Experience of parents in delivering pediatric tuina to children with symptoms of attention deficit hyperactivity disorder during the COVID-19 pandemic: qualitative findings from focus group interviews.

BACKGROUND: Evidence suggests that pediatric tuina, a modality of traditional Chinese medicine (TCM), might have beneficial effects on the symptoms of attention deficit hyperactivity disorder (ADHD), such as overall improvements in concentration, flexibility, mood, sleep quality, and social functioning. This study was conducted to understand the facilitators and barriers in the delivery of pediatric tuina by parents to children with ADHD symptoms. METHODS: This is a focus group interview embedded in a pilot randomized controlled trial on parent-administered pediatric tuina for ADHD in preschool children. Purposive sampling was employed to invite 15 parents who attended our pediatric tuina training program to participate voluntarily in three focus group interviews. The interviews were audio-recorded and transcribed verbatim. The data were analyzed through template analysis. RESULTS: Two themes were identified: (1) facilitators of intervention implementation and (2) barriers to intervention implementation. The theme of the facilitators of intervention implementation included the subthemes of (a) perceived benefits to children and parents, (b) acceptability to children and parents, (c) professional support, and (d) parental expectations of the long-term effects of the intervention. The theme of barriers to intervention implementation included the subthemes of (a) limited benefits for children's inattention symptoms, (b) manipulation management difficulties, and (c) limitations of TCM pattern identification. CONCLUSION: Perceived beneficial effects on the children's sleep quality and appetite and parent-child relationships, as well as timely and professional support, mainly facilitated the implementation of parent-administered pediatric tuina. Slow improvements in the children's inattention symptoms and the possible inaccuracies of online diagnosis were the dominant barriers of the intervention. Parents have high expectations for the provision of long-term professional support during their practice of pediatric tuina. The intervention presented here can be feasibly used by parents.

"How are You Doing?" on the Healthy Aging of the Community-Dwelling Oldest-Old in the Shadow of the COVID-19 Pandemic.

OBJECTIVE: Globally, the oldest-old population is growing rapidly. Little is known about the perceived well-being of the community-dwelling oldest-old, especially during the COVID-19 pandemic. This study examined the oldest-old's perceptions of aging well and the COVID-related impacts on them. METHODS: Semi-structured in-depth interviews with 22 adults aged 85 or above were conducted with purposive sampling methods. Transcripts were analyzed using thematic analysis. RESULTS: Four main themes emerged: 1) sustaining functional ability; 2) staying active with a positive attitude; 3) feeling grateful for support from society and family; 4) COVID-19-related anxieties and policies destabilizing their well-being. DISCUSSION: This study provides direct evidence from the oldest-old on how they maintained their well-being. While they valued support from society and family, COVID-19-related measures disturbed their routines and prevented them from self-attaining well-being. The findings should be considered when developing interventions for this vulnerable group.

Tocilizumab, an IL6-receptor antibody, proved effective as adjuvant therapy for cytokine storm induced by severe infection in patients with hematologic malignancy.

Patients with hematological malignancies who experience severe infections are at risk of developing dangerous complications due to excessive inflammatory cytokines. To improve the prognosis, it is crucial to identify better ways to manage the systemic inflammatory storm after infection. In this study, we evaluated four patients with hematological malignancies who developed severe bloodstream infections during the agranulocytosis phase. Despite receiving antibiotics, all four patients presented elevated serum IL-6 levels as well as persistent hypotension or organ injury. Adjuvant therapy with tocilizumab, an IL-6-receptor antibody, was administered, and three of the four patients showed significant improvement. Unfortunately, the fourth patient died due to multiple organ failure caused by antibiotic resistance. Our preliminary experience suggests that tocilizumab, as an adjuvant therapy, may help alleviate systemic inflammation and reduce risk of organ injury in patients with elevated IL-6 levels and severe infection. Further randomized controlled trials are needed to confirm the effectiveness of this IL-6 targeting approach.

Long-term variations and potency of neutralizing antibodies against Omicron subvariants after CoronaVac-inactivated booster: A 7-month follow-up study.

