Virus Variants Research Articles

Low Prevalence of SARS-CoV-2 in Farmed and Free-Ranging White-Tailed Deer in Florida

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in multiple animal species, including white-tailed deer (WTD), raising concerns about zoonotic transmission, particularly in environments with frequent human interactions. To understand how human exposure influences SARS-CoV-2 infection in WTD, we compared infection and exposure prevalence between farmed and free-ranging deer populations in Florida. We also examined the timing and viral variants in WTD relative to those in Florida’s human population. Between 2020 and 2022, we collected respiratory swabs (N = 366), lung tissue (N = 245), retropharyngeal lymph nodes (N = 491), and serum specimens (N = 381) from 410 farmed and 524 free-ranging WTD. Specimens were analyzed using RT-qPCR for infection and serological assays for exposure. SARS-CoV-2 infection was detected in less than 1% of both northern Florida farmed (0.85%) and free-ranging (0.76%) WTD. No farmed deer possessed virus-neutralizing antibodies, while one free-ranging WTD tested positive for SARS-CoV-2 antibodies (3.45%). Viral sequences in infected WTD matched peaks in human cases and circulating variants, indicating human-to-deer spillover but at a lower frequency than reported elsewhere. Our findings suggest a reduced risk of SARS-CoV-2 spillover to WTD in northern Florida compared to other regions, highlighting the need for further research on transmission dynamics across North America.

Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies.

Intravitreal delivery of therapeutic transgenes to the retina via engineered viral vectors can provide sustained local concentrations of therapeutic proteins and thus potentially reduce the treatment burden and improve long-term vision outcomes for patients with neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy. We performed directed evolution in nonhuman primates (NHP) to invent an adeno-associated viral (AAV) variant (R100) with the capacity to cross vitreoretinal barriers and transduce all regions and layers of the retina following intravitreal injection. We then engineered 4D-150, an R100-based genetic medicine carrying 2 therapeutic transgenes: a codon-optimized sequence encoding aflibercept, a recombinant protein that inhibits VEGF-A, VEGF-B, and PlGF, and a microRNA sequence that inhibits expression of VEGF-C. Transduction, transgene expression, and biological activity were characterized in human retinal cells in vitro and in NHPs. R100 demonstrated superior retinal cell transduction in vitro and in vivo compared to AAV2, a commonly used wild-type AAV serotype in retinal gene therapies. Transduction of human retinal pigment epithelial cells in vitro by 4D-150 resulted in dose-dependent transgene expression and corresponding reductions in VEGF-A and VEGF-C. Intravitreal administration of 4D-150 to NHPs was well tolerated and led to robust retinal expression of both transgenes. In a primate model of laser-induced choroidal neovascularization, 4D-150 completely prevented clinically relevant angiogenic lesions at all tested doses. These findings support further development of 4D-150. Clinical trials are underway to establish the safety and efficacy of 4D-150 in individuals with wet AMD and DME.

Antibody screening-assisted multichannel nanoplasmonic sensing chip based on SERS for viral screening and variants identification

The Omicron variants of SARS-CoV-2 have been spreading globally and has never disappeared from our sight, indicating that its coexistence with humans has become a fact, and monitoring its evolution and spread remains a current task. Although polymerase chain reaction (PCR) is the most commonly used virus detection method, it requires labor-intensive and time-consuming procedures in a laboratory setting. Herein, a multichannel nanoplasmonic sensing chip based on surface enhanced Raman spectroscopy (SERS) was developed for detecting N and S proteins, as well as IgG and IgM, related to SARS-CoV-2 Omicron variants. Through a self-screening process, specific antibodies for on-site and rapid identification of important variants of concerns (VoCs) were obtained, and their binding was confirmed by protein structure analysis. The use of these S protein specific antibodies can accurately identify Omicron VoCs (BA. 5, BF.7，XBB.1.5) with the detection limit (LoD) at 0.16 pg/mL. Then, the proposed SERS array chip was integrated with a hand-held Raman spectrometer to successfully detect the Omicron subvariants in real saliva samples within only 20 minutes, greatly reducing the detection time of PCR. This sensing technology will provide a powerful and rapid point-of-care testing (POCT) method for virus diagnosis, subtype identification, and post infection antibody level monitoring.

