bluuebunny/crossref_metadata_2025 huggingface dataset:
Coagulopathy of Dengue and COVID-19: Clinical Considerations
Authors: Islam Amin , Cockcroft Christopher , Elshazly Shereen , Ahmed Javeed , Joyce Kevin , Mahfuz Huque , Islam Tasbirul , Rashid Harunor , Laher Ismail
Published: August 2022

Thrombocytopenia and platelet dysfunction commonly occur in both dengue and COVID-19 and are related to clinical outcomes. Coagulation and fibrinolytic pathways are activated during an acute dengue infection, and endothelial dysfunction is observed in severe dengue. On the other hand, COVID-19 is characterised by a high prevalence of thrombotic complications, where bleeding is rare and occurs only in advanced stages of critical illness; here thrombin is the central mediator that activates endothelial cells, and elicits a pro-inflammatory reaction followed by platelet aggregation. Serological cross-reactivity may occur between COVID-19 and dengue infection. An important management aspect of COVID-19-induced immunothrombosis associated with thrombocytopenia is anticoagulation with or without aspirin. In contrast, the use of aspirin, nonsteroidal anti-inflammatory drugs and anticoagulants is contraindicated in dengue. Mild to moderate dengue infections are treated with supportive therapy and paracetamol for fever. Severe infection such as dengue haemorrhagic fever and dengue shock syndrome often require escalation to higher levels of support in a critical care facility. The role of therapeutic platelet transfusion is equivocal and should not be routinely used in patients with dengue with thrombocytopaenia and mild bleeding. The use of prophylactic platelet transfusion in dengue fever has strained financial and healthcare systems in endemic areas, together with risks of transfusion-transmitted infections in low- and middle-income countries. There is a clear research gap in the management of dengue with significant bleeding.
Factors Influencing Second and Third Dose Observance during Seasonal Malaria Chemoprevention (SMC): A Quantitative Study in Burkina Faso, Mali and Niger
Authors: Somé Anyirékun Fabrice , Zongo Issaka , Sagara Issaka , Ibrahim Alkassoum , Ahanhanzo Césaire Damien , Agbanouvi-agassi Edoh Eddie , Sayi Dona Alain , Toe Lea Pare , Kabré Zachari , Nikiéma Frédéric , Bazié Thomas , Ouédraogo Sylvin , Sombié Issiaka , Dicko Alassane , Adehossi Eric , Ouédraogo Jean-Bosco , Dabiré Kounbobr Roch
Published: August 2022

This study aims to evaluate the factors influencing the adherence to the 2nd and 3rd doses of Amodiaquine (AQ) during seasonal malaria chemoprevention (SMC) in Burkina Faso, Mali, and Niger. Overall, 3132 people were interviewed during surveys between 2019 and 2020 in 15 health districts. In Burkina Faso, Mali, and Niger, the proportions of non-adherence were 4.15%, 5.60%, and 13.30%, respectively, for the 2nd dose and 3.98%, 5.60% and 14.39% for the 3rd dose. The main cause of non-adherence to the 2nd and 3rd doses was other illnesses in 28.5% and 29.78%, respectively, in Burkina Faso, 5.35% and 5.35% in Mali and 1.6% and 0.75% in Niger. It was followed by vomiting in 12.24% and 10.63% for Burkina and 2.45% and 3.78% in Niger. The last cause was refusal in 6.12% and 4.25% in Burkina, 33.9% and 15.25% in Mali and 0.8% and 1.51% in Niger. Non-adherence of doses related to parents was primarily due to their absence in 28.5% and 27.65% in Burkina, 16.07% and 16.07% in Mali and 7.37% and 6.06% in Niger. Traveling was the second cause related to parents in 12.24% and 12.76% in Burkina, 19.64% and 19.64% in Mali and 0.81% and 0.75% in Niger. Non-adherence related to community distributors was mainly due to missing the doses in 4.08% and 4.25% in Burkina, 23.21% and 23.21% in Mali, 77.04% and 76.51% in Niger. Our study reported very small proportions of non-adherence to 2nd and 3rd doses of SMC and identified the main causes of non-adherence. These findings will provide helpful information for policymakers and public health authorities to improve adherence to SMC
Laparoscopic Living Donor Nephrectomy—Single-Center Initial Experience
Authors: Małkiewicz Bartosz , Kamińska Dorota , Kobylański Maximilian , Łątkowska Małgorzata , Handzlik Wojciech , Dębiński Paweł , Krajewski Wojciech , Mazanowska Oktawia , Poznański Paweł , Banasik Mirosław , Patrzałek Dariusz , Janczak Dariusz , Krajewska Magdalena , Zdrojowy Romuald , Szydełko Tomasz
Published: August 2022

(1) Background: Donor nephrectomy for living donor kidney transplantation using minimally invasive techniques is a safe procedure that has been used for more than 20 years with excellent results. The total laparoscopic approach offers decreased postoperative pain, less incisional morbidity, and a shorter recovery time. (2) Methods: We present the results of a series of 43 laparoscopic donor nephrectomies performed in a single center. The procedures were performed in a systematic approach with transperitoneal access using four ports. The main renal artery and vein were ligated using a linear stapler fixed with an alternate triple row of titanium staples. The specimen was extracted in an endoscopic bag through an additional incision. (3) Results: All procedures were performed laparoscopically without conversion to open surgery. The average warm ischemia time was 4.73 min. In all recipients, immediate kidney allograft function was observed. (4) Conclusions: Total laparoscopic living donor nephrectomy is a safe procedure. It was performed successfully in all cases with a short surgical time, low morbidity, and 0% mortality.
Establishment of Recombinant Trisegmented Mopeia Virus Expressing Two Reporter Genes for Screening of Mammarenavirus Inhibitors
Authors: Oestereich Lisa , Wurr Stephanie , Becker-Ziaja Beate , Bockholt Sabrina , Pahlmann Meike , Cadar Daniel , Kümmerer Beate M. , Günther Stephan , Kerber Romy
Published: August 2022

