured. Thirty days after the second vaccine dose, 100% positivization occurred for anti-spike trimeric IgG and anti-spike RBD IgG, whilst 1.7% subjects remained anti-spike S1 IgA negative. The overall increase of antibodies level ratio over baseline after the second vaccine dose was 576.1 (IQR, 360.7-867.8) for anti-spike trimeric IgG, 1426.0 (IQR, 742.0-2698.6) for anti-spike RBD IgG, and 20.2 (IQR, 12.5-32.1) for anti-spike S1 IgA. Significant inverse association was found between age and overall increase of anti-spike trimeric IgG (r=-0.24; p=0.001) and anti-spike S1 IgA (r=-0.16; p=0.028), but not with anti-spike RBD IgG (r=-0.05; p=0.497).ConclusionsmRNA COVID-19 vaccination elicits sustained serum levels of anti-spike trimeric IgG and anti-spike RBD IgG, while also modestly but significantly increasing those of anti-spike S1 IgA.     

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India,June–July 2021: A population-based cross-sectional study

BackgroundIndia began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and findingsWe did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.ConclusionsNearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India.     

Attitudes toward COVID-19 vaccines in Chinese college students

Background: Vaccination is an important preventative measure against the coronavirus disease 19 (COVID-19) pandemic. To implement vaccination and immunization programs effectively, it is essential to investigate public attitudes toward COVID-19 vaccines. This study examined the attitudes of Chinese college students toward COVID-19 vaccines and their associated factors. Methods: A cross-sectional study was conducted in college students nationwide from December 27, 2020 to January 18, 2021. Attitudes toward COVID-19 vaccines and acceptance of future vaccination programs were assessed. Results: Totally, 2,881 college students participated in this survey; of them, 76.3% (95% CI: 74.8% - 77.9%) were willing to accept a COVID-19 vaccine in the future. Multiple logistic analysis revealed that students living in urban (OR=1.409, 95% CI: 1.152 - 1.724, p=0.001) and those studying health-related courses (OR=1.581, 95% CI: 1.291 - 1.935, p<0.001) were more likely to have a positive attitude toward COVID-19 vaccines. In addition, those who were worried about being infected with COVID-19 (very much vs no, OR=1.690, 95% CI: 1.212-2.356, p=0.002), heard previously about COVID-19 vaccines (OR=1.659, 95% CI: 1.268-2.170, p<0.001), believed that vaccines are safe (Yes vs No, OR=3.570, 95% CI: 1.825-6.980), thought that vaccines can protect people from being infected with COVID-19 (Yes vs No, OR=1.957, 95% CI: 1.286-2.979, p=0.002), and had encouraged their family and friends to have a vaccine (Yes vs No, OR=17.745, 95% CI: 12.271-25.660, p<0.001) had higher acceptance of COVID-19 vaccination. Conclusions: A high rate of acceptance of COVID-19 vaccines was found among Chinese college students. However, vaccine uptake may be reduced by concerns about vaccine safety and efficacy. Alleviating these concerns and enhancing public confidence in vaccines are crucial for future immunization programs against the COVID-19 pandemic.     

SARS-CoV-2 vaccine uptake in a multi-ethnic UK healthcare workforce: A cross-sectional study

BackgroundHealthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce.Methods and findingsWe conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26–0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62–0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction.ConclusionsEthnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.

In a cross-sectional study, Dr. Christopher A. Martin and colleagues investigate factors associated with SARS-CoV-2 vaccine uptake in a multi-ethnic healthcare workforce in UK.     

Comparative analysis of antibody responses to SARS-CoV-2 in various populations

This paper aimed to analyze antibody responses to SARS-CoV-2 in various populations. Two hundred and six COVID-19 patients, 46 convalescent patients, and 270 healthy population were enrolled. Antibodies against nucleocapsid protein (N) and spike protein''s receptor-binding domain (RBD), and neutralizing antibody were detected. The results demonstrated both anti-N and anti-RBD antibodies could be detected in about 80% of COVID-19 patients and 90% of convalescent patients, while no antibodies could be detected in some convalescents and patients even after 14 days post-onset of symptoms. The level of anti-RBD antibody strongly correlated with the neutralizing activity of sera from these two cohorts. The titer of neutralizing antibody was lower in convalescents than that in active COVID-19 patients. In addition, the titer of neutralizing antibody was less than 1:80 in none of the severe COVID-19 patients, 18.8% in non-severe COVID-19 patients, and 32.6% in convalescents. The study suggests that the level of anti-RBD antibody is closely related to neutralization activity in COVID-19 patients and convalescents. Some SARS-CoV-2-infected cases trigger a weak antiviral immune response, and the level of neutralizing antibody may have a faster decay rate.     

