This study aimed to assess the real-world effectiveness of vaccines and hybrid immunity in preventing infections during the Omicron prevalent period in Hong Kong. This study analyzed vaccination records and COVID-19 confirmed case records from 1 January 2022 to 28 January 2023 and included a total of 7,165,862 individuals with vaccination or infection records. This study found that an additional vaccine dose offered increased protection against Omicron BA.1/2 and BA.4 infections for individuals without prior infections in general. Hybrid immunity, acquired through vaccination and natural infection, was found to be significantly stronger than that provided by vaccines alone. The Comirnaty Original/Omicron BA.4/5 bivalent vaccine, introduced in December 2022, was associated with a lower risk of BA.4 infection when administered as a booster dose after three doses of CoronaVac. However, individuals with four doses of the CoronaVac vaccine did not exhibit a significantly lower risk of infection compared to those with three doses during the BA.4 dominant period. This study highlights the importance of promoting booster shot uptake and encouraging vaccination among those who have recovered from COVID-19 infections. The potential immune imprinting effect associated with the Comirnaty and CoronaVac vaccine underscores the need for continued surveillance and research to optimize vaccination strategies for emerging variants.

The COVID-19 (coronavirus disease 2019) pandemic had an extensive impact on global morbidity and mortality. Several other common respiratory viruses, such as the influenza virus and respiratory syncytial virus (RSV), are endemic or epidemic agents causing acute respiratory infections that are easily transmissible and pose a significant threat to communities due to efficient person-to-person transmission. These viruses can undergo antigenic variation through genetic mutations, resulting in the emergence of novel strains or variants, thereby diminishing the effectiveness of current vaccines, and necessitating ongoing monitoring and adjustment of vaccine antigens. As the virus-specific immunity is maintained only for several weeks or months after the infection, there is an emergent need to develop effective and durable vaccines. Additionally, specific populations, such as elderly or immunocompromised individuals, may exhibit reduced immune responses to respiratory viruses, posing significant challenges to develop vaccines that elicit durable and potent immunity. We present a comprehensive review of the molecular mechanisms underlying the pathogenesis and virulence of common respiratory viruses, such as RSV, influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We discuss several vaccine approaches that are under development. A thorough understanding of the current strategies and the challenges encountered during the vaccine development process can lead to the advancement of effective next-generation vaccines.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown.

Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated.

The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination.

The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Recent observations have suggested that HZ is associated with vaccination against COVID-19. To investigate the association between the vaccine and HZ severity, a single-centre, cross-sectional study of all patients diagnosed with HZ and 2 control diagnoses (cellulitis and bone fractures), between 2017 and 2021, was performed. Hospital visits and hospitalization rates were compared. All medical records of patients diagnosed with HZ in the first year after the COVID-19 vaccination campaign began were reviewed, in order to generate a retrospective cohort comparing vaccinated and unvaccinated patients with HZ. All participants had received the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. During the study period, 2,413 patients were diagnosed with HZ, and when normalized to control diagnoses the number of cases remained stable. The retrospective cohort included 365 patients. A multivariate analysis controlling for sex, age, autoimmune diseases, malignancies, and immunosuppressive therapy showed higher admission rates in vaccinated compared with unvaccinated individuals (odds ratio (OR) 2.75, 95% CI 1.27-5.96, p = 0.01). However, matching techniques and stratification by age, used to better control for confounders, invalidated these findings. No differences were observed in other variables indicative of disease severity (hospital stay length and complications). In conclusion, COVID-19 vaccination was not found to be associated with an increased risk of HZ-related admission and complications.

