Measures employed to combat COVID-19 included public lockdowns and vaccination campaigns. Israel’s extensive public health system produced data demonstrating the real-world results of these measures. Our objective was to evaluate the health and economic outcomes of the measures to cope with COVID-19. Publicly available datasets from the Israeli Ministry of Health were used to model the parameters of the pandemic in Israel. The Oxford COVID-19 Government Response Tracker was used for quantitative data on government policies. Data on the Israeli economy were taken from the Central Bureau of Statistics. Our models demonstrate that the first lockdown prevented 1022 COVID-19 deaths at the cost of 36.4–38.6 billion NIS. The second lockdown prevented 1970 COVID-19 deaths and cost 18–21 billion NIS. These lifesaving effects were observed with a time lag from the declaration of lockdown. The primary vaccination campaign cost 1 billion NIS and prevented 4750 COVID-19 deaths. The first vaccination booster campaign prevented 650 COVID-19 deaths and cost 51.1 million NIS. Therefore, the cost per prevented COVID-19 death is 10–36 million NIS with a national lockdown versus 210,000 NIS in the primary vaccination campaign and 79,000 NIS in the first booster campaign. In conclusion, both lockdowns and vaccination campaigns effectively lower COVID-19 deaths, but the cost to avoid one COVID-19 death with effective vaccination is 50–466 times lower than with a lockdown. Full article

Zoonotic coronaviruses (CoV) have emerged twice and have caused severe respiratory diseases in humans. Due to the frequent outbreaks of different human coronaviruses (HCoVs), the development of a pan-HCoV vaccine is of great importance. Various conserved epitopes shared by HCoVs are reported to induce cross-reactive T-cell responses. Therefore, this study aimed to design a multi-epitope vaccine, targeting the HCoV spike protein. Genetic analysis revealed that the spike region is highly conserved among SARS-CoV-2, bat SL-CoV, and SARS-CoV. By employing the immunoinformatic approach, we prioritized 20 MHC I and 10 MHCII conserved epitopes to design a multi-epitope vaccine. This vaccine candidate is anticipated to strongly elicit both humoral and cell-mediated immune responses. These results warrant further development of this vaccine into real-world application. Full article

(1) Background: SARS-CoV-2 infections are associated with an increased risk of hospital admissions especially in the elderly (age ≥ 65 years) and people with multiple comorbid conditions. (2) Methods: We investigated the effect of additional booster vaccinations following the primary vaccination series of mRNA, inactivated whole virus, or vector vaccines on infections with the SARS-CoV-2 delta variant in the total Hungarian elderly population. The infection, hospital admission, and 28-day all-cause mortality of elderly population was assessed. (3) Results: A total of 1,984,176 people fulfilled the criteria of elderly including 299,216 unvaccinated individuals, while 1,037,069 had completed primary vaccination and 587,150 had obtained an additional booster. The primary vaccination series reduced the risk of infection by 48.88%, the risk of hospital admission by 71.55%, and mortality by 79.87%. The booster vaccination had an additional benefit, as the risk of infection, hospital admission, and all-cause mortality were even lower (82.95%; 92.71%; and 94.24%, respectively). Vaccinated patients needing hospitalization suffered significantly more comorbid conditions, indicating a more vulnerable population. (4) Conclusions: Our data confirmed that the primary vaccination series and especially the booster vaccination significantly reduced the risk of the SARS-CoV-2 delta-variant-associated hospital admission and 28-day all-cause mortality in the elderly despite significantly more severe comorbid conditions. Full article