The long-term protective efficacy of neutralizing antibodies (Nabs) against Omicron subvariants after inactivated booster vaccines remains elusive. During the follow-up study, 54 healthy volunteers aged 20-31 years received inactivated CoronaVac booster vaccinations and were monitored for 221 days. The dynamic efficacy and durability of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.2, and BA4/5 were assessed using a pseudotyped virus neutralization assay at up to nine time points post immunization. The antibody response against Omicron subvariants was substantially weaker than D614G, with BA.4/5 being the least responsive. The geometric mean titer (GMT) of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.1, and BA.4/5 was 2.2-, 1.7-, 1.8-, and 2.2-fold lower than that against D614G (ps < 0.0001). The gap in Nab response between Omicron subvariants was pronounced during the 2 weeks-2 months following booster vaccination (ps < 0.05). Seven months post booster, the antibody potency against D614G was maintained at 100% (50% for Nab titers ≥ 100 50% inhibitory dilution [EC50 ]), whereas at 77.3% for BA.1, 90.9% for BA.2, 86.4% for BA.2.12.1, and 86.4% for BA.4/5 (almost 20% for Nab titers ≥ 100 EC50 ). Despite the inevitable immune escape, Omicron subvariants maintained sustained and measurable antibody potency post-booster vaccination during long-term monitoring, which could help optimize immunization strategies.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery.

People with acute COVID-19 due to SARS-CoV-2 infection experience a range of symptoms, but major factors contributing to severe clinical outcomes remain to be understood. Emerging evidence suggests associations between the gut microbiome and the severity and progression of COVID-19. To better understand the host-microbiota interactions in acute COVID-19, we characterized the intestinal microbiome of patients with active SARS-CoV-2 infection in comparison to recovered patients and uninfected healthy controls. We performed 16S rRNA sequencing of stool samples collected between May 2020 and January 2021 from 20 COVID-19-positive patients, 20 COVID-19-recovered subjects and 20 healthy controls. COVID-19-positive patients had altered microbiome community characteristics compared to the recovered and control subjects, as assessed by both α- and ß-diversity differences. In COVID-19-positive patients, we observed depletion of Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae, as well as decreased relative abundances of the genera Faecalibacterium, Adlercreutzia, and the Eubacterium brachy group. The enrichment of Prevotellaceae with COVID-19 infection continued after viral clearance; antibiotic use induced further gut microbiota perturbations in COVID-19-positive patients. In conclusion, we present evidence that acute COVID-19 induces gut microbiota dysbiosis with depletion of particular populations of commensal bacteria, a phenomenon heightened by antibiotic exposure, but the general effects do not persist post-recovery.

Pseudorabies virus-induced expression and antiviral activity of type I or type III interferon depend on the type of infected epithelial cell.

Type I and III Interferons (IFNs) are the initial antiviral cytokines produced in response to virus infection. These IFNs in turn bind to their respective receptors, trigger JAK-STAT signaling and induce the expression of IFN-stimulated genes (ISGs) to engage antiviral functions. Unlike the receptor for type I IFNs, which is broadly expressed, the expression of the type III IFN receptor is mainly confined to epithelial cells that line mucosal surfaces. Accumulating evidence has shown that type III IFNs may play a unique role in protecting mucosal surfaces against viral challenges. The porcine alphaherpesvirus pseudorabies virus (PRV) causes huge economic losses to the pig industry worldwide. PRV first replicates in the respiratory tract, followed by spread via neurons and via lymph and blood vessels to the central nervous system and internal organs, e.g. the kidney, lungs and intestinal tract. In this study, we investigate whether PRV triggers the expression of type I and III IFNs and whether these IFNs exert antiviral activity against PRV in different porcine epithelial cells: porcine kidney epithelial cells (PK-15), primary respiratory epithelial cells (PoREC) and intestinal porcine epithelial cells (IPEC-J2). We show that PRV triggers a multiplicity of infection-dependent type I IFN response and a prominent III IFN response in PK-15 cells, a multiplicity of infection-dependent expression of both types of IFN in IPEC-J2 cells and virtually no expression of either IFN in PoREC. Pretreatment of the different cell types with equal amounts of porcine IFN-λ3 (type III IFN) or porcine IFN-α (type I IFN) showed that IFN-α, but not IFN-λ3, suppressed PRV replication and spread in PK-15 cells, whereas the opposite was observed in IPEC-J2 cells and both types of IFN showed anti-PRV activity in PoREC cells, although the antiviral activity of IFN-α was more potent than that of IFN-λ3 in the latter cell type. In conclusion, the current data show that PRV-induced type I and III IFN responses and their antiviral activity depend to a large extent on the epithelial cell type used, and for the first time show that type III IFN displays antiviral activity against PRV in epithelial cells from the respiratory and particularly the intestinal tract.

Clinical significance of neutrophil extracellular traps biomarkers in thrombosis.

