Breakthrough infection by hepatitis B virus in a vaccinated blood donor: An emerging threat for transfusion safety in low-endemic countries?

We present the case of a breakthrough infection by hepatitis B virus (HBV), intending to warn about the challenge that HBV represents for transfusion safety. Virological markers for HBV infection were assayed during a blood donor screening by detection of HBsAg, anti-HBc, and viral nucleic acid (HBV DNA) by a nucleic acid test (NAT). Additionally, samples were analyzed for detection of immunoglobulin M anti-HBc, HBeAg, anti-HBe, and anti-HBs. A first-time donor repeatedly tested positive for HBV DNA by NAT and nonreactive for HBV-serological markers of infection. He stated having completed the anti-HBV vaccination schedule; thus, study of anti-Hbs resulted in reactive at protective level (18 mIU/mL). The donor denied clinical symptoms of hepatitis and remained healthy during the follow-up period. 95 days postdonation, NAT was negative, seroconversion of anti-HBc ab was detected, and a significant increase in anti-HBs concentration was measured (>1000 mIU/mL). This is the first case of HBV-breakthrough infection reported in Argentina and to our knowledge, this potential threat to transfusion safety is novel in an HBV low-endemic region with high coverage of HBV vaccination. The occurrence of breakthrough infections challenges the current protocols for the identification of HBV-infected subjects, could be a source of silent HBV transmission.

Severity of SARS-CoV-2 infection among vaccinated individuals: A hospital-based study.

Introduction: Post-vaccination infections impart the need for real-world data on protection conferred by the vaccines against SARS-CoV-2. We aimed to evaluate the severity of post-vaccination COVID-19 and the predictors of severe disease. Methods: This cross-sectional study analysed data from 307 patients admitted to the University Hospital KDU with confirmed COVID- 19 from March 1st to November 1st, 2021, after receiving at least a single dose of a vaccine against SARS-CoV-2. Vaccination status and the disease severity were classified using standard definitions. A binary logistic regression model was fitted to investigate severe/critical disease predictors. Results: Of the surveyed patients, 122(39.7%) were fully vaccinated, 127(41.4%) were partially vaccinated and 58 (18.9%) had developed the disease within 14 days of the first vaccine dose. Most were Sinopharm vaccine recipients (52.4 %). Non- severe disease was observed among 249(81.1%) patients and 47(15.3%) had severe disease, while 11(3.6%) needed ICU care (critical illness). Severe/critical disease was reported among 32(25.2%) partially vaccinated and 13(22.4%) patients who developed the disease within 14 days of the first vaccine dose. Of the patients deemed to have vaccine breakthrough infections (122 fully vaccinated patients), 13(10.6%) suffered severe/critical disease. Patients with comorbidity experienced more severe/critical illness (adjusted odds ratio [AOR]= 3.684, P=0.003) than those without pre-existing medical conditions. Disease progression to severe or critical illness was significantly higher among Sinopharm recipients than Covisheild recipients (AOR:2.064, P=0.048). Conclusions: Comorbidity was the most important predictor of severe COVID-19 irrespective of the vaccination status. Observed higher incidence of severe disease among Sinopharm recipients warrants more extensive population studies.

Presenting clinical symptoms of post-COVID-19 breakthrough infection: Predictors of mortality in a Middle Eastern population.

