Stability of SARS-CoV-2 and persistence of viral nucleic acids on common foods and widely used packaging material surfaces.

SARS-CoV-2 is still spreading globally. Studies have reported the stability of SARS-CoV-2 in aerosols and on surfaces under different conditions. However, studies on the stability of SARS-CoV-2 and viral nucleic acids on common food and packaging material surfaces are insufficient. The study evaluated the stability of SARS-CoV-2 using TCID50 assays and the persistence of SARS-CoV-2 nucleic acids using droplet digital polymerase chain reaction on various food and packaging material surfaces. Viral nucleic acids were stable on food and material surfaces under different conditions. The viability of SARS-CoV-2 varied among different surfaces. SARS-CoV-2 was inactivated on most food and packaging material surfaces within 1 day at room temperature but was more stable at lower temperatures. Viruses survived for at least 1 week on pork and plastic at 4°C, while no viable viruses were detected on hairtail, orange, or carton after 3 days. There were viable viruses and a slight titer decrease after 8 weeks on pork and plastic, but titers decreased rapidly on hairtail and carton at -20°C. These results highlight the need for targeted preventive and disinfection measures based on different types of foods, packaging materials, and environmental conditions, particularly in the cold-chain food trade, to combat the ongoing pandemic.

A Comparison of Clinical Characteristics of Infections with SARS-CoV-2 Omicron Subvariants BF.7.14 and BA.5.2.48 - China, October-December 2022.

What is already known about this topic?: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, the clinical manifestations resulting from different SARS-CoV-2 variants may demonstrate significant variation. What is added by this report?: We conducted a comparative analysis of the clinical features associated with SARS-CoV-2 Omicron subvariants BF.7.14 and BA.5.2.48 infections. The results of our study indicate that there are no substantial differences in clinical manifestations, duration of illness, healthcare-seeking behaviors, or treatment between these two subvariants. What are the implications for public health practice?: Timely identification of alterations in the clinical spectrum is crucial for researchers and healthcare practitioners in order to enhance their comprehension of clinical manifestations, as well as the progression of SARS-CoV-2. Furthermore, this information is beneficial for policymakers in the process of revising and implementing appropriate countermeasures.

Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.

Pulmonary fibrosis is a typical sequela of coronavirus disease 2019 (COVID-19), which is linked with a poor prognosis for COVID-19 patients. However, the underlying mechanism of pulmonary fibrosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 induced pulmonary fibrosis by activating pulmonary fibroblasts. N protein interacted with the transforming growth factor ß receptor I (TßRI), to disrupt the interaction of TßRI-FK506 Binding Protein12 (FKBP12), which led to activation of TßRI to phosphorylate Smad3 and boost expression of pro-fibrotic genes and secretion of cytokines to promote pulmonary fibrosis. Furthermore, we identified a compound, RMY-205, that bound to Smad3 to disrupt TßRI-induced Smad3 activation. The therapeutic potential of RMY-205 was strengthened in mouse models of N protein-induced pulmonary fibrosis. This study highlights a signaling pathway of pulmonary fibrosis induced by N protein and demonstrates a novel therapeutic strategy for treating pulmonary fibrosis by a compound targeting Smad3.

Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Epidemiological features, genomic characteristics, and origin tracing of the COVID-19 outbreaks in Beijing from January to September 2022.

Different variants of severe acute respiratory syndrome coronavirus 2 have been discovered globally. At present, the Omicron variant has been extensively circulated worldwide. There have been several outbreaks of the Omicron variant in China. Here, we investigated the epidemiologic, genetic characteristics, and origin-tracing data of the outbreaks of COVID-19 in Beijing from January to September 2022. During this time, 19 outbreaks occurred in Beijing, with the infected cases ranging from 2 to 2230. Two concern variants were detected, with eight genotypes. Based on origin tracing analysis, two outbreaks were from the cold-chain transmission and three from items contaminated by humans. Imported cases have caused other outbreaks. Our study provided a detailed analysis of Beijing's outbreaks and valuable information to control the outbreak's spread.

Characterisation of SARS-CoV-2 variants in Beijing during 2022: an epidemiological and phylogenetic analysis.

