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Background: Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients., Results: This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%., Conclusion: While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses., (© 2024. The Author(s).)

Pathogenic viral infections have become a serious public health issue worldwide. Viruses can infect all cell-based organisms and cause varying injuries and damage, resulting in diseases or even death. With the prevalence of highly pathogenic viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is urgent to develop efficient and safe approaches to inactivate pathogenic viruses. Traditional methods of inactivating pathogenic viruses are practical but have several limitations. Electromagnetic waves, with high penetration capacity, physical resonance, and non-contamination, have emerged as a potential strategy to inactivate pathogenic viruses and have attracted increasing attention. This paper reviews the recent literature on the effects of electromagnetic waves on pathogenic viruses and their mechanisms, as well as promising applications of electromagnetic waves to inactivate pathogenic viruses, to provide new ideas and methods for this inactivation. [ABSTRACT FROM AUTHOR]

The early identification of asymptomatic yet infectious cases is vital to curb the 2019 coronavirus (COVID-19) pandemic and to control the disease in the post-pandemic era. In this paper, we propose a fast, inexpensive and high-throughput approach using painless nasal-swab self-collection followed by direct RT-qPCR for the sensitive PCR detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This approach was validated in a large prospective cohort study of 1038 subjects, analysed simultaneously using (1) nasopharyngeal swabs obtained with the assistance of healthcare personnel and analysed by classic two-step RT-qPCR on RNA isolates and (2) nasal swabs obtained by self-collection and analysed with direct RT-qPCR. Of these subjects, 28.6% tested positive for SARS-CoV-2 using nasopharyngeal swab sampling. Our direct RT-qPCR approach for self-collected nasal swabs performed well with results similar to those of the two-step RT-qPCR on RNA isolates, achieving 0.99 positive and 0.98 negative predictive values (cycle threshold [Ct] < 37). Our research also reports on grey-zone viraemia, including samples with near-cut-off Ct values (Ct ≥ 37). In all investigated subjects (n = 20) with grey-zone viraemia, the ultra-small viral load disappeared within hours or days with no symptoms. Overall, this study underscores the importance of painless nasal-swab self-collection and direct RT-qPCR for mass testing during the SARS-CoV-2 pandemic and in the post-pandemic era. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood. Methods: We conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected. Results: A total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P < 0.001), as well as in-hospital mortality (50.0% vs. 13.7%, P < 0.001), independent of age, disease severity, sepsis, lymphocyte count and C-Reactive protein. In addition, the risk for 180-day mortality increased with the SARS-CoV-2 RNA load in plasma. Plasma cytokines, including IL-6, IL-8 and IL-10, were higher in patients with SARS-CoV-2 RNAemia. Conclusions: Our study indicates that SARS-CoV-2 RNAemia serves as a useful biomarker for predicting mortality, especially long-term mortality, in older adult patients hospitalized in pulmonary intermediate care units. Trial registration: Chinese Clinical Trial Registry website (No. ChiCTR2300067434). [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases. The pathophysiology of COVID-19 uses the following three mechanisms: (1) inflammasome activation mechanism; (2) cGAS–STING signaling mechanism; and (3) SAMHD1 tetramerization mechanism, which leads to IFN-I production. Interactions between the host and virus govern induction, resulting in multiorgan impacts. The NLRP3 with cGAS–STING constitutes the primary immune response. The expression of SARS-CoV-2 ORF3a, NSP6, NSP7, and NSP8 blocks innate immune activation and facilitates virus replication by targeting the RIG-I/MDA5, TRIF, and cGAS–STING signaling. SAMHD1 has a target motif for CDK1 to protect virion assembly, threonine 592 to modulate a catalytically active tetramer, and antiviral IFN responses to block retroviral infection. Plastic and allosteric nucleic acid binding of SAMHD1 modulates the antiretroviral activity of SAMHD1. Therefore, inflammasome activation, cGAS–STING signaling, and SAMHD1 tetramerization explain acute kidney injury, hepatic, cardiac, neurological, and gastrointestinal injury of COVID-19. It might be necessary to effectively block the pathological courses of diverse diseases. Highlights: 1. DNA-driven immune response connects with NLRP3 and controls its inflammasome activity, which leads to IFN-I production via STING. The NLRP3 with cGAS-STING constitutes the primary immune response. 