Choroiditis following severe acute respiratory syndrome coronavirus 2 infection in unvaccinated identical twins

ABSTRACT Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis.

SARS-CoV-2 infection and vaccination in patients with pituitary diseases: the experience of a Brazilian reference center.

PURPOSE: To evaluate the prevalence and characteristics of SARS-CoV-2 infection, and the prevalence, efficacy, and safety of anti-SARS-CoV-2 vaccination in patients with pituitary diseases. METHODS: Observational, cross-sectional study of adult patients with pituitary diseases followed in a reference center. Clinical data were collected and a questionnaire about SARS-CoV-2 infection, vaccination and its possible adverse effects was applied. COVID-19 disease severity was defined as mild, moderate, and severe according to the WHO classification. RESULTS: 145 patients were studied (79 women; age 50 ± 15.8 years; duration of pituitary disease 16.8 ± 11.5 years), the cause of pituitary disease was tumoral in 74.5%, and 45.9% were on glucocorticoid replacement due to ACTH deficiency. SARS-CoV-2 infection was confirmed in 51 patients (35.2%; 32 women; age 53.8 ± 14.8 years, 22 before vaccination), with 28 (54.9%), 17 (33.3%) and 6 (11.8%) cases of mild, moderate, and severe disease, respectively, and hospitalization was indicated in 7 (14%) cases. One mild case presented pituitary apoplexy after SARS-CoV-2 infection. Advanced age was a risk factor for COVID-19. Patients with moderate and severe forms of COVID-19 had higher prevalence of dyslipidemia and duration of pituitary disease. All but one of the participants were vaccinated against COVID-19, and 60.4% had adverse events, the most common local pain (54.0%), fever (33.3%), and headache (18.4%), with one case of alopecia and two of persistent fatigue. CONCLUSION: The prevalence of SARS-CoV-2 infection in our cohort was 35.2%, including 14% of moderate and severe cases requiring hospitalization. The vaccination was universal and safe.

To prescribe or not: a two-center retrospective observational study of antibiotics usage and outcomes of COVID-19 in Turkey.

This retrospective cohort study conducted in Turkey between December 2020 and June 2022 aimed to assess antibiotic use, bacterial co-infections, and the associated factors on mortality in hospitalized patients with mild-to-severe COVID-19. Among the 445 patients, 80% received antibiotics, with fluoroquinolones being the most common choice, followed by beta-lactams and combinations. Various clinical and laboratory parameters, including symptoms, comorbidities, CCI, oxygen requirements, and CRP levels were observed to be elevated in the antibiotic group. Non-survivors had more ICU admissions and longer hospital stays compared to survivors. We conducted a multivariate Cox regression analysis to evaluate factors related to mortality. However, we did not find an association between antibiotic use and mortality [HR 2.7 (95% CI 0.4-20)]. The study identified significant factors associated with an antibiotic prescription, such as CCI (OR 1.6), CRP (OR 2.3), and ICU admission (OR 8.8), (p < 0.05). The findings suggest re-evaluating the necessity of antibiotics in COVID-19 cases based on clinical assessments, focusing on the presence of bacterial infections rather than empirical treatment. Further research is necessary to more accurately identify patients with bacterial co-infections who would benefit from antibiotic treatment.

Indirect effectiveness of a novel SAR-COV-2 vaccine (SCB-2019) in unvaccinated household contacts in the Philippines: A cluster randomised analysis.