Highly pathogenic Arenaviruses, like the Lassa Virus (LASV), pose a serious public health threat in affected countries. Research and development of vaccines and therapeutics are urgently needed but hampered by the necessity to handle these pathogens under biosafety level 4 conditions. These containment restrictions make large-scale screens of antiviral compounds difficult. Therefore, the Mopeia virus (MOPV), closely related to LASV, is often used as an apathogenic surrogate virus. We established for the first time trisegmented MOPVs (r3MOPV) with duplicated S segments, in which one of the viral genes was replaced by the reporter genes ZsGreen (ZsG) or Renilla Luciferase (Rluc), respectively. In vitro characterization of the two trisegmented viruses (r3MOPV ZsG/Rluc and r3MOPV Rluc/ZsG), showed comparable growth behavior to the wild type virus and the expression of the reporter genes correlated well with viral titer. We used the reporter viruses in a proof-of-principle in vitro study to evaluate the antiviral activity of two well characterized drugs. IC50 values obtained by Rluc measurement were similar to those obtained by virus titers. ZsG expression was also suitable to evaluate antiviral effects. The trisegmented MOPVs described here provide a versatile and valuable basis for rapid high throughput screening of broadly reactive antiviral compounds against arenaviruses under BSL-2 conditions.
Epstein–Barr Virus and Human Herpesvirus-6 Reactivation in Acute COVID-19 Patients
Authors: Brooks Bailey , Tancredi Christina , Song Yufeng , Mogus Alemu Tekewe , Huang Meei-Li W. , Zhu Haiying , Phan Tuan L. , Zhu Harrison , Kadl Alexandra , Woodfolk Judith , Jerome Keith R. , Zeichner Steven L.
Published: August 2022

Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein–Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.
Comparative Evaluation of the Foot-and-Mouth Disease Virus Permissive LF-BK αVβ6 Cell Line for Senecavirus A Research
Authors: Mason Jessica , Primavera Victoria , Martignette Lauren , Clark Benjamin , Barrera Jose , Simmons Janine , Hurtle William , Neilan John G. , Puckette Michael
Published: August 2022

Senecavirus A (SVA) is a member of the family Picornaviridae and enzootic in domestic swine. SVA can induce vesicular lesions that are clinically indistinguishable from Foot-and-mouth disease, a major cause of global trade barriers and agricultural productivity losses worldwide. The LF-BK αVβ6 cell line is a porcine-derived cell line transformed to stably express an αVβ6 bovine integrin and primarily used for enhanced propagation of Foot-and-mouth disease virus (FMDV). Due to the high biosecurity requirements for working with FMDV, SVA has been considered as a surrogate virus to test and evaluate new technologies and countermeasures. Herein we conducted a series of comparative evaluation in vitro studies between SVA and FMDV using the LF-BK αVβ6 cell line. These include utilization of LF-BK αVβ6 cells for field virus isolation, production of high virus titers, and evaluating serological reactivity and virus susceptibility to porcine type I interferons. These four methodologies utilizing LF-BK αVβ6 cells were applicable to research with SVA and results support the current use of SVA as a surrogate for FMDV.
Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in Tyrol, Austria: Updated Analysis Involving 22,607 Blood Donors Covering the Period October 2021 to April 2022
Authors: Seekircher Lisa , Siller Anita , Astl Manfred , Tschiderer Lena , Wachter Gregor A. , Pfeifer Bernhard , Huber Andreas , Gaber Manfred , Schennach Harald , Willeit Peter
Published: August 2022

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Median age of participants was 45.3 years (IQR: 30.9–55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8–86.0%) to 95.8% (94.9–96.4%), and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271–296) to 1437 (1360–1518) BAU/mL. The percentages of participants in categories with undetectable levels and detectable levels at <500, 500–<1000, 1000–<2000, 2000–<3000, and ≥3000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2–19.9; p-value < 0.001). In conclusion, anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.
SARS-CoV-2 Genetic Diversity and Lineage Dynamics in Egypt during the First 18 Months of the Pandemic
Authors: Roshdy Wael H. , Khalifa Mohamed K. , San James Emmanuel , Tegally Houriiyah , Wilkinson Eduan , Showky Shymaa , Martin Darren Patrick , Moir Monika , Naguib Amel , Elguindy Nancy , Gomaa Mokhtar R. , Fahim Manal , Abu Elsood Hanaa , Mohsen Amira , Galal Ramy , Hassany Mohamed , Lessells Richard J. , Al-Karmalawy Ahmed A. , EL-Shesheny Rabeh , Kandeil Ahmed M. , Ali Mohamed A. , de Oliveira Tulio
Published: August 2022

COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages.
Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors
Authors: Singh Parmit , Li Wen , Bedwell Gregory , Fadel Hind , Poeschla Eric , Engelman Alan
Published: August 2022