2. The expression of SARS-CoV-2 ORF3a, NSP6, NSP7, and NSP8 blocks innate immune activation and facilitates virus replication by targeting the RIG-I/MDA5, TRIF, and cGAS-STING signaling. 3. Plastic and allosteric nucleic acid binding of SAMHD1 reduces the magnitude of IFN and induction of virus-specific cytotoxic T cells. SAMHD1-deficient cells detect and activate IFN-I-mediated self ISG gene expression via cGAS–STING. 4. SAMHD1 autonomously controls viral infection through innate and adaptive immunity at the level of the infected cell. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has underscored the critical role of sequencing technology in disease control and outbreak response. However, resource limitations and challenging environments often impede such efforts in low and middle-income countries. This study aimed to investigate the spectrum of viral co-infections, particularly with human viral pathogens, in SARS-CoV-2 positive individuals in Sierra Leone using metagenomic sequencing, evaluating the feasibility of utilizing this technology for epidemiological and evolutionary surveillance of pathogens related to public health in low-income environments. Methods: We retrospectively collected and analyzed 98 nasopharyngeal swab specimens from SARS-CoV-2 positive individuals in Sierra Leone. Samples were pre-processed locally and transferred to China via FTA cards for metagenomic sequencing, which was performed using the Novaseq platform. The study focused on the identification of nasopharyngeal viruses co-infecting with SARS-CoV-2, with a deeper analysis of significant human viral pathogens such as HPV. Results: The study identified 22 viral taxa from 20 families, including 4 human viruses. Notably, 19.4% of samples showed HPV co-infection with 34 distinct types, predominantly beta and gamma HPVs. Multiple HPV types were found in individual samples, indicating a high complexity of viral co-infections. Conclusions: The identification of a wide range of co-infecting viruses, particularly multiple HPV genotypes, highlights the complexity of viral interactions and their potential implications for public health. These findings enhance our understanding of viral co-infections and provide valuable insights for public health interventions in Sierra Leone. Further research is needed to explore the clinical significance of these findings and their impact on disease outcomes. [ABSTRACT FROM AUTHOR]

Background: During the pandemic, whole genome sequencing was critical to characterize SARS-CoV-2 for surveillance, clinical and therapeutical purposes. However, low viral loads in specimens often led to suboptimal sequencing, making lineage assignment and phylogenetic analysis difficult. We propose an alternative approach to sequencing these specimens that involves sequencing in triplicate and concatenation of the reads obtained using bioinformatics. This proposal is based on the hypothesis that the uncovered regions in each replicate differ and that concatenation would compensate for these gaps and recover a larger percentage of the sequenced genome. Results: Whole genome sequencing was performed in triplicate on 30 samples with Ct > 32 and the benefit of replicate read concatenation was assessed. After concatenation: i) 28% of samples reached the standard quality coverage threshold (> 90% genome covered > 30x); ii) 39% of samples did not reach the coverage quality thresholds but coverage improved by more than 40%; and iii) SARS-CoV-2 lineage assignment was possible in 68.7% of samples where it had been impaired. Conclusions: Concatenation of reads from replicate sequencing reactions provides a simple way to access hidden information in the large proportion of SARS-CoV-2-positive specimens eliminated from analysis in standard sequencing schemes. This approach will enhance our potential to rule out involvement in outbreaks, to characterize reinfections and to identify lineages of concern for surveillance or therapeutical purposes. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, antigen diagnostic tests were frequently used for screening, triage, and diagnosis. Novel instrument-based antigen tests (iAg tests) hold the promise of outperforming their instrument-free, visually-read counterparts. Here, we provide a systematic review and meta-analysis of the SARS-CoV-2 iAg tests' clinical accuracy. Methods: We systematically searched MEDLINE (via PubMed), Web of Science, medRxiv, and bioRxiv for articles published before November 7th, 2022, evaluating the accuracy of iAg tests for SARS-CoV-2 detection. We performed a random effects meta-analysis to estimate sensitivity and specificity and used the QUADAS-2 tool to assess study quality and risk of bias. Sub-group analysis was conducted based on Ct value range, IFU-conformity, age, symptom presence and duration, and the variant of concern. Results: We screened the titles and abstracts of 20,431 articles and included 114 publications that fulfilled the inclusion criteria. Additionally, we incorporated three articles sourced from the FIND website, totaling 117 studies encompassing 95,181 individuals, which evaluated the clinical accuracy of 24 commercial COVID-19 iAg tests. The studies varied in risk of bias but showed high applicability. Of 24 iAg tests from 99 studies assessed in the meta-analysis, the pooled sensitivity and specificity compared to molecular testing of a paired NP swab sample were 76.7% (95% CI 73.5 to 79.7) and 98.4% (95% CI 98.0 to 98.7), respectively. Higher sensitivity was noted in individuals with high viral load (99.6% [95% CI 96.8 to 100] at Ct-level ≤ 20) and within the first week of symptom onset (84.6% [95% CI 78.2 to 89.3]), but did not differ between tests conducted as per manufacturer's instructions and those conducted differently, or between point-of-care and lab-based testing. Conclusion: Overall, iAg tests have a high pooled specificity but a moderate pooled sensitivity, according to our analysis. The pooled sensitivity increases with lower Ct-values (a proxy for viral load), or within the first week of symptom onset, enabling reliable identification of most COVID-19 cases and highlighting the importance of context in test selection. The study underscores the need for careful evaluation considering performance variations and operational features of iAg tests. [ABSTRACT FROM AUTHOR]

Influenza and SARS-CoV-2 are two major respiratory pathogens that cocirculate in humans and cause serious illness with the potential to exacerbate disease in the event of co-infection. To develop a bivalent vaccine, capable of protecting against both infections, we inserted the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein into hemagglutinin (HA) molecule or into the open reading frame of the truncated nonstructural protein 1 (NS1) of live attenuated influenza vaccine (LAIV) virus and assessed phenotypic characteristics of the rescued LAIV-RBD viruses, as well as their immunogenicity in mouse and Syrian hamster animal models. A panel of 9 recombinant LAIV-RBD viruses was rescued using the A/Leningrad/17 backbone. Notably, only two variants with RBD insertions into the HA molecule could express sufficient quantities of RBD protein in infected MDCK cells. Intranasal immunization of mice induced high levels of anti-influenza antibody responses in all chimeric LAIV-RBD viruses, which was comparable to the LAIV virus vector. The RBD-specific antibody responses were most pronounced in the variant expressing RBD194 fragment as a chimeric HA protein. This candidate was further tested in Syrian hamsters and was shown to be immunogenic and capable of protecting animals against both infections. [ABSTRACT FROM AUTHOR]

Purpose: Besides the well-established efficacy in preventing severe COVID-19, the impact of early treatments, namely antivirals and monoclonal antibodies (mAbs), on the time length to negativization of SARS-CoV-2 nasal swabs is still unclear. The aim of this study was to compare the efficacy of different early treatments in reducing the SARS-CoV-2 viral shedding, identifying a single drug that might potentially lead to a more rapid negativization of SARS-CoV-2 nasal swab. Methods: This was a single-centre, retrospective, observational study conducted at Ospedale Luigi Sacco in Milan. Data of high-risk COVID-19 patients who received early treatments between 23 December 2021 and March 2023 were extracted. The comparison across treatments was conducted using the Kruskall-Wallis test for continuous variables. Dunn's