Background: Protozoa of the genus Leishmania are characterized by their capacity to target macrophages and Dendritic Cells (DCs). These microorganisms could thus be exploited for the delivery of antigens to immune cells. Leishmania tarentolae is regarded as a non-pathogenic species; it was previously used as a biofactory for protein production and has been considered as a candidate vaccine or as an antigen delivery platform. However, results on the type of immune polarization determined by L. tarentolae are still inconclusive. Methods: DCs were derived from human monocytes and exposed to live L. tarentolae, using both the non-engineered P10 strain, and the same strain engineered for expression of the spike protein from SARS-CoV-2. We then determined: (i) parasite internalization in the DCs; and (ii) the capacity of the assayed strains to activate DCs and the type of immune polarization. Results: Protozoan parasites from both strains were effectively engulfed by DCs, which displayed a full pattern of maturation, in terms of MHC class II and costimulatory molecule expression. In addition, after parasite infection, a limited release of Th1 cytokines was observed. Conclusions: Our results indicate that L. tarentolae could be used as a vehicle for antigen delivery to DCs and to induce the maturation of these cells. The limited cytokine release suggests L. tarentolae as a neutral vaccine vehicle that could be administered in association with appropriate immune-modulating molecules. Full article

The COVID-19 pandemic is the biggest public health threat facing the world today. Multiple vaccines have been approved; however, the emergence of viral variants such as the recent Omicron raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac, Beijing, China) vaccine was used; however, it is important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had a history of infection by SARS-CoV-2 prior to immunization, while others did not. We analyzed RBD-specific and neutralizing-antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45–90 days post infection or vaccination, followed by a steady decline over time. In those with a previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection, followed by immunization, resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease. Full article

Background: Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time. Objective: We aim to describe clinical and sociodemographic characteristics associated with COVID-19 infection at least 14 days after booster vaccination in the Israeli population. Methods: We conducted a population-based study among adult members of Leumit Health Services (LHS) in Israel. Nasopharyngeal swabs were examined for SARS-CoV-2 by real-time RT-PCR. The hematological and biochemical parameters in the peripheral blood before booster vaccination were evaluated. Results: Between 1 February 2021 and 30 November 2021, 136,683 individuals in LHS were vaccinated with a booster (third dose) of the BNT162b2 vaccine. Of these, 1171 (0.9%) were diagnosed with COVID-19 by testing positive for SARS-CoV-2 RT-PCR at least >14 days after the booster vaccination. The COVID-19-positive group was characterized by higher rates of chronic kidney disease than the matched COVID-19-negative group (43 (3.7%) vs. 3646 (2.7%); p = 0.039). Anemia, lower peripheral blood lymphocytes, monocytes, basophils, C3 Complement, cholesterol, and prothrombin time were also associated with COVID-19 after booster vaccination. Conclusion: People with chronic kidney disease and anemia should be included in possible future annual SARS-CoV-2 vaccination recommendations. Full article

SARS-CoV-2 infection is known to lead to severe morbidity and mortality in patients with liver cirrhosis. For this reason, vaccination of these patients against COVID-19 is widely recommended. However, data regarding immunogenicity in patients with liver cirrhosis is limited and even less is known about the kinetics of antibody response, as well as the optimal timing of booster immunization. We analyzed immunogenicity in 110 patients with liver cirrhosis after receiving two doses of the mRNA-based vaccine BNT162b2 following the standard protocol and compared these results to a control group consisting of 80 healthcare workers. One hundred and six patients with liver cirrhosis (96%) developed antibodies against SARS-CoV-2, compared to 79 (99%) in the control group (p = 0.400). Still, the median SARS-CoV-2 IgG titer was significantly lower in patients with liver cirrhosis compared to the control group (939 vs. 1905 BAU/mL, p = 0.0001). We also analyzed the strength of the antibody response in relation to the time between the second dose and antibody detection. Antibody titers remained relatively stable in the control group while showing a rapid and significant decrease in patients with liver cirrhosis. In conclusion, our data reveals a favorable initial outcome after vaccination with the COVID-19 vaccine BNT162b2 in cirrhotic patients but show a rapid deterioration of the antibody response after time, thereby giving a strong hint towards the importance of early booster immunization for this group of patients. Full article

Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3–4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections. Full article

