Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has ...rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.
We conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.
Out of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015–0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain.
The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.
Abstract
Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1–23.3). When compared ...with 5174 contemporaneous samples sequenced in our laboratory, VOCs were significantly enriched among breakthrough infections (P < .05).
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus that belongs to the Coronaviridae family. SARS-CoV-2 is an enveloped spherical-shaped virus. The ribonucleic acid ...(RNA) is oriented in a 5’-3’direction which makes it a positive sense RNA virus, and the RNA can be read directly as a messenger RNA. The nonstructural protein 14 (nsp14) has proofreading activity which allows the rate of mutations to stay low. A change in the genetic sequence is called a mutation. Genomes that differ from each other in genetic sequence are called variants. Variants are the result of mutations but differ from each other by one or more mutations. When a phenotypic difference is demonstrated among the variants, they are called strains. Viruses constantly change in two different ways, antigenic drift and antigenic shift. SARS-CoV-2 genome is also prone to various mutations that led to antigenic drift resulting in escape from immune recognition. The Center of Disease Control and Prevention (CDC) updates the variant strains in the different classes. The classes are variant of interest, variant of concern and variant of high consequence. The current variants included in the variant of interest by the USA are: B.1.526, B.1.525, and P.2; and those included in the variant of concern by the USA are B.1.1.7, P.1, B.1.351, B.1.427, and B.1.429. The double and triple mutant variants first reported in India have resulted in a massive increase in the number of cases. Emerging variants not only result in increased transmissibility, morbidity and mortality, but also have the ability to evade detection by existing or currently available diagnostic tests, which can potentially delay the diagnosis and treatment, exhibit decreased susceptibility to treatment including antivirals, monoclonal antibodies and convalescent plasma, possess the ability to cause reinfection in previously infected and recovered individuals, and vaccine breakthrough cases in fully vaccinated individuals. Hence, continuation of precautionary measures, genomic surveillance and vaccination plays an important role in the prevention of spread, early identification of variants, prevention of mutations and viral replication, respectively.
Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.
We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an ...infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing.
Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.043). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms.
Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals.
Wellcome and NIH/NIAID
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.
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.
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.
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.
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.
COVID-19 has been a significant threat to many countries worldwide. COVID-19 remains a threat even in the presence of vaccination. The study formulates and analyzes a non-linear deterministic ...mathematical model to investigate the dynamics of COVID-19 in the presence of vaccination. Numerical results show that increasing the treatment rates with a relatively high vaccination rate might subdue the virus in the population. Also, decreasing the vaccine inefficacy increases the vaccine efficacy, and this may result in a population free of the virus. We further show that increasing the vaccination rate as against the vaccine inefficacy, the effective contact rate for COVID-19 and the modification parameter that accounts for increased infectiousness for COVID-19, the virus responsible for COVID-19 can be eradicated from the population. The sensitivity analysis results deduce that hidden factors are driving the model dynamics. These hidden factors must be given special attention and minimized. These factors includes the incubation periods for vaccinated and unvaccinated individuals, the fractions for vaccinated and unvaccinated individuals, and the transition rates for vaccinated and unvaccinated individuals
•Propose a new non-linear deterministic mathematical model to study the population dynamics of COVID-19.•Formulate a new COVID-19 model in the presence of vaccination.•Analyze the proposed model for disease-free equilibrium.•Examine the model for local stability and global stability.•Conduct numerical experiments to demonstrate the dynamic behavior.
Abstract
We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations ...was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.
Background: The novel SARS-CoV-2 pandemic has inflicted a major blow on public health worldwide accounting for millions of deaths and subsequent socio-economic consequences. The main challenge for ...scientists and researchers has been to restrain transmission of the virus and prevent severe respiratory disease. Novel promising vaccines aim to fulfil these expectations, although new variants of the coronavirus have emerged. The present manuscript aims to add to the knowledge, through a case of an immunodeficient patient, who developed remarkably favorable recovery from SARS-CoV-2 pneumonia after having been fully vaccinated against the novel coronavirus.