BACKGROUND: Though observational evidence supports indirect effects of SARS-CoV-2 vaccines, randomised experiments are lacking. To address this gap, the double-blinded, prospective follow-up of the household contacts (HHCs) of Philippine participants of the individually-randomised, placebo-controlled trial of the adjuvanted-subunit protein COVID-19 vaccine, SCB-2019, (EudraCT, 2020-004272-17; ClinicalTrials.gov, NCT04672395) was analyzed in a cluster-randomised fashion. METHODS: Over an eight-week period, HHCs were followed by rRT-PCR and paired rapid antibody tests (RATs) to detect symptomatic (SCI, primary) and all (ACI, secondary) SARS-CoV-2 infection. A standard analysis estimated the indirect effectiveness of SCB-2019 for each endpoint, excluding HHC RAT-positive at enrollment. A secondary analysis employed enzyme-linked immunosorbent assay (ELISA) results to correct for suspected bias. FINDINGS: SCB-2019 (N = 3470) and placebo (N = 3225) exposed HHCs contributed to at least one analysis. The standard analysis estimated that SCB-2019 reduced the risk of SCI by 83% (95% confidence/credible interval [CI: 32% to 96%), with no effect against ACI. The bias-corrected relative risk reduction was 97% (95% CI: 74% to 100%) for SCI and 79% (95% CI: 14% to 96%) for ACI, with an estimated one SARS-CoV-2 infection prevented per 4.8 households where one member received SCB-2019. INTERPRETATION: SCB-2019 demonstrated bias-corrected indirect effectiveness against SARS-CoV-2 infection among HHC, even at a modest coverage level in the household (approximately 25%). Further research into the indirect effects of SARS-CoV-2 vaccines is needed to optimize the impact of limited doses in low and middle-income settings.

Potential of 6'­hydroxy justicidin B from Justicia procumbens as a therapeutic agent against coronavirus disease 2019.

BACKGROUND: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6'-Hydroxy justicidin B (6'-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties. HYPOTHESIS/PURPOSE: The aim of the present study was to assess the effectiveness and safety of 6'-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19. METHODS: The efficacy of 6'-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs. RESULTS: The anti-SARS-CoV-2 efficacy of 6'-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6'-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6'-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6'-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6'-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6'-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions. CONCLUSION: This research highlights both the antiviral efficacy and safety profile of 6'-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6'-HJB was demonstrated using modern scientific methodologies and standards.

Carboxy-PEG-thiol functionalized gold nanoparticle conjugates for the detection of SARS-CoV-2: Detection tools and analytical method development.

Addressing the need for accessible SARS-CoV-2 testing, carboxy-PEG 12-thiol functionalized gold nanoparticles conjugates were developed for rapid point-of-care (POC) detection against SARS-CoV-2 spike protein, pseudo-SARS-CoV-2, and authentic Beta SARS-CoV-2 virus particles. These conjugates leverage gold nanoparticles (AuNPs) as signal transducers, cross-linked to either angiotensin-converting enzyme 2 (ACE2) or SARS-CoV-2 spike protein receptor-binding domain (RBD) antibodies as bioreceptors and showed a distinct color shift from pink to blue. To assess their POC feasibility, the conjugates were integrated into facemasks and breathalyzers, wherein aerosolized SARS-CoV-2 antigens were successfully detected, producing a color change within 10 and 30 minutes for the breathalyzer and facemask prototypes, respectively. Furthermore, we explored quantitative analysis using varying concentrations of SARS-CoV-2 spike protein. Both conjugates demonstrated a linear relationship between blue color intensity and virus concentration, with linear ranges of 0.08-0.6 ng/mL and 0.04-0.5 ng/mL, respectively. Low limits of detection and quantification were also achieved. They exhibited specificity, responding solely to SARS-CoV-2 even in complex matrices containing diverse proteins, including the SARS-CoV-1 spike protein. Precision tests yielded coefficient of variations below 2 %, showcasing their remarkable reproducibility. This work presents a promising approach for rapid, sensitive, and specific POC detection of SARS-CoV-2 paving the way for improved pandemic response and management.

Harnessing traditional Chinese medicine polysaccharides for combatting COVID-19.