During the early phase of the COVID-19 pandemic, several countries, including Thailand, provided two shots of CoronaVac to healthcare workers. Whereas ChAdOx1 nCoV-19 is the promising vaccine as the booster dose, the data on immunogenicity when administered after CoronaVac have been limited. The purpose of this study was to evaluate the immunogenicity of ChAdOx1 nCoV-19 as the third dose vaccine in healthcare workers who previously received two shots of CoronaVac. The blood samples were obtained before the third vaccination dose, and one month and three months after vaccination. All participants were measured for humoral immunity including anti-spike IgG and neutralizing antibody by ELISA. Twenty participants were stratified by random samples based on baseline IgG status for a cellular immunity function test at three-month post-vaccination, which included T cell and B cell functions by ELISpot. This study showed significant improvement for both humoral and cellular immunity one month after vaccination. Subgroup analysis indicated a significantly higher neutralizing antibody improvement for the population with a negative anti-spike IgG at baseline. Our study suggests that, while immunity level declines at three months post-vaccination, the level was sufficiently high to protect against SARS-CoV-2. Full article

The tolerance and safety of vaccination in pregnancy should be assessed in local populations based on ethnic differences across countries. Therefore, this study aimed to determine the tolerability of the BNT162b2 mRNA vaccination in pregnancy in a Polish population. An online questionnaire enquiring about the safety and tolerability of the BNT162b2 mRNA vaccine was distributed to pregnant and non-pregnant female healthcare professionals who had voluntarily received one or two doses of the COVID-19 vaccine in Poland. The two groups were compared simultaneously considering the COVID-19 infection status before vaccination. Compared with that noted in the control group, pregnant women in the COVID-19-free group were less likely to have fever (p = 0.002) or gastrointestinal symptoms (p = 0.009) after the second dose. In the COVID-19-exposed group, pregnant women were less likely to experience local skin reactions (p = 0.009), and myalgia (p = 0.003) after the first dose. After the second dose, the only noticeable difference was a lower incidence of myalgia (p = 0.001) in pregnant women. The tolerability of the BNT162b2 mRNA COVID-19 vaccine was similar in both the groups. No severe local, generalised, or pregnancy complications related to mother or foetus were observed. Good tolerability of the BNT162b2 mRNA COVID-19 vaccine in pregnancy in the Polish population may facilitate the decision to vaccinate pregnant women against COVID-19. Full article

An in-depth analysis of first-wave SARS-CoV-2 genome is required to identify various mutations that significantly affect viral fitness. In the present study, we performed a comprehensive in silico mutational analysis of 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), and spike (S) proteins with the aim of gaining important insights into first-wave virus mutations and their functional and structural impact on SARS-CoV-2 proteins. Our integrated analysis gathered 6000 SARS-CoV-2 sequences and identified 92 mutations in S, 37 in RdRp, and 11 in 3CLpro regions. The impact of these mutations was also investigated using various in silico approaches. Among these, 32 mutations in S, 15 in RdRp, and 3 in 3CLpro proteins were found to be deleterious in nature and could alter the structural and functional behavior of the encoded proteins. The D614G mutation in spike and the P323Lmutation in RdRp are the globally dominant variants with a high frequency. Most of the identified mutations were also found in the binding moiety of the viral proteins which determine their critical involvement in host–pathogen interactions and may represent drug targets. Furthermore, potential CD4⁺ and CD8⁺ T cell epitopes were predicted, and their overlap with genetic variations was explored. This study also highlights several hot spots in which HLA and drug selective pressure overlap. The findings of the current study may allow a better understanding of COVID-19 diagnostics, vaccines, and therapeutics. Full article

COVID-19 is still prevalent around the globe. Although some SARS-CoV-2 vaccines have been distributed to the population, the shortcomings of vaccines and the continuous emergence of SARS-CoV-2 mutant virus strains are a cause for concern. Thus, it is vital to continue to improve vaccines and vaccine delivery methods. One option is nasal vaccination, which is more convenient than injections and does not require a syringe. Additionally, stronger mucosal immunity is produced under nasal vaccination. The easy accessibility of the intranasal route is more advantageous than injection in the context of the COVID-19 pandemic. Nanoparticles have been proven to be suitable delivery vehicles and adjuvants, and different NPs have different advantages. The shortcomings of the SARS-CoV-2 vaccine may be compensated by selecting or modifying different nanoparticles. It travels along the digestive tract to the intestine, where it is presented by GALT, tissue-resident immune cells, and gastrointestinal lymph nodes. Nasal nanovaccines are easy to use, safe, multifunctional, and can be distributed quickly, demonstrating strong prospects as a vaccination method for SARS-CoV-2, SARS-CoV-2 variants, or SARS-CoV-n. Full article

