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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness led to the coronavirus disease 2019 (COVID-19) pandemic, which has caused enormous health and financial losses, as well as challenges to global health. Iron deficiency anaemia (IDA) has been linked to adverse outcomes in patients infected with SARS-COV-2. The present study aimed to assess the association between IDA and the severity of COVID-19 in hospitalized patients. For this purpose, a retrospective data analysis of 100 patients with COVID-19 was conducted. Data of patients hospitalized with SARS-COV-2 infection confirmed by RT-PCR were collected between June, 2021 and March, 2022. The collected data included patient demographics, comorbidities, clinical signs, symptoms and IDA medical laboratory findings, including complete blood count and iron profiles. The results revealed that patients with COVID-19 admitted to the isolation unit represented 61.0% of the study sample, whereas 39.0% were admitted to the intensive care unit (ICU). No patients had stage I IDA, whereas 4 patients (4%) had stage II IDA. Furthermore, 19 patients (19.0%) had stage III IDA. A significantly higher proportion of patients with IDA (69.6%) were admitted to the ICU compared with those without IDA (29.9%, P<0.001). Additionally, patients with IDA had a higher proportion of a history of stroke compared with those without IDA (17.4 vs. 2.6%, respectively, P=0.024). The most common comorbidities identified were hypertension (29%), diabetes (23%) and heart problems (17%). On the whole, the present study demonstrates significant associations between IDA and a longer hospitalization period. A greater incidence of complications was observed in the hospitalized patients who were SARS-COV-2-positive. Although further studies with larger sample sizes are required to confirm these findings, the results presented herein may provide insight for physicians as regards the prevention and treatment of patients with IDA who are infected with coronavirus.

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Lung diseases have complex pathogenesis and treatment challenges, showing an obvious increase in the rate of diagnosis and death every year. Therefore, elucidating the mechanism for their pathogenesis and treatment ineffective from novel views is essential and urgent. Methyltransferase-like 3 (METTL3) is a novel post-transcriptional regulator for gene expression that has been implicated in regulating lung diseases, including that observed in chronic conditions such as pulmonary fibrosis (PF), pulmonary arterial hypertension (PAH), and chronic obstructive pulmonary disease (COPD), as well as acute conditions such as pneumonia, severe acute respiratory syndrome coronavirus 2 infection, and sepsis-induced acute respiratory distress syndrome. Notably, a comprehensive summary and analysis of findings from these studies might help understand lung diseases from the novel view of METTL3-regulated mechanism, however, such a review is still lacking. Therefore, this review aims to bridge such shortage by summarising the roles of METTL3 in lung diseases, establishing their interrelationships, and elucidating the potential applications of METTL3 regarding diagnosis, treatment, and prognosis. The analysis collectively suggests METTL3 is contributable to the onset and progression of these lung diseases, thereby prospecting METTL3 as a valuable biomarker for their diagnosis, treatment, and prognosis. In conclusion, this review offers elucidation into the correlation between METTL3 and lung diseases in both research and clinical settings and highlights potential avenues for exploring the roles of METTL3 in the respiratory system.

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α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

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BACKGROUND: Co-infection with other pathogens can alter the severity and clinical outcomes of viral infections. However, the information regarding viral co-infections in pediatric coronavirus disease 2019 (COVID-19) cases is still limited. METHODS: This is a nationwide, retrospective cohort study using the data from the COVID-19 Registry Japan. The pediatric (<18 years), laboratory confirmed, hospitalized COVID-19 patients in the Omicron variant of concern predominant period (January 2022 to January 2024) were included. Co-infection was investigated by multiplex PCR. We compared clinical characteristics, symptoms, severity, and outcomes between children with and without co-infection. RESULTS: Among 245 hospitalized pediatric COVID-19 patients, 78 (31.8 %) had co-infections. The patient backgrounds of the "co-infection" and "SARS-CoV-2 alone" groups were similar, although age distribution was different, with a lower number of patients over 12 years in the co-infection group (n = 2, 2.6 % vs. n = 29, 17.4 %; P < 0.001). Among the patients with co-infection, the most common pathogen was enterovirus/rhinovirus (51.3 %), followed by parainfluenza virus (23.1 %) and adenovirus (12.8 %). Patients with co-infection more commonly had respiratory symptoms, including SpO2 < 96 %, shortness of breath, runny nose, and wheezing. Requirement of non-invasive oxygen support was higher in the co-infection group (n = 27, 34.6 % vs. n = 28, 16.8 %, P = 0.006). By multivariable logistic regression analysis, co-infection and presence of any comorbidity were identified as significant risk factors for necessity of oxygen therapy (odds ratio [95 % confidence interval] 2.44 [1.29-4.63] and 3.99 [2.07-7.82], respectively). CONCLUSIONS: Viral co-infection may increase the risk of respiratory distress in pediatric COVID-19 patients.

