Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.

Increasing polio coverage with safer vaccines: a pressing need in Latin America

Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.Copyright © 2022, Sociedad Chilena de Infectologia. All rights reserved.

IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Invasive disease caused by Haemophilus influenzae: report of 14 cases one year after the start of the COVID-19 pandemic

Haemophilus influenzae (Hi) causes invasive disease (IE). Capsulated strains are distinguished, such as serotype b (Hib), and non-typeable strains (HNT). One year after the COVID-19 pandemic was declared, we observed an increase in cases.The clinical-epidemiological characteristics of children with IE due to Hi admitted to the hospital (July 2021-July 2022) are described. There were 14 cases;12 previously healthy. Isolates: Hib (n = 6), Hi serotype a (n = 2), HNT (n = 5), 1 was not typed. Median age: 8.5 months (IQR 4-21). Manifestations: meningitis (n = 5), pneumonia (n = 6), cellulitis (n = 2), arthritis (n = 1). Nine had incomplete vaccination for Hib.We observed a 2.5-fold increase in EI per Hi compared to previous years. These data suggest a resurgence of Hib due to the fall in vaccination coverage and because other Hib non-b strains are on the rise.

ThEpiCAP-Study: Intrapandemic changing Etiology of CAP in Adults Admitted to Hospitals in Thuringia/Germany in 2021

The last both authors contributed equally Purpose To design clinical and public health policies, including immunization, during the COVID-19 pandemic, it is critical to monitor not only infections due to SARS-CoV-2 but other pathogens as well. We evaluated interim results from the first year of a multi-site study of community-acquired pneumonia (CAP) and early onset hospital-acquired pneumonia (HAP) in Germany to assess the contribution of different pathogens over time. Methods This multicenter trial is being conducted from January 2021 to December 2023 at three hospitals in Thuringia: Jena University Hospital (1396 beds), SRH Hospitals Gera (951 beds) and Suhl (653 beds). Adult hospitalized patients with CAP/early onset HAP are identified by a screening algorithm which includes assessment by a study physician. Study procedures included: health data collection, urine specimens (using S. pneumoniae serotype-specific urinary antigen detection assays (UAD-1/2) and BinaxNOW), and nasopharyngeal swabs (analyzed by multiplex microbiological analysis), disease severity assessments, mortality (follow-up to day 90), pathogen spectrum, and quality of life (follow-up to day 180). Results Within the first year (2021), 760 patients (58 % male, 70 % >= 60 years) were enrolled. ICU admission occurred in 16.1 % of cases, and 9.2 % required mechanical ventilation. Pathogens were identified for 553 cases. SARS-CoV-2 was identified in 78.4 % in the first half of the year while S. pneumoniae was detected in 6 cases (2.1 %;2/6 as a co-infection (0.7 %)). Other respiratory viruses were detected in 18 of 338 cases, of which 15 (4.2 %) were coinfections with SARS-CoV-2. In the second half of 2021, SARS-CoV-2 was identified in 58.3 % of cases, however, other pathogens occurred more frequently including S. pneumoniae 10.2 % (n/N = 34/333;13/34 as a co-infection with SARS-CoV-2 (3.9 %)) and other respiratory viruses 11.4 % (n/N = 41/360;11/41 as a co-infection with SARS-CoV-2 (3.0 %)). Influenza was not detected. Conclusion While SARS-CoV-2 remained the most common pathogen among patients with CAP/early onset HAP during the study year, other pathogens reemerged during the second half of 2021. Correspondingly, co-infections with SARS-CoV-2 increased, with pneumococci as the leading pathogen.

Identification and Comparison of the Sialic Acid-Binding Domain Characteristics of Avian Coronavirus Infectious Bronchitis Virus Spike Protein.

Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and GD (GI-7), and the corresponding region of M41 (GI-1), as the minimal SABD using truncated protein histochemistry and neuraminidase assays. Both α-2,3- and α-2,6-linked sialic acids on the surfaces of CEK cells can be used as attachment receptors by IBV, leading to increased infection efficiency. However, 9-O acetylation of the sialic acid glycerol side chain inhibits IBV S1 and SABD protein binding. We further constructed recombinant strains in which the S1 gene or the SABD in the GD and SD genomes were replaced with the corresponding region from M41 by reverse genetics. Infecting chickens with these viruses revealed that the virulence and nephrotropism of rSDM41-S1, rSDM41-206, rGDM41-S1, and rGDM41-206 strains were decreased to various degrees compared to their parental strains. A positive sera cross-neutralization test showed that the serotypes were changed for the recombinant viruses. Our results provide insight into IBV infection of host cells that may aid vaccine design. IMPORTANCE To date, only α-2,3-linked sialic acid has been identified as a potential host binding receptor for IBV. Here, we show the minimum region constituting the sialic acid binding domain (SABD) and the binding characteristics of the S1 subunit of spike (S) protein of IBV strains SD (GI-19), GD (GI-7), and M41 (GI-1) to various sialic acids. The 9-O acetylation modification partially inhibits IBV from binding to sialic acid, while the virus can also bind to sialic acid molecules linked to host cells through an α-2,6 linkage, serving as another receptor determinant. Substitution of the putative SABD from strain M41 into strains SD and GD resulted in reduced virulence, nephrotropism, and a serotype switch. These findings suggest that sialic acid binding has diversified during the evolution of γ-coronaviruses, impacting the biological properties of IBV strains. Our results offer insight into the mechanisms by which IBV invades host cells.

Patients with COVID-19 versus non-COVID-19 community-acquired pneumonia

Background: SARS-CoV-2 has emerged as a novel pathogen of community-acquired pneumonia (CAP). Aims and objectives: We aimed to compare characteristics, clinical outcomes and pneumococcal identification in patients with COVID-19 vs non-COVID-19 CAP. Method(s): EGNATIA is an ongoing, prospective study of adults >=19yo hospitalized with clinical and radiographicallyconfirmed CAP in Greece. The primary objective is to estimate the proportion of CAP due to pneumococcal serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13). Pneumococcus was identified using serotype-specific urinary antigen detection assays (UAD 1/2), BinaxNow and conventional cultures. Testing for SARS-CoV-2 was performed as per national guidelines. Result(s): We compared 202 patients with COVID-19 pneumonia during Apr2020-Mar2021 vs 1033 patients with nonCOVID-19 CAP during Nov2017-Oct2020. Patients with COVID-19 were younger (median age 68.8 vs 75.8 years) and had fewer comorbidities (67.8% with >=1 underlying condition vs 79.2%) than non-COVID-19 patients. Patients with COVID-19 less frequently reported past pneumonia episodes (0.5% vs 7.7%) but were more frequently nursing home residents (13.9% vs 6%). Patients with COVID-19 had less severe pneumonia presentation (CURB 65 3-5 6.4% vs 30.5%;PSI IV-V 41.1% vs 55.2%) but required mechanical ventilation more frequently (7.4% vs 1.9%) and had a longer hospital stay (mean 17.4 vs 9.6 days). In-hospital mortality was similar between the 2 groups (7.9% in COVID-19 vs 8.9% in non-COVID-19). Pneumococcus was identified less frequently in patients with COVID-19 vs non-COVID-19 CAP (4% vs 11.1%). Conclusion(s): Significant differences were identified in patients with COVID-19 vs non-COVID-19 CAP.

Viral enteritis in cattle: To well known viruses and beyond

Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

The dynamic change of serotype distribution and antimicrobial resistance of pneumococcal isolates since PCV13 administration and COVID-19 control in Urumqi, China.

Objective: This study aims to analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from children aged 8 days to 7 years in Urumqi, China, between 2014 to 2021, during which PCV13 was introduced in the private sector's immunization program and COVID-19 control was administrated in the last 2 years. Methods: Serotypes of S. pneumoniae isolates were determined by Quellung reaction, and their susceptibility against 14 antimicrobials were tested. According to the start year of PCV13 administration (2017) and COVID-19 control (2020), the study period was divided into three stages: 2014-2015, 2018-2019, and 2020-2021. Results: A total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018-2019 from 30.7% in 2014-2015 and then decreased significantly to 18.1% in 2020-2021 (χ 2 = 7.716, P < 0.05), while the resistance rate to ceftriaxone (non-meningitis) continuously declined from 16.0% in 2014-2015 to 1.4% in 2018-2019 and 0% in 2020-2021 (Fisher = 24.463, P < 0.01). Conclusion: The common serotypes of S. pneumoniae isolated from children in Urumqi were types 19F, 19A, 23F, 6B, and 6A, which we found to have no marked change since the PCV13 introduction and the COVID-19 control However, the resistance rate to oral penicillin and ceftriaxone significantly declined in the COVID-19 control stage.