BACKGROUND: Due to the national dynamic zero-COVID strategy in China, there were no persistent local transmissions of SARS-CoV-2 in Beijing before December, 2022. However, imported cases have been frequently detected over the past 3 years. With soaring growth in the number of COVID-19 cases in China recently, there are concerns that there might be an emergence of novel SARS-CoV-2 variants. Routine surveillance of viral genomes has been carried out in Beijing over the last 3 years. Spatiotemporal analyses of recent viral genome sequences compared with that of global pooled and local data are crucial for the global response to the ongoing COVID-19 pandemic. METHODS: We routinely collected respiratory samples covering both imported and local cases in Beijing for the last 3 years (of which the present study pertains to samples collected between January and December, 2022), and then randomly selected samples for analysis. Next-generation sequencing was used to generate the SARS-CoV-2 genomes. Phylogenetic and population dynamic analyses were performed using high-quality complete sequences in this study. FINDINGS: We obtained a total of 2994 complete SARS-CoV-2 genome sequences in this study, among which 2881 were high quality and were used for further analysis. From Nov 14 to Dec 20, we sequenced 413 new samples, including 350 local cases and 63 imported cases. All of these genomes belong to the existing 123 Pango lineages, showing there are no persistently dominant variants or novel lineages. Nevertheless, BA.5.2 and BF.7 are currently dominant in Beijing, accounting for 90% of local cases since Nov 14 (315 of 350 local cases sequenced in this study). The effective population size for both BA.5.2 and BF.7 in Beijing increased after Nov 14, 2022. INTERPRETATION: The co-circulation of BF.7 and BA.5.2 has been present in the current outbreak since Nov 14, 2022 in Beijing, and there is no evidence that novel variants emerged. Although our data were only from Beijing, the results could be considered a snapshot of China, due to the frequent population exchange and the presence of circulating strains with high transmissibility. FUNDING: National Key Research and Development Program of China and Strategic Priority Research Program of the Chinese Academy of Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Serial Increases in Human Leukocyte Antigen-DR Expression and Decreases in Interleukin-10 Expression in Alveolar Monocytes of Survivors of Pneumonia-Related Acute Respiratory Distress Syndrome.

ARDS is a potentially lethal syndrome. HLA-DR expression in monocytes reflects their activation and antigen-presenting capacity. However, the correlation between clinical outcomes and HLA-DR expression in alveolar monocytes/macrophages in patients with pneumonia-related ARDS remains unclear. Thus, we determined the trends of HLA-DR and cytokine expressions in alveolar monocytes using repeated measurements to answer this question. Thirty-one pneumonia patients with respiratory failure and ARDS without coronavirus disease 2019 between November 2019 and November 2021 were enrolled in our intensive care unit and three without complete data were excluded. Interleukin (IL)-10, IL-12, and HLA-DR expression in bronchoalveolar lavage (BAL) monocytes were determined on days one and eight. Monocyte HLA-DR expression (mHLA-DR) and CD4 T lymphocytes percentages in BAL cells of survivors increased remarkably after seven days. Monocyte IL-10 expression and monocytes percentages in BAL cells of survivors decreased substantially after seven days. The mHLA-DR was negatively correlated with disease severity scores on day one and eight. In conclusion, serial increases in HLA-DR expression and decreases in IL-10 expression were observed in BAL monocytes of survivors of pneumonia-related ARDS. More studies are needed to confirm this point of view, and then development of a therapeutic agent restoring mHLA-DR and preventing IL-10 production can be considered.

Using neutrophil to lymphocyte ratio to predict discharge among geriatric patients with influenza infection in emergency department.

The neutrophil-to-lymphocyte ratio (NLR) is used to predict the prognosis of various diseases, such as coronavirus disease 2019, community-acquired pneumonia, bacteremia, and endocarditis. However, NLR has never been reported to predict patient discharge in geriatric patients with influenza infection. This retrospective case-control study enrolled geriatric patients (≥65 years) with influenza virus infection who visited the emergency department of a medical center between January 01, 2010 and December 31, 2015. Demographic data, vital signs, past histories, influenza subtypes, outcomes, and disposition were analyzed. The optimal NLR cut-off value to predict patient discharge was determined using the Youden index. We also evaluated the accuracy of NLR in predicting patient discharge using logistic regression and receiver operating characteristic analysis. The study included 409 geriatric patients in the emergency department with a mean age of 79.5 years and an approximately equal sex ratio. NLR was significantly lower in the discharged group than in the nondischarged group (5.8 ± 3.7 vs 9.7 ± 8.4). Logistic regression revealed that patients with NLR ≤ 6.5 predicted discharge with an odds ratio of 3.62. The Hosmer-Lemeshow goodness-of-fit test was calculated as 0.36, and the adjusted area under the receiver operating characteristic was 0.75. The negative predictive value of NLR ≤ 6.5, to predict patient discharge, was 91.8%. NLR ≤ 6.5 is a simple and easy-to-obtain laboratory tool to guide the physicians to discharge geriatric patients with influenza infection in the crowded emergency department.

Genomic characteristics of SARS-CoV-2 in Beijing, China, 2021.

At present, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, which has emerged multiple variants and brought a threat to global public health. To analyze the genomic characteristics and variations of SARS-CoV-2 imported into Beijing, we collected the respiratory tract specimens of 112 cases of coronavirus disease 2019 (COVID-19) from January to September 2021 in Beijing, China, including 40 local cases and 72 imported cases. The whole-genome sequences of the viruses were sequenced by the next-generation sequencing method. Variant markers and phylogenic features of SARS-CoV-2 were analyzed. Our results showed that in all 112 sequences, the mutations were concentrated in spike protein. D614G was found in all sequences, and mutations including L452R, T478K, P681R/H, and D950N in some cases. Furthermore, 112 sequences belonged to 23 lineages by phylogenetic analysis. B.1.1.7 (Alpha) and B.1.617.2 (Delta) lineages were dominant. Our study drew a variation image of SARS-CoV-2 and could help evaluate the potential risk of COVID-19 for pandemic preparedness and response.