Neutrophil extracellular traps (NETs) may be associated with the development of thrombosis. Experimental studies have confirmed the presence of NETs in thrombi specimens and potential role of NETs in the mechanisms of thrombosis. Clinical studies also have demonstrated significant changes in the levels of serum or plasma NETs biomarkers, such as citrullinated histones, myeloperoxidase, neutrophil elastase, nucleosomes, DNA, and their complexes in patients with thrombosis. This paper aims to comprehensively review the currently available evidence regarding the change in the levels of NETs biomarkers in patients with thrombosis, summarize the role of NETs and its biomarkers in the development and prognostic assessment of venous thromboembolism, coronary artery diseases, ischemic stroke, cancer-associated thromboembolism, and coronavirus disease 2019-associated thromboembolism, explore the potential therapeutic implications of NETs, and further discuss the shortcomings of existing NETs biomarkers in serum and plasma and their detection methods.

Sarcopenia and its association with objectively measured life-space mobility and moderate-to-vigorous physical activity in the oldest-old amid the COVID-19 pandemic when a physical distancing policy is in force.

INTRODUCTION: The oldest-old are highly vulnerable to sarcopenia. Physical distancing remains a common and effective infection-control policy to minimize the risk of COVID-19 transmission during the pandemic. Sarcopenia is known to be associated with impaired immunity. Moderate-to-vigorous physical activity (MVPA) and life-space mobility (LSM) are potential strategies for minimizing the risk of sarcopenia. However, a physical distancing policy might jeopardize the practice of MVPA and LSM. The purposes of this study were to identify the prevalence of sarcopenia and examine the association between MVPA and LSM with sarcopenia in the community-dwelling oldest-old during the COVID-19 pandemic. METHODS: This study employed a cross-sectional and observational design. The study was conducted in 10 community centres for older people in Hong Kong during the period of the COVID-19 pandemic (September to December 2020). Eligible participants were the oldest-old people aged ≥85 years, who were community-dwelling and had no overt symptoms of cognitive impairment or depression. Key variables included sarcopenia as measured by SARC-F, LSM as measured by a GPS built into smartphones, and MVPA as measured by a wrist-worn ActiGraph GT3X+. Variables were described by mean and frequency. A multiple linear regression was employed to test the hypotheses. The dependent variable was sarcopenia and the independent variables included LSM and MVPA. RESULTS: This study recruited 151 eligible participants. Their mean age was 89.8 years and the majority of them were female (n = 93/151, 61.6%). The prevalence of sarcopenia was 24.5% (n = 37/151) with a margin of error of 6.86%. MVPA was negatively associated with sarcopenia in older people (ß = - 0.002, SE = 0.001, p = 0.029). However, LSM was not associated with sarcopenia. CONCLUSION: The prevalence of sarcopenia in the community-dwelling oldest-old population is high. MVPA is negatively associated with sarcopenia. LSM is unrelated to sarcopenia. Sarcopenia should be recognized and the oldest-old with sarcopenia should be accorded priority treatment during the COVID-19 pandemic.

A Gradient pH-Sensitive Polymer-Based Antiviral Strategy via Viroporin-Induced Membrane Acidification.

Lipid-membrane-targeting strategies hold great promise to develop broad-spectrum antivirals. However, it remains a big challenge to identify novel membrane-based targets of viruses and virus-infected cells for development of precision targeted approaches. Here, it is discovered that viroporins, viral-encoded ion channels, which have been reported to mediate release of hydrogen ions, trigger membrane acidification of virus-infected cells. Through development of a fine-scale library of gradient pH-sensitive (GPS) polymeric nanoprobes, the cellular membrane pH transitions are measured from pH 6.8-7.1 (uninfection) to pH 6.5-6.8 (virus-infection). In response to the subtle pH alterations, the GPS polymer with sharp response at pH 6.8 (GPS6.8 ) selectively binds to virus-infected cell membranes or the viral envelope, and even completely disrupts the viral envelope. Accordingly, GPS6.8 treatment exerts suppressive effects on a wide variety of viruses including SARS-CoV-2 through triggering viral-envelope lysis rather than affecting immune pathway or viability of host cells. Murine viral-infection models exhibit that supplementation of GPS6.8 decreases viral titers and ameliorates inflammatory damage. Thus, the gradient pH-sensitive nanotechnology offers a promising strategy for accurate detection of biological pH environments and robust interference with viruses.

Combining nanotechnology with the multifunctional roles of neutrophils against cancer and inflammatory disease.