Genomic epidemiology of invasive Group A Streptococcus infections in Argentina, 2023: high prevalence of emm1-global and detection of emm1 hypervirulent lineages.

The aim of this study is to describe the genomic epidemiology of invasive Group A Streptococcus (iGAS) in Argentina during 2023. A total of 476 invasive GAS isolates were subtyped and analyzed by whole-genome sequencing. A high prevalence of the emm1-type strain was observed. Among the emm1 strains, two highly virulent international variants, emm1-UK and emm1-DK, were identified. Additionally, a local variant, called emm1-ST1319, was detected. This seminal study provides initial insights into the genomic landscape of iGAS, contributing to active surveillance to monitor emerging virulent emm1 lineages and cross-border transmission in South America.IMPORTANCEAmid the increase in invasive Streptococcus pyogenes infections in Argentina in 2023, the implementation of genomic analysis of isolates allowed us to detect at the national level the prevalence of the emm1 type and within the M1 type, emerging national and international hypervirulent lineages. These findings from our report shed light on the distribution of invasive Group A Streptococcus, laying the foundation for genomic surveillance of this pathogen.

A deep learning approach predicting the activity of COVID-19 therapeutics and vaccines against emerging variants

Understanding which viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are labor intensive and cannot capture the full spectrum of variants. We present a deep learning approach to predict changes in neutralizing antibody activity of COVID-19 therapeutics and vaccine-elicited sera/plasma against emerging viral variants. Our approach leverages data of 67,885 unique SARS-CoV-2 Spike sequences and 7,069 in vitro assays. The resulting model accurately predicted fold changes in neutralizing activity (R2 = 0.77) for a test set (N = 980) of data collected up to eight months after the training data. Next, the model was used to predict changes in activity of current therapeutic and vaccine-induced antibodies against emerging SARS-CoV-2 lineages. Consistent with other work, we found significantly reduced activity against newer XBB descendants, notably EG.5, FL.1.5.1, and XBB.1.16; primarily attributed to the F456L spike mutation.

Systematic review and meta-analysis of COVID-19 mRNA vaccine effectiveness against hospitalizations in adults

Abstract Background During the Coronavirus disease 2019 (COVID-19) pandemic, Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 vaccines were central to the global pandemic control measures. Methods Here we conducted a systematic review and meta-analysis to evaluate their real-world vaccine effectiveness (VE). Our study focussed on those that reported the efficacy of these vaccines against COVID-19 hospitalization. Hospitalization was chosen as the primary outcome as it directly reflects the ability of the vaccine in preventing severe disease. A literature search was undertaken using Medline and Embase on 25/2/2024. From this, 50 studies out of 18,347 articles were included for further analysis. Results High VE against hospitalization was reported for both the BNT162b2 and mRNA-1273 COVID-19 vaccines when used either as a primary vaccination series (2-dose) or following an additional booster dose (3-dose). Meta-analysis indicated that the pooled VE estimates for each of these vaccination protocols ranged from 84% to 86%, suggesting strong protectiveness. Our data also imply that booster doses can restore waning effectiveness, with no significant differences observed in VE between the 2-dose and 3-dose protocols. However, subgroup analysis revealed an association between the presence of the Omicron variant and a drop in VE, indicating that future emerging SARS-CoV-2 virus variants could similarly affect VE. Conclusions Our review underscores the importance of ongoing research to ensure vaccine strategies remain effective against evolving variants. Our study also identified the need for expanding data collection to include underrepresented populations.