The psychological impact of COVID-19 outbreak on medical staff and the general public.

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

Research progress in anti-coronavirus effect and safety of chloroquine

Coronavirus, identified as a zoonotic pathogen, can cause pulmonary infections and even a pandemic. Corona Virus Disease 2019 (COVID-19), which was induced by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), struck the world in December 2019. There is no specific drug for coronavirus. As a classical antimalarial drug, chloroquine has been proved to have antiviral activity by changing the pH of endocytosis, via autophagy reactions and by changing the glycosylation mode of the virus envelope. At the cellular level, chloroquine has inhibitory effects on SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV- 2. Recent clinical research results are beginning to show that chloroquine can improve the success rate and prognosis. Chloroquine has been used less clinically in recent years due to the many adverse reactions it causes. The safety of chloroquine used in coronavirus infection requires in-depth evaluation. This article summarizes research progress in the anti-coronavirus effect and safety of chloroquine in order to provide reference for its clinical application.

Prolonged Mechanical Ventilation: Outcomes and Management

The number of patients requiring prolonged mechanical ventilation (PMV) is increasing worldwide, placing a burden on healthcare systems. Therefore, investigating the pathophysiology, risk factors, and treatment for PMV is crucial. Various underlying comorbidities have been associated with PMV. The pathophysiology of PMV includes the presence of an abnormal respiratory drive or ventilator-induced diaphragm dysfunction. Numerous studies have demonstrated that ventilator-induced diaphragm dysfunction is related to increases in in-hospital deaths, nosocomial pneumonia, oxidative stress, lung tissue hypoxia, ventilator dependence, and costs. Thus far, the pathophysiologic evidence for PMV has been derived from clinical human studies and experimental studies in animals. Moreover, recent studies have demonstrated the outcome benefits of pharmacological agents and rehabilitative programs for patients requiring PMV. However, methodological limitations affected these studies. Controlled prospective studies with an adequate number of participants are necessary to provide evidence of the mechanism, prognosis, and treatment of PMV. The great epidemiologic impact of PMV and the potential development of treatment make this a key research field.

Importation of SARS-CoV-2 Omicron variant in Beijing, China.

Omicron (B.1.1.529), the fifth variant of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was firstly identified in November 2021 in South Africa. Omicron contains far more genome mutations than any other VOCs ever found, raising significant concerns about its increased transmissibility and immune evasion. Here, we report the importation of the Omicron variant into Beijing, China, in December 2021. Full-length genome sequences of five imported strains were obtained, with their genetic features characterized. Each strain contained 57 to 61 nucleotide substitutions, 39 deletions, and 9 insertions in the genome. Thirty to thirty-two amino acid changes were found in the spike proteins of the five strains. The phylogenetic tree constructed by the maximum likelihood method showed that all five imported genomes belonged to Omicron (BA.1) (alias of B.1.1.529.1), which is leading to the current surge of coronavirus disease 2019 (COVID-19) cases worldwide. The globally increased COVID-19 cases driven by the Omicron variant pose a significant challenge to disease prevention and control in China. Continuous viral genetic surveillance and increased testing among international travellers are required to contain this highly contagious variant.

Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro.

BACKGROUND: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. METHODS: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. FINDINGS: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. INTERPRETATION: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Pneumonia rebound after stopping steroid in a patient with COVID-19: A case report.

Patients with severe coronavirus disease 2019 (COVID-19) can develop a systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction. The current treatment guideline recommends the use of corticosteroids in patients who require supplemental oxygen or are mechanically ventilated. This study reports a patient with severe COVID-19 pneumonia. Initially, the patient was treated with dexamethasone for 10 days and remdesivir for 5 days. There was clinical improvement following the treatments. However, on day 15, the patient experienced rebound pneumonia and clinical deterioration. His clinical condition improved until dexamethasone was re-administered. This case demonstrates the rebound phenomenon after the steroid was discontinued. The duration and timing of steroids are crucial to reduce the risk of prolonged systemic inflammation and rebound pneumonia.

Network pharmacology studies on the effect of chai-ling decoction in Coronavirus disease 2019

Background: Chai-Ling decoction (CLD), derived from a modification of Xiao-Chai-Hu (XCH) decoction and Wu-Ling-San (WLS) decoction, has been used to treat the early-stage of coronavirus disease 2019 (COVID-19). However, the mechanisms of CLD in COVID-19 remain unknown. In this study, the potential mechanisms of CLD in COVID-19 were preliminarily investigated based on network pharmacology and molecular docking method.

Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-CoV-2 Infection in vitro (preprint)

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/432949v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@127e6c4org.highwire.dtl.DTLVardef@9f6d3aorg.highwire.dtl.DTLVardef@bbfe3borg.highwire.dtl.DTLVardef@2ffad8_HPS_FORMAT_FIGEXP M_FIG C_FIG