test with Bonferroni adjustment was performed for post-hoc comparisons of days to negativization. Secondly, a negative binomial regression adjusted for age, sex, number of comorbidities, immunosuppression, and SARS-CoV-2 vaccination status was implemented. Results: Data from 428 patients receiving early treatments were collected. The majority were treated with Nirmatrelvir/Ritonavir and were affected by SARS-CoV-2 Omicron infection with BA.2 sublineage. The median length time to SARS-CoV-2 nasal swab negativization was 9 days [IQR 7–13 days]. We found that Nirmatrelvir/Ritonavir determined a significant decrease of the length time to SARS-CoV-2 nasal swab negativization compared to mAbs (p = 0.003), but not compared to Remdesivir (p = 0.147) and Molnupiravir (p = 0.156). Conclusion: Our findings highlight the importance of promptly treating high-risk COVID-19 patients with Nirmatrelvir/Ritonavir, as it also contributes to achieving a faster time to negative SARS-CoV-2 nasal swabs. [ABSTRACT FROM AUTHOR]

COVID-19 is a complex disease that can lead to fatal respiratory failure with extrapulmonary complications, either as a direct result of viral invasion in multiple organs or secondary to oxygen supply shortage. Liver is susceptible to many viral pathogens, and due to its versatile functions in the body, it is of great interest to determine how hepatocytes may interact with SARS-CoV-2 in COVID-19 patients. Liver injury is a major cause of death, and SARS-CoV-2 is suspected to contribute significantly to hepatopathy. Owing to the lack of knowledge in this field, further research is required to address these ambiguities. Therefore, we aimed to provide a comprehensive insight into host-virus interactions, underlying mechanisms, and associated risk factors by collecting results from epidemiological analyses and relevant laboratory experiments. Backed by an avalanche of recent studies, our findings support that liver injury is a sequela of severe COVID-19, and certain pre-existing liver conditions can also intensify the morbidity of SARS-CoV-2 infection in synergy. Notably, age, sex, lifestyle, dietary habits, coinfection, and particular drug regimens play a decisive role in the final outcome and prognosis as well. Taken together, our goal was to unravel these complexities concerning the development of novel diagnostic, prophylactic, and therapeutic approaches with a focus on prioritizing high-risk groups. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus (A.) fumigatus culture media (i.e., supernatant) possessed protease activity that was sufficient to activate the SARS-CoV-2 spike protein. Methods: The supernatant was first analysed for protease activity. Thereafter, it was assessed to determine if it possessed proteolytic activity to cleave a fluorogenic mimetic peptide of the SARS-CoV-2 spike protein that contained the S1/S2 site and a full-length spike protein contained in a SARS-CoV-2 pseudovirion. To complement this, a computer-based tool, HADDOCK, was used to predict if A. fumigatus alkaline protease 1 could bind to the SARS-CoV-2 spike protein. Results: We show that the supernatant possessed proteolytic activity, and analyses of the molecular docking parameters revealed that A. fumigatus alkaline protease 1 could bind to the spike protein. To confirm the in silico data, it was imperative to provide experimental evidence for enzymatic activity. Here, it was noted that the A. fumigatus supernatant cleaved the mimetic peptide as well as transduced the HEK-293T cells with SARS-CoV-2 pseudovirions. Conclusion: These results suggest that A. fumigatus secretes a protease(s) that activates the SARS-CoV-2 spike protein. Importantly, should these two infectious agents co-occur, there is the potential for A. fumigatus to activate the SARS-CoV-2 spike protein, thus aggravating COVID-19 development. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Introduction: The sudden arrival of the COVID-19 pandemic placed significant stresses on supply chains including viral transport medium (VTM). The VTM that was urgently required needed to support viral replication, as well as other routine diagnostic approaches. We describe the preparation and validation testing of VTM for rapidly expanding diagnostic testing, where the capacity of the VTM to preserve viral integrity, for culture, isolation and full sequence analysis, was maintained. Methods: VTM was prepared using different methods of sterilization then 'spiked' with virus. The VTM was investigated using viral culture in Vero cells, and for nucleic acid detection by quantitative PCR. Results: The best results were obtained by filter and autoclave-based sterilization. The VTM proved robust for culture-based analyses provided the inoculated VTM was stored at 4 °C, and tested within 48 h. The filtered VTM also supported PCR-based diagnosis for at least 5 days when the mock inoculated VTM was held at room temperature. Discussion: The manual handling of VTM production, including filling and sterilization, was optimized. SARS-CoV-2 was spiked into VTM to assess different sterilization methods and measure the effects of storage time and temperature upon VTM performance. While most diagnostic protocols will not require replication competent virus, the use of high quality VTM will allow for the next phase of laboratory analysis in the COVID-19 pandemic, including drug and antibody susceptibility analysis of re-isolated SARS-CoV-2, and for the testing of vaccine escape mutants. [ABSTRACT FROM AUTHOR]

Background: Omicron's high transmissibility and variability present new difficulties for COVID-19 vaccination prevention and therapy. In this article, we analyzed the sensitivity of vaccine-induced antibodies as well as the effect of booster vaccinations against Omicron sublineages. Methods: We looked for Randomized Controlled Trials and cohort studies that reported the COVID-19 vaccines against Omicron sublineages up to 28 July 2022 through PubMed, the Cochrane Library, EMBASE, and Web of Science. Quantitative synthesis was carried out using Stata 16.0 and RevMa5.3, then the serum NT50 and antibody sensitivity to neutralize Omicron sublineages were assessed before and after booster vaccination. This study was registered with PROSPERO number CRD42022350477. Results: This meta-analysis included 2138 patients from 20 studies, and the booster vaccination against Omicron sublineages showed a significant difference compared to 2 dosage: BA.1/BA.1.1 (SMD = 0.80, 95% CI: 0.75–0.85, P = 0.00), BA.2/BA.2.12.1 (SMD = 0.77, 95% CI: 0.69–0.85, P = 0.00), BA.3 (SMD = 0.91, 95% CI: 0.83–1.0, P = 0.00), and BA.4/5 (SMD = 0.77, 95% CI: 0.60–0.94, P = 0.00). The sensitivity of vaccines-induced antibodies decreased by at least 5-folds after booster vaccination, particularly in the case of BA.4/5 which had the most notable decline in vaccine effectiveness. Conclusion: After the booster vaccination, the NT50 and the neutralization ability of vaccine-induced antibodies increased, but the susceptibility of antibodies decreased compared with the control virus, which may be a clue for future Omicron sublineages prevention. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 has evolved several strategies to overcome host cell defenses by inducing cell injury to favour its replication. Many viruses have been reported to modulate the intracellular redox balance, affecting the Nuclear factor erythroid 2-Related Factor 2 (NRF2) signaling pathway. Although antioxidant modulation by SARS-CoV-2 infection has already been described, the viral factors involved in modulating the NRF2 pathway are still elusive. Given the antagonistic activity of ORF6 on several cellular pathways, we investigated the role of the viral protein towards NRF2-mediated antioxidant response. The ectopic expression of the wt-ORF6 protein negatively impacts redox cell homeostasis, leading to an increase in ROS production, along with a decrease in NRF2 protein and its downstream controlled genes. Moreover, when investigating the Δ61 mutant, previously described as an inactive nucleopore proteins binding mutant, we prove that the oxidative stress induced by ORF6 is substantially related to its C-terminal domain, speculating that ORF6 mechanism of action is associated with the inhibition of nuclear mRNA export processes. In addition, activation by phosphorylation of the serine residue at position 40 of NRF2 is increased in the cytoplasm of wt-ORF6-expressing cells, supporting the presence of an altered redox state, although NRF2 nuclear translocation is hindered by the viral protein to fully antagonize the cell response. Furthermore, wt-ORF6 leads to phosphorylation of a stress-activated serine/threonine protein kinase, p38 MAPK, suggesting a role of the viral protein in regulating p38 activation. These findings strengthen the important role of oxidative stress in the pathogenesis of SARS-CoV-2 and identify ORF6 as an important viral accessory protein hypothetically involved in modulating the antioxidant response during viral infection. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 outbreak has hit Beijing since mid-Nov, 2022, with soaring growth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. Therefore, it is vital to determine the clinical manifestations of epidemic SARS-CoV-2 strains in paediatric patients. Methods: In this study, nucleic acid tests (NATs) for SARS-CoV-2 were performed in paediatric outpatients with symptoms of acute respiratory tract infection during 18 Nov–6 Dec, 2022. Half of the outpatients positive for SARS-CoV-2 were randomly selected to screen for other respiratory pathogens, whereas those with low cycle threshold values in SARS-CoV-2 NATs were amplified and sequenced to determine the SARS-CoV-2 variants. Finally, children positive for SARS-CoV-2 with clinical information in detail were enrolled in a follow-up study to identify potential factors significantly associated with long recovery. Results: Among 9625 paediatric outpatients tested for nucleic acid of SARS-CoV-2, 733 (7.62%, 733/9625) were identified as SARS-CoV-2 NAT positive, with only three (0.82%, 3/366) co-infected with other pathogens among 366 randomly selected patients, and 71 (62.83%) determined as Omicron subvariant BF.7 and 42 (37.22%) as BA.5.2 among 113 successfully sequenced. Among the 681 patients with complete clinical information, fever was the most common symptom (96.8%). In a follow-up study of 592 patients, 46.96% became asymptomatic on the third day and 65.71% on the fifth day. Only 1.7% of infected children experienced febrile seizures. Combined with abnormal C-reactive protein, a higher percentage of antibiotics administration was observed. More co-living members and longer duration of first symptoms served as independent risk factors for long-term recovery, especially in children vaccinated for SARS-CoV-2. Conclusions: BF.7 and BA.5.2 were the dominate Omicron subvariants and caused milder infections during the SARS-CoV-2 outbreak in Beijing. The number of co-living members and duration of first symptoms were independent risk factors for long-term recovery. [ABSTRACT FROM AUTHOR]

Background: Although three years after the outbreak of SARS-CoV-2, the virus is still having a significant impact on human health and the global economy. Infection through respiratory droplets is the main transmission route, but the transmission of the virus by surface contact cannot be ignored. Hand sanitizers and antiviral films can be applied to control SARS-CoV-2, but sanitizers and films show drawbacks such as resistance of the virus against ethanol and environmental problems including the overuse of plastics. Therefore, this study suggested applying natural substrates to hand sanitizers and antiviral films made of biodegradable plastic (PLA). This approach is expected to provide advantages for the easy control of SARS-CoV-2 through the application of natural substances. Methods: Antiviral disinfectants and films were manufactured by adding caffeic acid and vanillin to ethanol, isopropyl alcohol, benzalkonium chloride, and PLA. Antiviral efficacies were evaluated with slightly modified international standard testing methods EN 14,476 and ISO 21,702. Results: In suspension, all the hand sanitizers evaluated in this study showed a reduction of more than 4 log within 2 min against HCoV-229E. After natural substances were added to the hand sanitizers, the time needed to reach the detection limit of the viral titer was shortened both in suspension and porcine skin. However, no difference in the time needed to reach the detection limit of the viral titer was observed in benzalkonium chloride. In the case of antiviral films, those made using both PLA and natural substances showed a 1 log reduction of HCoV-229E compared to the neat PLA film for all treatment groups. Furthermore, the influence of the organic load was evaluated according to the number of contacts of the antiviral products with porcine skin. Ten rubs on the skin resulted in slightly higher antiviral activity than 50 rubs. Conclusion: This study revealed that caffeic acid and vanillin can be effectively used to control HCoV-229E for hand sanitizers and antiviral films. In addition, it is recommended to remove organic matter from the skin for maintaining the antiviral activity of hand sanitizer and antiviral film as the antiviral activity decreased as the organic load increased in this study. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders. [ABSTRACT FROM AUTHOR]