Neuraminidase Antibody Response to Homologous and Drifted Influenza A Viruses After Immunization with Seasonal Influenza Vaccines

Background/Objectives: Humoral immunity directed against neuraminidase (NA) of the influenza virus may soften the severity of infection caused by new antigenic variants of the influenza viruses. Evaluation of NA-inhibiting (NI) antibodies in combination with antibodies to hemagglutinin (HA) may enhance research on the antibody response to influenza vaccines. Methods: The study examined 64 pairs of serum samples from patients vaccinated with seasonal inactivated trivalent influenza vaccines (IIVs) in 2018 according to the formula recommended by the World Health Organization (WHO) for the 2018–2019 flu season. Antibodies against drift influenza viruses A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09 and A/Brisbane/34/2018(H3N2) were studied before vaccination and 21 days after vaccination. To assess NI antibodies, we used an enzyme-linked lectin assay (ELLA) with pairs of reassortant viruses A/H6N1 and A/H6N2. Anti-HA antibodies were detected using a hemagglutination inhibition (HI) test. The microneutralization (MN) test was performed in the MDCK cell line using viruses A/H6N1 and A/H6N2. Results: Seasonal IIVs induce a significant immune response of NI antibodies against influenza A/H1N1pdm09 and A/H3N2 viruses. A significantly reduced ‘herd’ immunity to drift influenza A/H1N1pdm09 and A/H3N2 viruses was shown, compared with previously circulating strains. This reduction was most pronounced in strains possessing neuraminidase N2. Seasonal IIVs caused an increase in antibodies against homologous and drifted viruses; however, an increase in antibodies to drifting viruses was observed more often among older patients. The level of NI antibodies for later A/H1N1pdm09 virus in response to IIVs was statistically significantly lower among younger people. After IIV vaccination, the percentage of individuals with HI antibody levels ≥ 1:40 and NI antibody levels ≥ 1:20 was 32.8% for drift A/H1N1pdm09 virus and 17.2% for drift A/H3N2 virus. Antisera containing HI and NI antibodies exhibited neutralizing properties in vitro against viruses with unrelated HA of the H6 subtype. Conclusions: Drift A/H1N1pdm09 and A/H3N2 viruses demonstrated significantly lower reactivity to HI and NI antibodies against early influenza viruses. In response to seasonal IIVs, the level of seroprotection has increased, including against drift influenza A viruses, but protective antibody levels against A/H1N1pdm09 have risen to a greater extent. A reduced immune response to the N1 protein of the A/H1N1pdm09 drift virus was obtained in individuals under 60 years of age. Based on our findings, it is hypothesized that in the cases of a HA mismatch, vaccination against N1-containing influenza viruses may be necessary for individuals under 60, while broader population-level vaccination against N2-containing viruses may be required.

Experimental evolution at ecological scales allows linking of viral genotypes to specific host strains.

Viruses shape microbial community structure and activity through the control of population diversity and cell abundances. Identifying and monitoring the dynamics of specific virus-host pairs in nature is hampered by the limitations of culture-independent approaches such as metagenomics, which do not always provide strain-level resolution, and culture-based analyses, which eliminate the ecological background and in-situ interactions. Here, we have explored the interaction of a specific "autochthonous" host strain and its viruses within a natural community. Bacterium Salinibacter ruber strain M8 was spiked into its environment of isolation, a crystallizer pond from a coastal saltern, and the viral and cellular communities were monitored for one month using culture, metagenomics, and microscopy. Metagenome sequencing indicated that the M8 abundance decreased sharply after being added to the pond, likely due to forces other than viral predation. However, the presence of M8 selected for two species of a new viral genus, Phoenicisalinivirus, for which 120 strains were isolated. During this experiment, an assemblage of closely related viral genomic variants was replaced by a single population with the ability to infect M8, a scenario which was compatible with the selection of a genomic variant from the rare biosphere. Further analysis implicated a viral genomic region putatively coding for a tail fiber protein to be responsible for M8 specificity. Our results indicate that low abundance viral genotypes provide a viral seed bank that allows for a highly specialized virus-host response within a complex ecological background.

Identification of compounds from natural Peruvian sources as potential inhibitors of SARS-CoV-2 Mpro mutations by virtual screening and computational simulations.