Objectives: The highly transmissible COVID-19 Delta variant (DV) has contributed to a surge in cases and exacerbated the worldwide public health crisis. Several COVID-19 vaccines play a significant role in a high degree of protection against the DV. The primary purpose of this meta-analysis is to estimate the pooled effectiveness of the COVID-19 vaccines against the DV in terms of risk ratio (RR) among fully vaccinated, compared to unvaccinated populations. Methods: We carried out a systematic review, with meta-analysis of original studies focused on COVID-19 vaccines effectiveness against a DV clinical perspective among fully COVID-19 vaccinated populations, compared to placebo (unvaccinated populations), published between 1 May 2021 and 30 September 2021. Eleven studies containing the data of 17.2 million participants were identified and included in our study. Pooled estimates of COVID-19 vaccines effectiveness (i.e., risk ratio, RR) against the DV with 95% confidence intervals were assessed using random-effect models. Publication bias was assessed using Egger’s regression test and funnel plot to investigate potential sources of heterogeneity and identify any differences in study design. Results: A total population of 17.2 million (17,200,341 people) were screened for the COVID-19 vaccines’ effectiveness against the DV. We found that 61.13% of the study population were fully vaccinated with two doses of COVID-19 vaccines. The weighted pooled incidence of COVID-19 infection was more than double (20.07%) among the unvaccinated population, compared to the fully vaccinated population (8.16%). Overall, the effectiveness of the COVID-19 vaccine against the DV was 85% (RR = 0.15, 95% CI: 0.07–0.31). The effectiveness of COVID-19 vaccines varied slidably by study designs, 87% (RR = 0.13, 95% CI: 0.06–0.30) and 84% (RR = 0.16, 95% CI: 0.02, 1.64) for cohort and case-control studies, respectively. Conclusions: The effectiveness of COVID-19 vaccines were noted to offer higher protection against the DV among populations who received two vaccine doses compared with the unvaccinated population. This finding would help efforts to maximise vaccine coverage (i.e., at least 60% to 70% of the population), with two doses among vulnerable populations, in order to have herd immunity to break the chain of transmission and gain greater overall population protection more rapidly. Full article

Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccines have been recently associated with acute myocarditis, predominantly in healthy young males. Out of 231,989 vaccines administrated in our region (Marche, Italy), we report a case series of six healthy patients (four males and two females, 16.5 years old (Q1, Q3: 15, 18)) that experienced mRNA-COVID-19-vaccines side effects. All patients were hospitalized due to fever and troponins elevation following the second dose of an mRNA-based COVID-19 vaccine. Cardiovascular magnetic resonance (CMR) was performed 72–96 h after vaccination. All patients were treated with colchicine and ibuprofen. Myocarditis was prevalent in males. It was characterized by myocardial edema and late gadolinium enhancement (LGE) in the lateral wall of the left ventricle (LV). One patient showed sole right ventricular involvement, while the females presented with myopericarditis (myocarditis + pericardial effusion). All patients in our series had preserved LV ejection fraction and remained clinically stable during a relatively short inpatient hospital stay. One case presented with atrial tachycardia. At the follow-up, no significant CMR findings were documented after a three-month medical treatment. According to other recently published case series, our report suggests a possible association between acute myocarditis and myopericarditis with mRNA COVID-19 vaccination in healthy young adults and pediatric patients. Not only males are involved, while some arrhythmic manifestations are possible, such as atrial tachycardia. Conversely, we here highlight the benign nature of such complications and the absence of CMR findings after a three-month medical treatment with colchicine and ibuprofen. Full article