With the global spread of COVID-19 posing ongoing challenges to public health systems, there is an ever-increasing demand for effective therapeutics that can mitigate both viral transmission and disease severity. This review surveys the landscape of polysaccharides derived from traditional Chinese medicine, acclaimed for their medicinal properties and potential to contribute to the COVID-19 response. We specifically focus on the capability of these polysaccharides to thwart SARS-CoV-2 entry into host cells, a pivotal step in the viral life cycle that informs transmission and pathogenicity. Moreover, we delve into the concept of trained immunity, an innate immune system feature that polysaccharides may potentiate, offering an avenue for a more moderated yet efficacious immune response against various pathogens, including SARS-CoV-2. Our comprehensive overview aims to bolster understanding of the possible integration of these substances within anti-COVID-19 measures, emphasizing the need for rigorous investigation into their potential applications and underlying mechanisms. The insights provided here strongly support ongoing investigations into the adjunctive use of polysaccharides in the management of COVID-19, with the anticipation that such findings could lead to a deeper appreciation and clearer elucidation of the antiviral potentials inherent in complex Chinese herbal remedies.

Use of high-resolution fluorescence in situ hybridization for fast and robust detection of SARS-CoV-2 RNAs.

Early, rapid, and accurate diagnostic tests play critical roles not only in the identification/management of individuals infected by SARS-CoV-2, but also in fast and effective public health surveillance, containment, and response. Our aim has been to develop a fast and robust fluorescence in situ hybridization (FISH) detection method for detecting SARS-CoV-2 RNAs by using an HEK 293 T cell culture model. At various times after being transfected with SARS-CoV-2 E and N plasmids, HEK 293 T cells were fixed and then hybridized with ATTO-labeled short DNA probes (about 20 nt). At 4 h, 12 h, and 24 h after transfection, SARS-CoV-2 E and N mRNAs were clearly revealed as solid granular staining inside HEK 293 T cells at all time points. Hybridization time was also reduced to 1 h for faster detection, and the test was completed within 3 h with excellent results. In addition, we have successfully detected 3 mRNAs (E mRNA, N mRNA, and ORF1a (-) RNA) simultaneously inside the buccal cells of COVID-19 patients. Our high-resolution RNA FISH might significantly increase the accuracy and efficiency of SARS-CoV-2 detection, while significantly reducing test time. The method can be conducted on smears containing cells (e.g., from nasopharyngeal, oropharyngeal, or buccal swabs) or smears without cells (e.g., from sputum, saliva, or drinking water/wastewater) for detecting various types of RNA viruses and even DNA viruses at different timepoints of infection.

Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariants.

Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in the human population, controlling the COVID-19 pandemic has been challenging. Understanding how the virus enhances its fitness during a pandemic could offer valuable insights for more effective control of viral epidemics. In this manuscript, we review the evolution of SARS-CoV-2 from early 2022 to the end of 2023-from Omicron BA.2 to XBB descendants. Focusing on viral evolution during this period, we provide concrete examples that SARS-CoV-2 has increased its fitness by enhancing several functions of the spike (S) protein, including its binding affinity to the ACE2 receptor and its ability to evade humoral immunity. Furthermore, we explore how specific mutations modify these functions of the S protein through structural alterations. This review provides evolutionary, molecular, and structural insights into how SARS-CoV-2 has increased its fitness and repeatedly caused epidemic surges during the pandemic.

Development of a double-antibody sandwich ELISA for detection of SARS-CoV-2 variants based on nucleocapsid protein-specific antibodies.