Allosteric integrase (IN) inhibitors (ALLINIs), which are promising preclinical compounds that engage the lens epithelium-derived growth factor (LEDGF)/p75 binding site on IN, can inhibit different aspects of human immunodeficiency virus 1 (HIV-1) replication. During the late phase of replication, ALLINIs induce aberrant IN hyper-multimerization, the consequences of which disrupt IN binding to genomic RNA and virus particle morphogenesis. During the early phase of infection, ALLINIs can suppress HIV-1 integration into host genes, which is also observed in LEDGF/p75-depelted cells. Despite this similarity, the roles of LEDGF/p75 and its paralog hepatoma-derived growth factor like 2 (HDGFL2) in ALLINI-mediated integration retargeting are untested. Herein, we mapped integration sites in cells knocked out for LEDGF/p75, HDGFL2, or both factors, which revealed that these two proteins in large part account for ALLINI-mediated integration retargeting during the early phase of infection. We also determined that ALLINI-treated viruses are defective during the subsequent round of infection for integration into genes associated with speckle-associated domains, which are naturally highly targeted for HIV-1 integration. Class II IN mutant viruses with alterations distal from the LEDGF/p75 binding site moreover shared this integration retargeting phenotype. Altogether, our findings help to inform the molecular bases and consequences of ALLINI action.
SARS-CoV-2 Is Persistent in Placenta and Causes Macroscopic, Histopathological, and Ultrastructural Changes
Authors: Parcial André , Salomão Natália , Portari Elyzabeth , Arruda Laíza , de Carvalho Jorge , de Matos Guedes Herbert , Conde Thayana , Moreira Maria , Batista Marcelo , Paes Marciano , Rabelo Kíssila , Gomes-Silva Adriano
Published: August 2022

SARS-CoV-2 is a virus that belongs to the Betacoronavirus genus of the Coronaviridae family. Other coronaviruses, such as SARS-CoV and MERS-CoV, were associated with complications in pregnant women. Therefore, this study aimed to report the clinical history of five pregnant women infected with SARS-CoV-2 (four symptomatic and one asymptomatic who gave birth to a stillborn child) during the COVID-19 pandemic. They gave birth between August 2020 to January 2021, a period in which there was still no vaccination for COVID-19 in Brazil. In addition, their placental alterations were later investigated, focusing on macroscopic, histopathological, and ultrastructural aspects compared to a prepandemic sample. Three of five placentas presented SARS-CoV-2 RNA detected by RT-PCRq at least two to twenty weeks after primary pregnancy infection symptoms, and SARS-CoV-2 spike protein was detected in all placentas by immunoperoxidase assay. The macroscopic evaluation of the placentas presented congested vascular trunks, massive deposition of fibrin, areas of infarctions, and calcifications. Histopathological analysis showed fibrin deposition, inflammatory infiltrate, necrosis, and blood vessel thrombosis. Ultrastructural aspects of the infected placentas showed a similar pattern of alterations between the samples, with predominant characteristics of apoptosis and detection of virus-like particles. These findings contribute to a better understanding of the consequences of SARS-CoV-2 infection in placental tissue, vertical transmission.
HBx 128–133 Deletion Affecting HBV Mother-to-Child Transmission Weakens HBV Replication via Reducing HBx Level and CP/ENII Transcriptional Activity
Authors: Song Yarong , Lu Ying , Li Yi , Liu Minmin , Zhuang Hui , Li Jie , Wang Jie
Published: August 2022

Some infants born to hepatitis B surface antigen (HBsAg)-positive mothers, especially born to hepatitis B e antigen (HBeAg)-positive mothers, can still be infected with hepatitis B virus (HBV) through mother-to-child transmission (MTCT) of HBV and develop chronic HBV infection. At present, the virological factors affecting HBV MTCT are still unclear. In this study, we found that the mutation rates of amino acids in the HBV X region were high, and there were obvious differences between the immunoprophylaxis success group and the immunoprophylaxis failure group of HBeAg-positive mothers. Specifically, the mutation rate of HBx 128–133 deletion (x128–133del) or corresponding nucleotide 1755–1772 deletion (nt1755–1772del) in the immunoprophylaxis success group was significantly higher than that in the immunoprophylaxis failure group. Furthermore, we found that x128–133del could weaken HBV replication by reducing the level of the HBx protein due to the increased proteasome-dependent degradation of HBx protein, and the transcriptional activity of HBV core promoter (CP)/enhancer II (ENII) due to the attenuated binding capacity of hepatocyte nuclear factor 4α (HNF4α) to HBV CP/ENII. This study suggests that x128–133del may contribute to immunoprophylaxis success, which may be helpful in clarifying the virological mechanism affecting HBV MTCT and formulating an optimal immunization strategy for children born to HBeAg-positive mothers.
Epidemiological Features of the Highly Pathogenic Avian Influenza Virus H5N1 in a Densely Populated Area of Lombardy (Italy) during the Epidemic Season 2021–2022
Authors: Bellini Silvia , Scaburri Alessandra , Colella Erika Molica , Cerioli Monica Pierangela , Cappa Veronica , Calò Stefania , Tironi Marco , Chiari Mario , Nassuato Claudia , Moreno Ana , Farioli Marco , Merialdi Giuseppe
Published: August 2022