Objective: Breakthrough COVID-19 infections are common following immunisation with various types of vaccines. The patterns of infections have not been well established. We aimed to analyse the signs and symptoms of post vaccination infections in addition to the need for hospital admission, ER visit and supplemental oxygen in relation to age and gender. Methods: A cross-sectional cohort study was conducted in JUH from March 2021 to August 2022, we interviewed 1479 individuals who are >15 years of age and got a breakthrough infection. The statistical analysis was performed using STATA statistical software. Results: Out of the 1479 cases, 50.2 % and 69.4 % were females and less than 45 years of age respectively. Symptoms of cough, fever and headache were reported by nearly 50 % of the patients, while one-third complained of dyspnoea. We found that participants older than 45 years had worse clinical outcomes (P-value < 0.001). 13 deaths were identified in this study due to breakthrough infection, 92.3 % of them were older than 45 years (P-value < 0.001). Participants ≥45 years who experienced a breakthrough infection of COVID-19 were 0.7 times less likely to be females using adjusted logistic regression. Conclusion: This study indicates that despite more severe symptoms reported in younger patients, the major clinical outcomes were worse among older patients, which makes age a major risk for poor outcomes regardless of symptoms. Thus, older people should be evaluated carefully when presenting with mild symptoms of COVID-19 breakthrough infection. The study also confirms that there is no difference in the incidence of COVID-19 breakthrough infections between males and females. Prospective studies are needed to risk stratify COVID-19 breakthrough infections, which should take into account variants of the virus and comorbidities.

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales.

Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods: We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings: Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32-1.51)), older adults (≥80 years vs 18-49 years; 10.43 (8.06-13.50)), underweight (BMI <18.5 vs BMI 25.0-29.9; 2.94 (2.51-3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15-10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23-1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21-1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation: Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding: National Core Studies-Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Adolescents With Breakthrough COVID-19 Infections Requiring Hospitalization: A Multicenter Retrospective Study.

Background Vaccines have the most important role in the battle against the COVID-19 pandemic. With the widespread use of vaccines, COVID-19 has remarkably declined. Adolescents were vaccinated after approvals for this age group, which was later than adults, and a nationwide vaccination program was implemented in August 2021 in Turkey for adolescents ≥12 years of age. Therefore, we aimed to determine the effects of the COVID-19 nationwide adolescent vaccination program on adolescent hospitalizations due to COVID-19 and multisystem inflammatory syndrome in children (MIS-C) by comparing two periods, including the vaccination period (VP) and the pre-VP (PVP). The second aim of this study is to compare the clinical features and disease severity of vaccine-breakthrough COVID-19 hospitalizations with unvaccinated individuals in the VP. Methods A retrospective multicenter study was conducted to determine and compare the number of hospitalizations due to COVID-19 and MIS-C between the VP (September 1, 2021, to August 31, 2022) and PVP (September 1, 2020, to August 31, 2021). We also compared the characteristics, risk factors, and outcomes of breakthrough infections of adolescents aged 12-18, which required hospitalization with the same age group of unvaccinated hospitalized individuals during the VP. Results During the study period, 3967 children (0-18 years) were hospitalized in the PVP and 5143 (0-18 years) in the VP. Of them, 35.4% were adolescents (12-18 years) in the PVP, and this rate was 18.6% in the VP; relative risk was 0.6467 (95% confidence interval [CI]: 0.6058-0.6904; p < 0.001). Patients with breakthrough COVID-19 were older (201 vs. 175 months, p < 0.001) and less commonly hospitalized for COVID-19 (81.5% vs. 60.4%, p < 0.001, odds ratio [OR]: 0.347 [95% CI: 0.184-0.654]). The majority of these infections were asymptomatic and mild (32% vs.72.9%: p < 0.001, OR: 5.718 [95% CI: 2.920-11.200]), and PICU admission was less frequently required (p = 0.011, OR: 0.188 [95% CI: 0.045-0.793]). Most breakthrough COVID-19 infections occurred within three months after the last vaccine dose (54.2%). Conclusions This study demonstrated a significant decrease in adolescent hospitalizations due to COVID-19 and MIS-C after implementing COVID-19 vaccines in Turkey. Breakthrough cases were less severe and mostly occurred three months after the last dose. This study emphasizes the importance of COVID-19 vaccines and that parents' decisions may be changed, particularly those who hesitate to or refuse vaccination.

Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections.

Background: Vaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19. Methods: A nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission. Results: In total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015). Conclusion: We observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results.

Impact of vaccination on SARS-CoV-2 evolution and immune escape variants.