Polyethylene glycol (PEG) plays important roles in stabilizing and lengthening circulation time of lipid nanoparticle (LNP) vaccines. Nowadays various levels of PEG antibodies have been detected in human blood, but the impact and mechanism of PEG antibodies on the in vivo performance of LNP vaccines has not been clarified thoroughly. By illustrating the distribution characteristics of PEG antibodies in human, the present study focused on the influence of PEG antibodies on the safety and efficacy of LNP-mRNA vaccine against COVID-19 in animal models. It was found that PEG antibodies led to shortened blood circulation duration, elevated accumulation and mRNA expression in liver and spleen, enhanced expression in macrophage and dendritic cells, while without affecting the production of anti-Spike protein antibodies of COVID-19 LNP vaccine. Noteworthily, PEG antibodies binding on the LNP vaccine increased probability of complement activation in animal as well as in human serum and led to lethal side effect in large dosage via intravenous injection of mice. Our data suggested that PEG antibodies in human was a risky factor of LNP-based vaccines for biosafety concerns but not efficacy.

The coronavirus disease 2019 (COVID-19) pandemic poses a disruptive impact on public health and the global economy. Fortunately, the development of COVID-19 vaccines based on in vitro-transcribed messenger RNA (IVT mRNA) has been a breakthrough in medical history, benefiting billions of people with its high effectiveness, safety profile, and ease of large-scale production. This success is the result of decades of continuous RNA research, which has led to significant improvements in the stability and expression level of IVT mRNA through various approaches such as sequence optimization and improved preparation processes. IVT mRNA sequence optimization has been shown to have a positive effect on enhancing the mRNA expression level. The innovation of IVT mRNA purification technology is also indispensable, as the purity of IVT mRNA directly affects the success of downstream vaccine preparation processes and the potential for inducing unwanted side effects in therapeutic applications. Despite the progress made, challenges related to IVT mRNA sequence design and purification still require further attention to enhance the quality of IVT mRNA in the future. In this review, we discuss the latest innovative progress in IVT mRNA design and purification to further improve its clinical efficacy.

The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented.

This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood.

Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups.

A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups.

NCT05109559.

SARS-CoV-2, a newly discovered coronavirus, has been linked to the COVID-19 pandemic and is currently an important public health issue. Despite all the work done to date around the world, there is still no viable treatment for COVID-19. This study examined the most recent evidence on the efficacy and safety of several therapeutic options available including natural substances, synthetic drugs and vaccines in the treatment of COVID-19. Various natural compounds such as sarsapogenin, lycorine, biscoclaurine, vitamin B₁₂, glycyrrhizic acid, riboflavin, resveratrol and kaempferol, various vaccines and drugs such as AZD1222, mRNA-1273, BNT162b2, Sputnik V, and remdesivir, lopinavir, favipiravir, darunavir, oseltamivir, and umifenovir, resp., have been discussed comprehensively. We attempted to provide exhaustive information regarding the various prospective therapeutic approaches available in order to assist researchers and physicians in treating COVID-19 patients.

Age-related declines in immune response pose a challenge in combating diseases later in life. Influenza (flu) infection remains a significant burden on older populations and often results in catastrophic disability in those who survive infection. Despite having vaccines designed specifically for older adults, the burden of flu remains high and overall flu vaccine efficacy remains inadequate in this population. Recent geroscience research has highlighted the utility in targeting biological aging to improve multiple age-related declines. Indeed, the response to vaccination is highly coordinated, and diminished responses in older adults are likely not due to a singular deficit, but rather a multitude of age-related declines. In this review we highlight deficits in the aged vaccine responses and potential geroscience guided approaches to overcome these deficits. More specifically, we propose that alternative vaccine platforms and interventions that target the hallmarks of aging, including inflammation, cellular senescence, microbiome disturbances, and mitochondrial dysfunction, may improve vaccine responses and overall immunological resilience in older adults. Elucidating novel interventions and approaches that enhance immunological protection from vaccination is crucial to minimize the disproportionate effect of flu and other infectious diseases on older adults.

There is a need to establish the effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in reducing COVID-19-related hopitalization of patients in Jordan. As the vaccination program accelerates, it is important to determine whether the vaccines' effectiveness (VE) has successfully reduced the number of acute cases admitted to hospital.