In the last two years, there have been three major epidemic seasons in the territory of the European Union and the HPAI epizootic in 2021–2022 is the most severe in recent history. In Italy, the disease was introduced to dense poultry areas with serious economic consequences for the entire sector. In Lombardy, the analysis of the risk factors was carried out, also taking into account the density of domestic birds. In the most affected areas, 66.7% of the outbreaks occurred in the areas with the highest poultry density and the likelihood of an outbreak occurring increased with an increase in the density of birds per km2. In cells 10 × 10 km with a density greater than 10,000 birds/km2, the probability of outbreak occurrence was over 66.7%. The provinces involved in the last epidemic were the same involved in previous epidemics and, given the risk factors present in the area, it is plausible that the risk remains high also for future epidemic seasons. Therefore, to avoid the repetition of similar events, certain control measures shall be strengthened and vaccination considered as a complementary tool for the control of HPAI virus in risk areas.
Characterization of Transcriptional Responses to Genomovirus Infection of the White Mold Fungus, Sclerotinia sclerotiorum
Authors: Pedersen Connor J. , Marzano Shin-Yi Lee
Published: August 2022

Soybean leaf-associated gemygorvirus-1 (SlaGemV−1) is a CRESS-DNA virus classified in the family Genomoviridae, which causes hypovirulence and abolishes sclerotia formation in infected fungal pathogens under the family Sclerotiniaceae. To investigate the mechanisms involved in the induction of hypovirulence, RNA-Seq was compared between virus-free and SlaGemV−1-infected Sclerotinia sclerotiorum strain DK3. Overall, 4639 genes were differentially expressed, with 50.5% up regulated and 49.5% down regulated genes. GO enrichments suggest changes in integral membrane components and transmission electron microscopy images reveal virus-like particles localized near the inner cell membrane. Differential gene expression analysis focused on genes responsible for cell cycle and DNA replication and repair pathways, ubiquitin proteolysis, gene silencing, methylation, pathogenesis-related, sclerotial development, carbohydrate metabolism, and oxalic acid biosynthesis. Carbohydrate metabolism showed the most changes, with two glycoside hydrolase genes being the most down regulated by −2396.1- and −648.6-fold. Genes relating to pathogenesis showed consistent down regulation with the greatest being SsNep1, SsSSVP1, and Endo2 showing, −4555-, −14.7-, and −12.3-fold changes. The cell cycle and DNA replication/repair pathways were almost entirely up regulated including a putative cyclin and separase being up regulated 8.3- and 5.2-fold. The oxalate decarboxylase genes necessary for oxalic acid catabolism and oxalic acid precursor biosynthesis genes and its metabolism show down regulations of −17.2- and −12.1-fold changes. Sclerotial formation genes also appear differentially regulated including a melanin biosynthesis gene Pks1 and a sclerotia formation gene Sl2 with fold changes of 3.8 and −2.9.
Monkeypox, a Literature Review: What Is New and Where Does This concerning Virus Come From?
Authors: Tiecco Giorgio , Degli Antoni Melania , Storti Samuele , Tomasoni Lina Rachele , Castelli Francesco , Quiros-Roldan Eugenia
Published: August 2022

Among the Poxviridae family, orthopoxvirus is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus (VARV) (the causative agent of smallpox), monkeypox virus (MPXV), cowpox virus (CPXV), and vaccinia virus (VACV). These orthopoxviruses still remain a public health concern as VACV or CPXV still cause emerging endemic threads, especially in developing countries. MPXV is able to cause sporadic human outbreaks of a smallpox-like zoonotic disease and, in May 2022, hundreds of cases related to MPXV have been reported from more than 30 countries around the globe. At the end of July, monkeypox (MPX) outbreak was even declared a global health emergency by the World Health Organization (WHO). Many aspects remain unclear regarding this outbreak and a deep understanding of orthopoxvirus might have crucial and evident implications. During the era in which people under 45 years old are not protected against VACV, the potential use of orthopoxviruses as a biological weapon raises global concern considering the rapid spreading of the current MPX outbreak in vulnerable populations. Hence, we review the most recent evidence about phylogenesis, pathogenesis, prevention, and treatment for this concerning disease.
Are Viral Infections Key Inducers of Autoimmune Diseases? Focus on Epstein–Barr Virus
Authors: Takei Masami , Kitamura Noboru , Nagasawa Yosuke , Tsuzuki Hiroshi , Iwata Mitsuhiro , Nagatsuka Yasuko , Nakamura Hideki , Imai Kenichi , Fujiwara Shigeyoshi
Published: August 2022

It is generally accepted that certain viral infections can trigger the development of autoimmune diseases. However, the exact mechanisms by which these viruses induce autoimmunity are still not understood. In this review, we first describe hypothetical mechanisms by which viruses induce some representative autoimmune diseases. Then, we focus on Epstein–Barr virus (EBV) and discuss its role in the pathogenesis of rheumatoid arthritis (RA). The discussion is mainly based on our own previous findings that (A) EBV DNA and its products EBV-encoded small RNA (EBER) and latent membrane protein 1 (LMP1) are present in the synovial lesions of RA, (B) mRNA expression of the signaling lymphocytic activation molecule-associated protein (SAP)/SH2D1A gene that plays a critical role in cellular immune responses to EBV is reduced in the peripheral T cells of patients with RA, and (C) EBV infection of mice reconstituted with human immune system components (humanized mice) induced erosive arthritis that is pathologically similar to RA. Additionally, environmental factors may contribute to EBV reactivation as follows: Porphyromonas gingivalis peptidylarginine deiminase (PAD), an enzyme required for citrullination, engenders antigens leading to the production of citrullinated peptides both in the gingiva and synovium. Anti-citrullinated peptides autoantibody is an important marker for diagnosis and disease activity of RA. These findings, as well as various results obtained by other researchers, strongly suggest that EBV is directly involved in the pathogenesis of RA, a typical autoimmune disease.
Double and Triple Combinations of Broadly Neutralizing Antibodies Provide Efficient Neutralization of All HIV-1 Strains from the Global Panel
Authors: Kochina Evgeniya A. , Urusov Felix A. , Kruglov Artem A. , Glazkova Dina V. , Shipulin German A. , Bogoslovskaya Elena V.
Published: August 2022

