Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Factors affecting psychological health and career choice among medical students in eastern and western region of China after COVID-19 pandemic.

Introduction: To unearth superior countermeasures that improve psychological health and upgrade the quality of employment for medical students in China in post-epidemic era, this study was designed to determine the possible factors affecting psychological status and future career choice of this population. Methods: A cross-sectional observational study was carried out. Depression Anxiety Stress Scale-21 (DASS-21) and Insomnia Severity Index (ISI) were applied to measure psychological state. Chi-square and logistic regression analyses were adopted to filtrate related factors for psychological health and employment intention. Results: A total of 936 medical students, including 522 from eastern universities and 414 from western universities, were enrolled in the study. Anxiety among students in China's western universities was higher than that in China's eastern universities (30.4% vs. 22.0%), but no differences in the occurrences of stress (11.4% vs. 13.4%), depression (28.7% vs. 24.5%) and insomnia (30.7% vs. 25.7%). Grades, academic ranking, household income, attitudes about COVID-19 were associated with the occurrence of psychological problems. In addition, major, education level, academic ranking, family income, and clinical experience may affect the choice of future employment location and employment income. Notably, household income affected by COVID-19 and the perception of epidemic prevention and control resulted in changes in future employment region and income. COVID-19 can lead medical students with psychological problems to have a negative attitude toward future employment. Encouragingly, multiple activities, namely, proactive consideration of employment, taking part in career planning training lectures and timely adjustment of career planning, were beneficial to the professional identity of medical students. Conclusion: This study suggests that medical student psychology is influenced by COVID-19 and academic and financial pressures; actively coping with COVID-19 and making career planning in advance will contribute to optimizing future employment. Our findings provide a potent guideline for relevant departments to accurately adjust job deployment and for medical students to actively choose a career in the future.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection.

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection

Booster immunizations and breakthrough infections can elicit SARS-CoV-2 Omicron subvariants neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4–6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants. Graphical Zhu et al. report that a two-dose CoronaVac or ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity and Delta, BA.1 and BA.2 breakthrough infection induce neutralization against earlier Omicron variants, but not for BQ.1.1 and XBB, up to 5 months after vaccination or infection.

A new method for solving the mobile payment scheduling problem using harris hawks optimization algorithm during the COVID-19 pandemic

The Coronavirus Disease 2019 (COVID-19) epidemic is causing once-in-a-century upheavals in global civilization. Payment systems have advanced lately, from simple cash or credit card transactions to various forms of mobile payment systems. This transformation is occurred due to COVID 19 and shifts in the economy, the growth of social networks, technical advancements on the Internet, and the increased usage of mobile devices. Throughout COVID19, this article offers a unique approach to the payment scheduling issue, which seeks out a timetable that enhances the project's stakeholders' benefit. Both the sponsor and the contractor in a project want to have a strong payment plan on their own. To create an equal schedule between the sponsor and the development team, the timing of payments and the completion periods of project activities are decided concurrently. The Harris hawks optimization method is designed to tackle the problem because of its high NP-hardness. Harris hawks optimization is a novel meta-heuristic nature-inspired optimizer inspired by how Harris hawks hunt food in nature. By comparing the suggested Harris hawks optimization optimizer to existing nature-inspired methods, the efficacy of the suggested Harris hawks optimization optimizer is determined. The Harris hawks optimization algorithm appears to be highly promising based on the statistical findings and comparisons. The MATLAB simulator's simulation findings confirm the algorithm's superiority over earlier efforts regarding energy, cost, delay time, and net value.

It is time to acknowledge coronavirus transmission via frozen and chilled foods: Undeniable evidence from China and lessons for the world.