Neutrophils, the most abundant leukocytes in humans, play a crucial role in acute inflammation during infection and tumorigenesis. Neutrophils are the major types of cells recruited to the inflammation sites induced by pathogens, exhibiting great homing ability towards inflammatory disorders and tumor sites. Therefore, a neutrophil-based drug delivery system (NDDS) has become a promising platform for anti-cancer and anti-inflammatory treatment. Recent decades have witnessed the huge progress of applying nanomaterials in drug delivery. Nanomaterials are regarded as innovative components to enrich the field of neutrophil-based therapies due to their unique physiochemical characteristics. In this review, the latest advancement of combining diverse nanomaterials with an NDDS for cancer and inflammatory disease treatment will be summarized. It is discussed how nanomaterials empower the therapeutic area of an NDDS and how an NDDS circumvents the limitations of nanomaterials. Moreover, based on the finding that neutrophils are closely involved in the progression of cancer and inflammatory diseases, emerging therapeutic strategies that target neutrophils will be outlined. Finally, as neutrophils were demonstrated to play a central role in the immunopathology of COVID-19, which causes necroinflammation that is responsible for the cytokine storm and sepsis during coronavirus infections, novel therapeutic approaches that anchor neutrophils against the pathological consequences related to COVID-19 will be highlighted as well.

Patient and Clinical Factors at Admission Affect the Levels of Neutralizing Antibodies Six Months after Recovering from COVID-19.

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAbhigh, n = 153) and low (NAblow, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAblow group, a larger proportion of the NAbhigh group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) µg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO2 levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657-0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.

The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion.

Virus infection has been consistently threatening public health. The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. cGAS recognizes the pathogenic DNA in the cytosol and then synthesizes 2'3'-cyclic GMP-AMP (2'3'cGAMP). As the second messenger, cGAMP activates STING and induces the following cascade to produce type I interferon (IFN-I) to protect against infections. However, viruses have evolved numerous strategies to hinder the cGAS-STING signal transduction, promoting their immune evasion. Here we outline the current status of the viral evasion mechanism underlying the regulation of the cGAS-STING pathway, focusing on how post-transcriptional modifications, viral proteins, and non-coding RNAs involve innate immunity during viral infection, attempting to inspire new targets discovery and uncover potential clinical antiviral treatments.

Separable Microneedle Patch to Protect and Deliver DNA Nanovaccines Against COVID-19.

The successful control of coronavirus disease 2019 (COVID-19) pandemic is not only relying on the development of vaccines, but also depending on the storage, transportation, and administration of vaccines. Ideally, nucleic acid vaccine should be directly delivered to proper immune cells or tissue (such as lymph nodes). However, current developed vaccines are normally treated through intramuscular injection, where immune cells do not normally reside. Meanwhile, current nucleic acid vaccines must be stored in a frozen state that may hinder their application in developing countries. Here, we report a separable microneedle (SMN) patch to deliver polymer encapsulated spike (or nucleocapsid) protein encoding DNA vaccines and immune adjuvant for efficient immunization. Compared with intramuscular injection, SMN patch can deliver nanovaccines into intradermal for inducing potent and durable adaptive immunity. IFN-γ+CD4/8+ and IL-2+CD4/8+ T cells or virus specific IgG are significantly increased after vaccination. Moreover, in vivo results show the SMN patches can be stored at room temperature for at least 30 days without decreases in immune responses. These features of nanovaccines-laden SMN patch are important for developing advanced COVID-19 vaccines with global accessibility.

Determinants and Dynamics of SARS-CoV-2 Infection in a Diverse Population: 6-Month Evaluation of a Prospective Cohort Study.

BACKGROUND: We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population. METHODS: A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months. RESULTS: Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4-3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels. CONCLUSIONS: In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection.Clinical Trials Registration. NCT04336215.

Interaction of serum proteins with SARS-CoV-2 RBD.

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systematically investigate the interaction of serum proteins with the SARS-CoV-2 RBD by molecular docking and all-atom molecular dynamics simulations. It is found that non-specific immunoglobulins (Ig) indeed cannot effectively bind to the SARS-CoV-2 RBD while human serum albumin (HSA) may have some potential in blocking its infection (to ACE2). More importantly, we find that the RBD can cause significant structural changes in Apolipoprotein E (ApoE), by which SARS-CoV-2 may hijack the metabolic pathway of ApoE to facilitate its cell entry. The present study enhances the understanding of the role of protein corona in the bio-behaviors of SARS-CoV-2, which may aid the more precise and personalized treatment for COVID-19 infection in the clinic.