To determine the efficacy of Pfizer-BioNTech and Sinopharm COVID-19 vaccines among Jordanian patients admitted to Prince Hamza hospital, a single center case-control study was performed. The study analyzed the hospitalization rates of vaccinated (n = 536) and unvaccinated (n = 585) individuals across the 2-month period from February 6 to April 6, 2022. The cases were patients who tested positive for SARS-CoV-2 ("case-patients"), whilst the control group were hospital patients who did not test positive for SARS-CoV-2 ("control-patients").

This study found that among 1,121 total participants (561 cases and 560 control), the overall vaccine effectiveness (VE) among the participants was 84% (95% Cl 79-88%). VE was higher in females (88%, 95% Cl 84-93%) than in males (77%, 95% Cl 67-84%) (p < 0.001), and it was highest in those between the ages of 18 and 28-years-old (95%, 95% CI 86-98%). For patients with pre-existing conditions, including chronic heart disease, chronic lung disease, and diabetes, VE was higher compared to patients with no comorbidities, though the difference was not statistically significant. Finally, in comparing all vaccinated participants, VE was higher for those who received the Pfizer vaccine (VE = 92%, 95% CI 88-94%) (OR 0.08, 95% CI 0.06-0.12) than for those who received the Sinopharm vaccine (VE = 67%, 95% CI 52-78%) (OR 0.33, 95% CI 0.22-0.48); (p = 0.011).

Overall, Pfizer and Sinopharm vaccines were found to be effective in limiting hospitalizations for acute cases of coronavirus among Jordanian adult's patient's cohort between February 6 and April 6, 2022, especially among patients with comorbidities.

The traditional complications of diabetes mellitus are well known and continue to pose a considerable burden on millions of people living with diabetes mellitus. However, advances in the management of diabetes mellitus and, consequently, longer life expectancies, have resulted in the emergence of evidence of the existence of a different set of lesser-acknowledged diabetes mellitus complications. With declining mortality from vascular disease, which once accounted for more than 50% of deaths amongst people with diabetes mellitus, cancer and dementia now comprise the leading causes of death in people with diabetes mellitus in some countries or regions. Additionally, studies have demonstrated notable links between diabetes mellitus and a broad range of comorbidities, including cognitive decline, functional disability, affective disorders, obstructive sleep apnoea and liver disease, and have refined our understanding of the association between diabetes mellitus and infection. However, no published review currently synthesizes this evidence to provide an in-depth discussion of the burden and risks of these emerging complications. This Review summarizes information from systematic reviews and major cohort studies regarding emerging complications of type 1 and type 2 diabetes mellitus to identify and quantify associations, highlight gaps and discrepancies in the evidence, and consider implications for the future management of diabetes mellitus.

Vaccination remains the primary measure to prevent the spread of the SARS-CoV-2 virus, further necessitating the use of effective licensed vaccines.

From Dec 25, 2020, to July 11, 2021, we conducted a multicenter, randomised, single-blind, placebo-controlled phase 3 efficacy trial of the QazCovid-in® vaccine with a 180-day follow-up period in three clinical centres in Kazakhstan. A total of 3000 eligible participants aged 18 years or older were randomly assigned (4:1) to receive two doses of the vaccine (5 μg each, 21 days apart) or placebo administered intramuscularly. QazCovid-in® is a whole-virion formaldehyde-inactivated anti-COVID-19 vaccine, adjuvanted with aluminium hydroxide. The primary endpoint was the incidence of symptomatic cases of the SARS-CoV-2 infection confirmed by RT-PCR starting from day 14 after the first immunisation. The trial was registered with ClinicalTrials.gov NCT04691908.

The QazCovid-in® vaccine was safe over the 6-month monitoring period after two intramuscular immunisations inducing only local short-lived adverse events. The concomitant diseases of participants did not affect the vaccine safety. Out of 2400 vaccinated participants, 31 were diagnosed with COVID-19; 43 COVID-19 cases were recorded in 600 placebo participants with onset of 14 days after the first dose within the 180-day observation period. Only one severe COVID-19 case was identified in a vaccine recipient with a comorbid chronic heart failure. The protective efficacy of the QazCovid-in® vaccine reached 82·0% (95% CI 71.1-88.5) within the 180-day observation period.