Since the broke out of the novel coronavirus disease at the end of 2019, nearly 650 million people have been infected around the globe, and >6.6 million have died from this disease. The first wave of infections in mainland China had been effectively controlled within a short period, with no domestic cases of infection for 56 consecutive days from April 16, 2020. Nonetheless, the re-emergence of several outbreaks in multiple Chinese cities posed a new challenge for public health authorities after new cases of infections were found in Xinfadi Market in Beijing on June 11, 2020. In the following series of re-emergent outbreaks, findings from epidemiological investigations suggested that more than twenty re-emergent outbreaks were caused by fomite transmission, predominantly via imported frozen and chilled foods contaminated by the SARS-CoV-2 virus. Seven of the eleven incidents involving frozen and chilled foods were identified by screening individuals with occupational exposure to imported cold-chain foods and associated individuals. Evidence showed that low temperatures and poor ventilation typically maintained through cold-chain logistics create amenable environments for the survival of SARS-CoV-2, making transnational cold chain logistics a congenial vehicle to spread the virus through global transport of consumer goods. To address this gap, here we present a scrutiny of the findings from epidemiological investigations in recent re-emergent outbreaks in China caused by fomite transmission via imported foods and goods. A national regime of traceable cold-chain foods and reinforced customs inspection protocols were established by public health authorities in mainland China as emergency responses to recurring outbreaks from fomite transmission via imported goods. We urge that more attention needs to be given to this specific route of pathogenic transmission to ensure biosecurity and to increase the preparedness for epidemic or pandemic scenarios by the global food industry and logistics carriers.

Corrigendum to: Do Stay at Home Orders and Cloth Face Coverings Control COVID-19 in New York City? Results From a SIER Model Based on Real-world Data.

[This corrects the article DOI: 10.1093/ofid/ofaa442.].

Sulfur atom modification on thymine improves the specificity and sensitivity of DNA polymerization and detection.

Although accurate base-pairing ensures specificity of molecular recognition, DNA polymerization and DNA amplification, there are many non-specific pairings that arise from mismatched pairs, such as the T/G wobble pair. We have found that by using 2-S-TTP (STTP), we can minimize T/G mismatch, improve the DNA polymerization specificity and enhance the detection sensitivity (up to 20 fold), without significantly compromising the polymerization efficiency (the extension rate ratio of TTP vs.STTP is 1.08). With the STTP strategy, DNA polymerization is more specific and allows the detection of pathogens (such as COVID-19) in single digits (up to 5 copies), which is not possible with conventional RT-PCR. We have discovered that STTP can generally promote much higher specificity and sensitivity in DNA polymerization and nucleic acid detection than canonical TTP.

MultiR-Net: A Novel Joint Learning Network for COVID-19 segmentation and classification.

The outbreak of COVID-19 has caused a severe shortage of healthcare resources. Ground Glass Opacity (GGO) and consolidation of chest CT scans have been an essential basis for imaging diagnosis since 2020. The similarity of imaging features between COVID-19 and other pneumonia makes it challenging to distinguish between them and affects radiologists' diagnosis. Recently, deep learning in COVID-19 has been mainly divided into disease classification and lesion segmentation, yet little work has focused on the feature correlation between the two tasks. To address these issues, in this study, we propose MultiR-Net, a 3D deep learning model for combined COVID-19 classification and lesion segmentation, to achieve real-time and interpretable COVID-19 chest CT diagnosis. Precisely, the proposed network consists of two subnets: a multi-scale feature fusion UNet-like subnet for lesion segmentation and a classification subnet for disease diagnosis. The features between the two subnets are fused by the reverse attention mechanism and the iterable training strategy. Meanwhile, we proposed a loss function to enhance the interaction between the two subnets. Individual metrics can not wholly reflect network effectiveness. Thus we quantify the segmentation results with various evaluation metrics such as average surface distance, volume Dice, and test on the dataset. We employ a dataset containing 275 3D CT scans for classifying COVID-19, Community-acquired Pneumonia (CAP), and healthy people and segmented lesions in pneumonia patients. We split the dataset into 70% and 30% for training and testing. Extensive experiments showed that our multi-task model framework obtained an average recall of 93.323%, an average precision of 94.005% on the classification test set, and a 69.95% Volume Dice score on the segmentation test set of our dataset.