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study

BackgroundTo the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic.Methods and findingsWe conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28).When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected.ConclusionsWe observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

In a national retrospective study, Sylvie Epelboin and colleagues investigate obstetrical outcomes and maternal morbidities among pregnant women with a COVID-19 diagnosis in France.     

Randomized Controlled Field Trial to Assess the Immunogenicity and Safety of Rift Valley Fever Clone 13 Vaccine in Livestock

BackgroundAlthough livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa.MethodsIn a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1^st half of pregnancy, and group C animals in 2^nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365.ResultsIn vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 – 9.2) in cattle, 90.0 (95% CI, 25.1 – 579.2) in goats, and 40.0 (95% CI, 16.5 – 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals.ConclusionsThe results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle.     

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

BACKGROUND:Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose of the BNT162b2 SARS-CoV-2 vaccine is efficacious in the general population, but responses in patients receiving hemodialysis are uncertain.METHODS:We obtained serial plasma from patients receiving hemodialysis and health care worker controls before and after vaccination with 1 dose of the BNT162b2 mRNA vaccine, as well as convalescent plasma from patients receiving hemodialysis who survived COVID-19. We measured anti–receptor binding domain (RBD) immunoglobulin G (IgG) levels and stratified groups by evidence of previous SARS-CoV-2 infection.RESULTS:Our study included 154 patients receiving hemodialysis (135 without and 19 with previous SARS-CoV-2 infection), 40 controls (20 without and 20 with previous SARS-CoV-2 infection) and convalescent plasma from 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG was undetectable at 4 weeks in 75 of 131 (57%, 95% confidence interval [CI] 47% to 65%) patients receiving hemodialysis, compared with 1 of 20 (5%, 95% CI 1% to 23%) controls (p < 0.001). No patient with nondetectable levels at 4 weeks developed anti-RBD IgG by 8 weeks. Results were similar in non-immunosuppressed and younger individuals. Three patients receiving hemodialysis developed severe COVID-19 after vaccination. Among those with previous SARS-CoV-2 infection, median anti-RBD IgG levels at 8 weeks in patients receiving hemodialysis were similar to controls at 3 weeks (p = 0.3) and to convalescent plasma (p = 0.8).INTERPRETATION:A single dose of BNT162b2 vaccine failed to elicit a humoral immune response in most patients receiving hemodialysis without previous SARS-CoV-2 infection, even after prolonged observation. In those with previous SARS-CoV-2 infection, the antibody response was delayed. We advise that patients receiving hemodialysis be prioritized for a second BNT162b2 dose at the recommended 3-week interval.

Patients with end-stage kidney disease receiving incentre hemodialysis have been uniquely vulnerable during the COVID-19 pandemic. For these patients, unlike for most other people, self-isolation to avoid exposure to SARS-CoV-2 is impossible. Most patients receiving hemodialysis must leave their homes 3 times weekly to receive their life-saving treatments, often in shared spaces for hours at a time. COVID-19 case fatality rates are 20%–30% for patients receiving hemodialysis —10 times higher than in the general population.^1,2 Advanced age, multiple comorbidities and blunted immune response likely all contribute to the high COVID-19 death rates in this population. Some hemodialysis centres have thus prioritized these patients for vaccination.To facilitate wider vaccine distribution during current shortages, ³ the National Advisory Committee on Immunization of Canada has recommended delaying the second dose of the BNT162b2 vaccine from 3 to 16 weeks.⁴ In a randomized controlled trial (RCT), the clinical efficacy of the BNT162b2 was reported to be greater than 80% at 3 weeks after the first dose.⁵ However, no patients receiving hemodialysis were enrolled in this trial.⁵ Patients with end-stage kidney disease receiving hemodialysis often have impairments in both humoral and cellular immune responses⁶ and are noted to have lower antibody responses to other vaccines.⁷ Whether patients receiving hemodialysis develop robust immune responses after vaccination against SARS-CoV-2 remains uncertain.⁸ Data are required to better inform Canadian public health policy on whether second doses of vaccine can be safely delayed in this population.Usually, once clinical trials are completed, antibody levels can be used as surrogate measures of vaccine efficacy, such as with hepatitis B⁹ and influenza.¹⁰ With respect to the novel coronavirus SARS-CoV-2, although there is increasing understanding of the antibodies that best correlate with viral neutralization and T-cell responses,^11,12 assays vary from laboratory to laboratory and as yet there are no internationally accepted standards defining what antibody levels constitute immunity.¹³ The only way to evaluate vaccine efficacy using antibody levels, therefore, is through direct experimental comparison with controls who are known to reliably develop immunity after vaccination (i.e., healthy individuals similar to those enrolled in the RCT showing vaccine efficacy⁵) or who have developed immunity after natural infection (i.e., survivors of COVID-19).We sought to determine whether short-term antibody responses after a single dose of the BNT162b2 mRNA vaccine are comparable between patients receiving hemodialysis and healthy individuals, and how this compares with antibody responses in patients receiving hemodialysis who survived natural infection with SARS-CoV-2.     