The use of broadly neutralizing antibodies (bNAbs) is a promising approach to HIV-1 treatment. In this work, we evaluate the neutralizing activity of the following HIV-1 bNAbs: VCR07-523, N6, PGDM1400, CAP256-VRC26.25, 10-1074, PGT128, 10E8, and DH511.11P, which are directed to different Env surface epitopes. We used the global panel of HIV-1 pseudoviruses to analyze the bNAbs’ potency and chose the most potent ones. To achieve maximum neutralization breadth and minimum IC50 concentration, the most effective antibodies were tested in double and triple combinations. Among the doubles, the combinations of N6+PGDM1400 and N6+PGT128 with IC50 ≤ 0.3 µg/mL proved to be the most effective. The most effective triple combination was N6+PGDM1400+PGT128. Our data demonstrate that this combination neutralizes pseudoviruses of the global HIV-1 panel with IC50 ≤ 0.11 µg/mL and IC80 ≤ 0.25 µg/mL.
Regional Association between Mean Air Temperature and Case Numbers of Multiple SARS-CoV-2 Lineages throughout the Pandemic
Authors: Mattiuzzi Camilla , Henry Brandon M. , Lippi Giuseppe
Published: August 2022

The association between mean air temperature and new SARS-CoV-2 case numbers throughout the ongoing coronavirus disease 2019 (COVID-19) pandemic was investigated to identify whether diverse SARS-CoV-2 lineages may exhibit diverse environmental behaviors. The number of new COVID-19 daily cases in the province of Verona was obtained from the Veneto Regional Healthcare Service, whilst the mean daily air temperature during the same period was retrieved from the Regional Agency for Ambient Prevention and Protection of Veneto. A significant inverse correlation was found between new COVID-19 daily cases and mean air temperature in Verona up to Omicron BA.1/BA.2 predominance (correlation coefficients between −0.79 and −0.41). The correlation then became positive when the Omicron BA.4/BA.5 lineages were prevalent (r = 0.32). When the median value (and interquartile range; IQR) of new COVID-19 daily cases recorded during the warmer period of the year in Verona (June–July) was compared across the three years of the pandemic, a gradual increase could be seen over time, from 1 (IQR, 0–2) in 2020, to 22 (IQR, 11–113) in 2021, up to 890 (IQR, 343–1345) in 2022. These results suggest that measures for preventing SARS-CoV-2 infection should not be completely abandoned during the warmer periods of the year.
The Genetic Characterization of the First Detected Bat Coronaviruses in Poland Revealed SARS-Related Types and Alphacoronaviruses
Authors: Orłowska Anna , Smreczak Marcin , Thor Katarzyna , Niedbalska Magda , Pawelec Dominika , Trębas Paweł , Rola Jerzy
Published: August 2022

Bats are a major global reservoir of alphacoronaviruses (alphaCoVs) and betaCoVs. Attempts to discover the causative agents of COVID-19 and SARS have revealed horseshoe bats (Rhinolophidae) to be the most probable source of the virus. We report the first detection of bat coronaviruses (BtCoVs) in insectivorous bats in Poland and highlight SARS-related coronaviruses found in Rhinolophidae bats. The study included 503 (397 oral swabs and 106 fecal) samples collected from 20 bat species. Genetically diverse BtCoVs (n = 20) of the Alpha- and Betacoronavirus genera were found in fecal samples of two bat species. SARS-related CoVs were in 18 out of 58 lesser horseshoe bat (Rhinolophus hipposideros) samples (31%, 95% CI 20.6–43.8), and alphaCoVs were in 2 out of 55 Daubenton’s bat (Myotis daubentonii) samples (3.6%, 95% CI 0.6–12.3). The overall BtCoV prevalence was 4.0% (95% CI 2.6–6.1). High identity was determined for BtCoVs isolated from European M. daubentonii and R. hipposideros bats. The detection of SARS-related and alphaCoVs in Polish bats with high phylogenetic relatedness to reference BtCoVs isolated in different European countries but from the same species confirms their high host restriction. Our data elucidate the molecular epidemiology, prevalence, and geographic distribution of coronaviruses and particularly SARS-related types in the bat population.
IFIT3 and IFIT5 Play Potential Roles in Innate Immune Response of Porcine Pulmonary Microvascular Endothelial Cells to Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus
Authors: Wu Yanmei , Song Xiaoxiao , Cui Defeng , Zhang Tao
Published: August 2022