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SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal-Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

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To verify if data obtained in the prehospital evaluation of patients with severe acute respiratory syndrome (SARS) during the initial response to the COVID-19 pandemic is associated with clinical outcomes: mechanical ventilation, hospital discharge, and death. This is a retrospective analysis involving secondary data from the Emergency Medical Service (EMS) records and the Health Surveillance Information System of patients assisted by the EMS in Manaus, from January to June 2020, the period of the first peak of COVID-19 cases. The combination of the two databases yielded a total of 1.190 patients, who received a first EMS response and were later admitted to hospital with SARS and had data on clinical outcomes of interest available. Patients were predominantly male (754, 63.4%), with a median age of 66 (IQR: 54.0-78.0) years. SARS illness before medical assistance was associated to need for invasive mechanical ventilation (IMV, p < 0.001). Lower pre-hospital SpO2 was associated to death (p = 0.025). Death was more common among patients with respiratory support needs, especially in the invasive ventilation group (262/287; 91.3%) (p < 0.001). In addition, IMV was more common among elderly individuals (p < 0.001). Patients admitted to ICU had a greater chance of dying when compared to non-ICU admitted patients (p < 0.001), and closely related to IMV (p < 0.001). Patients in ICU were also older (p = 0.003) and had longer hospital stay (p < 0.001). Mortality was associated with mechanical ventilation (p < 0.001), ICU admission (p < 0.001), and older age (p < 0.001). Patients who died had a shorter length of both ICU and total hospital stay (p < 0.001). Prehospital EMS may provide feasible and early recognition of critical patients with SARS in strained healthcare systems, such as in low-resource settings and pandemics.

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Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy.

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BACKGROUND: Japan implemented strict border control measures and all incoming passengers were subject to entry screening with reverse transcription-polymerase chain reaction or antigen testing. From late 2020, exit screening within 72 h of departure to Japan also became mandatory. In this study, we evaluated the effectiveness of the exit screening policy in Japan by analyzing airport screening data from October 2020 to April 2022. METHODS: In addition to assessing entry screening data over time of passengers from the United Kingdom, we examined the prevalence of coronavirus disease 2019 (COVID-19) in the United Kingdom based on the Office of National Statistics infection survey. We constructed a statistical model that described entry screening positivity over time using Office of National Statistics prevalence data as the explanatory variable. Ideally, the time-dependent patterns of entry screening and Office of National Statistics prevalence data should resemble each other; however, we found that, sometimes, they were different and regarded the difference to statistically partly reflect the effectiveness of exit screening. RESULTS: The average proportion positive in one month before mandatory exit screening was implemented among Japanese passengers was 0.67% (95% confidence interval [CI]: 0.45, 0.98), whereas the proportion positive decreased to 0.49% (95% CI: 0.21, 1.15) in the first month of exit screening. Adjusting for time-dependent prevalence at the origin, we concluded that exit screening contributed to reducing passenger positivity by 59.3% (95% CI: 19.6, 81.3). The overall positivity values among passengers during the Delta and Omicron variant periods were 3.46 times and 1.46 times that during the pre-Delta variant period, respectively. CONCLUSIONS: We used a simplistic statistical model and empirical data from passengers arriving in Japan from the United Kingdom to support that exit screening helped to reduce the proportion positive by 59%. Although the proportion positive later increased considerably and precluded preventing the introduction of imported cases, submitting a certificate for a negative test result contributed to reducing the positivity among travelers.