Colloidal gold immunochromatographic assay (GICA) is an effective screening method for identifying detectable anti-SARS-CoV-2 neutralizing antibodies.

INTRODUCTION: A large number of COVID-19 patients are in recovery, and millions of people are vaccinated for COVID-19 globally. This calls for a rapid screening strategy of SARS-CoV-2 protective antibodies, generated in rehabilitated and vaccinated populations. METHODS: Serum samples collected over a follow-up period of six months from 306 COVID-19 cases discharged from Wuhan Tongji Hospital were analyzed. Anti-S Abs were detected by colloidal gold immunochromatographic assay (GICA), and neutralizing antibodies (nAbs) were detected by chemiluminescent microparticle immunoassay (CMIA). RESULTS: Most COVID-19 survivors tested positive for anti-S Abs (83.7%) and nAbs (98.0%) 6 months after being discharged from the hospital, and the levels of anti-S Abs in the blood were highly positively correlated with nAbs (r = 0.652, P < 0.0001). The positivity rate of nAbs for patients with anti-S Abs positive was 100%. CONCLUSIONS: There is a good agreement between anti-S Abs detected by GICA and nAbs detected by CMIA. It indicates that anti-S Abs detected by GICA may be used as a cheaper screening strategy for detectable SARS-CoV-2 nAbs in COVID-19 convalescent individuals.

Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. METHODS: Genome-wide screening was used to establish intraviral and viral-host interactomes. Quantitative proteomics was used to investigate the peripheral blood mononuclear cell (PBMC) proteome signature in COVID-19. FINDINGS: We elucidated 286 host proteins targeted by SARS-CoV-2 and >350 host proteins that are significantly perturbed in COVID-19-derived PBMCs. This signature in severe COVID-19 PBMCs reveals a significant upregulation of cellular proteins related to neutrophil activation and blood coagulation, as well as a downregulation of proteins mediating T cell receptor signaling. From the interactome, we further identified that non-structural protein 10 interacts with NF-κB-repressing factor (NKRF) to facilitate interleukin-8 (IL-8) induction, which potentially contributes to IL-8-mediated chemotaxis of neutrophils and the overexuberant host inflammatory response observed in COVID-19 patients. CONCLUSIONS: Our study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks but it also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms, representing a powerful resource in the pursuit of therapeutic interventions. FUNDING: National Key Research and Development Project of China, National Natural Science Foundation of China, National Science and Technology Major Project, Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission, Shanghai Municipal Key Clinical Specialty, Innovative Research Team of High-level Local Universities in Shanghai, Interdisciplinary Program of Shanghai Jiao Tong University, SII Challenge Fund for COVID-19 Research, Chinese Academy of Sciences (CAS) Large Research Infrastructure of Maintenance and Remolding Project, and Chinese Academy of Sciences Key Technology Talent Program.

General practitioner trainees' career perspectives after COVID-19: a qualitative study in China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a worldwide public health emergency that has put great pressure on medical workers and the medical system. General Practitioners (GPs) played an important role in controlling the epidemic, and GP trainees also took an active part in this approach. This study was to explore Chinese GP trainees' career perspectives after COVID-19. METHODS: We conducted a qualitative research study which included 12 GP trainees from three teaching hospitals in China. Semi-structured telephone interviews were conducted. Grounded theory and thematic analysis were used to code the data and identify categories and factors. RESULTS: Eleven participants chose to continue a GP career after COVID-19, and nearly half of the participants strengthened their determination to dedicate themselves to this career. Only one participant decided to change the career choice because of interest in another specialty. Four main themes influencing GP trainees' perceptions of career development after COVID-19 emerged from the interviews: changes of GPs' work content in COVID-19, challenges of being a GP, psychological changes of the career, how to provide better primary care. Although some negative psychological changes existed, most of participants were inspired by role models and medical colleagues. They had more in-depth understanding of GPs' role and responsibility during COVID-19, and exhibited intensions for self-improvement in career development, especially in public health education and self-protection in preventing infectious diseases. In addition, the wide use of telemedicine provided a new work way for GP trainees. However, challenges, such as increased workloads, low income, lack of resources in primary medical institutions, and distrust of GPs are faced by trainees during the outbreak. CONCLUSIONS: Overall, no substantial changes were seen in the career choice of GP trainees after COVID-19 outbreak. However, they were inspired and had an in-depth understanding about the GP's work and responsibility during an epidemic. Owing to the challenges faced by the GPs, measures are needed to improve the GP education and work environment in the training phase.