Vaccines and host genetic factors can influence the SARS-CoV-2 evolution and emergence of new variants. Even vaccinated cases get affected as virus continues to evolve, raising concerns about vaccine efficacy and the emergence of immune escape variants. Here, we have analyzed 2295 whole-genome sequences of SARS-CoV-2 collected from vaccinated and unvaccinated cases to evaluate the impact of vaccines on virus diversity within hosts. Our comparative analysis revealed a significant higher incidence of intra-host single nucleotides variants (iSNVs) in vaccinated cases compared to unvaccinated ones (p value<0.0001). Furthermore, we have found that specific mutational processes, including APOBEC (C > T) mediated and ADAR1 (A > G) mediated mutations, were found more prevalent in vaccinated cases. Vaccinated cases exhibited higher accumulation of nonsynonymous mutation than unvaccinated cases. Fixed iSNVs were predominantly located in the ORF1ab and spike genes, several key omicron defining immune escape variants S477N, Q493R, Q498R, Y505H, L452R, and N501Y were identified in the RBD domain of spike gene in vaccinated cases. Our findings suggest that vaccine plays an important role in the evolution of the virus genome. The virus genome acquires random mutations due to error-prone replication of the virus, host modification through APOBEC and ADAR1 mediated editing mechanism, and oxidative stress. These mutations become fixed in the viral population due to the selective pressure imposed by vaccination.

Approaches to pandemic prevention - the chromatin vaccine.

Developing effective vaccines against viral infections have significant impacts on development, prosperity and well-being of human populations. Thus, successful vaccines such as smallpox and polio vaccines, have promoted global societal well-being. In contrast, ineffective vaccines may fuel arguments that retard scientific progress. We aim to stimulate a multilevel discussion on how to develop effective vaccines against recent and future pandemics by focusing on acquired immunodeficiency syndrome (AIDS), coronavirus disease (COVID) and other viral infections. We appeal to harnessing recent achievements in this field specifically towards a cure for current pandemics and prevention of the next pandemics. Among these, we propose to apply the HIV DNA in chromatin format - an end product of aborted HIV integration in episomal forms, i.e., the chromatin vaccines (cVacc), to elicit the epigenetic silencing and memory that prevent viral replication and infection.

The Impact of Vaccination Among Hospitalized Patients with the Diagnosis of COVID-19.

Objective: We aimed to investigate the vaccination status and the risk factors for the intensive care unit (ICU) support need of the laboratory-confirmed breakthrough COVID-19 infection inpatients. Materials and Methods: This multi-center point-prevalence study was conducted on inpatients, divided into two groups as 'fully' and 'partially' vaccinated according to COVID-19 vaccination status. Results: Totally 516 patients were included in the study. The median age was 65 (55-77), and 53.5% (n=276) of the patients were male. Hypertension (41.9%, n=216), diabetes mellitus (DM) (31.8%, n=164), and coronary artery disease (CAD) (16.3%, n=84) were the predominant comorbidities. Patients were divided into two groups ICU (n=196) and non-ICU (n=301). Hypertension (p=0.026), DM (p=0.048), and congestive heart failure (CHF) (p=0.005) were significantly higher in ICU patients and the median age was younger among non-ICU patients (p=0.033). Of patients, 16.9% (n=87) were fully vaccinated, and this group's need for ICU support was statistically significantly lower (p=0.021). Conclusion: We conclude that older age, hypertension, DM, CHF, and being partially vaccinated were associated with the need for ICU support. Therefore, all countries should continuously monitor post-vaccination breakthrough COVID-19 infections to determine the national booster vaccine administration approach that will provide vulnerable individuals the highest protection.