Characterization of Functional Antibody and Memory B-Cell Responses to pH1N1 Monovalent Vaccine in HIV-Infected Children and Youth

Objectives

We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children.

Methods

Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1.

Results

At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets.

Conclusions

HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load.

Trial Registration

ClinicalTrials.gov NCT00992836     

Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.     

Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases

BackgroundBrazil faced a yellow fever(YF) outbreak in 2016–2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality.ObjectiveThis study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression.Methods and ResultsA total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3–1292.2) vs.731 (95%CI 593.6–900.2), p<0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05).ConclusionFractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas.Trial registrationThis clinical trial was registered with Clinicaltrials.gov (#{"type":"clinical-trial","attrs":{"text":"NCT03430388","term_id":"NCT03430388"}}NCT03430388).     

Ethnic inequalities in COVID-19 vaccine uptake and comparison to seasonal influenza vaccine uptake in Greater Manchester,UK: A cohort study

BackgroundCOVID-19 vaccine uptake is lower amongst most minority ethnic groups compared to the White British group in England, despite higher COVID-19 mortality rates. Here, we add to existing evidence by estimating inequalities for 16 minority ethnic groups, examining ethnic inequalities within population subgroups, and comparing the magnitudes of ethnic inequalities in COVID-19 vaccine uptake to those for routine seasonal influenza vaccine uptake.Methods and findingsWe conducted a retrospective cohort study using the Greater Manchester Care Record, which contains de-identified electronic health record data for the population of Greater Manchester, England. We used Cox proportional hazards models to estimate ethnic inequalities in time to COVID-19 vaccination amongst people eligible for vaccination on health or age (50+ years) criteria between 1 December 2020 and 18 April 2021 (138 days of follow-up). We included vaccination with any approved COVID-19 vaccine, and analysed first-dose vaccination only. We compared inequalities between COVID-19 and influenza vaccine uptake adjusting by age group and clinical risk, and used subgroup analysis to identify populations where inequalities were widest. The majority of individuals (871,231; 79.24%) were White British. The largest minority ethnic groups were Pakistani (50,268; 4.75%), ‘other White background’ (43,195; 3.93%), ‘other ethnic group’ (34,568; 3.14%), and Black African (18,802; 1.71%). In total, 83.64% (919,636/1,099,503) of eligible individuals received a COVID-19 vaccine. Uptake was lower compared to the White British group for 15 of 16 minority ethnic groups, with particularly wide inequalities amongst the groups ‘other Black background’ (hazard ratio [HR] 0.42, 95% CI 0.40 to 0.44), Black African (HR 0.43, 95% CI 0.42 to 0.44), Arab (HR 0.43, 95% CI 0.40 to 0.48), and Black Caribbean (HR 0.43, 95% CI 0.42 to 0.45). In total, 55.71% (419,314/752,715) of eligible individuals took up influenza vaccination. Compared to the White British group, inequalities in influenza vaccine uptake were widest amongst the groups ‘White and Black Caribbean’ (HR 0.63, 95% CI 0.58 to 0.68) and ‘White and Black African’ (HR 0.67, 95% CI 0.63 to 0.72). In contrast, uptake was slightly higher than the White British group amongst the groups ‘other ethnic group’ (HR 1.11, 95% CI 1.09 to 1.12) and Bangladeshi (HR 1.08, 95% CI 1.05 to 1.11). Overall, ethnic inequalities in vaccine uptake were wider for COVID-19 than influenza vaccination for 15 of 16 minority ethnic groups. COVID-19 vaccine uptake inequalities also existed amongst individuals who previously took up influenza vaccination. Ethnic inequalities in COVID-19 vaccine uptake were concentrated amongst older and extremely clinically vulnerable adults, and the most income-deprived. A limitation of this study is the focus on uptake of the first dose of COVID-19 vaccination, rather than full COVID-19 vaccination.ConclusionsEthnic inequalities in COVID-19 vaccine uptake exceeded those for influenza vaccine uptake, existed amongst those recently vaccinated against influenza, and were widest amongst those with greatest COVID-19 risk. This suggests the COVID-19 vaccination programme has created additional and different inequalities beyond pre-existing health inequalities. We suggest that further research and policy action is needed to understand and remove barriers to vaccine uptake, and to build trust and confidence amongst minority ethnic communities.

