Death Reporting in Breakthrough and Unvaccinated SARS-CoV-2 Infection Cases.

Vaccines are undeniably an important tool for controlling infectious disease outbreaks, and they are the most certain way to end the epidemic risk. This brief report describes the characteristics of coronavirus disease 2019 (COVID-19) deaths among breakthrough and unvaccinated cases hospitalized in Fars province in the south of Iran. This cross-sectional study was performed to compare breakthrough and unvaccinated death cases in Fars, Iran (February 2, to August 19, 2021). Among 444,728 fully vaccinated people, 60,800 breakthrough cases were detected. Thus, 501 died, of which 297 (297/501) cases were hospitalized and compared with the unvaccinated dead group. The median age for breakthrough and unvaccinated cases was estimated 79 and 65 y, respectively. All signs and symptoms of COVID-19 were more frequent in the unvaccinated group. Decreasing O2 saturation (less than 93%) happened more often in the unvaccinated group significantly. Unvaccinated dead patients had significantly shorter hospital stays. These patients received 66.63% Sinopharm, 0.67% Sputnik, 0.67% COVIran Barekat, and 31.99% AstraZeneca vaccines. None of them were health-care staff. Equitable access to safe and effective vaccines is critical to ending the COVID-19 pandemic. As vaccine uptake increases, we observed a decrease in mortality and protection from severe forms of the disease.

COVID-19 Risk Compensation? Examining Vaccination Uptake among Recovered and Classification of Breakthrough Cases.

The study has two primary aims: the first is to examine the uptake of COVID-19 vaccination patterns among those previously infected, and the second is an evaluation of the period elapsed between the patient's latest dose of the vaccine and the infection itself by demographic group. A retrospective study was conducted from 1 March 2020, to 31 May 2022, in Israel. The study found that among Israelis, vaccination uptake following infection is relatively low. When examining gender, one sees that the immunization rate among recovering females is higher than among men. Similarly, differences in uptake exist between age groups. When examining the interval between vaccine dose and infection according to age groups, the most significant breakthrough infection rate is among the ages of 20−59 (1−6 days­0.3%; 7−13 days­0.48%; two to three weeks­0.3%, p < 0.001). This study reveals potential reservoir groups of virus spread. Among previously infected, low vaccination uptake levels are observed (first dose­30−40%, second dose­16−27%, third dose­9% and fourth dose­2%, p < 0.001), despite findings that indicate surging reinfection rates. Among vaccinated, two critical groups (0−19; 20−59) exhibit highest levels of breakthrough cases varying per vaccine doses, with statistically significant findings (p < 0.001). These population groups may be subject to a false sense of security as a result of perceived acquired long-term immunity prompting low perceived risk of the virus and non-vigilance with protective behavior. The findings point to the possibility that individuals engage in more risky health behavior, per the Peltzman effect.

Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients.

As solid organ transplant recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received 3 doses of BNT162b2 mRNA vaccine. Associations among breakthrough infection (BTI), vaccine responses, and patient characteristics were explored in 54 patients. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of 6 months after booster vaccination. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate Analyses identified the avidity of SARS-CoV-2 receptor binding domain binding IgG, neutralizing antibodies, and SARS-CoV-2 S2-specific interferon gamma responses as correlates of protection against BTI. No demographic or clinical parameter correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific interferon gamma responses. In conclusion, T cell responses may help compensate for the suboptimal antibody response to booster vaccination in kidney transplant recipients. Further studies are needed to confirm these findings.

Breakthrough cases of Omicron and Delta variants of SARS-CoV-2 during the fifth wave in Pakistan.

COVID-19 pandemic has severely affected Pakistan with 1,557,134 cases as of August 4, 2022. However, the data regarding breakthrough infections in Pakistan is scant. Hence, the objective was to analyze SARS-CoV-2 breakthrough infections with respect to vaccines and variants during the fifth wave in Pakistan. Therefore, the Department of Virology (NIH, Pakistan) genotyped 2,467 randomly selected individuals between November 2021 and February 2022 using the SNPsig® SARS-CoV-2 (EscapePLEX) kit (PrimerDesign, UK). P681R and K417N mutations were used to distinguish delta and omicron. Data on the patient's age, gender, date of collection, variant, and vaccination status were analyzed using Statistical Package for Social Sciences (SPSS) software. Among 2,467 genotyped samples, Omicron was detected in 58.6% (n = 1445), Delta in 40.4% (n = 998) and undetermined/wildtype variant in 24 samples. The vaccination status of omicron-positive patients showed (49.7%; n = 718/1445) and Delta-positive patients (39.67%; n = 396/998) to be fully vaccinated. Of note, a high percentage 85% of breakthrough cases (n = 947) were identified among fully vaccinated individuals (n = 1114). Among them, 85.9% (n = 617/718) belonged to omicron and 83.3% (n = 330/396) to delta. Moreover, 76.7% (n = 855) of vaccinated individuals (n = 1114) received Sinopharm (n = 432) and Sinovac (n = 423) vaccines. The majority of breakthrough subjects who contracted Omicron were vaccinated with Sinopharm (93.0%, n = 256) and delta with Cansino (100%, n = 44). Individuals vaccinated with Sinovac showed the most frequent breakthrough cases for both Omicron and Delta variant between the 4th and 6th months (n = 278) after primary vaccination as compared to the 7th to 9th months (n = 24) category. While in case of Sinopharm, maximum breakthrough cases occurred between 7th to 9th months (n = 234) as compared to the 4th to 6th months (n = 120) after primary vaccination. Omicron and Delta breakthrough cases in men (n = 364 and 193) are more frequently seen than women (n = 253 and 138) respectively and breakthrough majority cases (n = 392) occurred in individuals aged 18-33 years. Breakthrough cases limiting monitoring in Pakistan impose a substantial constraint on policymakers' ability to take timely effective decisions. Since the current study consists of only a 2,467-genotyped sample, comprehensive data should be analyzed.