The COVID-19 pandemic, driven by the SARS-CoV-2 virus, has posed a severe threat to global public health. Rapid, reliable, and easy-to-use detection methods for SARS-CoV-2 variants are critical for effective epidemic prevention and control. The N protein of SARS-CoV-2 serves as an ideal target for antigen detection. In this study, we achieved soluble expression of the recombinant SARS-CoV-2 N protein using an Escherichia coli expression system and generated specific monoclonal antibodies by immunizing BALB/c mice. We successfully developed 10 monoclonal antibodies against the N protein, designated 5B7, 5F2-C11, 5E2-E8, 6C3-D8, 7C8, 9F2-E9, 12H5-D11, 13G2-C10, 14E9-F6, and 15H3-E10. Using these antibodies, we established a sandwich ELISA with 6C3-D8 as the capture antibody and 5F2-C11 as the detection antibody. The assay demonstrated a sensitivity of 0.78 ng/mL and showed no cross-reactivity with MERS-CoV, HCoV-OC43, HCoV-NL63, and HCoV-229E. Furthermore, this method successfully detected both wild-type SARS-CoV-2 and its variants, including Alpha, Beta, Delta, and Omicron. These findings indicate that our sandwich ELISA exhibits excellent sensitivity, specificity, and broad-spectrum applicability, providing a robust tool for detecting SARS-CoV-2 variants.

Radiotracers for Molecular Imaging of Angiotensin-Converting Enzyme 2.

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

A descriptive review on the real-world impact of Moderna, inc. COVID-19 vaccines.

INTRODUCTION: Since the original COVID-19 vaccines were developed, abundant clinical trial and real-world evidence evaluating the efficacy, effectiveness, and safety of COVID-19 vaccines has been collected. Knowledge of the relative benefits and risks of COVID-19 vaccines is essential for building trust within target populations, ensuring they remain effectively and safely protected against an enduring infectious threat. AREAS COVERED: This descriptive review discusses the benefits and risks associated with marketed Moderna, Inc. mRNA-based COVID-19 vaccines, focusing on their real-world effectiveness and safety profiles in various age groups. Adverse events of interest and potential benefits of vaccination are reviewed, including reduced risk for severe COVID-19 and long-term health outcomes, reduced economic and societal costs, and reduced risk for SARS-CoV-2 transmission. EXPERT OPINION: Post-marketing safety and real-world data for Moderna, Inc. COVID-19 mRNA vaccines strongly support a positive benefit - risk profile favoring vaccination across all age groups. Although COVID-19 is no longer considered a global health pandemic, health risks associated with SARS-CoV-2 infection remain high. Concerted efforts are required to engage communities and maintain protection through vaccination. Continued surveillance of emerging variants and monitoring of vaccine safety and effectiveness are crucial for ensuring sustained protection against SARS-CoV-2.

Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.

BACKGROUND: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. METHODS: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. RESULTS: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). CONCLUSION: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.

Design, synthesis, and evaluation of novel oxyacanthine derivatives for anti-SARS-CoV-2 activity.

Here, we report the synthesis of a series of oxyacanthine derivatives and evaluation for their anti-SARS-CoV-2 activity in Vero E6 cells. In order to eliminate the potential metabolic activation caused by para-methylene phenol moiety in oxyacanthine, totally 29 derivatives were designed and synthesized, resulting in 23 compounds with antivirus IC50 below 5.00 µM and 9 compounds with antivirus IC50 below 1.00 µM. Among them, amides compound 4a and 4d exhibited potent anti-SARS-CoV-2 activity and the most favorable selectivity index (SI) in vitro with the SI values of 115 and 70, respectively. The pharmacokinetic properties of 4a and 4d were also assessed. Much more improved exposure in mice, longer half-life (T1/2), and increased oral bioavailability were observed for both compounds 4a and 4d compared with oxyacanthine.

Genomic Surveillance and Evolutionary Dynamics of Influenza A Virus in Sri Lanka.