Ruth Elizabeth Watkinson and colleagues estimate inequalities in Covid-19 vaccine uptake for 16 minority ethnic groups and compare them to those in routine seasonal Influenza vaccine uptake.     

Understanding COVID-19 vaccine demand and hesitancy: A nationwide online survey in China

BackgroundThis study attempts to understand coronavirus disease 2019 (COVID-19) vaccine demand and hesitancy by assessing the public’s vaccination intention and willingness-to-pay (WTP). Confidence in COVID-19 vaccines produced in China and preference for domestically-made or foreign-made vaccines was also investigated.MethodsA nationwide cross-sectional, self-administered online survey was conducted on 1–19 May 2020. The health belief model (HBM) was used as a theoretical framework for understanding COVID-19 vaccination intent and WTP.ResultsA total of 3,541 complete responses were received. The majority reported a probably yes intent (54.6%), followed by a definite yes intent (28.7%). The perception that vaccination decreases the chances of getting COVID-19 under the perceived benefit construct (OR = 3.14, 95% CI 2.05–4.83) and not being concerned about the efficacy of new COVID-19 vaccines under the perceived barriers construct (OR = 1.65, 95% CI 1.31–2.09) were found to have the highest significant odds of a definite intention to take the COVID-19 vaccine. The median (interquartile range [IQR]) of WTP for COVID-19 vaccine was CNY¥200/US$28 (IQR CNY¥100–500/USD$14–72). The highest marginal WTP for the vaccine was influenced by socio-economic factors. The majority were confident (48.7%) and completely confident (46.1%) in domestically-made COVID-19 vaccine. 64.2% reported a preference for a domestically-made over foreign-made COVID-19 vaccine.ConclusionsThe findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intent and WTP. It is important to improve health promotion and reduce the barriers to COVID-19 vaccination.     

Durability of the humoral immune response in recovered COVID-19 patients

BackgroundThe immunological factors involved in protection against the disease caused by SARS-CoV-2 are insufficiently defined and understood. However, previous knowledge pertaining to the related SARS virus and other human coronaviruses may prove useful. Population-based serosurveys measuring anti-SARS-CoV-2 antibodies may provide a pattern for estimating infection degrees and observing the development of the epidemic. In this study, we aimed to investigate the persistence of antibody against the SARS-CoV-2 in recovered patients in Al Madinah region of Saudi Arabia.Materials and methodsA total of 150 recovered COVID-19 patients participated in this study. All the patients tested positive for the presence of SARS-CoV-2 RNA, using qualitative RT-PCR. An ELISA was used to measure anti-Spike (S) IgG antibodies in serum samples and screen for their persistence at various time points post-infection.ResultsThe patients were categorized as asymptomatic (27.3%), mild (28%) and moderate (44.7%) according to the disease severity. Amongst them, 35.3% were females (n = 53) and 64.7% were males (n = 97). Significant anti-S IgG antibody levels were observed among the different groups, with the patients in moderate group exhibiting the highest levels followed by the mild group; while the lowest levels were detected among the asymptomatic. There was a significant positive correlation between the patients’ age and anti-S IgG antibody concentrations (Pearson r = 0.45; p < 0.001).ConclusionOur findings provide a solid evidence to support the use of an anti-S IgG ELISA as a diagnostic tool to indicate SARS-CoV-2 infection. IgG seropositivity was sustained in recovered patients up to a hundred days' post-infection, the latest time point for antibody measurement in our study. Ours is the first report in Saudi Arabia to investigate the durability of humoral immune response in recovered COVID-19 patients.     