Two immunisations with the inactivated QazCovid-in® vaccine achieved 82·0% (95% CI 71.1-88.5) protective efficacy against COVID-19 within a 180-day follow-up period.

The work was funded by the Science Committee of the Ministry of Education and Science of Kazakhstan within the framework of the Scientific and Technical Program "Development of a vaccine against coronavirus infection COVID-19". State registration number 0.0927.

To evaluate IgG production in a group of vaccinated and unvaccinated subjects previously infected, or not, with SARS-CoV-2.

A total of 316 subjects were enrolled at different times after vaccination and/or infection. IgG against target S1 subunit of the spike protein of SARS-COV-2 was assessed by a chemiluminescent microparticle immunoassay. Participant data was collected using a clinical-epidemiological survey.

A total of 56.2% (n = 146) of our cohort was vaccinated, with 27.5% (n = 36) reporting a previous infection. Of these, all were IgG positive at the time of the study, regardless of gender, age category, vaccine type, and elapsed time since vaccination. The vaccinated group without a previous infection (72.5%, n = 95) showed a slightly lower IgG seropositivity and median values, overall, although significantly higher in females and lower with the ChAdOx1 nCoV-19 (AstraZeneca) vaccine. Vaccinated subjects above the age of 65 showed a trend towards higher median IgG values (13,911.0 AU/mL), when previously infected with SARS-CoV-2, but comparatively lower IgG median value (5158.7 AU/mL) in its absence. In all vaccinated groups, IgG antibody production increased at 1-2 weeks, peaking at 4-6 weeks. Afterward, IgG decreased progressively but almost all subjects (97.7%, n = 128) were seropositive for the remainder of our study. Fully vaccinated individuals with a past infection showed a lower IgG rate of decrease versus their uninfected counterparts (17.9 vs 22.6%, respectively).

Our findings suggest a higher effect of vaccination on the production IgG antibodies, as opposed to natural infection. Nonetheless, in general, antibody titers waned rapidly.

We analyze the relaxation of non-pharmaceutical interventions (NPIs) under an increasing number of vaccinations in Germany. For the spread of SARS-CoV-2 we employ a SIR-type model that accounts for age-dependence and includes realistic contact patterns between age groups. The implementation of NPIs occurs on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. We account for spatial heterogeneity and commuting activities in between regions in Germany, and the testing of commuters is considered as a further NPI. We include the ongoing vaccination process and analyze the effect of the B.1.617.2 (Delta) variant, which is considered to be 40%-60% more infectious then the currently dominant B.1.1.7 (Alpha) variant. We explore different opening scenarios under the ongoing vaccination process by assuming that local restrictions are either lifted in early July or August with or without continued wearing of masks and testing. Our results indicate that we can counteract the resurgence of SARS-CoV-2 despite the Delta variant with appropriate timing for the relaxation of NPIs. In all cases, however, school children are hit the hardest.

Vaccine hesitancy among healthcare providers can compromise public confidence in vaccination during the ongoing COVID-19 global epidemic and increase susceptibility to life-threatening disease. We sought to investigate predictors of openness to vaccination among healthcare workers who choose not to be vaccinated against COVID-19 in order to explore potential solutions.

Physicians, physician assistants, and nurses who chose not to be vaccinated were surveyed to decipher reasons for vaccine refusal and personal loss due to the virus along with demographic variables. Multivariate logistic regression analysis evaluated whether provider role, parenthood, and death of family or friends were associated with strong versus relative vaccine refusal.