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Background: Patients with hematologic malignancies (HMs) may be immunocompromised after receiving anti-tumor therapy. Those who also have the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection face many challenges, including a lack of effective antiviral drugs. This study aimed to investigate the clinical features of the SARS-CoV-2 Omicron variant infection in children with HMs, and the effectiveness of Paxlovid. Methods: A retrospective, non-randomized study was conducted on pediatric patients with HMs infected with the SARS-CoV-2 Omicron variant who had been admitted to the Shanghai Children's Medical Center, Shanghai, China from December 1, 2022 to March 1, 2023. The Paxlovid-treated group (Group P) comprised 21 patients, and the non-Paxlovid-treated group (Group N) comprised 21 patients. The patients' demographic data, clinical features, and therapeutic outcomes were collected. Statistical tests were used to evaluate the effectiveness of the treatment and related factors. Results: The clinical course of the SARS-CoV-2 Omicron variant infection for most of the children with HMs was non-severe (97.6%), and only one child progressed to severe disease (2.4%). The most common symptoms were fever (66.7%) and cough (52.4%). Compared with the children in Group N, those in Group P had worse clinical characteristics, including those who previously underwent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T (CAR-T) cell treatment (71.4% vs. 28.6%, P=0.005), and those in the myelosuppressive phase (57.1% vs. 4.8%, P<0.001). Most of the children in Group P were treated with more than two types of antibiotics (76.2% vs. 42.9%, P=0.02). The patients treated with Paxlovid within 5 days of diagnosis had a median viral clearance time of 5 days [interquartile range (IQR), 4-8 days], which was significantly shorter than that of the patients who were not treated with Paxlovid (P=0.03). There were no significant differences in the clinical outcomes between the two groups after the propensity score matching (PSM) analyses. Eight patients (19%) had repeat-positive (re-positive) test results. No factor was found to be statistically significant in predicting re-positive test results based on the binary logistic regression analysis. Conclusions: Administering Paxlovid within 5 days of the diagnosis of the SARS-CoV-2 Omicron variant infection in children may effectively shorten the clearance time of the virus, but there is still the possibility the patients may have re-positive test results.

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Background The mortality and morbidity of thrombotic events in patients with coronavirus disease 2019 (COVID-19) are increasing worldwide. The clinical impact of prophylactic anticoagulation regimens among these patients in Iran remains unclear. This study aimed to evaluate the use of prophylactic anticoagulants and outcomes among COVID-19 patients admitted to a tertiary referral hospital. Methodology Patients diagnosed with COVID-19 and hospitalized between March 20 and June 20, 2020, were included in this longitudinal study after obtaining informed consent. Demographic and clinical data were collected from the hospital information system and medical records. Outcomes during this period were also evaluated. The data were entered into the preparation checklist and analyzed using SPSS version 24 software (IBM Corp., Armonk, NY, USA), employing chi-square, Fisher's exact, and Mann-Whitney U tests. Results Of the 831 enrolled patients, 51.9% were female, and 10.6% needed to be admitted to the intensive care unit (ICU). The mean age of the patients was 57.16 ± 17.32 years, and the mortality rate was estimated to be 9.4%. Mortality rates were significantly higher at older ages, in men, patients with ICU admission, severe pulmonary involvement, malignancy, airway obstruction, ischemic heart disease, and previous cerebrovascular accidents. ICU admission and mortality were statistically significantly higher in those who received concurrent prophylactic anticoagulants and aspirin than in other individuals. Conclusions Our study demonstrated that administering prophylactic aspirin with or without anticoagulant agents in COVID-19 patients did not reduce mortality rates or ICU transfers. However, it is worth noting that anticoagulant prescription was associated with a decrease in ICU admissions, which could potentially alleviate the significantly higher mortality rates observed among ICU patients in this study. Further research is needed to explore the potential benefits of anticoagulants in COVID-19 treatment.