Twenty Years of Medically-Attended Pediatric Varicella and Herpes Zoster in Ontario,Canada: A Population-Based Study

ObjectiveTo determine if reductions in medically-attended pediatric varicella and herpes zoster occurred in Ontario, Canada, after publicly-funded varicella immunization was implemented in 2004.MethodsFor fiscal years (FY) 1992-2011, we examined data on varicella and herpes zoster physician office visits, emergency department (ED) visits, hospitalizations (including for varicella-associated skin and soft tissue infections [SSTI]), and intensive care unit (ICU) admissions, among those aged <18 years. The pre-vaccine, privately-available, and vaccine program eras were FY1992-1998, FY1999-2003, and FY2004-2011, respectively. We used Poisson regressionand Kruskal-Wallis tests (all at the p<0.05 level of significance), and compared rates using incidence rate ratios (IRRs) and 95% confidence intervals (CIs).ResultsIncidence of varicella office visits declined over the study period from a high of 25.1/1,000 in FY1994 to a low of 3.2/1,000 in FY2011. ED visits and hospitalizations followed similar patterns of decreasing rates later in the study period. IRRs comparing the vaccine program versus pre-vaccine eras were 0.29 (95%CI: 0.26-0.32) for office visits, 0.29 (95%CI: 0.21-0.40) for ED visits, and 0.41 (95%CI: 0.10-1.69) for hospitalizations. Annual declines in varicella office visits were 7.7%, 9.1%, 8.4%, and 8.4% per year among children aged <1 year, 1-4 years, 5-11 years, and ≥12 years, respectively (all p<0.001). Age-specific rates of varicella-associated SSTI declined significantly among children <12 years (p<0.001) and rates of ICU admissions decreased significantly for children <1 year (p = 0.02). (p<0.001) over the study period. For children aged 5-17 years, herpes zoster office visits decreased whereas ED visits increased (both p<0.001) and there was a small, non-significant (p = 0.07), decrease in hospitalizations.ConclusionMedically-attended varicella decreased during the study period, particularly since varicella vaccine was publicly-funded. Results suggest immunization program-related changes in varicella epidemiology, including herd effects, demonstrated by reductions in varicella in program-ineligible age groups. We did not observe a consistent impact on herpes zoster.     

Social determinants of mortality from COVID-19: A simulation study using NHANES

BackgroundThe COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level.Methods and findingsWe estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%–59.6%, p < 0.001), individuals with income below the median (67.5%, 95% CI 63.4%–71.5%, p < 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% –27.9%, p < 0.001), and veterans (19.5%, 95% CI 15.8%–23.4%, p < 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents.ConclusionsSubstantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.

In this simulation study, Benjamin Seligman and colleagues explore socio-demographic factors associated with COVID-19 deaths in the US.     

Accumulating Impact of Smoking and Co-morbidities on Severity and Mortality of COVID-19 Infection: A Systematic Review and Meta-analysis

BackgroundHigh prevalence, severity, and formidable morbidity have marked the recent emergence of the novel coronavirus disease (COVID-19) pandemic. The significant association with the pre-existing co-morbid conditions has increased the disease burden of this global health emergency, pushing the patients, healthcare workers and facilities to the verge of complete disruption.MethodsMeta-analysis of pooled data was undertaken to assess the cumulative risk assessment of multiple co-morbid conditions associated with severe COVID-19. PubMed, Scopus, and Google Scholar were searched from January 1^st to June 27^th 2020 to generate a well-ordered, analytical, and critical review. The exercise began with keying in requisite keywords, followed by inclusion and exclusion criteria, data extraction, and quality evaluation. The final statistical meta-analysis of the risk factors of critical/severe and non-critical COVID-19 infection was carried out on Microsoft Excel (Ver. 2013), MedCalc (Ver.19.3), and RevMan software (Ver.5.3).ResultsWe investigated 19 eligible studies, comprising 12037 COVID-19 disease patients, representing the People’s Republic of China (PRC), USA, and Europe. 18.2% (n = 2200) of total patients had critical/severe COVID-19 disease. The pooled analysis showed a significant association of COVID-19 disease severity risk with cardiovascular disease (RR: 3.11, p < 0.001), followed by diabetes (RR: 2.06, p < 0.001), hypertension (RR: 1.54, p < 0.001), and smoking (RR: 1.52, p < 006).ConclusionThe review involved a sample size of 12037 COVID-19 patients across a wide geographical distribution. The reviewed reports have focussed on the association of individual risk assessment of co-morbid conditions with the heightened risk of COVID-19 disease. The present meta-analysis of cumulative risk assessment of co-morbidity from cardiovascular disease, diabetes, hypertension, and smoking signals a novel interpretation of inherent risk factors exacerbating COVID-19 disease severity. Consequently, there exists a definite window of opportunity for increasing survival of COVID-19 patients (with high risk and co-morbid conditions) by timely identification and implementation of appropriately suitable treatment modalities.