Observations on 73 Vaccine breakthrough COVID-19 infected patients and its individualized homeopathic treatment

Since the initiation of vaccine rollout, breakthrough COVID-19 infections have been reported. While conventional therapy is the accepted mode of treatment, there has been little recognition of the role played by the alternative therapies like homeopathy. The purposes of this study were to identify the clinico-symptomatic profile of the vaccine breakthrough covid-19 infections and to assess the response of individualized homoeopathic treatment in these breakthrough cases. A retrospective data analysis of patients treated with homoeopathic medicines who confirmed the breakthrough infection criteria: positive infection ≥14 days after completion of both the recommended doses of an authorized COVID-19 vaccine was conducted. IBM SPSS Statistics 21.0 was used for data analysis with a p-value below 0.05 defined as significant. WHO Clinical Progression Scale and Outcome in Relation to Impact on Daily Living score were used as outcome measures. In total 73 cases were reported to be vaccine breakthrough infections. The median recovery time reported in the data set was 9 ± 2 days. While 5 patients dropped out, 68 (93.15%) patients responded positively to homeopathic treatment, and 55 (75.34%) recovered completely with normalized serological markers/ nasal swabs/ HRCT Chest. About 29 (39.72%) of these presented with mild clinical manifestations, 26 (35.61%) moderate, 17 (23.28%) severe and 1 (1.36%) was critical. 10 homeopathic remedies were prescribed to these 73 patients. Majority of the patients attained an ORIDL score of 4. Maximum patients reported a WHO clinical Progression score of 3. Statistical analysis showed a significant response to homeopathic treatment in the study group. Vaccine breakthrough cases occur in a fraction of vaccinated people. Despite the limited number of study subjects, homoeopathy showed some promising results in the present setup. The response rate was highest in the moderate and severe cases which suggest the importance of consideration of alternative medicine in the current pandemic. Further exploratory research studies and comparative clinical trials may be encouraged.

Efectividad de las vacunas contra SARS-CoV-2 en hospitalizados con fallas vacunales en 10 hospitales de la CCINSHAE / Effectiveness of SARS-CoV-2 vaccines in hospitalized patients with vaccine failures in 10 CCINSHAE hospitals

Resumen: Objetivo: Evaluar la efectividad de las vacunas contra SARS-CoV-2 para evitar muerte e intubación en pacientes hospitalizados con Covid-19. Material y métodos: Se presentó un análisis de 3 565 hospitalizaciones por SARS-CoV-2 de personas mayores de 20 años de edad, reportadas con fines de salud pública por 10 hospitales de especialidad. Se comparó a los egresados por mejoría (2 094) con los fallecidos (1 471) en modelos mixtos de regresión logística ajustados por edad, sexo, número de comorbilidades y el hospital como variable aleatoria. Resultados: Un esquema completo de vacunación, con cinco tipos de vacunas disponibles, tuvo un efecto protector para muerte o intubación (RM: 0.67, IC95%: 0.54,0.83, 33% de protección); y para muerte (RM: 0.80, IC95%: 0.64,0.99, 20% de protección) estos datos se compararon con los que no habían sido vacunados. Todas las vacunas aplicadas mostraron un efecto protector con un RM<0.8, con intervalos de confianza variables. Conclusiones: El antecedente de vacunación reduce los riesgos de ser intubado y morir, aun en pacientes previamente vacunados y hospitalizados con Covid-19 grave.

Abstract: Objective: To evaluate the effectiveness of SARS-CoV-2 vaccines to avoid death and intubation in hospitalized patients with Covid-19. Materials and methods: We present an analysis of 3 565 hospitalizations for SARS-CoV-2 in people over 20 years of age, reported for public health purposes by 10 specialty hospitals, comparing those discharged for improvement (2 094) with those who died (1 471) in mixed models of logistic regression adjusted for age, sex, number of comorbidities and the reporting hospital as a random variable. Results: A complete vaccination schedule, with five types of vaccine available, had a protective effect for death or intubation (OR: 0.67, CI95%: 0.54,0.83, 33% protection) and for death (OR: 0.80, CI95%: 0.64,0.99, 20% protection) compared to those who had not been vaccinated. All the applied vaccines in the Mexican program showed a protective effect with an OR<0.8, with variable confidence intervals. Conclusions: Even in patients previously vaccinated and hospitalized with severe Covid-19, a history of vaccination reduces the risks of being intubated and dying.