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OBJECTIVE: To describe the use of primary care telehealth following the rapid reduction of in-person pediatric primary care availability during the severe acute respiratory syndrome coronavirus 2 pandemic and how this varied by community-level social determinants and individual-level social needs. METHODS: We conducted a retrospective cohort study of children 0 to 17 years across 16 sites within Nationwide Children's Hospital Primary Care Network from March 22 to July 31, 2020, and a preceding comparator period (2019). The study population includes 107,629 patient encounters. We compared visit type (in-person vs telehealth), demographics, presence of individual social needs, and community social determinants using the Child Opportunity Index 2.0 (COI). To assess telehealth utilization, we compared the ratio of 2019 to 2020 primary care visits across levels of COI. We trained a linear regression model predicting the number of telehealth encounters in 2020 using individual patient characteristics and COI. RESULTS: Patients in census tracts with high and very high levels of opportunity maintained the highest relative encounter volume (2020:2019) at the beginning of the pandemic (0.78 and 0.73, respectively, compared to 65% for children living in very low opportunity neighborhoods; P < 0.001). Patients with caregiver-reported social needs (housing, transportation, utilities, food) had relatively greater telehealth use following the start of the public health emergency. CONCLUSIONS: Volume of primary care visits decreased least for high and very high-opportunity neighborhoods yet individual social needs were associated with higher relative use of telemedicine. Findings suggest that telehealth was an important modality to deliver care to children with social needs but does not overcome community-level barriers.

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Myocarditis is characterized as local or diffuse inflammatory lesions in the myocardium, primarily caused by viruses and other infections. It is a common cause of sudden cardiac death and dilated cardiomyopathy. In recent years, the global prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the widespread vaccination have coincided with a notable increase in the number of reported cases of myocarditis. In light of the potential threat that myocarditis poses to global public health, numerous studies have sought to elucidate the pathogenesis of this condition. However, despite these efforts, effective treatment strategies remain elusive. To collate the current research advances in myocarditis, and thereby provide possible directions for further research, this review summarizes the mechanisms involved in viral invasion of the organism and primarily focuses on how viruses trigger excessive inflammatory responses and in result in different types of cell death. Furthermore, this article outlines existing therapeutic approaches and potential therapeutic targets for the acute phase of myocarditis. In particular, immunomodulatory treatments are emphasized and suggested as the most extensively studied and clinically promising therapeutic options.

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Background and Aim: Although reverse zoonotic transmission events from humans to domestic cats have been described, there is currently little evidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) circulation in stray cats. Due to the evidence of natural and experimental infections in cats and the capacity to disseminate the virus among them, this study aimed to identify the SARS-CoV-2 antigen in stray cats from the Federal University of Sergipe in Brazil. Materials and Methods: One hundred twenty six stray cats from the university were screened for SARS-CoV-2 antigens by random sampling. Throat swab samples were tested for the virus using rapid antigen detection tests. Results: Of the 126 animals tested, 30 (23.60%) were positive for SARS-CoV-2 antigens. To our knowledge, for the first time, this study detected the SARS-CoV-2 antigen in stray cats and confirmed the presence of SARS-CoV-2 infections in Brazil's stray cat population. Conclusion: The detection of SARS-CoV-2 in stray cats poses a risk for infected and healthy animals and possibly for humans who attend the university daily. As a limitation of the study, the small sample size necessitates caution when interpreting the results. This underscores the need for further research in this area to help control diseases in stray animals during potential pandemics. This highlights the need for monitoring and controlling the spread of the virus in stray animal populations.