Our previous study has demonstrated that porcine pulmonary microvascular endothelial cells (MVECs) are susceptible to highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). The innate immune response of MVECs infected with HP-PRRSV would play important roles in controlling virus proliferation, resisting cellular injury, and preventing the virus from spreading to other tissues and organs. Type I interferon is one of the most effective antiviral cytokines in the innate immune response, and interferon-induced proteins with tetratricopeptide repeats (IFITs) are members of interferon-stimulated genes induced by viruses and other pathogens, which are crucial in inhibiting virus proliferation and regulating the innate immune response. However, their effects on HP-PRRSV-induced innate immunity in porcine pulmonary MVECs remain unclear. Here, the roles of IFITs in porcine pulmonary MVECs infected with the HP-PRRSV HN strain were investigated, and the effects of astragalus polysaccharides (APS), a widely used traditional Chinese herbal ingredient with the immunopotentiating effect, on them were studied. The results showed that more autophagosomes were observed in HP-PRRSV-infected MVECs, and the expression of IFN-α, IFIT3, and IFIT5 decreased or increased at different time points after infection. When silencing the genes of IFIT3 or IFIT5, the HP-PRRSV replication in MVECs was significantly increased. The expression of IFIT3 and IFIT5 could be upregulated by APS, whose inhibitory effects on the HP-PRRSV replication significantly declined when the genes of IFIT3 or IFIT5 were silenced. The results suggest that IFIT3 and IFIT5 play an important role in inhibiting the HP-PRRSV replication in porcine pulmonary MVECs, and APS suppress the multiplication of HP-PRRSV by upregulating their expression.
Enhanced Immunogenicity of an Influenza Ectodomain Matrix-2 Protein Virus-like Particle (M2e VLP) Using Polymeric Microparticles for Vaccine Delivery
Authors: Gomes Keegan Braz , Menon Ipshita , Bagwe Priyal , Bajaj Lotika , Kang Sang-Moo , D’Souza Martin J.
Published: August 2022

In this study, we demonstrate how encapsulating a conserved influenza ectodomain matrix-2 protein virus-like particle (M2e5x VLP) into a pre-crosslinked bovine serum albumin (BSA) polymeric matrix enhances in vitro antigen immunogenicity and in vivo efficacy. The spray-dried M2e5x VLP-loaded BSA microparticles (MPs) showed enhanced stimulation of antigen presenting cells (APCs), as confirmed through nitrite production and increased antigen–cell interactions seen in real time using live-cell imaging. Next, to further boost the immunogenicity of M2e5x VLP microparticles, M2e5x MPs were combined with Alhydrogel® and monophosphoryl lipid-A (MPL-A®) adjuvant microparticles. M2e5x VLP MPs and the combination VLP M2e5x VLP + Alhydrogel® + MPL-A® MPs elicited a significant increase in the expression of antigen-presenting molecules in dendritic cells compared to M2e5x VLP alone. Lastly, for preliminary evaluation of in vivo efficacy, the vaccine was administered in mice through the skin using an ablative laser. The M2e5x VLP + Alhydrogel® + MPL-A® MPs were shown to induce high levels of M2e-specific IgG antibodies. Further, a challenge with live influenza revealed heightened T-cell stimulation in immune organs of mice immunized with M2e5x VLP + Alhydrogel® + MPL-A® MPs. Hence, we utilized the advantages of both VLP and polymeric delivery platforms to enhance antigen immunogenicity and adaptive immunity in vivo.
Hypovirulence of Colletotrichum gloesporioides Associated with dsRNA Mycovirus Isolated from a Mango Orchard in Thailand
Authors: Suharto Aditya R. , Jirakkakul Jiraporn , Eusebio-Cope Ana , Salaipeth Lakha
Published: August 2022

The pathogenic fungus Colletotrichum gloeosporioides causes anthracnose disease, which is an important fungal disease affecting the production of numerous crops around the world. The presence of mycoviruses, however, may have an impact on the pathogenicity of the fungal host. Here, we describe a double-stranded RNA (dsRNA) mycovirus, which was isolated from a field strain of C. gloeosporioides, Ssa-44.1. The 2939 bp genome sequence comprises two open reading frames (ORFs) that encode for a putative protein and RNA-dependent RNA polymerase (RdRp). The Ssa-44.1 mycovirus is a member of the unclassified mycovirus family named Colletotrichum gloeosporioides RNA virus 1 strain Ssa-44.1 (CgRV1-Ssa-44.1), which has a phylogenetic similarity to Colletotrichum gleosporioides RNA virus 1 (CgRV1), which was isolated from citrus leaves in China. In C. gloeosporioides, CgRV1-Ssa-44.1 was shown to be linked to hypovirulence. CgRV1-Ssa-44.1 has a low spore transfer efficiency but can successfully spread horizontally to isogenic virus-free isolates. Furthermore, CgRV1-Ssa-44.1 had a strong biological control impact on C. gloeosporioides on mango plants. This study is the first to describe a hypovirulence-associated mycovirus infecting C. gloeosporioides, which has the potential to assist with anthracnose disease biological management.
Third Early “Booster” Dose Strategy in France of bnt162b2 SARS-CoV-2 Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients Enhances Neutralizing Antibody Responses
Authors: Ahmed-Belkacem Abdelhakim , Redjoul Rabah , Brillet Rozenn , Ahnou Nazim , Leclerc Mathieu , López-Molina Dennis Salomón , Soulier Alexandre , Gourgeon Aurélie , Rodriguez Christophe , Maury Sébastien , Pawlotsky Jean-Michel , Fourati Slim
Published: August 2022