The predominant reasons for vaccine hesitancy in this cohort of health care workers who had access to, but chose not to be vaccinated (n=500) were a concern for vaccine side effects (69.6%) and the belief that the vaccines are inadequately studied (61.6%). Being a physician, a parent, and having no experience of death in the family or friends had 2.64 times (95% CI: 1.65-4.23, p < 0.001), 1.72 times (95% CI: 1.05-2.81, p = 0.032), and 1.70 times (95% CI: 1.06-2.72, p = 0.028) the odds of strong vaccine refusal, respectively. Older age (35 and up) respondents were 1.83 times (95% CI: 1.24-2.68, p = 0.002) more likely to be open to vaccination.

More doses of CoronaVac have been administered worldwide than any other COVID-19 vaccine. However, the effectiveness of COVID-19 inactivated vaccines in pregnant women is still unknown. We estimated the vaccine effectiveness (VE) of CoronaVac against symptomatic and severe COVID-19 in pregnant women in Brazil.

We conducted a test-negative design study in all pregnant women aged 18-49 years with COVID-19-related symptoms in Brazil from March 15, 2021, to October 03, 2021, linking records of negative and positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests to national vaccination records. We also linked records of test-positive cases with notifications of severe, hospitalised or fatal COVID-19. Using logistic regression, we estimated the adjusted odds ratio and VE against symptomatic COVID-19 and against severe COVID-19 by comparing vaccine status in test-negative subjects to test-positive symptomatic cases and severe cases.

Of the 19,838 tested pregnant women, 7424 (37.4%) tested positive for COVID-19 and 588 (7.9%) had severe disease. Only 83% of pregnant women who received the first dose of CoronaVac completed the vaccination scheme. A single dose of the CoronaVac vaccine was not effective at preventing symptomatic COVID-19. The effectiveness of two doses of CoronaVac was 41% (95% CI 27.1-52.2) against symptomatic COVID-19 and 85% (95% CI 59.5-94.8) against severe COVID-19.

A complete regimen of CoronaVac in pregnant women was effective in preventing symptomatic COVID-19 and highly effective against severe illness in a setting that combined high disease burden and marked COVID-19-related maternal deaths.

Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines.

Humoral responses to coronavirus disease 2019 (COVID-19) vaccines in hemodialysis (HD) patients can direct vaccination policy.

We compared 409 COVID-19-naïve HD patients from 13 HD units in Israel to 148 non-dialysis-dependent COVID-19-naïve controls. Twenty-four previously infected (antinucleocapsid positive) HD patients were analysed separately. Blood samples were obtained ≥14 days post-vaccination (BNT162b2, Pfizer/BioNTech) to assess seroconversion rates and titers of anti-spike (anti-S) and neutralizing antibodies.

The median time from vaccination to blood sample collection was 82 days [interquartile range (IAR) 64-87] and 89 days (IQR 68-96) for HD patients and controls, respectively. Seroconversion rates were lower in HD patients compared with controls for both anti-S and neutralizing antibodies (89% and 77% versus 99.3%, respectively; P < 0.0001). Antibody titers were also significantly lower in HD patients compared with controls {median 69.6 [IQR 33.2-120] versus 196.5 [IQR 118.5-246], P < 0.0001; geometric mean titer [GMT] 23.3 [95% confidence interval (CI) 18.7-29.1] versus 222.7 [95% CI 174-284], P < 0.0001, for anti-S and neutralizing antibodies, respectively}. Multivariate analysis demonstrated dialysis dependence to be strongly associated with lower antibody responses and antibody titers waning with time. Age, low serum albumin and low lymphocyte count were also associated with lower seroconversion rates and antibody titers. HD patients previously infected with sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had no difference in their seroconversion rates or antibody titers compared with COVID-19-naïve patients.

This study demonstrates diminished and waning humoral responses following COVID-19 vaccination in a large and diverse cohort of HD patients, including those previously infected with SARS-CoV-2. Considering these results and reduced vaccine effectiveness against variants of concern, in addition to continued social distancing precautions, a third booster dose should be considered in this population.