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Background: The association of COVID-19 with hearing loss (HL) is unclear among young adults and needs to be investigated. This study was conducted to determine the association of COVID-19 with HL and sudden sensorineural hearing loss (SSNHL) in young adults. Methods: This nationwide population-based cohort study used data from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service. The study population consisted of young adult citizens aged 20-39 years without a history of HL. All participants were followed up from July 1, 2022 until HL, death, or December 31, 2022. A positive diagnosis of SARS-CoV-2 infection was determined through laboratory testing employing real-time reverse transcription polymerase chain reaction assays using nasopharyngeal or oropharyngeal swabs. The primary and secondary outcomes were HL and SSNHL, respectively. Age, sex, household income, Charlson comorbidity index, COVID-19 vaccination, hypertension, diabetes, and dyslipidemia-adjusted subdistribution hazard ratios (aSHRs) and 95% confidence intervals (CIs) were evaluated using the Fine-Gray subdistribution hazard regression model, considering overall death as a competing event to compare the aSHRs between COVID-19 positive and negative groups. Findings: A total of 6,716,879 young adults were eligible for the analyses. During 40,260,757 person-months (PMs) of follow-up, 38,269 cases of HL and 5908 cases of SSNHL were identified. The risk of HL (incidence: 11.9 versus 3.4/10,000 PMs; SHR, 3.51; 95% CI, 3.39-3.63; aSHR, 3.44; 95% CI, 3.33-3.56; P < 0.0001) and SSNHL (incidence: 1.8 versus 0.5/10,000 PMs; SHR, 3.58; 95% CI, 3.29-3.90; aSHR, 3.52; 95% CI, 3.23-3.83; P < 0.0001) was higher in COVID-19 group as compared to no COVID-19 group. In the sensitivity analyses that evaluated HL and SSNHL risks after adopting multiple imputations, utilizing inverse probability of treatment weighting, limiting study population to the cohort with a health screening examination, the results were consistent to the primary analysis. Interpretation: Our findings suggest a heightened risk of HL and SSNHL following COVID-19 in young adults. Due to study limitations, including the lack of objective audiological data, issues with generalizability to other populations, and the retrospective design, careful interpretation is necessary. Further studies with objective audiological data and a longer follow-up period are warranted. Funding: IITP (Institute for Information & Communications Technology Planning & Evaluation; IITP-2024- RS-00156439) and Jeju National University Hospital Research Fund (2023).

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This work proposed a simple and ultrasensitive nanozyme-based immunoassay on a filtration device for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (NP). Gold core porous platinum shell nanoparticles (Au@Pt NPs) were synthesized with high catalytic activity to oxidize 3,3',5,5'-tetramethylbenzidine, leading to an oblivious color change. The filtration device was designed based on the size difference of magnetic beads, filter membrane pore, and Au@Pt NPs. A simple, rapid, and consistent washing procedure can be performed with the help of a plastic syringe. This detection method could realize the quantitative detection of SARS-CoV-2 NP within 80 min for point-of-care needs. The limit of detection for the SARS-CoV-2 antigen was 0.01 ng/mL in buffer. The coefficients of variation of the assay were 1.78% for 10 ng/mL SARS-CoV-2 antigen, 2.03% for 1 ng/mL SARS-CoV-2 antigen, and 2.34% for the negative sample, respectively. The specificity of the detection platform was verified by the detection of various respiratory viruses. This simple and effective detection system was expected to promote substantial progress in the development and application of virus immunodetection technology.

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The ongoing COVID-19 pandemic is a persistent challenge, with continued breakthrough infections despite vaccination efforts. This has spurred interest in alternative preventive measures, including dietary and herbal interventions. Previous research has demonstrated that herbal medicines can not only inhibit cancer progression but also combat viral infections, including COVID-19 by targeting SARS-CoV-2, indicating a multifaceted potential to address both viruses and cancer. Here, we found that the Kang Guan Recipe (KGR), a novel herbal medicine formula, associates with potent inhibition activity against the SARS-CoV-2 viral infection. We demonstrate that KGR exhibits inhibitory activity against several SARS-CoV-2 variants of concern (VOCs). Mechanistically, we found that KGR can block the interaction of the viral spike and human angiotensin-converting enzyme 2 (ACE2). Furthermore, we assessed the inhibitory effect of KGR on SARS-CoV-2 viral entry in vivo, observing that serum samples from healthy human subjects having taken KGR exhibited suppressive activity against SARS-CoV-2 variants. Our investigation provides valuable insights into the potential of KGR as a novel herbal-based preventive and therapeutic strategy against COVID-19.