Case presentation: An 82-year-old Caucasian male with a history of metastatic pancreatic cancer was admitted with signs and symptoms of pneumonia. Workup revealed a positive SARS-CoV-2 real time - polymerase chain reaction (RT-PCR) and further investigation identified a B.1.1.7 variant. The imaging essays showed extensive lung disease. Interestingly, the patient had already received the second dose of the BNT162b2 (Pfizer) vaccine against the new coronavirus 16 days prior. After having been treated with appropriate antiviral and antibiotical agents the patient showed significantly favorable recovery and no need for high oxygen flows and no complications presented. The patient was discharged after six days of hospitalization in good condition, with no need for supplementary oxygen at home.
Conclusions: Despite breakthrough cases, vaccination against COVID-19 is crucial for restraining the novel coronavirus. Further studies should be carried out in order to determine the optimal strategies for large-scale vaccination while minimizing the risk of further and faster evolution of the virus.
Background: The COVID-19 pandemic resulted in significant mortality and morbidity globally. The introduction of various COVID-19 vaccines at record time generated hope among people and doubts and ...apprehension regarding their safety. The study was done to estimate the incidence of COVID-19 vaccine breakthrough infections among Health Care Workers working in a tertiary care hospital and evaluate the outcome of these infections. Methods: A prospective Cohort study was conducted among 6342 healthcare workers in a tertiary care hospital having received at least one dose of any COVID-19 vaccine. They were followed up for COVID-19 vaccine breakthrough infection for one year by epidemiological investigations. Data on COVID-19-positive healthcare workers was obtained through personal interviews and case records. Results: 490 (7.9%) developed COVID-19 vaccine breakthrough infection during the study period. The majority of them (96.7%) were asymptomatic, and 16 (3.3%) of them developed complications needing hospitalization with 2 deaths. A statistically significant association was found in sex, healthcare worker categories, co-morbidities, and Blood groups. Conclusion: COVID-19 vaccination among healthcare workers reduces the incidence, severity, and complications of COVID-19 vaccine breakthrough infections. The risk of acquiring COVID-19 vaccine breakthrough infections was higher among males, partially vaccinated individuals, people with co-morbidities, and those involved in the regular care of COVID-19 patients. COVID-19-appropriate behaviour and receiving all the primary doses of vaccine will be instrumental in COVID-19 control.
•Allele-specific RT-qPCR assay for quantitative detection of the Omicron variant.•Assay validated against 10-month longitudinal wastewater treatment plant samples.•SARS-CoV-2 RNA concentrations and ...variant frequencies in wastewater agree with clinical data.•Assays reveal the rapid displacement of the Delta variant by the Omicron variant.•Assays derived enable accurate tracking of the dynamics of variant displacement.
On November 26, 2021, the B.1.1.529 COVID-19 variant was classified as the Omicron variant of concern (VOC). Reports of higher transmissibility and potential immune evasion triggered flight bans and heightened health control measures across the world to stem its distribution. Wastewater-based surveillance has demonstrated to be a useful complement for clinical community-based tracking of SARS-CoV-2 variants. Using design principles of our previous assays that detect SARS-CoV-2 variants (Alpha and Delta), we developed an allele-specific RT-qPCR assay which simultaneously targets the stretch of mutations from Q493R to Q498R for quantitative detection of the Omicron variant in wastewater. We report their validation against 10-month longitudinal samples from the influent of a wastewater treatment plant in Italy. SARS-CoV-2 RNA concentrations and variant frequencies in wastewater determined using these variant assays agree with clinical cases, revealing rapid displacement of the Delta variant by the Omicron variant within three weeks. These variant trends, when mapped against vaccination rates, support clinical studies that found the rapid emergence of SARS-CoV-2 Omicron variant being associated with an infection advantage over Delta in vaccinated persons. These data reinforce the versatility, utility and accuracy of these open-sourced methods using allele-specific RT-qPCR for tracking the dynamics of variant displacement in communities through wastewater for informed public health responses.
Display omitted
PDF