Vaccination using mutated receptor binding domains of SARS-CoV-2: Evidence for partial immune escape but not serotype formation.

Introduction: SARS-CoV-2 has developed a number of Variants of Concern (VOC) with increased infectivity and/or reduced recognition by neutralizing antibodies specific for the receptor binding domain (RBD) of the spike protein. Extended studies of other viruses have shown that strong and broad viral escape from neutralizing serum antibodies is typically associated with the formation of serotypes. Methods: To address the question of serotype formation for SARS-CoV-2 in detail, we generated recombinant RBDs of VOCs and displayed them on virus-like particles (VLPs) for vaccination and specific antibody responses. Results: As expected, mice immunized with wild type (wt) RBD generated antibodies that recognized wt RBD well but displayed reduced binding to VOC RBDs, in particular those with the E484K mutation. Unexpectedly, however, antibodies induced by the VOC vaccines typically recognized best the wt RBDs, often more than the homologous VOC RBDs used for immunization. Hence, these data do not reveal different serotypes but represent a newly observed viral evolution, suggesting a unique situation where inherent differences of RBDs are responsible for induction of neutralizing antibodies. Discussion: Therefore, besides antibody (fine) specificity, other qualities of antibodies (e.g. their affinity) determine neutralizing capability. Immune escape of SARS-CoV-2 VOCs only affects a fraction of an individual's serum antibodies. Consequently, many neutralizing serum antibodies are cross-reactive and thus protective against multiple current and future VOCs. Besides considering variant sequences for next generation vaccines, broader protection will be achieved with vaccines that induce elevated titers of high-quality antibodies.

Microbiological and clinical characteristics of Streptococcus pneumoniae serotype 3 infection and risk factors for severe outcome: A multicenter observational study.

BACKGROUND/PURPOSE: Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and microbiological characteristics of Streptococcus pneumoniae serotype 3 infection in Taiwan and identify the risk factors associated with severe clinical outcome. METHODS: A multicenter observational study was conducted to analyze serotype 3 isolates collected between 2012 and 2021. Demographics, comorbidities, and risk categories were statistically compared with clinical outcome. Antimicrobial susceptibility testing and multilocus sequence typing were performed. RESULTS: A total of 146 isolates were collected, including 12 isolates regarded as colonizers. Among 134 infected cases, 54 (40.3%) were aged 65 and older. Mortality was significantly associated with diabetes mellitus, immunosuppression, immunodeficiency, high-risk status, and older age. Susceptibility rates were high to levofloxacin (98.9%), moxifloxacin (100%), vancomycin (100%), and ceftriaxone (97.3%). 25.3% (37/146) of the isolates showed intermediate susceptibility and 0.7% (1/146) showed resistance to penicillin. ST180 was the dominant sequence type. ST13 and ST9625 isolates were less susceptible to penicillin and ceftriaxone. CONCLUSIONS: Serotype 3 infection showed a high mortality rate, especially in patients with older ages and comorbidities. Although the incidence rates decreased during the COVID-19 pandemic, serotype 3 remained as an important cause of infection after the implementation of PCV13. Developing a more effective vaccine against serotype 3 and monitoring the antimicrobial-resistant sequence types are necessary.