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The ongoing COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to multiple waves of infections globally. As the virus continues to evolve, new variants have emerged, some with concerning changes in transmissibility and virulence. Among these variants, the "FLiRT Variants" have recently gained attention due to their potential to alter the dynamics of transmission and disease severity. According to the Infectious Disease Society of America, the nickname 'FLiRT' is based on the technical names for their mutations. The FLiRT variants, particularly KP.2, seem to exhibit heightened transmissibility in comparison to earlier Omicron sub-variants. Additionally, they demonstrate a capacity to evade immunity conferred by prior infection and vaccines, although the full extent of this evasion is still being investigated. In this article, we review the characteristics of the FLiRT variants, including their genetic mutations, epidemiological features, potential impact on public health measures, and implications for vaccine efficacy. We also discuss strategies for surveillance, prevention, and mitigation efforts to control the spread of this variant and mitigate its impact on global health.

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models.

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Since coronavirus disease infection-19 (COVID-19) entry to the cells is angiotensin enzyme receptor (ACEII) dependent, extrapulmonary manifestations have been suspected. Ocular manifestations reported in several studies to involve the anterior as well as posterior eye segments. However, the predominance of the anterior eye segment reduced the attention of the scientific community on the posterior eye segment. Our results showed that the incidence of changes in the posterior eye segment is 1/5 of the anterior eye segment. Posterior eye segment manifestations include acute macular neuroretinopathy and paracentral middle maculopathy, central retinal vein/artery occlusion, reactivation of previous uveitis, varicella zoster virus-related acute retinal necrosis in an immunocompromised patient, chorioretinitis, macular hemorrhage, paracentral acute middle maculopathy, retinal detachment, and vitritis with outer retinal abnormalities. The pathogenesis of posterior eye segment manifestations under COVID-19 includes viremia, autoimmune vasculitis, hyperimmune response, coagulopathy, and cytokine storm. A full ophthalmological examination is crucial for patients recovering from COVID-19. The paper provided up-to-date manifestations with potential underlying pathophysiological mechanisms of development, as well as pathogenetic therapy.

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Introduction: Data on the management of patients aged more than 85 years with chronic hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequential infections are lacking. Methods: The current study described the management of an older couple aged more than 85 years with these above-mentioned two diseases treated with 12 weeks of sofosbuvir/velpatasvir (Epclusa®) and 5 days of nirmatrelvir/ritonavir (Paxlovid®) sequentially. The effectiveness and safety profiles were closely monitored during therapy and till 9 months posttreatment. Results: In late March 2023, the husband with the main complaint of repeated gingival bleeding and asymptomatic wife were 86 and 85 years old, and had HCV RNA levels of 91,800 and 6,630,000 IU/mL, respectively. On the fourth day of sofosbuvir/velpatasvir treatment, the husband had a moderate headache, and the wife had severe headache and moderate fever and dizziness. We then found that their SARS-CoV-2 test results were positive. After careful consideration, the expert panel decided to treat the couple with oral nirmatrelvir/ritonavir (300 mg/100 mg, twice daily) beginning on the fifth day of sofosbuvir/velpatasvir treatment for 5 days. During the 5 days of nirmatrelvir/ritonavir treatment, the patient's symptoms and signs gradually improved, and the patient was negative for SARS-CoV-2 RNA on the fifth day of nirmatrelvir/ritonavir therapy. Meanwhile, the husband's HCV RNA was not detectable after one week of sofosbuvir/velpatasvir treatment till posttreatment month 9, and his ALT level was normal beginning at week 1 of sofosbuvir/velpatasvir treatment. Moreover, the wife's HCV RNA was not detectable after week 4 of sofosbuvir/velpatasvir treatment till posttreatment month 9. Notably, no other symptoms or signs occurred during the treatment or follow-up period, and other serum biochemical parameters remained stable until 9 months after the discontinuation of sofosbuvir/velpatasvir treatment. Conclusion: The older couple aged more than 85 years with chronic HCV and SARS-CoV-2 sequential infection were safely cured by the sofosbuvir/velpatasvir and nirmatrelvir/ritonavir sequential treatment. Discussion: This study suggested that old age should not be a barrier to HCV/SARS-CoV-2 treatment. Given that the proportion of older HCV-infected patients is increasing, clinical trials of direct-acting antiviral agents should include older HCV-infected individuals.