Loneliness, depression, anxiety, and post-traumatic stress disorder among Chinese adults during COVID-19: A cross-sectional online survey.

OBJECTIVES: This study aims to investigate the potential factors associated with mental health outcomes among Chinese adults during the Coronavirus disease 2019 (COVID-19) epidemic. METHODS: This is an online cross-sectional survey conducted among Chinese adults in February 2020. Outcome measurements included the three-item UCLA Loneliness Scale (UCLA-3), two-item Patient Health Questionnaire (PHQ-2), two-item Generalized Anxiety Disorder Questionnaire (GAD-2), and two items from the Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale. COVID-19 related factors, physical health, lifestyle, and self-efficacy were also measured. Univariable and multivariable logistic regressions were performed. RESULTS: This study included 1456 participants (age: 33.8±10.5 years; female: 59.1%). The prevalence of depressive symptoms, anxiety symptoms, loneliness, and PTSD symptoms were 11.3%, 7.6%, 38.7%, and 33.9%, respectively. In multivariable analysis, loneliness was associated with being single, separated/divorced/widowed, low level of education, current location, medication, more somatic symptoms, lower self-efficacy, and going out frequently. Depression was associated with fear of infection, binge drinking, more somatic symptoms, lower self-efficacy, and longer screen time. Anxiety was associated with more somatic symptoms and lower self-efficacy. PTSD symptoms were associated with more somatic symptoms, lower self-efficacy, higher perceived risk of infection, fear of infection, and self-rated more negative influence due to the epidemic (p<0.05). CONCLUSIONS: Mental health problems during the COVID-19 epidemic were associated with various biopsychosocial and COVID-19 related factors. Psychological interventions should be aware of these influencing factors and prioritize support for those people at higher risk.

Physical and mental health outcomes including behavior and attitudes in people having social contacts with COVID-19 patients

The novel coronavirus (COVID-19) infection has spread worldwide since late 2019. People who have social contacts with COVID-19 patients might be at higher risk of physical or mental health problems. This study investigated whether people who had social contacts with COVID-19 patients would have poorer physical or mental outcomes, and different attitudes and behaviors. Chinese adults were recruited to fill in an online survey using snowball sampling during 21st-26nd February 2020. Physical symptoms, psychological outcomes, quality of life, COVID-19 related attitudes, and behaviors were measured. The differences in the outcomes between participants who had COVID-19 social contacts and those who had not were analyzed. The survey included 1,447 non-infected eligible participants. Among those, 173 (12.0%) reported at least one confirmed/suspected case in their social contacts. In the multiple regression adjusted for demographic data, the presence of confirmed/suspected infection cases in one's social contacts was significantly associated with poorer physical and mental outcomes, lower health-related quality of life, and different COVID-19 related attitudes and behaviors (p < 0.05). In conclusion, people who had social contacts with COVID-19 patients were at risk of adverse health outcomes. Future studies are needed to understand the long-term impacts. Similarly, strategies to improve health outcomes for these people are needed.

A severe case of human coronavirus 229E pneumonia in an elderly man with diabetes mellitus: a case report.

BACKGROUND: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults. CASE PRESENTATION: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed. CONCLUSION: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.

Impact of COVID-19 on loneliness, mental health, and health service utilisation: a prospective cohort study of older adults with multimorbidity in primary care.