Role of CT Imaging for the Management of COVID-19

Aim: To evaluate the role of high-resolution Computer tomography imaging in the management of COVID-19. Study design: Prospective study Place and duration of study: Jinnah Postgraduate Medical Centre Karachi from 1st December 2021 to 31st May 2022. Methodology: One hundred patients suspected to be suffering from COVID-19 were enrolled. All patients underwent Reverse transcriptase-based polymerase chain reaction tests (RT-PCR). The patients were divided into positive or negative depending upon their test results. A high-resolution computed tomography scan was followed in every patient and the results were compared with the reverse transcriptase-based polymerase chain reaction tests findings. The sensitivity and Specificity of the CT scan test were assessed. Result(s): The mean age of the patients was 59+/-6.5 years. There were 60 (60%) male and 40 (40%) female patients. Around 58% of the patients were found as positive on PCR while 42% were negative. There 75% of the cases were positive for novel coronavirus on high-resolution computed tomography scan while only 25% were negative. Conclusion(s): Chest HRCT-scan proved to be a better and more sensitive tool for the diagnosis of novel coronavirus and can be considered as an alternative screening tool for COVID-19 confirmation. Copyright © 2022 Authors. All rights reserved.

Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5-host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Virus Neutralization Assay for Turkey Coronavirus Infection

Turkey coronavirus (TCoV) infection induces the production of protective antibodies against the sequent exposure of TCoV. Serological tests to determine TCoV-specific antibodies are critical to evaluate previous exposure to TCoV in the turkey flocks and differentiate serotypes from different isolates or strains. A specific virus neutralization assay using embryonated turkey eggs and immunofluorescent antibody assay for determining TCoV-specific neutralizing antibodies is described in this chapter. Virus neutralization titer of turkey serum from turkeys infected with TCoV is the dilution of serum that can inhibit TCoV infection in 50 % of embryonated turkey eggs. Virus neutralization assay for TCoV is useful to monitor the immune status of turkey flocks infected with TCoV for the control of the disease. Copyright © Springer Science+Business Media New York 2016.

Effects of aqueous and ethanolic extracts of costus (Saussurea lappa) against Pneumococcal TIGR4 growth

A long historical reputation for folk plant therapy has gained the trust of people. The World Health Organisation (WHO) states that 80% of the world's population relies on traditional medicinal plants. The roots of Saussurea lappa (S. lappa) were extracted by both aqueous and ethanol solutions before being investigated against Streptococcus pneumoniae ( S. pneumoniae) TIGR4. Inhibition zones were also measured. Statistical analysis demonstrated that the aqueous extract of S. lappa had an obvious bacteriostatic effect, whereas the ethanolic extract suppressed the bacterial cell densities at all experimental times. The bacterial viable counts showed that all pneumococci died at 5 hr post-inoculation when using 1% of 4 mg/ml S. lappa. On the other hand, live bacterial cells were detected until 11 hr in the absence of the plant extract. Moreover, disc diffusion methods illustrated a clear biological effect against S. pneumoniae. This highlights strong promise for S. lappa against this aggressive bacterium and might offer an alternative natural preventative candidate that possibly facilitates complications following respiratory viral infection (RVIs), such as coronaviruses.

Combination of Cefditoren and N-acetyl-l-Cysteine Shows a Synergistic Effect against Multidrug-Resistant Streptococcus pneumoniae Biofilms.

Biofilm formation by Streptococcus pneumoniae is associated with colonization of the upper respiratory tract, including the carrier state, and with chronic respiratory infections in patients suffering from chronic obstructive pulmonary disease (COPD). The use of antibiotics alone to treat recalcitrant infections caused by biofilms is insufficient in many cases, requiring novel strategies based on a combination of antibiotics with other agents, including antibodies, enzybiotics, and antioxidants. In this work, we demonstrate that the third-generation oral cephalosporin cefditoren (CDN) and the antioxidant N-acetyl-l-cysteine (NAC) are synergistic against pneumococcal biofilms. Additionally, the combination of CDN and NAC resulted in the inhibition of bacterial growth (planktonic and biofilm cells) and destruction of the biofilm biomass. This marked antimicrobial effect was also observed in terms of viability in both inhibition (prevention) and disaggregation (treatment) assays. Moreover, the use of CDN and NAC reduced bacterial adhesion to human lung epithelial cells, confirming that this strategy of combining these two compounds is effective against resistant pneumococcal strains colonizing the lung epithelium. Finally, administration of CDN and NAC in mice suffering acute pneumococcal pneumonia caused by a multidrug-resistant strain was effective in clearing the bacteria from the respiratory tract in comparison to treatment with either compound alone. Overall, these results demonstrate that the combination of oral cephalosporins and antioxidants, such as CDN and NAC, respectively, is a promising strategy against respiratory biofilms caused by S. pneumoniae. IMPORTANCE Streptococcus pneumoniae is one of the deadliest bacterial pathogens, accounting for up to 2 million deaths annually prior to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccines have decreased the burden of diseases produced by S. pneumoniae, but the rise of antibiotic-resistant strains and nonvaccine serotypes is worrisome. Pneumococcal biofilms are associated with chronic respiratory infections, and treatment is challenging, making the search for new antibiofilm therapies a priority as biofilms become resistant to traditional antibiotics. In this work, we used the combination of an antibiotic (CDN) and an antioxidant (NAC) to treat the pneumococcal biofilms of relevant clinical isolates. We demonstrated a synergy between CDN and NAC that inhibited and treated pneumococcal biofilms, impaired pneumococcal adherence to the lung epithelium, and treated pneumonia in a mouse pneumonia model. We propose the widely used cephalosporin CDN and the repurposed drug NAC as a new antibiofilm therapy against S. pneumoniae biofilms, including those formed by antibiotic-resistant clinical isolates.