Modeling the Transmission of the SARS-CoV-2 Delta Variant in a Partially Vaccinated Population.

In a population with ongoing vaccination, the trajectory of a pandemic is determined by how the virus spreads in unvaccinated and vaccinated individuals that exhibit distinct transmission dynamics based on different levels of natural and vaccine-induced immunity. We developed a mathematical model that considers both subpopulations and immunity parameters, including vaccination rates, vaccine effectiveness, and a gradual loss of protection. The model forecasted the spread of the SARS-CoV-2 delta variant in the US under varied transmission and vaccination rates. We further obtained the control reproduction number and conducted sensitivity analyses to determine how each parameter may affect virus transmission. Although our model has several limitations, the number of infected individuals was shown to be a magnitude greater (~10×) in the unvaccinated subpopulation compared to the vaccinated subpopulation. Our results show that a combination of strengthening vaccine-induced immunity and preventative behavioral measures like face mask-wearing and contact tracing will likely be required to deaccelerate the spread of infectious SARS-CoV-2 variants.

Does the COVID-19 Vaccine Still Work That "Most of the Confirmed Cases Had Been Vaccinated"? A Content Analysis of Vaccine Effectiveness Discussion on Sina Weibo during the Outbreak of COVID-19 in Nanjing.

In July 2021, breakthrough cases were reported in the outbreak of COVID-19 in Nanjing, sparking concern and discussion about the vaccine's effectiveness and becoming a trending topic on Sina Weibo. In order to explore public attitudes towards the COVID-19 vaccine and their emotional orientations, we collected 1542 posts under the trending topic through data mining. We set up four categories of attitudes towards COVID-19 vaccines, and used a big data analysis tool to code and manually checked the coding results to complete the content analysis. The results showed that 45.14% of the Weibo posts (n = 1542) supported the COVID-19 vaccine, 12.97% were neutral, and 7.26% were doubtful, which indicated that the public did not question the vaccine's effectiveness due to the breakthrough cases in Nanjing. There were 66.47% posts that reflected significant negative emotions. Among these, 50.44% of posts with negative emotions were directed towards the media, 25.07% towards the posting users, and 11.51% towards the public, which indicated that the negative emotions were not directed towards the COVID-19 vaccine. External sources outside the vaccine might cause vaccine hesitancy. Public opinions expressed in online media reflect the public's cognition and attitude towards vaccines and their core needs in terms of information. Therefore, online public opinion monitoring could be an essential way to understand the opinions and attitudes towards public health issues.

Immune Profile and Clinical Outcome of Breakthrough Cases After Vaccination With an Inactivated SARS-CoV-2 Vaccine.

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.

The BNT162b2 vaccine effectiveness against new COVID-19 cases and complications of breakthrough cases: A nation-wide retrospective longitudinal multiple cohort analysis using individualised data.

BACKGROUND: The rapid vaccination campaign against COVID-19 in Israel relied on the BNT162b2 vaccine. We performed a longitudinal analysis of multiple cohorts, using individual data, to evaluate the effectiveness of the vaccine against new and breakthrough cases. METHODS: We estimated vaccine effectiveness (VE) for 27 consecutive cohorts, each comprised of individuals vaccinated on specific days. VE against new COVID-19 cases was evaluated for five SARS-CoV-2-related outcomes: infection, symptomatic disease, hospitalisation, severe/critical disease and death. For breakthrough cases, rate reduction was evaluated for hospitalisation, severe/critical disease and death. Outcomes were evaluated at predetermined time-periods after vaccination, the last one dedicated to individuals who became SARS-CoV-2-positive 22-28 days after the second dose. FINDINGS: The highest VE estimates against new cases in ≥16 year old individuals, for all outcomes, were reached at the 15-21 day period after the second dose, ranging between 97.7% (95% CI: 95.9-98.7%) for deaths and 98.6% (95% CI: 97.8-99.1%) for severe/critical disease. VE estimates of the 14-20 day period after the first dose ranged between 54.3% (95% CI: 50.6-57.8%) for infection and 77.3% (95% CI: 71.2-82.1%) for severe/critical disease. VE rose more slowly among ≥80 year old individuals. Rate reductions of breakthrough complications were highest at the 22-28 day period after the second dose, ranging between 47.4% (95% CI: 4.3-71.2%) for death and 66.2% (95% CI: 44.2-79.6%) for severe/critical disease. INTERPRETATION: The BNT162 vaccine is highly effective in preventing new SARS-CoV-2 cases. Among ≥80 year old individuals, high effectiveness develops more slowly. In breakthrough cases, vaccination reduces complications and death. FUNDING: None.

Review of COVID-19 Variants and COVID-19 Vaccine Efficacy: What the Clinician Should Know?

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.