Although the COVID-19 pandemic has diminished in intensity, the virus continues to circulate globally. The SARS-CoV-2 main protease (Mpro) is a key enzyme in the life cycle of the virus, making it important for the development of treatments against future variants of the virus. In this work, Peruvian natural compounds were evaluated against different mutations of the SARS-CoV-2 Mpro. In silico techniques such as virtual screening, all-atom molecular dynamics simulations, and energy estimation analysis were applied. Of the tested compounds by virtual screening, rutin was identified as the best binding agent against the different proposed Mpro mutations. In addition, computational simulations and energy estimation analysis demonstrated the high structural and energetic stability between the Mpro-rutin systems. Overall, our study identified rutin as the most promising compound with a strong affinity for various Mpro mutations, potentially playing a key role in the development of new treatments for emerging viral variants.

SARS-CoV-2 entry and fusion are independent of ACE2 localization to lipid rafts.

Membrane fusion occurs at the early stages of SARS-CoV-2 replication, during entry of the virus, and later during the formation of multinucleated cells called syncytia. Fusion is mediated by the binding of the viral Spike protein to its receptor ACE2. Lipid rafts are dynamic nanodomains enriched in cholesterol and sphingolipids. Rafts can act as platforms for entry of different viruses by localizing virus receptors, and attachment factors to the same membrane domains. Here, we first demonstrate that cholesterol depletion by methyl-beta-cyclodextrin inhibits Spike-mediated fusion and entry. To further study the role of ACE2 lipid raft localization in SARS-CoV-2 fusion and entry, we designed a GPI-anchored ACE2 construct. Both ACE2 and ACE2-GPI proteins were similarly expressed at the plasma membrane. Through membrane flotation assays, we show that in different cell lines, ACE2-GPI localizes predominantly to raft domains of the plasma membrane while ACE2 is non-raft associated. We then compare the ability of ACE2 and ACE2-GPI to permit SARS-CoV-2 entry, replication, and syncytia formation of different viral variants. We find little difference in the two proteins. Our results demonstrate that SARS-CoV-2 entry and fusion are cholesterol-dependent and raft-independent processes.IMPORTANCERafts are often exploited by viruses and used as platforms to enhance their entry into the cell or spread from cell to cell. The membrane localization of ACE2 and the role of lipid rafts in SARS-CoV-2 entry and cell-to-cell spread are poorly understood. The function of lipid rafts in viral fusion is often studied through their disruption by cholesterol-depleting agents. However, this process may have off-target impacts on viral fusion independently of lipid-raft disruption. Therefore, we created an ACE2 construct that localizes to lipid rafts using a GPI anchor. Conversely, wild-type ACE2 was non-raft associated. We find that the localization of ACE2 to lipid rafts does not modify the fusion dynamics of SARS-CoV-2.

SARS-CoV-2 evolution balances conflicting roles of N protein phosphorylation.

All lineages of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, contain mutations between amino acids 199 and 205 in the nucleocapsid (N) protein that are associated with increased infectivity. The effects of these mutations have been difficult to determine because N protein contributes to both viral replication and viral particle assembly during infection. Here, we used single-cycle infection and virus-like particle assays to show that N protein phosphorylation has opposing effects on viral assembly and genome replication. Ancestral SARS-CoV-2 N protein is densely phosphorylated, leading to higher levels of genome replication but 10-fold lower particle assembly compared to evolved variants with low N protein phosphorylation, such as Delta (N:R203M), Iota (N:S202R), and B.1.2 (N:P199L). A new open reading frame encoding a truncated N protein called N*, which occurs in the B.1.1 lineage and subsequent lineages of the Alpha, Gamma, and Omicron variants, supports high levels of both assembly and replication. Our findings help explain the enhanced fitness of viral variants of concern and a potential avenue for continued viral selection.