Background: Influenza A has been named as a priority pathogen by the WHO due to the potential to cause pandemics. Genomic sequencing of influenza strains is important to understand the evolution of the influenza strains and also to select the appropriate influenza vaccines to be used in the different influenza seasons in Sri Lanka. Therefore, we sought to understand the molecular epidemiology of the influenza viruses in the Western Province of Sri Lanka, including mutational analysis to investigate the evolutionary dynamics. Methodology: A total of 349 individuals presenting with fever and respiratory symptoms were enrolled in this study from November 2022 to May 2024. Nasopharyngeal and oropharyngeal specimens were collected and screened using quantitative PCR to detect Influenza A, Influenza B, and SARS-CoV-2. Subtyping and genomic sequencing was carried out on influenza A strains using Oxford Nanopore Technology. Results: Influenza A was detected in 49 (14 %) patients, influenza B in 20 (5.7%) and SARS-CoV-2 in 41 (11.7%). Co-infections were observed in five participants. The phylogenetic analysis assigned the H1N1 HA gene sequences within the 6B.1A.5a.2a clade. The HA gene of the H1N1 sequences in 2023 were assigned as belonging to the subclades C.1, C.1.2, and C.1.8, while the 2024 sequences were assigned to subclades C.1.8 and C.1.9. The H3N2 sequences from 2023 were assigned to the 3C.2a1b.2a.2a.1b clade and subclade G.1.1.2, while the 2024 sequences were assigned to the 3C.2a1b.2a.2a.3a.1 clade and subclade J.2. The K54Q, A186T, Q189E, E224A, R259K, K308R, I418V, and X215A amino acid substitutions were seen in the H1N1 in the 2023 and 2024 sequences. The 2024 H1N1 sequences additionally exhibited further substitutions, such as V47I, I96T, T120A, A139D, G339X, K156X, and T278S. Conclusion: In this first study using genomic sequencing to characterize the influenza A strains in Sri Lanka, which showed different influenza A viruses circulating in an 18-month period. As the Sri Lankan strains also had certain mutations of unknown significance, it would be important to continue detailed surveillance of the influenza strains in Sri Lanka to choose the most suitable vaccines for the population and the timing of vaccine administration.

Differential associations between SARS-CoV-2 infection, perceived burden of the pandemic and mental health in the German population-based cohort for digital health research.

Understanding the potential adverse effects of the COVID-19-pandemic on mental health remains a challenge for public health. Differentiation between potential consequences of actual infection with SARS-CoV-2 and the subjective burden of the pandemic due to measures and restrictions to daily life still remains elusive. Therefore, we investigated the differential association between infection with SARS-Cov-2 and subjective burden of the pandemic in a study cohort of 7601 participants from the German population-based cohort for digital health research (DigiHero), who were recruited between March 4th and April 25th 2022. Data was collected using the online survey tool LimeSurvey® between March and October 2022 in consecutive surveys, which included questionnaires on infection status and symptoms following COVID-19 as well as retrospective assessment of the subjective burden of the pandemic. We observed an association of a past SARS-CoV-2 infection on deteriorated mental health related symptoms, whereas no association or interaction with burden of the pandemic occurred. The association was driven by participants with persistent symptoms 12 weeks after infection. On a symptom specific level, neuropsychiatric symptoms such as exhaustion and fatigue, concentration deficits and problems with memory function were the primary drivers of the association with small effect sizes between 0.048 and 0.062 ηp2.

Understanding antibody magnitude and durability following vaccination against SARS-CoV-2.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in transient antibody response against the spike protein. The individual immune status at the time of vaccination influences the response. Using mathematical models of antibody decay, we determined the dynamics of serum immunoglobulin G (IgG) and serum immunoglobulin A (IgA) over time. Data fitting to longitudinal IgG and IgA titers was used to quantify differences in antibody magnitude and antibody duration among infection-naïve and infection-positive vaccinees. We found that prior infections result in more durable serum IgG and serum IgA responses, with prior symptomatic infections resulting in the most durable serum IgG response and prior asymptomatic infections resulting in the most durable serum IgA response. These findings can guide vaccine boosting schedules.

RT-qPCR Testing and Performance Metrics in the COVID-19 Era.