Intranasal delivery of a chimpanzee adenovirus vector expressing a pre-fusion spike (BV-AdCoV-1) protects golden Syrian hamsters against SARS-CoV-2 infection.

We evaluated the immunogenicity and protective ability of a chimpanzee replication-deficient adenovirus vectored COVID-19 vaccine (BV-AdCoV-1) expressing a stabilized pre-fusion SARS-CoV-2 spike glycoprotein in golden Syrian hamsters. Intranasal administration of BV-AdCoV-1 elicited strong humoral and cellular immunity in the animals. Furthermore, vaccination prevented weight loss, reduced SARS-CoV-2 infectious virus titers in the lungs as well as lung pathology and provided protection against SARS-CoV-2 live challenge. In addition, there was no vaccine-induced enhanced disease nor immunopathological exacerbation in BV-AdCoV-1-vaccinated animals. Furthermore, the vaccine induced cross-neutralizing antibody responses against the ancestral strain and the B.1.617.2, Omicron(BA.1), Omicron(BA.2.75) and Omicron(BA.4/5) variants of concern. These results demonstrate that BV-AdCoV-1 is potentially a promising candidate vaccine to prevent SARS-CoV-2 infection, and to curtail pandemic spread in humans.

A Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an In Silico Structure-Based Drug Discovery.

Dengue fever is a mosquito-borne disease that claims the lives of millions of people around the world. A number of factors like disease's non-specific symptoms, increased viral mutation, growing antiviral drug resistance due to reduced susceptibility, unavailability of an effective vaccine for dengue, weak immunity against the virus, and many more are involved. Dengue belongs to the Flaviviridae family of viruses. The two species of the vector transmitting dengue are Aedes aegypti and Aedes albopictus, with the former one being dominant. Serotypes 2 of dengue fever are spread to the human body and cause severe illness. Recently, dengue has imposed an aggressive effect synergistically with the COVID-19 pandemic. As a result, we concentrated our efforts on finding a potential therapeutic. For this, we chose natural compounds to fight dengue fever, which is currently regarded as successful among many drug therapies. Following this, we started the in silico experiment with 922 plant extracts as lead compounds to fight serotype 2. In this study, we used SwissADME for analyzing ligand drug-likeness, pkCSM for designing an ADMET profile, Autodock vina 4.2 and Swissdock tools for molecular docking, and finally Desmond for molecular dynamics simulation. Ultimately 45 were found effective against the 2'O methyltransferase protein of serotype 2. CHEMBL376820 was found as possible therapeutic candidates for inhibiting methyltransferase protein in this thorough analysis. Nevertheless, more in vitro and in vivo research are required to substantiate their potential therapeutic efficacy.

Effect of COVID-19 Pandemic on Invasive Pneumococcal Disease in Children, Catalonia, Spain.

We analyzed the effect of COVID-19 on healthcare demand and invasive pneumococcal disease in children in Catalonia, Spain. Compared with 2018-2019, we noted large reductions in healthcare activities and incidence of invasive pneumococcal disease in 2020. These changes likely resulted from nonpharmaceutical measures implemented during the COVID-19 pandemic.