BACKGROUND: The COVID-19 pandemic has impacted the psychological health and health service utilisation of older adults with multimorbidity, who are particularly vulnerable. AIM: To describe changes in loneliness, mental health problems, and attendance to scheduled medical care before and after the onset of the COVID-19 pandemic. DESIGN AND SETTING: Telephone survey on a pre-existing cohort of older adults with multimorbidity in primary care. METHOD: Mental health and health service utilisation outcomes were compared with the outcomes before the onset of the COVID-19 outbreak in Hong Kong using paired t-tests, Wilcoxon's signed-rank test, and McNemar's test. Loneliness was measured by the De Jong Gierveld Loneliness Scale. The secondary outcomes (anxiety, depression, and insomnia) were measured by the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder tool, and the Insomnia Severity Index. Appointments attendance data were extracted from a computerised medical record system. Sociodemographic factors associated with outcome changes were examined by linear regression and generalised estimating equations. RESULTS: Data were collected from 583 older (≥60 years) adults. There were significant increases in loneliness, anxiety, and insomnia, after the onset of the COVID-19 outbreak. Missed medical appointments over a 3-month period increased from 16.5% 1 year ago to 22.0% after the onset of the outbreak. In adjusted analysis, being female, living alone, and having >4 chronic conditions were independently associated with increased loneliness. Females were more likely to have increased anxiety and insomnia. CONCLUSION: Psychosocial health of older patients with multimorbidity markedly deteriorated and missed medical appointments substantially increased after the COVID-19 outbreak.

Do Stay at Home Orders and Cloth Face Coverings Control COVID-19 in New York City? Results From a SIER Model Based on Real-world Data.

BACKGROUND: Public health interventions have been implemented to contain the outbreak of coronavirus disease 2019 (COVID-19) in New York City. However, the assessment of those interventions-for example, social distancing and cloth face coverings-based on real-world data from published studies is lacking. METHODS: The Susceptible-Exposed-Infectious-Removed (SEIR) compartmental model was used to evaluate the effect of social distancing and cloth face coverings on the daily culminative laboratory confirmed cases in New York City (NYC) and COVID-19 transmissibility. The latter was measured by Rt reproduction numbers in 3 phases that were based on 2 interventions implemented during this timeline. RESULTS: Transmissibility decreased from phase 1 to phase 3. The initial R0 was 4.60 in phase 1 without any intervention. After social distancing, the Rt value was reduced by 68%, while after the mask recommendation, it was further reduced by ~60%. CONCLUSIONS: Interventions resulted in significant reduction of confirmed case numbers relative to predicted values based on the SEIR model without intervention. Our findings highlight the effectiveness of social distancing and cloth face coverings in slowing down the spread of severe acute respiratory syndrome coronavirus 2 in NYC.

Protection against COVID-19 injury by qingfei paidu decoction via anti-viral, anti-inflammatory activity and metabolic programming.

Qingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.

Transmission Potential of Asymptomatic and Paucisymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections: A 3-Family Cluster Study in China.

Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.

What Caused the Outbreak of COVID-19 in China: From the Perspective of Crisis Management.

Since the first known case of a COVID-19 infected patient in Wuhan, China on 8 December 2019, COVID-19 has spread to more than 200 countries, causing a worldwide public health crisis. The existing literature fails to examine what caused this sudden outbreak from a crisis management perspective. This article attempts to fill this research gap through analysis of big data, officially released information and other social media sources to understand the root cause of the crisis as it relates to China's current management system and public health policy. The article draws the following conclusions: firstly, strict government control over information was the main reason for the early silencing of media announcements, which directly caused most people to be unprepared and unaware of COVID-19. Secondly, a choice between addressing a virus with an unknown magnitude and nature, and mitigating known public panic during a politically and culturally sensitive time, lead to falsehood and concealment. Thirdly, the weak autonomous management power of local public health management departments is not conducive for providing a timely response to the crisis. Finally, the privatization of many state-owned hospitals led to the unavailability of public health medical resources to serve affected patients in the Wuhan and Hubei Province. This article suggests that China should adopt a Singaporean-style public health crisis information management system to ensure information disclosure and information symmetry and should use it to monitor public health crises in real time. In addition, the central government should adopt the territorial administration model of a public health crisis and increase investment in public health in China.