The COVID-19 pandemic highlighted the crucial role of diagnostic testing in managing infectious diseases, particularly through the use of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tests. RT-qPCR has been pivotal in detecting and quantifying viral RNA, enabling the identification and management of SARS-CoV-2 infections. However, despite its widespread use, there remains a notable gap in understanding fundamental diagnostic metrics such as sensitivity and specificity among many scientists and healthcare practitioners. This gap is not merely academic; it has profound implications for interpreting test results, making public health decisions, and affecting patient outcomes. This review aims to clarify the distinctions between laboratory- and field-based metrics in the context of RT-qPCR testing for SARS-CoV-2 and summarise the global efforts that led to the development and optimisation of these tests during the pandemic. It is intended to enhance the understanding of these fundamental concepts among scientists and healthcare professionals who may not be familiar with the nuances of diagnostic test evaluation. Such knowledge is crucial for accurately interpreting test results, making informed public health decisions, and ultimately managing infectious disease outbreaks more effectively.

Viral Factors in Modulation of Host Immune Response: A Route to Novel Antiviral Agents and New Therapeutic Approaches.

Viruses utilize host cells at all stages of their life cycle, from the transcription of genes and translation of viral proteins to the release of viral copies. The human immune system counteracts viruses through a variety of complex mechanisms, including both innate and adaptive components. Viruses have an ability to evade different components of the immune system and affect them, leading to disruption. This review covers contemporary knowledge about the virus-induced complex interplay of molecular interactions, including regulation of transcription and translation in host cells resulting in the modulation of immune system functions. Thorough investigation of molecular mechanisms and signaling pathways that are involved in modulating of host immune response to viral infections can help to develop novel approaches for antiviral therapy. In this review, we consider new therapeutic approaches for antiviral treatment. Modern therapeutic strategies for the treatment and cure of human immunodeficiency virus (HIV) are considered in detail because HIV is a unique example of a virus that leads to host T lymphocyte deregulation and significant modulation of the host immune response. Furthermore, peculiarities of some promising novel agents for the treatment of various viral infections are described.

Clinical characteristics and risk factors of severe COVID-19 in hospitalized neonates with omicron variant infection: a retrospective study.

BACKGROUND: Reports on coronavirus disease 2019 (COVID-19) in neonates are limited, especially in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) Omicron variant. This study aims to analyze the clinical characteristics and identify risk factors associated with severe COVID-19 in neonates infected with Omicron variant. METHODS: The study population was represented by neonates with COVID-19, who were admitted to The Affiliated Children's Hospital of Xi'an Jiaotong University in northwest China, from December 10, 2022 to January 20, 2023. Chinese Center for Disease Control and Prevention (CDC) announced that all local COVID-19 cases were infected with Omicron variant during the study period. Clinical and laboratory data were collected retrospectively. We used logistic regression analysis to investigate the risk factors for severe COVID-19, and derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: A total of 108 neonates, with median age of 18.1 days (interquartile range 9.4-23.0), were affected by COVID-19, of whom 84 had a mild disease, while 24 a severe one (22.2%). Of them, 6.5% were premature. No deaths were observed in the study population. The most common clinical manifestations were fever (88.9%) and cough (55.6%), with 5 cases (4.6%) complicated by pneumonia. 4 cases (3.7%) received respiratory support, including 2 cases of high-flow oxygen and 2 cases of continuous positive airway pressure. Gestational age at birth (OR: 0.615; 95% CI: 0.393-0.961), neutrophil count (NEU) (OR:0.576; 95% CI : 0.344-0.962) and lymphocyte count (LYM) (OR: 0.159; 95% CI: 0.063-0.401) were independent risk factors for severe COVID-19. The combination of NEU and LYM had the largest receiver operating characteristic area under the curve [0.912 (95% CI:0.830-0.993)] for identifying severe COVID-19, with a sensitivity of 0.833 and a specificity of 0.917. CONCLUSIONS: The general presentations and outcomes of neonatal COVID-19 caused by Omicron variant were not severe, and very few patients required respiratory support. The simultaneous decrease in NEU and LYM can be used to identify severe infection.