Stimulation of immunity by vaccination may elicit adverse events. There is currently inconclusive evidence on the relationship between herpes zoster related hospitalization and COVID-19 vaccination. This study aimed to evaluate the effect of inactivated virus (CoronaVac, Sinovac) and mRNA (BNT162b2, BioNTech/Fosun Pharma) COVID-19 vaccine on the risk of herpes zoster related hospitalization.

Self-controlled case series (SCCS) analysis was conducted using the data from the electronic health records in Hospital Authority and COVID-19 vaccination records in the Department of Health in Hong Kong. We conducted the SCCS analysis including patients with a first primary diagnosis of herpes zoster in the hospital inpatient setting between February 23 and July 31, 2021. A confirmatory analysis by nested case-control method was also conducted. Each herpes zoster case was randomly matched with ten controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression and logistic regression models were used to assess the potential excess rates of herpes zoster after vaccination.

From February 23 to July 31, 2021, a total of 16 and 27 patients were identified with a first primary hospital diagnosis of herpes zoster within 28 days after CoronaVac and BNT162b2 vaccinations. The incidence of herpes zoster was 7.9 (95% Confidence interval [CI]: 5.2-11.5) for CoronaVac and 7.1 (95% CI: 4.1-11.5) for BNT162b2 per 1,000,000 doses administered. In SCCS analysis, CoronaVac vaccination was associated with significantly higher risk of herpes zoster within 14 days after first dose (adjusted incidence rate ratio [aIRR]=2.67, 95% CI: 1.08-6.59) but not in other periods afterwards compared to the baseline period. Regarding BNT162b2 vaccination, a significantly increased risk of herpes zoster was observed after first dose up to 14 days after second dose (0-13 days after first dose: aIRR=5.23, 95% CI: 1.61-17.03; 14-27 days after first dose: aIRR=5.82, 95% CI: 1.62-20.91; 0-13 days after second dose: aIRR=5.14, 95% CI: 1.29-20.47). Using these relative rates, we estimated that there has been an excess of approximately 5 and 7 cases of hospitalization as a result of herpes zoster after every 1,000,000 doses of CoronaVac and BNT162b2 vaccination, respectively. The findings in the nested case control analysis showed similar results.

We identified an increased risk of herpes zoster related hospitalization after CoronaVac and BNT162b2 vaccinations. However, the absolute risks of such adverse event after CoronaVac and BNT162b2 vaccinations were very low. In locations where COVID-19 is prevalent, the protective effects on COVID-19 from vaccinations will greatly outweigh the potential side effects of vaccination.

The project was funded by Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No.COVID19F01). FTTL (Francisco Tsz Tsun Lai) and ICKW (Ian Chi Kei Wong)'s posts were partly funded by D²4H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission.

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in fully vaccinated individuals are receiving intense scrutiny because of their importance in determining how long restrictions to control virus transmission will need to remain in place in highly vaccinated populations as well as in determining the need for additional vaccine doses or changes to the vaccine formulations and/or dosing intervals. Measurement of breakthrough infections is challenging outside of randomized, placebo-controlled, double-blind field trials. However, laboratory and observational studies are necessary to understand the impact of waning immunity, viral variants and other determinants of changing vaccine effectiveness against various levels of coronavirus disease 2019 (COVID-19) severity. Here, we describe the approaches being used to measure vaccine effectiveness and provide a synthesis of the burgeoning literature on the determinants of vaccine effectiveness and breakthrough rates. We argue that, rather than trying to tease apart the contributions of factors such as age, viral variants and time since vaccination, the rates of breakthrough infection are best seen as a consequence of the level of immunity at any moment in an individual, the variant to which that individual is exposed and the severity of disease being considered. We also address key open questions concerning the transition to endemicity, the potential need for altered vaccine formulations to track viral variants, the need to identify immune correlates of protection, and the public health challenges of using various tools to counter breakthrough infections, including boosters in an era of global vaccine shortages.

The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.