Optimization of pan-lyssavirus LN34 assay for streamlined rabies diagnostics by real-time RT-PCR

Reliable, validated diagnostic tests are critical for rabies control in animals and prevention in people. We present a performance assessment and updates to the LN34 real-time RT-PCR assay for rabies diagnosis in postmortem animal brain samples. In two U.S. laboratories during 2017 to 2022, routine used of the LN34 assay produced excellent diagnostic sensitivity (99.72% to 100%) and specificity (99.99% to 100%) compared to the direct fluorescence antibody test (DFA). Almost all (>90%) DFA indeterminate results caused by non-specific or atypical fluorescence were negative by LN34 testing, representing up to 111 cases where unnecessary post-exposure prophylaxis could be avoided. LN34 assay original primer sequences showed low sensitivity for some rare lyssaviruses. Increased primer concentration combined with new primer formulation showed improved performance for impacted lyssaviruses with no loss in performance across diverse rabies virus variants from clinical samples. The updated LN34 and internal control assays were combined into a single-well LN34 multiplexed (LN34M) format, run at half reagent volumes. The LN34M assay showed similar detection of rabies virus to the singleplexed assay with simplified assay set-up, lower cost, and improved quality controls.

Post-COVID recovery is faster after an infection with the SARS-CoV-2 Omicron variant: a population-based cohort study

Abstract Purpose Post-COVID-19 condition (PCC) poses a substantial burden to affected individuals, health care systems, and society as a whole. We examined factors associated with recovery from PCC, focusing on the vaccination status prior to infection and the virus variant. Methods Our analyses are based on the population-based cohort study for digital health research in Germany (DigiHero). Respondents who reported a SARS-CoV-2 infection and COVID-related symptoms ≥ 12 weeks post-infection were classified as having PCC. Those with ongoing PCC were followed-up in six-month intervals based on their date of infection. We used a Cox model for interval-censored data to analyze PCC recovery. Results Among the 4,529 respondents with PCC included in our analyses, about 26%, 19%, 36%, and 44% of those infected during dominance of the SARS-CoV-2 wildtype, Alpha, Delta, and Omicron variant had recovered one year after infection, respectively. When stratifying by virus variant, vaccination was not associated with a faster recovery. Conversely, those infected with Omicron (HR = 2.20; 95%CI: 1.96–2.48) or Delta (HR = 1.69; 95%CI: 1.43–2.01) recovered faster than those infected with the SARS-CoV-2 wildtype or Alpha strain. Conclusion Although the recovery from PCC is faster for the newer virus variants, still a substantial fraction of those who developed PCC after an infection with the Omicron variant report prolonged persistence of symptoms.

Enhancement of systemic and lung-localized CD4<sup>+</sup> T-cell immune responses by truncation of NS1 protein of a seasonal live influenza vaccine strain

Introduction. There is a large variety of licensed influenza vaccines worldwide, but their common limitation is rather narrow specificity and inability to protect against antigenic-drift variants of influenza virus. Therefore, optimization of immunogenic and cross-protective properties of licensed influenza vaccines is an urgent priority of public health agenda. One such approach is to modulate the immunogenic properties of live attenuated influenza vaccine (LAIV) by truncating the open reading frame of influenza virus non-structural protein 1 (NS1). The main objective of this study is to evaluate the immunogenic properties of the H1N1 seasonal LAIV strain by truncation of the NS1 protein to 126 amino acides. Materials and methods. Using reverse genetics technique, two H1N1 LAIV strains with full-length and truncated NS1 protein with three consecutive stop codons added after the 126th amino acid residue were obtained.C57BL/6J mice were immunized intranasally with the vaccine candidates, twice at a three-week interval. Seven days after the second immunization, cells were isolated from spleen and lung tissues and stimulated with whole wild-type H1N1 influenza virus. Levels of systemic and tissue-resident cytokine-producing CD4+ and CD8+ memory T cells were assessed by intracellular cytokine staining assay with flow cytometry. Replication of engineered vaccine strains in in vitro and in vivo systems was also evaluated. Results. Truncation of NS1 protein of the LAIV strain significantly increased the levels of virus-specific CD4+ effector memory T cells in spleens and the levels of CD4+ tissue-resident memory T cells in lungs of mice after two-dose immunization, indicating a higher potential for protection against influenza infection of the LAIV NS126 vaccine strain compared to the classical variant of LAIV. Importantly, the LAIV NS126 strain also had a more pronounced attenuated phenotype in mice than its classical counterpart.