Immunocompromised individuals generally fail to mount efficacious immune humoral responses following vaccination. The emergence of SARS-CoV-2 variants of concern has raised the question as to whether levels of anti-spike protein antibodies achieved after two or three doses of the vaccine efficiently protect against breakthrough infection in the context of immune suppression. We used a fluorescence-based neutralization assay to test the sensitivity of SARS-CoV-2 variants (ancestral variant, Beta, Delta, and Omicron BA.1) to the neutralizing response induced by vaccination in highly immunosuppressed allogeneic HSCT recipients, tested after two and three doses of the BNT162b2 vaccine. We show that neutralizing antibody responses to the Beta and Delta variants in most immunocompromised HSCT recipients increased after three vaccine doses up to values similar to those observed in twice-vaccinated healthy adults and were significantly lower against Omicron BA.1. Overall, neutralization titers correlated with the amount of anti-S-RBD antibodies measured by means of enzyme immunoassay, indicating that commercially available assays can be used to quantify the anti-S-RBD antibody response as a reliable surrogate marker of humoral immune protection in both immunocompetent and immunocompromised individuals. Our findings support the recommendation of additional early vaccine doses as a booster of humoral neutralizing activity against emerging variants, in HSCT immunocompromised patients. In the context of Omicron circulation, it further emphasizes the need for reinforcement of preventive measures including the administration of monoclonal antibodies in this high-risk population.
Evaluation of Saliva as a Matrix for RT-PCR Analysis and Two Rapid Antigen Tests for the Detection of SARS-CoV-2
Authors: De Meyer Julie , Goris Hanne , Mortelé Olivier , Spiessens An , Hans Guy , Jansens Hilde , Goossens Herman , Matheeussen Veerle , Vandamme Sarah
Published: August 2022

The use of saliva for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sparks debate due to presumed lower sensitivity and lack of standardization. Our aim was to evaluate the performance characteristics of (i) saliva collected by the ORAcollectTM device as a matrix for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR), and (ii) 2 saliva rapid antigen tests (AgRDT). From 342 ambulatory individuals, both a nasopharyngeal swab and saliva sample via ORAcollectTM were obtained for a SARS-CoV-2 RT-PCR test. Furthermore, 54 and 123 additionally performed the V-ChekTM or WhistlingTM saliva AgRDT. In total, 35% of individuals screened positive for SARS-CoV-2 via nasopharyngeal swab. Saliva, as a matrix for the RT-PCR, had a specificity of 96.5% and a negative predictive value (NPV) of 91.3%. Interestingly, 6 out of 8 patients thought to be false positive in saliva re-tested positive by nasopharyngeal sampling after 2 to 9 days. Both V-ChekTM and WhistlingTM AgRDT had a lack of sensitivity, resulting in an NPV of 66.9 and 67.3%, respectively. Saliva proved to be a sensitive and specific matrix for SARS-CoV-2 detection by the RT-PCR. In this setting, saliva might have an earlier window of detection than the nasopharyngeal swab. By contrast, both AgRDT showed an unacceptably low sensitivity and NPV.
The Cost-Effectiveness of Vaccination of Older Adults with an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Other Available Quadrivalent Vaccines in Germany
Authors: Kohli Michele A. , Maschio Michael , Cartier Shannon , Mould-Quevedo Joaquin , Fricke Frank-Ulrich
Published: August 2022

Enhanced quadrivalent influenza vaccines that include an adjuvant (aQIV) or a high dose of antigen (QIV-HD), which stimulate a stronger immune response in older adults than the standard vaccine (QIVe), are now approved. The objective of this research is to compare available vaccines and determine the cost-effectiveness of immunizing persons aged 65 years and above with aQIV compared to QIVe and QIV-HD in Germany. A compartmental transmission model calibrated to outpatient visits for influenza in Germany was used to predict the number of medically attended infections using the three vaccines. The rates of hospitalizations, deaths, and other economic consequences were estimated with a decision tree using German data where available. Based on meta-analysis, the rVE of −2.5% to 8.9% for aQIV versus QIV-HD, the vaccines are similar clinically, but aQIV is cost saving compared to QIV-HD (unit cost of EUR 40.55). All results were most sensitive to changes in vaccine effectiveness. aQIV may be cost-effective compared to QIVe depending on the willingness to pay for additional benefits in Germany. As aQIV and QIV-HD are similar in terms of effectiveness, aQIV is cost saving compared to QIV-HD at current unit prices.
Organisational and Structural Drivers of Childhood Immunisation in the European Region: A Systematic Review
Authors: Valdecantos Ronan Lemwel , Palladino Raffaele , Lo Vecchio Andrea , Montella Emma , Triassi Maria , Nardone Antonio
Published: August 2022

Despite the implementation of widespread vaccination programs, the European Health Systems continue to experience care challenges attributable to organizational and structural issues. This study aimed to review the available data on aspects within the organizational and structural domains that might impact vaccination coverage. We searched a comprehensive range of databases from 1 January 2007 to 6 July 2021 for studies that reported quantitative or qualitative research on interventions to raise childhood vaccine coverage. Outcome assessments comprised organizational and structural factors that contribute to vaccine concern among pediatric parents, as well as data reported influencing the willingness to vaccinate. To analyze the risk of bias, the Ottawa, JBI’s (Joanna Briggs Institute) critical appraisal tool, and Amstar quality assessment were used accordingly. The inclusion criteria were met by 205 studies across 21 articles. The majority of the studies were conducted in the United Kingdom (6), the European Union (3), and Italy (3). A range of interventions studied in primary healthcare settings has been revealed to improve vaccination coverage rates including parental engagement and personalization, mandatory vaccination policies, program redesign, supply chain design, administering multiple/combination vaccines, improved vaccination timing and intervals, parental education and reminders, surveillance tools and Supplemental Immunisation Activity (SIA), and information model.
Construction of a Novel Infectious Clone of Recombinant Herpesvirus of Turkey Fc-126 Expressing VP2 of IBDV
Authors: Shah Abid Ullah , Wang Zhisheng , Zheng Yating , Guo Rongli , Chen Saisai , Xu Mengwei , Zhang Chuanjian , Liu Yamei , Wang Jichun
Published: August 2022