Viral infections causing pandemics and chronic diseases are the main culprits implicated in devastating global clinical and socioeconomic impacts, as clearly manifested during the current COVID-19 pandemic. Immunoprophylaxis via mass immunisation with vaccines has been shown to be an efficient strategy to control such viral infections, with the successful and recently accelerated development of different types of vaccines, thanks to the advanced biotechnological techniques involved in the upstream and downstream processing of these products. However, there is still much work to be done for the improvement of efficacy and safety when it comes to the choice of delivery systems, formulations, dosage form and route of administration, which are not only crucial for immunisation effectiveness, but also for vaccine stability, dose frequency, patient convenience and logistics for mass immunisation. In this review, we discuss the main vaccine delivery systems and associated challenges, as well as the recent success in developing nanomaterials-based and advanced delivery systems to tackle these challenges. Manufacturing and regulatory requirements for the development of these systems for successful clinical and marketing authorisation were also considered. Here, we comprehensively review nanovaccines from development to clinical application, which will be relevant to vaccine developers, regulators, and clinicians.

Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection between June 1 and July 27, the date of analysis. After controlling for potential confounders as age and comorbidities, we found a significant 1.51 fold (95% CI, 1.38-1.66) increased risk for infection for early vaccinees compared to those vaccinated later that was similar across all ages groups. The increased risk reached 2.26- fold (95% CI, 1.80-3.01) when comparing those who were vaccinated in January to those vaccinated in April. This preliminary finding of vaccine waning as a factor of time from vaccince should prompt further investigations into long-term protection against different strains.

Due to its leading role in fighting infections, the human immune system has been the focus of many studies in the context of Coronavirus disease 2019 (COVID-19). In a worldwide effort, the scientific community has transitioned from reporting about the effects of the novel coronavirus on the human body in the early days of the pandemic to exploring the body's many immunopathological and immunoprotecting properties that have improved disease treatment and enabled the development of vaccines. The aim of this review is to explain what happens to the immune system after recovery from COVID-19 and/or vaccination against SARS-CoV-2, the virus that causes the disease. We detail the way in which the immune system responds to a SARS-CoV-2 infection, including innate and adaptive measures. Then, we describe the role of vaccination, the main types of COVID-19 vaccines and how they protect us. Further, we explain the reason why immunity after COVID-19 infection plus a vaccination appears to induce a stronger response compared with virus exposure alone. Additionally, this review reports some correlates of protection from SARS-CoV-2 infection. In conclusion, we reinforce that vaccination is safe and important in achieving herd immunity.

Inadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.

BECAME is a single-centre, open-label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participants per arm will be also tested for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.

The trial is approved by local ethics committee of Rabin Medical Center (RMC-0192-21). All participants will be required to provide written informed consent. Results of this trial will be published; trial data will be available. Protocol amendments will be submitted to the local ethics committee.

NCT04961229.

Since the outbreak of SARS-CoV-2, antigenicity concerns continue to linger with emerging mutants. As recent variants have shown decreased reactivity to previously determined monoclonal antibodies (mAbs) or sera, monitoring the antigenicity change of circulating mutants is urgently needed for vaccine effectiveness. Currently, antigenic comparison is mainly carried out by immuno-binding assays. Yet, an online predicting system is highly desirable to complement the targeted experimental tests from the perspective of time and cost. Here, we provided a platform of SAS (Spike protein Antigenicity for SARS-CoV-2), enabling predicting the resistant effect of emerging variants and the dynamic coverage of SARS-CoV-2 antibodies among circulating strains. When being compared to experimental results, SAS prediction obtained the consistency of 100% on 8 mAb-binding tests with detailed epitope covering mutational sites, and 80.3% on 223 anti-serum tests. Moreover, on the latest South Africa escaping strain (B.1.351), SAS predicted a significant resistance to reference strain at multiple mutated epitopes, agreeing well with the vaccine evaluation results. SAS enables auto-updating from GISAID, and the current version collects 867K GISAID strains, 15.4K unique spike (S) variants, and 28 validated and predicted epitope regions that include 339 antigenic sites. Together with the targeted immune-binding experiments, SAS may be helpful to reduce the experimental searching space, indicate the emergence and expansion of antigenic variants, and suggest the dynamic coverage of representative mAbs/vaccines among the latest circulating strains. SAS can be accessed at https://www.biosino.org/sas.