Protective role of vaccination on the development of long COVID: data from a large, multicenter, prospective cohort study.

Long COVID, a highly heterogeneous syndrome affecting millions of people worldwide, is emerging as an urgent public health threat, but data on the predictors of specific clinical manifestations over long follow-up periods are limited. The aim of this study is to investigate the role of viral variants and other predictors in long COVID incidence and clinical manifestations. All COVID-19 patients aged > 18 years and hospitalized from March 1 2020 to April 2022 in two Italian University Hospitals were enrolled. Incidence and clinical presentation of long COVID were assessed through structured questionnaires delivered by phone calls. The association between possible risk factors collected during hospitalization and long COVID was reported using an adjusted logistic regression and reported as odds ratios (ORs) with their 95% confidence intervals (CIs). Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15-24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15-24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Overall, 54% reported long COVID symptomatology between 18 and 24 months. Multivariate analysis suggested that being vaccinated against SARS-CoV-2 was associated with reduced odds of reporting any long COVID symptomatology (OR: 0.34; 95% CI: 0.21-0.58), while infection with the Delta variant was a strong predictor (OR: 9.61, p < 0.0001) for the development of post-COVID conditions characterized by neuropsychiatric symptoms. In this study long COVID symptoms were still highly prevalent after 18-24 months of follow-up and, when compared to wild-type virus, infection with the Delta variant was associated with a higher risk of developing a neurological post-COVID condition.

Nucleotide and Amino Acid Analyses of Unique Infectious Bronchitis Virus (IBV) Variants from Canadian Poultry Flocks with Drop in Egg Production.

Infectious bronchitis (IB) is a highly infectious avian disease caused by the infectious bronchitis virus (IBV). The disease causes lesions mainly in the respiratory, reproductive, and renal systems and has a significant economic impact on the poultry industry worldwide. We discovered two unique IBV isolates (T-62: PP737794.1 and CL-61: PP783617.1) circulating in Canada and molecularly characterized them. The phylogenetic analysis revealed that the IBV isolates belong to genotype I and fall between lineages 25 and 7. Further analysis of the T-62 IBV isolate indicated that it is a potential recombinant of the Iowa state isolate (IA1162/2020-MW) and that the CL-61 strain of the IBV is also a recombinant IBV with the Connecticut (Conn) vaccine strain as its major parent. The S1 glycoprotein of the CL-61 and T-62 strains of the IBV had 85.7% and 73.2% amino acid (aa) identities respectively compared to the Conn vaccine strain. There were 67 and 129 aa substitutions among the S1 glycoprotein of the CL-61 and T-62 strains of the IBV compared to the Conn vaccine, respectively. Importantly, two and nineteen of these aa variations were in hypervariable regions 1 (HVR1) and HVR3. Finally, the two IBV isolates possessed a higher affinity for the sialic acid ligand compared to the DMV/1639 and Mass/SES IBV strains. Genetic recombination in the IBV results in the continual emergence of new variants, posing challenges for the poultry industry. As indicated by our analyses, live attenuated vaccine strains play a role in the genetic recombination of the IBV, resulting in the emergence of variants.

Identification of raccoon rabies virus variant in a stray kitten: the role of veterinary practitioners in detection and reporting of a non-native zoonotic pathogen-Nebraska, 2023.

Rabies is a fatal encephalitic disease affecting all mammals. This report describes identification of raccoon rabies virus variant isolated from a stray kitten in an urban Midwestern city that is nonendemic for this virus variant. The kitten originally presented with nonspecific neurologic abnormalities. Astute veterinary, wildlife, and public health professionals played a critical role in the identification of this fatal zoonotic disease and the extensive public health and wildlife management response that ensued. This case serves as an important reminder of the risk of rabies in unvaccinated animals or those without known vaccination status, including stray animals.