The increased virulence of infectious bursal disease virus (IBDV) is a threat to the chicken industry. The construction of novel herpesvirus of turkey-vectored (HVT) vaccines expressing VP2 of virulent IBDV may be a promising vaccine candidate for controlling this serious disease in chickens. We generated a novel infectious clone of HVT Fc-126 by inserting mini-F sequences in lieu of the glycoprotein C (gC) gene. Based on this bacterial artificial chromosome (BAC), a VP2 expression cassette containing the pMCMV IE promoter and a VP2 sequence from the virulent IBDV NJ09 strain was inserted into the noncoding area between the UL55 and UL56 genes to generate the HVT vector VP2 recombinant, named HVT-VP2-09. The recovered vectored mutant HVT-VP2-09 exhibited higher titers (p = 0.0202 at 36 h) or similar growth kinetics to the parental virus HVT Fc-126 (p = 0.1181 at 48 h and p = 0.1296 at 64 h). The high reactivation ability and strong expression of VP2 by HVT-VP2-09 in chicken embryo fibroblasts (CEFs) were confirmed by indirect immunofluorescence (IFA) and Western blotting. The AGP antibodies against IBDV were detected beginning at 3 weeks post-inoculation (P.I.) of HVT-VP2-09 in 1-day-old SPF chickens. Seven of ten chickens immunized with HVT-VP2-09 were protected post-challenge (P.C.) with the virulent IBDV NJ09 strain. In contrast, all chickens in the challenge control group showed typical IBD lesions in bursals, and eight of ten died P.C. In this study, we demonstrated that (i) a novel HVT BAC with the whole genome of the Fc-126 strain was obtained with the insertion of mini-F sequences in lieu of the gC gene; (ii) HVT-VP2-09 harboring the VP2 expression cassette from virulent IBDV exhibited in vitro growth properties similar to those of the parental HVT virus in CEF cells; and (iii) HVT-VP2-09 can provide efficient protection against the IBDV NJ09 strain.
The Effect of Strict Lockdown on Omicron SARS-CoV-2 Variant Transmission in Shanghai
Authors: Yang Haibo , Nie Hao , Zhou Dewei , Wang Yujia , Zuo Wei
Published: August 2022

Omicron, the current SARS-CoV-2 variant of concern, is much more contagious than other previous variants. Whether strict lockdown could effectively curb the transmission of Omicron is largely unknown. In this retrospective study, we compared the strictness of government lockdown policies in Shanghai and other countries. Based on the daily Omicron case number from 1 March 2022 to 30 April 2022, the effective reproductive numbers in this Shanghai Omicron wave were calculated to confirm the impact of strict lockdown on Omicron transmission. Pearson correlation was conducted to illustrate the determining factor of strict lockdown outcomes in the 16 different districts of Shanghai. After a very strict citywide lockdown since April 1st, the average daily effective reproductive number reduced significantly, indicating that strict lockdown could slow down the spreading of Omicron. Omicron control is more challenging in districts with higher population mobility and lockdown is more likely to decrease the number of asymptomatic carriers than the symptomatic cases. All these findings indicate that the strict lockdown could curb the transmission of Omicron effectively, especially for the asymptomatic spread, and suggest that differentiated COVID-19 prevention and control measures should be adopted according to the population density and demographic composition of each community.
Evaluation of Immune Responses and Protective Efficacy of a Novel Live Attenuated Salmonella Enteritidis Vaccine Candidate in Chickens
Authors: Shin Hyunjin , La Tae-Min , Lee Hong-Jae , Kim Taesoo , Song Seung-un , Park Eunjin , Park Gyu-Hyung , Choi In-Soo , Park Seung-Yong , Lee Joong-Bok , Lee Sang-Won
Published: August 2022

An ideal vaccine for controlling Salmonella infection in chicken flocks should be safe, inducing both humoral and cellular immunity. Live attenuated vaccines against Salmonella Enteritidis (S. Enteritidis) have been used as a potential control method of Salmonella infection in the poultry industry. However, live attenuated vaccines can persistently infect poultry for long periods and can become virulent revertant strains. In this study, we assessed the immune responses and protective efficacy of a temperature-sensitive attenuated S. Enteritidis mutant as a potential vaccine candidate. In addition, we evaluated the combined vaccine administration methods to maximize both humoral and cellular immune responses in chickens induced by the vaccine candidate. Immune responses and protective efficacy were compared between the Oral/IM group, vaccinated using one oral dose at four weeks old and a booster intramuscular dose at seven weeks old, and the IM/Oral group, vaccinated using one intramuscular dose at four weeks old and a booster oral dose at seven weeks old. The Oral/IM group showed stronger immune responses than those of the IM/Oral group. Spleens from the Oral/IM group showed a promising tendency of reduction of challenged Salmonella compared with those of other groups. Overall, the results indicated that the S. Enteritidis mutant strain is a promising live attenuated vaccine candidate with good efficacy.