To evaluate the effectiveness of the BNT162b2 messenger RNA vaccine in pregnant women, we conducted an observational cohort study of pregnant women aged 16 years or older, with no history of SARS-CoV-2, who were vaccinated between 20 December 2020 and 3 June 2021. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56 d after the second dose was 96% (95% confidence interval 89-100%) for any documented infection, 97% (91-100%) for infections with documented symptoms and 89% (43-100%) for COVID-19-related hospitalization. Only one event of severe illness was observed in the unvaccinated group and no deaths were observed in either group. In summary, the BNT162b2 mRNA vaccine was estimated to have high vaccine effectiveness in pregnant women, which is similar to the effectiveness estimated in the general population.

As of July 2021, over 3 billion doses of a COVID-19 vaccines have been administered globally, and there are now 19 COVID-19 vaccines approved for use in at least one country. Several of these have been shown to be highly effective both in clinical trials and real-world observational studies, some of which have included special populations of interest. A small number of countries have approved a COVID-19 vaccine for use in adolescents or children. These are laudable achievements, but the global vaccination effort has been challenged by inequitable distribution of vaccines predominantly to high income countries, with only 0.9% of people in low-income countries having received at least one dose of a COVID-19 vaccine. Addressing this inequity is of critical importance and will result in better control of SARS-CoV-2 globally. Other challenges include: the reduced protection from COVID-19 vaccines against some strains of SARS-CoV-2, necessitating the development of variant specific vaccines; and uncertainties around the duration of protection from vaccine-induced immunity.

The effects of the coronavirus disease-2019 (COVID-19) pandemic, particularly among those with chronic kidney disease (CKD), who commonly have defects in humoral and cellular immunity, and the efficacy of vaccinations against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are uncertain. To inform public health and clinical practice, we synthesized published studies and preprints evaluating surrogate measures of immunity after SARS-CoV-2 vaccination in patients with CKD, including those receiving dialysis or with a kidney transplant. We found 35 studies (28 published, 7 preprints), with sample sizes ranging from 23 to 1140 participants and follow-up ranging from 1 week to 1 month after vaccination. Seventeen of these studies enrolled a control group. In the 22 studies of patients receiving dialysis, the development of antibodies was observed in 18% to 53% after 1 dose and in 70% to 96% after 2 doses of mRNA vaccine. In the 14 studies of transplant recipients, 3% to 59% mounted detectable humoral or cellular responses after 2 doses of mRNA vaccine. After vaccination, there were a few reported cases of relapse or de novo glomerulonephritis, and acute transplant rejection, suggesting a need for ongoing surveillance. Studies are needed to better evaluate the effectiveness of SARS-CoV-2 vaccination in these populations. Rigorous surveillance is necessary for detection of long-term adverse effects in patients with autoimmune disease and transplant recipients. For transplant recipients and those with suboptimal immune responses, alternate vaccination platforms and strategies should be considered. As additional data arise, the NephJC COVID-19 page will continue to be updated (http://www.nephjc.com/news/covid-vaccine).

When vaccines are in limited supply, expanding the number of people who receive some vaccine, such as by halving doses or increasing the interval between doses, can reduce disease and mortality compared with concentrating available vaccine doses in a subset of the population. A corollary of such dose-sparing strategies is that the vaccinated individuals may have less protective immunity. Concerns have been raised that expanding the fraction of the population with partial immunity to SARS-CoV-2 could increase selection for vaccine-escape variants, ultimately undermining vaccine effectiveness. We argue that, although this is possible, preliminary evidence instead suggests such strategies should slow the rate of viral escape from vaccine or naturally induced immunity. As long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation. Because there is little evidence of efficient immune selection of SARS-CoV-2 during typical infections, these population-level effects are likely to dominate vaccine-induced evolution.