An Active-Learning Framework for Educating Medical Students on SARS-CoV-2 Variants and COVID-19 Epidemiology

Background The emergence of multiple Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) variants presented an escalated risk to public health globally and prompted epidemiologic monitoring and classification. Health professionals are vital for patient education regarding Coronavirus Disease 2019 (COVID-19), discussing patient concerns, and providing guidance. Students enrolled in professional healthcare programs benefit from being adept with the evolution and spread of SARS-CoV-2 variants, and a team-based learning module can be helpful for applying foundational concepts to clinical problems. Methods This team-based learning (TBL) framework was developed in response to the COVID-19 pandemic and the emergence of viral variants. It was placed at the end of a hematology block within the first semester of year one of the medical school during the academic years 2021–2022. It consists of a 7-question readiness assurance process and a four-question application exercise. Results The average score increased from 58.8% (iRAT) to 85.9% (tRAT) (n=104). The post-session survey data showed an increase in students’ understanding of the classification of COVID-19 variants and the role of genetic mutations in viral pathogenesis. Qualitative data yielded positive feedback for the session, notably in students' ability to interpret phylogenetic trees and understand the role of variants. Conclusions This TBL framework cultivates higher-order thinking skills among medical students and effectively integrates virology, epidemiology, and pathology. Additionally, it provides a framework for developing a robust and up-to-date platform for the discussion of novel variants of COVID-19 or other infectious diseases.

Association of mRNA COVID-19 vaccination and reductions in Post-COVID Conditions following SARS-CoV-2 infection in a US prospective cohort of essential workers.

While there is evidence that COVID-19 vaccination protects against development of post-COVID conditions (PCC) after severe infection data are limited on whether vaccination reduces the risk after cases of less-severe non-hospitalized COVID-19 disease with more recent SARS-CoV-2 variant viruses. This study assessed whether COVID-19 vaccination was protective against subsequent development of PCC in persons with predominantly mild initial infections during both Delta and Omicron variant predominance. This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with PCR-confirmed SARS-CoV-2 infection between 6/28/2021 and 9/14/2022 were surveyed for PCC, defined by symptoms lasting >1 month after initial infection Cases were participants self-reporting PCC and controls were participants that did not self-report PCC. The exposure was mRNA COVID-19 vaccination (2 or 3 monovalent doses) versus no COVID-19 vaccination. Logistic regression was used to compare the odds of PCC among vaccinated and unvaccinated persons; additional analyses evaluating PCC subtypes were also performed. A total of 936 participants with documented SARS-CoV-2 infection were included; of these 23.6% (221) reported PCC and 83.3% (779) were vaccinated. Participants who received a 3rd COVID-19 monovalent mRNA dose prior to infection had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (aOR: 0.37; 95% CI: 0.16-0.85; aOR: 0.56; 95% CI: 0.32-0.97; aOR:0.48; 95% CI: 0.25-0.91). COVID-19 vaccination protected against development of PCC among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important tool for PCC prevention.

Local and Noninvasive Glyco-Virus Checkpoint Nanoblockades Restrict Sialylation for Prolonged Broad-Spectrum Epidemic Virus Therapy.

The coronavirus disease 2019 (COVID-19) pandemic has driven major advances in virus research. The role of glycans in viral infection has been revealed, with research demonstrating that terminal sialic acids are key receptors during viral attachment and infection into host cells. However, there is an urgent demand for universal tools to study the mechanism of sialic acids in viral infections, as well as to develop therapeutic agents against epidemic viruses through the downregulation of terminal sialic acid residues on glycans acting as a glyco-virus checkpoint to accelerate virus clearance. In this study, we developed a robust sialic acids blockade tool termed local and noninvasive glyco-virus checkpoint nanoblockades (LONG NBs), which blocked cell surface sialic acids by endogenously and continuously inhibiting the de novo sialic acids biosynthesis pathway. Furthermore, LONG NBs could accurately characterize the sialic acid-dependent profiles of multiple virus variants and protected the host against partial SARS-CoV-2, rotavirus, and influenza A virus infections after local and noninvasive administration. Our results suggest that LONG NBs represent a promising tool to facilitate in-depth research on the mechanism of viral infection, and serve as a broad-spectrum protectant against existing and emerging viral variants via glyco-virus checkpoint blockade.